Plexiinien ja semaforiinien yhteinen evolutionaalinen alkulähde selvitetty . Met RTK löytö.

torsdag 28 februari 2019

Plexiinien, semaforiinien ja MetRTK:n yhteisestä evoluutiotaustasta (suomennosta)

https://www.nature.com/articles/s41598-019-38512-y

 

Tiivistelmä (suomennosta) 

• Abstract

 Yksisoluisista monisoluisiin organismeihin siirtymisessä on tieteellinen kysymys, missä vaiheessa  evoluutiota alkoi esiintyä niitä geenejä, jotka  säätelivät solujen välisiä interaktioita.
PLEKSIINIT ja SEMAFORIINIT muodostavat  reseptori-ligandi-parin, joka säätelee  solujen  interaktioita hyvin laajalti  kehityksen aikana ja fysiologiassa.

• The transition from unicellular to multicellular organisms poses the question as to when genes that regulate cell-cell interactions emerged during evolution. The receptor and ligand pairing of plexins and semaphorins regulates cellular interactions in a wide range of developmental and physiological contexts.

Tässä tutkimuksessaan tiedemiehet tekivät katsauksen  yksisoluisista eukaryosyyteistä ja ei-bilateraalisista ja bilateraalisista  metazooista. He tekivät fylogeneettisia analyysejä   PLEKSIINIperheiden ja SEMAFORIINIperheiden   evoluutiosta. He havaitsivat pleksiinejä ja semaforiineja choanoflagellaateissa, mikä viittaisi  yhteiseen evolutionaaliseen alkuperään   Choanoflagellida ja Metazoa-linjoissa.
PLEXIINI-domeenirakenne  on kaikissa  kladeissa konservoitunut, mutta päinvastoin SEMAFORIINIT ovat  rakenteellisesti erilaisia. Choanoflagellate-semaforiinit ovat  transmembraanisia (TM) proteiineja, joissa on  useita fibronektiini- tyyppi- III-domeeneja N-terminaalisen SEMA-domeenin jälkeen ( merkitään Sema-FN).
Muita aiemmin  kirjattuja semaforiiniluokkia ovat  Ctenophora-semaforiinit, joissa on  peräkkäisiä immunoglobuliinidomeeneja (Sema-Ig)  ja  sekretoriset Echinodermata-semaforiinit (Sema-SP, Sema-SI) .
Tutkijat  tunnistivat myös  Met- reseptori tyrosiinikinaaseja, joilla oli  lyhentynyt plexiinin extrasellulaarinen domeeni ja näitä löytyi useissa bilateraalisissa kladeissa, mikä viittaisi  Bilateria- linjassa  yhteiseen  evolutionaaliseen alkuperään.
Lisäksi havaittin  uudentyyppinenkin Met-kaltainen RTK, jossa oli täydellinen  extrasellulaarinen plexiinidomeeni (Lophotrochoxoa ja Echinodermata- linjoissa) (merkitään   Met-LP RTK).
 Tutkijat vahvistavat PLEXIINIEN ja SEMAFORIINIEN   ikivanhat  funktiot sytoskeletaalisen dynamiikan ja soluadheesion säätelyssä, mistä voikin ennakoida niiden osuuden  aksoneja ohjaavina molekyyleinä.

• We surveyed here genomes of unicellular eukaryotes and of non-bilaterian and bilaterian Metazoa and performed phylogenetic analyses to gain insight into the evolution of plexin and semaphorin families. Remarkably, we detected plexins and semaphorins in unicellular choanoflagellates, indicating their evolutionary origin in a common ancestor of Choanoflagellida and Metazoa. The plexin domain structure is conserved throughout all clades; in contrast, semaphorins are structurally diverse. Choanoflagellate semaphorins are transmembrane proteins with multiple fibronectin type III domains following the N-terminal Sema domain (termed Sema-FN). Other previously not yet described semaphorin classes include semaphorins of Ctenophora with tandem immunoglobulin domains (Sema-IG) and secreted semaphorins of Echinoderamata (Sema-SP, Sema-SI). Our study also identified Met receptor tyrosine kinases (RTKs), which carry a truncated plexin extracellular domain, in several bilaterian clades, indicating evolutionary origin in a common ancestor of Bilateria. In addition, a novel type of Met-like RTK with a complete plexin extracellular domain was detected in Lophotrochozoa and Echinodermata (termed Met-LP RTK).

• Our findings are consistent with an ancient function of plexins and semaphorins in regulating cytoskeletal dynamics and cell adhesion that predates their role as axon guidance molecules.

 Johdanto

• Introduction

 PLEXIINIT ja SEMAFORIINIT  ovat solupintareseptoreita ja  ligandeja, jotka säätävät monia kehityksellisiä ja aikuisfysiologian aikaisia prosesseja. Näihin kuuluu  neuronaalinen kehitys, verisuoniston kehitys, immuunijärjestelmän aktivoituminen, luun homeostaasi ja epiteelin järjestäytyminen (organisoituminen) .

• Plexins and semaphorins are cell surface receptors and ligands that regulate multiple processes of development and adult physiology, including neural development, vascular development, immune system activation, bone homeostasis, and epithelial organization^{1,2,3,4,5,6,7,8,9}.

 SEMAFORIINIT tunnistettiin  repulsoivina (luotaantyöntävinä, karkoittavina)   aksoneja ohjaavina molekyyleinä heinäsirkoilta  ja  linnunpojilta.
PLEXIINEJÄ kuvattiin ensimmäisen  kerran Xenopus-lajin poikasten  hermojärjestelmän solupintamolekyyleistä  ja näissä PLEXIINEISSÄ  havaittiin  samanlaisia  molekulaarisia sekvenssejä   kuin Met- tyrosiinikinaasireseptorien (RTK) extrasellulaaridomeenissa.  

• Semaphorins were identified as repulsive axon guidance molecules in grasshopper and in chick^10,11. Plexins were first described as cell surface molecules in the nervous system of Xenopus tadpoles¹² and as molecules with sequence similarity to the extracellular domain of Met receptor tyrosine kinases (RTKs)¹³.

Selkärangattomien  bilateraalisten metazooien SEMAFORIINIT  ryhmiteltiin  sekvenssien samankaltaisuuden perusteella luokkiin 1 ja 2.
 Selkärankaisten SEMAFORIINIT ryhmiteltiin viiteen luokkaan: Luokat 3-7
Lisäksi  on yksi virusten semaforiinien luokka , V-luokka.
Lisätutkimukset  tunnistivat, että banaanikärpäsellä on myös luokan 5 semaforiineja, joten sitä esiintyy sekä selkärankaisissa että selkärangattomissa.
Virusten semaforiini on ilmeisesti johdannainen luokan 7 semaforiineista.
PLEXIINIT ryhmiteltiin  sekvenssiensä perusteella  mukaan  neljään  luokkaan (luokat A-D)

• Semaphorins of bilaterian Metazoa have been grouped by sequence similarity into two invertebrate classes (class 1 and 2) and five vertebrate classes (class 3–7), plus one class for viral semaphorins (class V)^14,15. Subsequent studies revealed that Drosophila melanogaster also has a class 5 semaphorin, thus class 5 semaphorins are present in both vertebrates and invertebrates¹⁶. The viral semaphorins appear to be all derived from class 7 semaphorins¹⁷.
• The plexins of vertebrates were grouped by sequence similarity into 4 classes (class A-D)¹⁸.

 Sekä PLEXIINEILLÄ että SEMAFORIINEILLA on rakenteellinen tunnusmerkkinsä. Se on N-terminaalinen Sema-domeeni, joka on  "seitsensiipinen beta-propelli", jossa  joka siipi muodostuu  neljästä antiparalleelista beta-tupesta.  Tällainen Sema-domeeni esiintyy yksinomaan plexiineissä, semaforiineissa ja Met-reseptorityrosiinikinaaseissa (Met RTK).  Plexiinit ja semaforiinit sitoutuvat toisiinsa juurin näiden  vastaavien Sema-domeeniensa  välityksellä.  Mutta Met RTK taas sitoo erittyneitä kasvutekijöitä kuten maksasolun kasvutekijää (HGF), joka on rakenteellisesti  semaforiineista poikkeava.

• Both plexins and semaphorins contain a structural hallmark: an N-terminal Sema domain, which is a seven-blade beta-propeller, with each blade formed by four anti-parallel beta-strands¹⁹. The Sema domain is exclusive of plexins, semaphorins, and Met RTKs¹⁹. Plexins and semaphorins bind to each other through their respective Sema domains^20,21,22. Met RTKs, on the other hand, bind to secreted growth factors such as hepatocyte growth factor (HGF) that are structurally different from semaphorins²³.

 NEUROPILIINIEN osuus: Luokan 3 semaforiinien  sitoutumisessa tarvitaan koreseptorina  neuropiliiniä, joka tekee kompleksin plexiinin kanssa. Näihin asti  ollaan oltu  sitä mieltä, että neuropiliinejä esiintyy vain selkäranakaisissa, vaikka  erittyneen semaforiinin koreseptorina toimii
C. Elegansissa  L1CAM -homologi LAD-2, mikä viittaisi siihen, että  selkärangattomissakin hyödynnettäneen  koreseptoria erittyneiden semaforiinin  sitomiseen. 

• For the binding of secreted class 3 semaphorins, neuropilin transmembrane proteins act as required co-receptors in a complex with plexins²⁴. To date, Neuropilins are considered exclusive of vertebrates²⁵, although in Caenorhabditis elegans, the L1CAM homolog LAD-2 acts as co-receptor for secreted semaphorins²⁶, suggesting that invertebrates may utilize other co-receptors for the binding of secreted semaphorins.

Minkälainen on PLEXIININ Sema-domeeni?
PLEXIINIEN Sema-domeenia seuraa  tyypillisesti PSI-domeeni (Plexiini, Semaforiini ja Integriini), joka on noin  50-60 aminohapon  pituinen kooltaan ja käsittää  konservoitua cysteiiniaminohappoa ja keskeisen  CxWC- motiivin.
 Plexiineillä on myös extrasellulaarinen IPT-domeeni ( Immunoglobuliinin kaltainen poimu, jonka jakaa keskenään Pleksiini ja Transkriptiotekijät) ja se on noin 95 aminohappoa ja muodostaa  beetatuppikimpun  jossa on on kaksi konservoitua cysteiiniä.
 Kidetutkimuksista on havaittu, että plexiinin extrasellulaaridomeenit muodostavat yhdessä  rengasrakenteen, jossa on Sema-domeenin perässä  kolme peräkkäistä PSI-IPT-jaksoa ja lisäksi kolme IPT- jaksoa, siis: Sema-PSI-IPT-PSI-IPT-IPT-IPT-IPT-TM ( transmembraaninen osa) . Poikkeuksia tästä plexiinin sterotyyppisestä  rakenteesta ovat  Plexiini-B1, jolla  on liitännäinen toisessa PSI-domeenissaan ja Plexiini-C1, jolta puuttuu yksi PSI-domeeni ja 2 IPT-domeenia.

• The Sema domain of plexins is typically followed by a PSI domain (plexins, semaphorins, and integrins), which is ~50–60 aa in size and contains up to 8 conserved cysteines with a central conserved CxWC motif ²⁷. Plexins also contain extracellular IPT domains (immunoglobin-like fold shared by plexins and transcription factors), which are ~95 aa in size, forming a beta-sheet bundle with two central conserved cysteines²⁷. It has been an intriguing finding from crystallographic studies that the plexin extracellular domains form together a ring structure, which consists of a Sema domain followed by three consecutive PSI-IPT domains and three more IPT domains, i.e. Sema-PSI-IPT-PSI-IPT-PSI-IPT-IPT-IPT-IPT-TM^28,29. Exceptions to this stereotypic domain pattern are Plexin-B1, which carries an insert in its second PSI domain, and Plexin-C1, which lacks one PSI and two IPT domains.

 Mitä on PLEXIINIEN  solunsisäisessä jaksossa, intrasellulaariosassa?
Plexiinissä on sytosoliin (solulimaan)  ulottuvassa  intrasellulariosassa  Ras-GAP (GTPaasia aktivoiva proteiini)-domeeni, joka inaktivoi pieniä G-proteiineja Rap1/2 perheestä.
Rap1/2 G-proteiineilla   on pleiotrooppinen verkostonsa effektoreita, vaikuttavia tekijöitä, jotka kontrolloivat  sytoskeletaalista  dynamiikkaa ja solujen adhesoitumisprosesseja.

• The intracellular part of plexins contains a Ras-GAP (GTPase activating protein) domain, which inactivates small G proteins of the Rap1/2 families³⁰. The Rap1/2 G proteins have a pleiotropic network of effectors that control cytoskeletal dynamics and cell adhesion processes³¹.

Aiemmissa   genomisissa  sekventoivissa  tutkimuksissa on tunnistettu  PLEXIINEILLÄ ja SEMAFORIINEILLA   olevan varhainen yhteinen  alkuperä  metazooisessa evoluutiossa.    Tässä tutkimuksessa  tehtiin  katsausta  lähtien  yksisoluisista eukaryosyyteistä  monimutkaisiin metazooisiin organismeihin  asti  jäljittäen   plexiinien ja semaforiinien evolutionaalista alkuperää  ja kuvattiin  niiden  intra- ja extrasellulaaristen domeenien järjestäytymiset.

• Previous genome sequencing studies have recognized that plexins and semaphorins have an early origin in metazoan evolution^32,33. In the current study, we surveyed plexins and semaphorins from unicellular eukaryotes to complex metazoan organisms to track their evolutionary origin and to describe their intra- and extracellular domains arrangements.

 Tutkijat  löysivät  PLEXIINEJÄ  ja SEMAFORIINEJA  jo chonoflagellaateilta, jotka ovat  muuan  yksisoluisten eukaryosyyttien ryhmä lähellä  metazooia.  Nämä  fylogeneettiset  analyysit viittaavat siihen, että  plexiinit ja semaforiinit  ovat  lähtöisin   chonoflagellaattojen ja metazooien yhteisestä alkulähteestä.
PLEXIINIT ovat säilyttäneet  stabiilin domeenijärjestyksen  kaikissa kladeissaan.
 SEMAFORIINIT ovat   muodostaneet evoluutiossa erilaisia luokkia vaihtelevin domeenijärjestyksin.
Mielenkiintoisena löytönä  tutkijoiden   Sema-domeenia sisältävien proteiinien analyyseissä  havaittiin uuden tyyppinen  Met:in kaltainen RTK, jossa on täydellinen  plexiinin ektodomeenirakenne.

• Remarkably, we detected plexins and semaphorins in choanoflagellates, a group of unicellular eukaryotes closely related to Metazoa³⁴. Our phylogenetic analyses suggest that plexins and semaphorins emerged in a common ancestor of choanoflagellates and Metazoa. Whereas plexins have maintained a stable domain arrangement throughout all clades, semaphorins have evolved into diverse classes with different domain arrangements. Interestingly, our analyses of Sema domain-containing proteins also revealed a novel type of Met-like RTK that contains a complete plexin ectodomain structure.

HUOM. tähän artikkeliin liittyy hyviä kuvia. Kts. LINKKI

Mitä tietoa semaforiineista löytyy suomenkielellä

http://finto.fi/mesh/fi/page/D040121 
Esimerkkinä semaforiini 3A

YLÄKÄSITE

• semaforiinit

KÄYTTÖHUOMAUTUS

MUUNKIELISET TERMIT

Semaphorin-3A

englanti

Collapsin-1

Collapsing Factor

Semaphorin D

Semaphorin 3A

Sema3A

Sem D

Collapsin 1

Collapsin

Semaforin-3A

ruotsi

http://jultika.oulu.fi/files/nbnfioulu-201705061719.pdf
Suomalainen tutkija  Ryynänen, Jussi  sanut apurahaa  luuston neuropiliini2-välitteisen semaforiinisignaloinin selvitämiseen.
Neuropilin2-välitteinen luuston semaforiini-signalointi Belgiassa.
Katolinen yliopisto, Leuven, Belgia

Tutkija Nina Perälä (Helsinki) on selvittänyt  plexiini2:ta, joka on semaforin reseptori.
 https://www.researchgate.net/publication/48336533_Plexin_B2_in_mouse_and_zebrafish_development'

Tutkija Saara Roininen  (Helsinki)  on maininnut plexiini-semaforiini-signaloinnin osuudesta munuaisen alkukehityksessa progradu-työssään, joka käsitteli ensisijaisesti  plexiini2- Ret-reseptorisignaloinnin. Semaforiinit ovat plexiinien ligandeja. 
http://urn.fi/URN:NBN:fi:hulib-201605191730

Kimmo Isoniemi  Jyväskylän yliopistossa teki pro gradutyön  2006  integriineistä  , filamiinista ja taliinista.  työssä mainitaan "PSI-domeeni"  eli  "pleksiini-semaforiini-integriini-domeeni", joka myös kaikissa semaforiiniproteiineissa on.
https://jyx.jyu.fi/bitstream/handle/123456789/11515/URN_NBN_fi_jyu-2006499.pdf?sequence=1
Teesin otsikko. Filamiini A:n ja taliinin sitoutuminen β7- ja β1A-integriinien sytoplasmisiin domeeneihin.

Hermoston kehityksestä on Oulun yliopistosta seuraava työ
http://jultika.oulu.fi/files/nbnfioulu-201605261999.pdf
Tutkija Sandra Harjuhaahto. "Hermoston kehitys –raskauden aikaisen alkoho-linkäytön vaikutus kehittyvään hermostoon"
Sitaatti: sivuilta 9 ja 10. 
"3.1.3 Neuronien erilaistuminen ja aksonien ohjautuminen kohdekudoksiin
 Hermosolujen muodostumista, neurogenesistä, säätelevät mekanismit aikaansaavat eroja neuronien rakenteessa, toiminnassa ja millaisia välittäjäainereseptoreja ne sisältävät. Neuronien erilaistumiseen vaikuttaa neuroblastien sijainnin ja syntymisajankohdan lisäksi monet transkriptiotekijät. Erityisesti bHlh-geeniperheen transkriptiotekijät säätelevät neuronien erilaistumista yhdessä muuan muassa Notch-signaaliproteiinien kanssa, jotka inhiboivat bHlh-tekijöiden erilaistumista aktivoivaa vaikutusta. Transkriptiotekijät toimivat kombinatorisesti, minkä seurauksena muodostuu erilaisia hermosolutyyppejä (Purveset al. 2008).
10 
Aktiopotentiaali välittyy neuroneissa aksoneita pitkin. Aksonien kulkeutuminen kohdekudoksiin on tärkeä osa hermoston oikeanlaista toimintaa. Aksonit kulkeutuvat kohteisiinsa kasvukartion avulla. Kulkua ohjaavat kontaktiohjaus ja kemotaksis. Kontaktiohjaus tapahtuu, kun aksoni aistii ympäristön solujen pintojen adheesiomolekyylejä. Kasvukartio aistii näiden adheesiomolekyylien muodostamia konsentraatiogradientteja. Ensimmäisen aksonin, pioneeriaksonin, saavuttua kohdekudokseen, muut samalle alueelle kulkevat aksonit hyödyntävät pioneeriaksonia kontaktiohjauksessa. Kohdesolut tuottavat lisäksi liukoisia ohjausmolekyylejä, kuten efriinit, semaforiinit ja Slit-perheen proteiinit, jotka toimivat joko aksonia houkuttelevina (attraktio)tai karkottavina (repulsio) tekijöinä, eli aksonin ohjautuminen tapahtuu kemotaksisesti. Samat signaalit ohjaavat myös hermostopienan solujen kulkeutumista (Gilbert 2014). Kasvukartiossa solun sytoskeletonin rakenteita, aktiinia ja tubuliinia, järjestetään kontrolloidusti uudelleen. Aktiinin dynaaminen polymerisaatio ja depolymerisaatio kasvukartion ulokkeessa määrittelee kasvun suunnan ja sitä kautta kasvukartion liikkeen (Purves et al. 2008). Syntyneiden neuroneiden ja niiden välisten yhteyksien määrä on kehittymisen aikana huomattavasti suurempi kuin kypsän hermoston lopullinen lukumäärä tulee olemaan. Neuronien määrää säädellään ohjelmoidun solukuoleman, apoptoosin, kautta. Neuronien eloonjäämiseen vaikuttavat ympäristön muut neuronit ja gliasolut sekä ekstrasellulaarisen tilan molekyylit. Kohdekudokset tuottavat kasvutekijöitä, neurotrofejä, jotka estävät apoptoosia. Koska kohdekudokset erittävät vain rajallisen määrän kasvutekijöitä, joutuvat neuronit kilpailemaan niistä (Sariola et al. 2006"

20 semaforiinia . lähdeartikkeleita (PubMed)

Terminologia:  Semaforiini, Semaforiner 

 https://finto.fi/mesh/sv/page/D039961

Semaphorins

2003, 2011 : ”Semaphorins constitute one of the largest families of repulsive and attractive growth cone guidance proteins. They affect the growth cone's actin cytoskeleton through interactions with receptor complexes composed of ligand-binding, signal-transducing, and modulatory subunits. Our understanding of the intracellular signal transduction machinery linking semaphorins to actin dynamics is limited; however, recent advances provide a more comprehensive view of the molecular basis of neuronal semaphorin signaling”.

” Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins.”

2010 ” Semaphorins are a large family, including both secreted and membrane associated proteins, many of which have been implicated as inhibitors or chemorepellents in axon pathfinding, fasciculation and branching, and target selection. All semaphorins possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Additional sequence motifs C-terminal to the semaphorin domain allow classification into distinct subfamilies. Results demonstrate that transmembrane semaphorins, like the secreted ones, can act as repulsive axon guidance cues. ”

(1) SEMA 3A (7q21.11) Semaphorin 3A

Muita nimiä: HH16, SemD, COLL1, SEMA1, SEMAD, SEMAL, coll-1, Hsema-1, SEMAIII, Hsema-III. Proteiini on vitaali normaalin neuronaalisen rakennemallin kehkeytymiselle. Proteiinin liiallista ilmenemää esiintyy skitsofreniassa ja eri tuumorisolulinjoissa. Proteiinin poikkeava vapautuminen liittyy Alzheimerin taudin etenemiseen.

https://www.ncbi.nlm.nih.gov/gene/10371

Also known as HH16; SemD; COLL1; SEMA1; SEMAD; SEMAL; coll-1; Hsema-I; SEMAIII; Hsema-III

Summary. This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

Expression: Broad expression in placenta (RPKM 2.5), gall bladder (RPKM 2.0) and 19 other tissues See more Orthologs mouse all

(2) SEMA4D (9q22.2) Semaphorin 4D

Muita nimiä: CD100, COLL4, SEMAJ, coll-4, C9orf154, M-sema-G.
https://www.ncbi.nlm.nih.gov/gene/10507
CD100; COLL4; SEMAJ; coll-4; C9orf164; M-sema-G

Expression Broad expression in lymph node (RPKM 12.0), appendix (RPKM 8.6) and 22 other tissues See more

Orthologs mouse all

Related articles in PubMed

1. VEGF and SEMA4D have synergistic effects on the promotion of angiogenesis in epithelial ovarian cancer. Chen Y, et al. Cell Mol Biol Lett, 2018. PMID 29308068, Free PMC Article
2. New aspects of the Seam4D-dependent control of lymphocyte activation. Kuklina EM, et al. Dokl Biol Sci, 2017 Mar. PMID 28508207
3. Genome-wide analysis identifies an african-specific variant in SEMA4D associated with body mass index. Chen G, et al. Obesity (Silver Spring), 2017 Apr. PMID 28296344, Free PMC Article
4. Characterization of the Effects of Semaphorin 4D Signaling on Angiogenesis. Zhou H, et al. Methods Mol Biol, 2017. PMID 27787869
5. Isolating Fc-Tagged SEMA4D Recombinant Protein from 293FT Cells. Soong J, et al.
   

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Combined detection of tumor-associated macrophages markers, CD68 and Sema4D, in gastric carcinoma tissue shows potential to predict the trend of gastric carcinoma progression.
2. SEMA4D coordinates with VEGF during angiogenesis via plexin-B1 in epithelial ovarian cancer.
3. Advanced peri-implantitis lesions showed higher levels of gene expression for Sem3A and Sem4D and lower levels of Sem4A in comparison to tissues obtained from a healthy dental implant.
4. knockdown of Sema4D in Head and neck squamous cell carcinomas (HNSCCs)cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion.
5. The results obtained make significant adjustments in understanding of Seam4D effects in lymphoid cells.
6. describe the transfection, purification, and visualization of Fc-tagged SEMA4D (semaphorin 4D) recombinant protein
7. describe the application of in vitro migration and tubulogenesis assays and the directed in vivo angiogenesis assay (DIVAA) in the measurement of the angiogenic potential of cell-derived and soluble SEMA4D
8. The positive expression of both Sema4D and PlexinB1 was found to be an independent risk factor for a worse survival in colorectal cancer.
9. Serum levels of soluble SEMA4D were elevated in patients with ANCA-associated vasculitis. Cell-surface expression of SEMA4D was downregulated, a consequence of proteolytic cleavage of membrane SEMA4D. Soluble SEMA4D exerted pro-inflammatory effects on endothelial cells. Membranous SEMA4D on neutrophils bound to plexin B2 on endothelial cells, and this interaction decreased NET formation.
10. We identified a novel genome-wide significant African-specific locus for BMI (SEMA4D, rs80068415). A novel variant in SEMA4D was significantly associated with body mass index. Carriers of the C allele were 4.6 BMI units heavier than carriers of the T allele.
    

(3) SEMA3F (3p21.31) Semaphorin 3F

Muita nimiä SEMA4, SEMAK, SEMA-IV . Geeni ilmenee endokriinisissä soluissa ja vaikuttaa autokriinisesti apoptoosia, estää soluproliferaatiota ja solun elossapysymistä toimien antitumorigeenisenä agenssina.

https://www.ncbi.nlm.nih.gov/gene/6405

Also known as SEMA4; SEMAK; SEMA-IV

Summary: This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin loop and a C-terminal basic domain. This gene is expressed by the endothelial cells where it was found to act in an autocrine fashion to induce apoptosis, inhibit cell proliferation and survival, and function as an anti-tumorigenic agent. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

Expression: Broad expression in skin (RPKM 21.7), esophagus (RPKM 16.4) and 19 other tissues See more

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. SEMA3F plays a role as a tumor suppressor in Oral squamous cell carcinoma cell proliferation, migration and invasion.
2. in situ hybridization analysis revealed that Sema 3C and Sema 3F are expressed at the RNA level in the endometriosis affected peritoneum
3. Semaphorin 3F placenta tissue expression was significantly reduced in preeclampsia. In addition, semaphorin 3F level at delivery was significantly lower in serum, amniotic fluid and venous umbilical blood of preeclamptic patients compared with normal pregnant women.
4. There is a positive association between the expression of AKAP12 and Semaphorin 3F in prostate cancer, suggesting that the activation of Semaphorin 3F by AKAP12 may be involved in prostate cancer progression and metastasis.
5. Study demonstrates an anti-tumoral role of SEMA3F in ileal NETs. We thus suggest that SEMA3F and/or its cellular signaling pathway could represent a target for ileal NET therapy.
6. SEMA3F was downregulated in colorectal cancer tissues as compared to matched adjacent non-tumor tissues
7. A new SEMA3F transcript is expressed in all breast cell lines and breast cancer biopsies, and is translated into a new semaphorin 3F isoform.
8. SEMA3F-NRP2 interactions inhibit intracellular PI-3K activity, mTORC2-dependent signaling, RhoA activity and cytoskeletal stress fiber formation.
9. Data indicate that semaphorin 3F (SEMA3F) and its receptor neuropilin-2 (NRP2) are expressed in the thymus.
10. SEMA3F functions as a suppressor of colorectal cancer metastasis by down-regulating the ASCL2-CXCR4 signaling axis.
    

(4) SEMA7A (15q24.1) Semaphorin 7A

Muita nimiä: JMH (John Milton Hagen blood group), CD108, SEMAL, CDw108, SEMAK1, H-Sema-L, H-SEMA-K1. GPI-ankkuroitunut kalvoglykoproteiini. Esiintyy aktivoiduissa lymfosyyteissä ja erytsosyyteissä ja osallistunee immunomodulaatioon ja neuronaalisiin prosesseihin. Proteiini kantaa JMH- veriryhmäantigeenia. Mutaatiot liittyvät alnetuneeseen luuston mineraalitiheyteen.

https://www.ncbi.nlm.nih.gov/gene/8482

Also known as JMH; CD108; SEMAL; CDw108; SEMAK1; H-Sema-L; H-SEMA-K1

Summary. This gene encodes a member of the semaphorin family of proteins. The encoded preproprotein is proteolytically processed to generate the mature glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein. The encoded protein is found on activated lymphocytes and erythrocytes and may be involved in immunomodulatory and neuronal processes. The encoded protein carries the John Milton Hagen (JMH) blood group antigens. Mutations in this gene may be associated with reduced bone mineral density (BMD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

Expression. Broad expression in testis (RPKM 25.1), spleen (RPKM 22.9) and 14 other tissues See more

Related articles in PubMed

1. Validation of semaphorin 7A and ala-β-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis. Cantó E, et al. J Neuroinflammation, 2014 Nov 13. PMID 25406498, Free PMC Article
2. Semaphorin 7A is expressed on airway eosinophils and upregulated by IL-5 family cytokines. Esnault S, et al. Clin Immunol, 2014 Jan. PMID 24333536, Free PMC Article
3. Semaphorin 7A protein variants differentially regulate T-cell activity. Gras C, et al. Transfusion, 2013 Feb. PMID 22845496
4. A new SEMA7A variant found in Native Americans with alloantibody. Richard M, et al. Vox Sang, 2011 Apr. PMID 20854351
5. Rapid detection of JMH antibodies with recombinant Sema7A (CD108) protein and the particle gel immunoassay. Seltsam A, et al. Transfusion, 2008 Jun. PMID 18422858
   

See all (47) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Sema7A has a significant role in atherosclerosis by mediating endothelial dysfunction in a beta1 integrin-dependent manner.
2. These findings indicate that Sema7A as a potent activator of T cells and monocytes in the immune response contributes to the inflammation and progression of rheumatoid arthritis
3. short hairpin-mediated silencing of SEMA7A reveals roles for semaphorin 7a in the promotion of DCIS growth, motility and invasion as well as lymphangiogenesis in the tumor microenvironment. Our studies also uncover a relationship between COX-2 and semaphorin 7a expression and suggest that semaphorin 7a promotes tumor cell invasion on collagen and lymphangiogenesis via activation of b1-integrin receptor
4. Our results identified FGL2, GAL, SEMA4D, SEMA7A, and IDO1 as new candidate genes that could be involved in MSCs-mediated immunomodulation. FGL2, GAL, SEMA4D, SEMA7A, and IDO1 genes appeared to be differentially transcribed in the different MSC populations. Moreover, these genes were not similarly modulated following MSCs-exposure to inflammatory signals
5. Sema3A and sema7A expression correlated with the inflammatory activity of the multiple sclerosis (MS) lesions, suggesting their involvement in the immunological process that takes place in MS.
6. SEMA7A has a role in the development of lung injury
7. This study demonstrates that Sema7A controls the assembly of actin-based protrusions that drive Dendritic cell migration in response to CCL21.
8. These results suggest that SEMA7a plays a role as a CSF biomarkers associated with the conversion to clinically definite multiple sclerosis in clinically isolated syndromes patients
9. heterozygous missense variants in SEMA3A and SEMA7A may modify the phenotype of Kallmann syndrome but most likely are not alone sufficient to cause the disorder
10. SEMA7A was expressed in the liver and was increased in the course of liver fibrosis, both in mice and in humans.
    

Submit: New GeneRIF Correction See all GeneRIFs (24)

(5) SEMA3C (7q21.11) Semaphorin 3C

Muita nimiä:SemE, SEMAE. Luokka III semaforiini. Geenimutaatio assosioituu Hirschprungin tautiin.
https://www.ncbi.nlm.nih.gov/gene/10512

Also known as SemE; SEMAE

Summary. This gene encodes a secreted glycoprotein that belongs to the semaphorin class 3 family of neuronal guidance cues. The encoded protein contains an N-terminal sema domain, integrin and immunoglobulin-like domains, and a C-terminal basic domain. Homodimerization and proteolytic cleavage of the C-terminal propeptide are necessary for the function of the encoded protein. It binds a neuropilin co-receptor before forming a heterotrimeric complex with an associated plexin. An increase in the expression of this gene correlates with an increase in cancer cell invasion and adhesion. Naturally occurring mutations in this gene are associated with Hirschsprung disease. [provided by RefSeq, May 2017]

Expression. Broad expression in prostate (RPKM 41.1), urinary bladder (RPKM 40.3) and 20 other tissues See more

Related articles in PubMed

1. Class 3 semaphorins are transcriptionally regulated by 1,25(OH)₂D₃ in osteoblasts. Ryynänen J, et al. J Steroid Biochem Mol Biol, 2017 Oct. PMID 28189595
2. A Sema3C Mutant Resistant to Cleavage by Furin (FR-Sema3C) Inhibits Choroidal Neovascularization. Toledano S, et al. PLoS One, 2016. PMID 28036336, Free PMC Article
3. Class 3 semaphorins in cardiovascular development. Valdembri D, et al. Cell Adh Migr, 2016 Nov. PMID 27439112, Free PMC Article Secreted class 3 semaphorins (Sema3), which signal through holoreceptor complexes that are formed by different subunits, such as neuropilins (Nrps), proteoglycans, and plexins, were initially characterized as fundamental regulators of axon guidance during embryogenesis. Subsequently, Sema3A, Sema3C, Sema3D, and Sema3E were discovered to play crucial roles in cardiovascular development, mainly acting through Nrp1 and Plexin D1, which funnels the signal of multiple Sema3 in vascular endothelial cells. Mechanistically, Sema3 proteins control cardiovascular patterning through the enzymatic GTPase-activating-protein activity of the cytodomain of Plexin D1, which negatively regulates the function of Rap1, a small GTPase that is well-known for its ability to drive vascular morphogenesis and to elicit the conformational activation of integrin adhesion receptors.

4. Class 3 semaphorins induce F-actin reorganization in human dendritic cells: Role in cell migration. Curreli S, et al. J Leukoc Biol, 2016 Dec. PMID 27406993, Free PMC Article
5. Expression of Semaphorin 3C in Breast Cancer and its Impact on Adhesion and Invasion of Breast Cancer Cells. Malik MF, et al. Anticancer Res, 2016 Mar. PMID 26977026
   

See all (46) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. in situ hybridization analysis revealed that Sema 3C and Sema 3F are expressed at the RNA level in the endometriosis affected peritoneum
2. Androgen receptor transcriptionally regulates semaphorin 3C in a GATA2-dependent manner in prostate tumor cells.
3. The exploratory genome-wide association studies confirmed APOE and identified the novel loci: rs2525776 near SEMA3C (P = 1 x 10(-8), OR = 3.3 [2.1-5.1]).
4. Aberrant expression of sema3c is correlated with poor prognosis of pancreatic ductal adenocarcinoma patients and promotes tumor growth and metastasis by activating ERK1/2 signaling pathway.
5. FR-sema3C could perhaps be used for the treatment of AMD.
6. SEMA3C plays a role in the progression of breast cancer and may positively influence breast cancer cell adhesion, invasion and proliferation, as well as being associated with grade of disease and estrogen receptor status.
7. Data show significant increases in semaphorin3C, 3D and their receptor neuropilin-2 in degenerate samples which were shown to contain nerves and blood vessels, compared to non-degenerate samples without nerves and blood vessels.
8. Increased levels of Sema3C protein may be associated with the progression of glioma tumor and have potential as a prognostic marker for outcome of glioma patients.
9. SEMA3C expression increased in the transition from normal to malignant breast lesions and correlated with microvessel density and tumour grade and is differentially regulated in the development of breast versus oral neoplasia.
10. Glioma stem cells preferentially secrete Sema3C and coordinately express PlexinA2/D1 receptors to activate Rac1/nuclear factor (NF)-kB signaling.
    

(6) SEMA3B (3p21.31) Semaphorin 3B

Muita nimiä: SemA, SEMA5, SEMAA, SemaV, LUCA-1. Aksonin liikakasvun estäjä. Tuumorisuppressori.
https://www.ncbi.nlm.nih.gov/gene/7869

Also known as SemA; SEMA5; SEMAA; semaV; LUCA-1

Summary. The protein encoded by this gene belongs to the class-3 semaphorin/collapsin family, whose members function in growth cone guidance during neuronal development. This family member inhibits axonal extension and has been shown to act as a tumor suppressor by inducing apoptosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

Expression. Broad expression in placenta (RPKM 31.6), small intestine (RPKM 29.6) and 20 other tissues See more

(7) SEMA3E (7q21.11) Semaphorin 3E

Muita nimiä SEMAH, coll-5, M-SEMAH, M-SemaK. Aksonin kasvussa toimiva ohjaava ligandi multimeeristen kompleksin avulla. Miltei joka kompleksissa on plexiiniproteiineja.

 https://www.ncbi.nlm.nih.gov/gene/9723

Also known as SEMAH; coll-5; M-SEMAH; M-SemaK

Summary Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

Expression. Biased expression in brain (RPKM 3.1), gall bladder (RPKM 2.2) and 13 other tissues See more

Related articles in PubMed

1. Overexpression of Semaphorin-3E enhances pancreatic cancer cell growth and associates with poor patient survival. Yong LK, et al. Oncotarget, 2016 Dec 27. PMID 27911862, Free PMC Article
2. Enhanced expression of semaphorin 3E is involved in the gastric cancer development. Maejima R, et al. Int J Oncol, 2016 Sep. PMID 27572291, Free PMC Article
3. Epigenetically downregulated Semaphorin 3E contributes to gastric cancer. Chen H, et al. Oncotarget, 2015 Aug 21. PMID 26036259, Free PMC Article
4. Neuronal chemorepellent Semaphorin 3E inhibits human airway smooth muscle cell proliferation and migration. Movassagh H, et al. J Allergy Clin Immunol, 2014 Feb. PMID 23932461
5. A role for class 3 semaphorins in prostate cancer. Blanc V, et al. Prostate, 2011 May. PMID 20949546 OBS!
   

See all (44) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Sema3E induced cell proliferation via acting through the MAPK/ERK pathway.
2. Sema3E could be considered an essential regulatory mediator involved in modulation of neutrophil migration throughout the course of neutrophilic inflammation.
3. Results show high expression level of SEMA3E which correlated with lymph node involvement, metastatic progression and a significant association with poor prognosis in gastric cancer patients. Also, in vitro studies reveal that SEMA3E caused cell proliferation and anchorage-independent cell growth in the intestinal type of gastric cancer.
4. suggested that miR-4282 is a tumor suppressor in colorectal carcinoma cells and exerted its inhibitory effect on the tumor cells through targeting Sema3E by inhibiting Sema3E translation or enhancing Sema3E mRNA degradation
5. This study aims to investigate whether the Tribbles 3 Q84R polymorphism has profound effects on serum semaphorin 3E and what effect semaphorin 3E exerts on carotid atherosclerosis.
6. This study suggests that NRP1 expression and LVD are independent factors that are likely to predict the risk of LN metastasis in squamous cell carcinoma (SCC)of the tongue, whereas the expression of VEGFC, VEGFR3, CCR7, and SEMA3E are nonindependent predictive factors
7. Authors suggest that silencing of Sema3E contributes to the pathogenesis of gastric cancer.
8. Findings suggest that Plexin-D1/class III semaphorin (Sema3E) axis is triggered in systemic sclerosis (SSc) endothelium.
9. Infantile hemangioma-derived stem cells and endothelial cells are inhibited by SEMA3E and SEMA3F.
10. these results identify SEMA3E as an essential gene for GnRH neuron development, uncover a neurotrophic function for SEMA3E in the developing brain
    

(8) SEMA5A (5p15.31), Semaphorin 5A

Muita nimiä semF, SEMAF. Geeni assosioituu hippokampin kokoon ja kognitiivisen kapasiteetiin erääseen laatuun. Autismialttiusgeeni. TACE(ADAM17) osallistuneen semaforiini 5A-eritykseen. Semaforiini 5A vaikuttaa MMP9 eritystä mahasyövässä.

https://www.ncbi.nlm.nih.gov/gene/9037

 Also known as semF; SEMAF

Summary. This gene belongs to the semaphorin gene family that encodes membrane proteins containing a semaphorin domain and several thrombospondin type-1 repeats. Members of this family are involved in axonal guidance during neural development. This gene has been implicated as an autism susceptibility gene.[provided by RefSeq, Jan 2010]

Expression. Broad expression in lung (RPKM 6.9), kidney (RPKM 6.5) and 24 other tissues See more , Orthologs mouse all

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Data provide evidences supporting the role of Sema5A in melanoma progression and the involvement of Bcl-2, miR-204 and c-Myb in regulating its expression.

2. SEMA5A gene is associated with hippocampal volume, and their interaction is associated with reasoning ability.
3. De novo translocation t(5;22)(p15.3;q11.21) associated with a partial deletion of SEMA5A identified in a patient with ASD.
4. Our data demonstrated that elevated serum Semaphorin5A (Sema5A) in SLE patients correlated with disease activity and are involved in kidney and blood system damage; ADAM17 might be involved in the release of secreted Sema5A.
5. data demonstrated that elevated serum Semaphorin5A in systemic lupus erythematosus patients correlated with disease activity and are involved in kidney and blood system damage; ADAM17 might be involved in the release of secreted Sema5A
6. Multigenerational autosomal dominant inheritance of 5p chromosomal deletions resulting in Cri-du-Chat Syndrome with SEMA5A, CTNND2, and ICE1 deficiencies has been described.
7. The Single-Nucleotide Polymorphism (SNP) of rs7702187 within the SEMA5A gene would be a high-penetrant risk factor for PD development.
8. Using human gastric cancer cell lines, found semaphorin 5A significantly promoted invasive & metastatic abilities of gastric cancer cell in vitro. Semaphorin 5A increased expression of MMP9 by activating phosphorylated ErK1/2 in gastric cancer cell.
9. Results suggest that a bioactive, secreted form of Sema5A-ECD has an intriguing and potentially important role in its ability to enhance pancreatic tumour invasiveness, angiogenesis and micrometastases.
10. Data show that Semaphorin 5A (Sema5A) and plexin-B3 inhibit glioma cell invasion through Rac1 inactivation.
    

Submit: New GeneRIF Correction See all GeneRIFs (26)

(9) SEMA4A (1q22) Semaphorin 4A

Muita nimiä RP35 (retinitis pigmentosa tyyppi 35), CORD10 (tappi-sauvadystrofia 10); Semaforiini 4A aktivoi T-soluvälitteistä immuniteettia (ILT4 on T-soluissa SEMA4A reseptori). Semaforiini 4A vaimentaaVEGF- välitteistä endoteelisolumigraatiota ja proliferaatiota koeputkessa ja angiogeneesiä in vivo.

https://www.ncbi.nlm.nih.gov/gene/64218

Also known as RP35; SEMB; SEMAB; CORD10

Summary This gene encodes a member of the semaphorin family of soluble and transmembrane proteins. Semaphorins are involved in numerous functions, including axon guidance, morphogenesis, carcinogenesis, and immunomodulation. The encoded protein is a single-pass type I membrane protein containing an immunoglobulin-like C2-type domain, a PSI domain and a sema domain. It inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons. It is an activator of T-cell-mediated immunity and suppresses vascular endothelial growth factor (VEGF)-mediated endothelial cell migration and proliferation in vitro and angiogenesis in vivo. Mutations in this gene are associated with retinal degenerative diseases including retinitis pigmentosa type 35 (RP35) and cone-rod dystrophy type 10 (CORD10). Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

Expression Broad expression in skin (RPKM 12.9), lymph node (RPKM 12.8) and 20 other tissues See more

Related articles in PubMed

1. On variants and disease-causing mutations: Case studies of a SEMA4A variant identified in inherited blindness. Bryant L, et al. Ophthalmic Genet, 2018 Jan-Feb. PMID 28805479, Free PMC Article
2. Doxorubicin-induced epithelial-mesenchymal transition through SEMA 4A in hepatocellular carcinoma. Pan JX, et al. Biochem Biophys Res Commun, 2016 Oct 28. PMID 27697528
3. Expression of Semaphorin 4A and its potential role in rheumatoid arthritis. Wang L, et al. Arthritis Res Ther, 2015 Aug 25. PMID 26303122, Free PMC Article
4. Germline variants in the SEMA4A gene predispose to familial colorectal cancer type X. Schulz E, et al. Nat Commun, 2014 Oct 13. PMID 25307848, Free PMC Article
5. Hypoxia-regulated components of the U4/U6.U5 tri-small nuclear riboprotein complex: possible role in autosomal dominant retinitis pigmentosa. Schmidt-Kastner R, et al. Mol Vis, 2008 Jan 25. PMID 18334927, Free PMC Article
   

See all (34) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Human oligodendrocytes undergo apoptosis when exposed to Sema4A and take up H-ferritin for meeting iron requirements and that these functions are mediated via the Tim-1 receptor. H-ferritin can block Sema4A-mediated cytotoxicity. Sema4A is detectable in the CSF of multiple sclerosis patients and HIV-seropositive persons and can induce oligodendrocyte cell death.
2. Advanced peri-implantitis lesions showed higher levels of gene expression for Sem3A and Sem4D and lower levels of Sem4A in comparison to tissues obtained from a healthy dental implant.
3. Here we show three families with retinal degeneration in which unaffected family members are either homozygous or heterozygous for the variant. The p.R713Q variant in SEMA4A is insufficient to cause either autosomal recessive or autosomal dominant retinitis pigmentosa and is unlikely to be pathogenic.
4. ILT-4 is a receptor for hSEMA4A)on activated CD4(+) T cells. hSEMA4A is highly expressed in human asthmatic lung tissue.
5. Suggest a role for Plexin-B1 as a ligand and Sema4A as a receptor and characterize a reverse signaling pathway downstream of Sema4A regulating cell migration via Scrib.
6. SEMA 4A confers doxorubicin resistance on hepatocellular carcinoma by inducing epithelialemesenchymal transition.
7. In this review, we summarized the current findings on neuroimmune Sema4A and Sema4D molecules in chronic inflammation underlying many diseases and discussed their positive or negative impacts on the implicated molecular and cellular processes
8. Sema4A activated the Akt pathway via Plexin D1 receptor in lung fibroblasts.Lung fibroblasts show elevated levels of Sema4A expression in systemic sclerosis patients.
9. Data suggest that increased expression of semaphorin 4A (Sema4A) is required to promote inflammation of rheumatoid arthritis (RA).

10. Germline variants in SEMA4A predispose to familial colorectal cancer type X.
    

(10) SEMA4C (2q11.2) , Semaphorin 4C

Muita nimiä SEMAF, SEMAI, SEMACL1, M-SEMA-F. Edistää imutiemetastaaseja tuumorien e imusoluissa. MikroRNA:lla kohdennetavissa oleva. SEMA4C on EMT:n positiivinen regulaattori.

 Https://www.ncbi.nlm.nih.gov/gene/54910

Also known as SEMAF; SEMAI; SEMACL1; M-SEMA-F Expression Ubiquitous expression in placenta (RPKM 20.2), endometrium (RPKM 13.1) and 24 other tissues See more Orthologs mouse all

Related articles in PubMed

1. Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C. Wei JC, et al. Clin Cancer Res, 2017 Jan 1. PMID 27401250
2. [Expression and clinical significance of Sema4C in esophageal cancer, gastric cancer and rectal cancer]. Ye SM, et al. Zhonghua Yi Xue Za Zhi, 2012 Jul 24. PMID 22944267
3. Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells. Zeng R, et al. Nephrol Dial Transplant, 2011 Apr. PMID 20959347, Free PMC Article
4. miR-25-3p reverses epithelial-mesenchymal transition via targeting Sema4C in cisplatin-resistance cervical cancer cells. Song J, et al. Cancer Sci, 2017 Jan. PMID 27743413, Free PMC Article
5. Erbin interacts with Sema4C and inhibits Sema4C-induced epithelial-mesenchymal transition in HK2 cells. Zhou QD, et al. J Huazhong Univ Sci Technolog Med Sci, 2013 Oct. PMID 24142719
   

(11) SEMA4F (2p13.1) , Semaphorin 4F

Muita nimiä S4F, SEMAM, SEMAW, M-SEMA, PRO2353, mSema-M. Luokan IV semaforiini. Osallistunee prostatasyövän neurogeneesiin, neurofibroomien muodostumiseen, rintasyövän tumorigeneesiin.
https://www.ncbi.nlm.nih.gov/gene/?term=SEMA4F

Also known as S4F; SEMAM; SEMAW; M-SEMA; PRO2353; m-Sema-M

Summary. This gene encodes a transmembrane class IV semaphorin family protein, which plays a role in neural development. This gene may be involved in neurogenesis in prostate cancer, the development of neurofibromas, and breast cancer tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

Expression. Broad expression in brain (RPKM 2.1), testis (RPKM 1.1) and 22 other tissues See more

Orthologs mouse all

 Related articles in PubMed

1. Proteomic approaches to the analysis of atopic dermatitis and new insights from interactomics. Park YD, et al. Proteomics Clin Appl, 2008 Mar. PMID 21136834
2. Cancer-related axonogenesis and neurogenesis in prostate cancer. Ayala GE, et al. Clin Cancer Res, 2008 Dec 1. PMID 19047084
3. Comprehensive gene and microRNA expression profiling reveals the crucial role of hsa-let-7i and its target genes in colorectal cancer metastasis. Zhang P, et al. Mol Biol Rep, 2012 Feb. PMID 21625861
4. NF1 loss disrupts Schwann cell-axonal interactions: a novel role for semaphorin 4F. Parrinello S, et al. Genes Dev, 2008 Dec 1. PMID 19056885, Free PMC Article
5. Fine mapping of the chromosome 2p12-16 dyslexia susceptibility locus: quantitative association analysis and positional candidate genes SEMA4F and OTX1. Francks C, et al. Psychiatr Genet, 2002 Mar. PMID 11901358
   

See all (26) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?(12) (12

1. data seems to indicate that SEMA4F is involved in tumour progression in breast cancer
2. Sema4F levels were strongly reduced in a panel of human neurofibromas, confirming the relevance of these findings to the human disease.
3. Fine mapping of the chromosome 2p12-16 dyslexia susceptibility candidate gene
   

 (12) SEMA6A (5q23.1) Semaphorin 6A

Muita nimiä: HT018, SEMA1, SEMAQ,VI A, SEMA6A1. Talamokortikaalisten ratojen asianmukainen muodostuminen. Angiogeneesin inhibiittori. Prognostinen biomarkkeri glioman hoidossa.
https://www.ncbi.nlm.nih.gov/gene/57556

Also known as VIA; SEMA; HT018; SEMAQ; SEMA6A1

Summary. The transmembrane semaphorin SEMA6A is expressed in developing neural tissue and is required for proper development of the thalamocortical projection (Leighton et al., 2001 [PubMed 11242070]).[supplied by OMIM, Feb 2011]

Expression Broad expression in adrenal (RPKM 13.5), placenta (RPKM 11.0) and 24 other tissues See more

Orthologs mouse all

Related articles in PubMed

1. Characterization of Semaphorin 6A-Mediated Effects on Angiogenesis Through Regulation of VEGF Signaling. Ohnuki H, et al. Methods Mol Biol, 2017. PMID 27787863, Free PMC Article
2. SEMA6A is a prognostic biomarker in glioblastoma. Zhao J, et al. Tumour Biol, 2015 Nov. PMID 26014517
3. From plasma membrane to cytoskeleton: a novel function for semaphorin 6A. Prislei S, et al. Mol Cancer Ther, 2008 Jan. PMID 18187809
4. The class 6 semaphorin SEMA6A is induced by interferon-gamma and defines an activation status of langerhans cells observed in pathological situations. Gautier G, et al. Am J Pathol, 2006 Feb. PMID 16436660, Free PMC Article
5. Comparative integromics on non-canonical WNT or planar cell polarity signaling molecules: transcriptional mechanism of PTK7 in colorectal cancer and that of SEMA6A in undifferentiated ES cells. Katoh M, et al. Int J Mol Med, 2007 Sep. PMID 17671748
   

See all (31) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. describes the experiments and methods enabling the characterization of Semaphorin 6A as a critical regulator of endothelial cell survival and vessel function
2. miR-203 induces the apoptosis of YD-38 human oral cancer cells by directly targeting SEMA6A.
3. our findings indicated that SEMA6A may be a potential prognostic biomarker in the treatment of Glioblastoma multiforme
4. Data suggest that Sema6A and Mical1 may represent new potential therapeutic targets in BRAFV600E melanoma.
5. We identified the SEMA6A and HLA-DP loci as significant contributors to risk for granulomatosis with polyangiitis.
6. Data show that miR-27a/b regulated the expression of the angiogenesis inhibitor semaphorin 6A (SEMA6A) in vitro and in vivo and targeted the 3'-untranslated region of SEMA6A.
7. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
8. Observational study of gene-disease association. (HuGE Navigator)
9. findings suggest for SEMA6A a novel function in the cytoskeleton and a role in modulating tubulin isotype composition and microtubule dynamics
10. NANOG-, SOX2-, and POU5F1 (OCT3/OCT4)-binding sites within intron 1 of the SEMA6A gene
    

Submit: New GeneRIF Correction See all GeneRIFs (11)

 (13) SEMA3D (7q21.11), Semaphorin 3D

Muita nimiä: Sema-Z2, coll-2 (collapsin family member). Tämä geenin koodaama proteiini sitoo neuropiliiniä ja on tärkeä kardiovaskulaarfisessa kehityksessä,.

https://www.ncbi.nlm.nih.gov/gene/223117

Also known as coll-2; Sema-Z2

Summary. This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal develoent.pm The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]

Expression. Biased expression in spleen (RPKM 23.4), thyroid (RPKM 18.9) and 13 other tissues See more

Related articles in PubMed

1. Decreased expression of semaphorin 3D is associated with genesis and development in colorectal cancer. Wang Z, et al. World J Surg Oncol, 2017 Mar 20. PMID 28320475, Free PMC Article
2. Possible association of the semaphorin 3D gene (SEMA3D) with schizophrenia. Fujii T, et al. J Psychiatr Res, 2011 Jan. PMID 20684831
3. Semaphorin profiling of periodontal fibroblasts and osteoblasts. Lallier TE. J Dent Res, 2004 Sep. PMID 15329371 OBS!
4. Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere's disease. Martín-Sierra C, et al. Eur J Hum Genet, 2017 Feb. PMID 27876815, Free PMC Article
5. CTNNA3 and SEMA3D: Promising loci for asthma exacerbation identified through multiple genome-wide association studies. McGeachie MJ, et al. J Allergy Clin Immunol, 2015 Dec. PMID 26073756, Free PMC Article
   

See all (19) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Low SEMA3D expression is associated with colorectal cancer.
2. Novel mutation in SEMA3D segregates with the complete phenotype with variable expressivity in two pedigrees with autosomal dominant familial Meniere's disease.
3. Data show significant increases in semaphorin3C, 3D and their receptor neuropilin-2 in degenerate samples which were shown to contain nerves and blood vessels, compared to non-degenerate samples without nerves and blood vessels.
4. CTNNA3 and SEMA3D: Promising loci for asthma exacerbation identified through multiple genome-wide association studies
5. Functional loss of semaphorin 3C and/or semaphorin 3D and their epistatic interaction with ret are critical to Hirschsprung disease liability.
6. Semaphorin 3d requires neuropilin 1 or PI3K/Akt, whereas semaphorin 3e requires plexin D1 in directing endothelial motility.
7. In the absence of Sema3d, endothelial tubes form in a region that is normally avascular
8. in this study we have analyzed three aminoacidic substitutions, A131T-SEMA3A, S598G-SEMA3A and E198K-SEMA3D. These variants result in an increase of SEMA proteins levels in the HSCR colon tissue.
9. This study provided strong evidence that SEMA3D confers susceptibility to schizophrenia, which could contribute to the neurodevelopmental impairments in the disorder.
10. Observational study of gene-disease association. (HuGE Navigator)
    

Submit: New GeneRIF Correction See all GeneRIFs (11)

 (14) SEMA6D (15q21.1) Semaphorin 6D

Muita nimiä: NC-000015-10
https://www.ncbi.nlm.nih.gov/gene/80031

Summary. Semaphorins are a large family, including both secreted and membrane associated proteins, many of which have been implicated as inhibitors or chemorepellents in axon pathfinding, fasciculation and branching, and target selection. All semaphorins possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Additional sequence motifs C-terminal to the semaphorin domain allow classification into distinct subfamilies. Results demonstrate that transmembrane semaphorins, like the secreted ones, can act as repulsive axon guidance cues. This gene encodes a class 6 vertebrate transmembrane semaphorin that demonstrates alternative splicing. Several transcript variants have been identified and expression of the distinct encoded isoforms is thought to be regulated in a tissue- and development-dependent manner. [provided by RefSeq, Nov 2010]

Expression

Broad expression in small intestine (RPKM 13.9), placenta (RPKM 10.4) and 19 other tissues See more

Related articles in PubMed

1. Expression of semaphorin 6D in gastric carcinoma and its significance. Zhao XY, et al. World J Gastroenterol, 2006 Dec 7. PMID 17143962, Free PMC Article
2. Knowing how to navigate: mechanisms of semaphorin signaling in the nervous system. He Z, et al. Sci STKE, 2002 Feb 12. PMID 11842242
3. Identification, characterization, and functional study of the two novel human members of the semaphorin gene family. Qu X, et al. J Biol Chem, 2002 Sep 20. PMID 12110693
4. Novel genetic variants modify the effect of smoking on carotid plaque burden in Hispanics. Della-Morte D, et al. J Neurol Sci, 2014 Sep 15. PMID 24954085, Free PMC Article
5. Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Takegahara N, et al. Nat Cell Biol, 2006 Jun. PMID 16715077
   

See all (20) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
2. Observational study of gene-disease association. (HuGE Navigator)
3. Semaphorin 6D may play an important role in the occurrence and development of gastric carcinoma, and is related to tumor angiogenesis.
4. identification, characterization, and functional study of the two novel human members of the semaphorin gene family
   

(15)  SEMA4B 15q25.1. Semaphorin 4B

Muita nimiä: SEMAC, SemC ( vain lyhyt teksti)

SemC; SEMAC

Expression

Ubiquitous expression in esophagus (RPKM 24.0), skin (RPKM 20.0) and 25 other tissues See more

Related articles in PubMed

1. SEMA4B inhibits growth of non-small cell lung cancer in vitro and in vivo. Jian H, et al. Cell Signal, 2015 Jun. PMID 25746385
2. SEMA4b inhibits MMP9 to prevent metastasis of non-small cell lung cancer. Jian H, et al. Tumour Biol, 2014 Nov. PMID 25095981
3. Hypoxia and hypoxia-inducible factor 1 repress SEMA4B expression to promote non-small cell lung cancer invasion. Jian H, et al. Tumour Biol, 2014 May. PMID 24474252
4. Sema domain of semaphorin 4B (SEMA4B), which is an interacting protein of LNM35, plays an important role in lung cancer invasion. However, the regulation mechanism of this protein is completely unknown. Here, we report that hypoxia and hypoxia mimic reagent could downregulate the expression of SEMA4B in human non-small cell lung cancer (NSCLC) lines. We provide evidences that SEMA4B is a direct target of hypoxia-inducible factor 1 (HIF-1). Silencing the expression of HIF-1α in cancer cells by RNA interference abolished hypoxia-repressed SEMA4B expression. Using luciferase reporter assay, we showed that HIF-1α recognized a hypoxia-responsive element (HRE) of SEMA4B gene, which is required for HIF-1-repressed SEMA4B expression. Moreover, ectopic expression of SEMA4B abolished invasion of hypoxia-induced NSCLC cells. Taken together, these data would shed novel insights on the mechanisms for invasion of hypoxia-induced NSCLC cells.
5. CLCP1 interacts with semaphorin 4B and regulates motility of lung cancer cells. Nagai H, et al. Oncogene, 2007 Jun 7. PMID 17213806
6. Murine semaphorin D/collapsin is a member of a diverse gene family and creates domains inhibitory for axonal extension. Püschel AW, et al. Neuron, 1995 May. PMID 7748561
   

(16)  SEMA4G , 10q24.31. Semaphorin 4G

Ei muita nimiä

https://www.ncbi.nlm.nih.gov/gene/57715

Summary Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

Expression

Broad expression in duodenum (RPKM 18.5), small intestine (RPKM 15.9) and 20 other tissues See more

These findings provide evidence that the miR-608 rs4919510 polymorphism may modify cancer susceptibility in a type-specific manner. Furthermore, SEMA4G may function as an oncogene or tumour suppressor to regulate tumour development in a type-specific manner. Further studies with experimental evaluations are warranted.

(17) SEMA6B , ( 19p13.3) Semaphorin 6B

Muita nimiä: SEM-SEMA-Y, SEMA VIB,SEMAN, SemaZ. PPAR säätää tämän geenin vahvasti alas. Tällä geenillä on assosiaatioita tuumorien differentioitumiseen ja metasaasiin.
https://www.ncbi.nlm.nih.gov/gene/10501

Also known as SEMAN; semaZ; SEMA-VIB; SEM-SEMA-Y

Summary. This gene encodes a member of the semaphorin family, a group of proteins characterized by the presence of a conserved semaphorin (sema) domain. Whereas some semaphorins are transmembrane proteins, others are secreted. Semaphorins play a major role in axon guidance. The protein encoded by this gene may be involved in both peripheral and central nervous system development. [provided by RefSeq, Jul 2008]

Expression Broad expression in brain (RPKM 18.7), spleen (RPKM 8.6) and 15 other tissues See more

Orthologs mouse all

Related articles in PubMed

1. The role of axon guidance factor semaphorin 6B in the invasion and metastasis of gastric cancer. Ge C, et al. J Int Med Res, 2013 Apr. PMID 23781008
2. Analysis of SEMA6B gene expression in breast cancer: identification of a new isoform. D'Apice L, et al. Biochim Biophys Acta, 2013 Oct. PMID 23665584
3. The human semaphorin 6B gene is down regulated by PPARs. Collet P, et al. Genomics, 2004 Jun. PMID 15177567
4. Human semaphorin 6B [(HSA)SEMA6B], a novel human class 6 semaphorin gene: alternative splicing and all-trans-retinoic acid-dependent downregulation in glioblastoma cell lines. Correa RG, et al. Genomics, 2001 May 1. PMID 11350127
5. Signal peptide prediction based on analysis of experimentally verified cleavage sites. Zhang Z, et al. Protein Sci, 2004 Oct. PMID 15340161, Free PMC Article
   

See all (9) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Semaphorin 6B is related to tumour differentiation and metastasis in vivo, and tumour cell migration, adhesion and invasion in vitro.
2. states a clear relation among breast cancer and SEMA6B expression; moreover we describe for the first time the SEMA6Ba protein and report here the analysis of SEMA6Ba RNA messenger, the protein expression and the cellular localization
3. Gene SEMA6B is strongly down regulated by peroxisome proliferator-activated receptors.
   

Submit: New GeneRIF Correction

(18)  SEMA3G, (3p21.1), Semaphorin 3G

Muita nimiä: Sem2. Tämän geenin transkriptio aktivoituu PPAR-gammalla.
https://www.ncbi.nlm.nih.gov/gene/56920

Also known as sem2

Summary. The transcription of this gene is activated by PPAR-gamma, and the resulting protein product plays a role in endothelial cell migration. Expression of this gene also inhibits tumor cell migration and invasion. [provided by RefSeq, Jul 2016]

Expression

Biased expression in fat (RPKM 51.5), placenta (RPKM 13.3) and 10 other tissues See more

Orthologs

mouse all

Related articles in PubMed

1. PPAR-γ promotes endothelial cell migration by inducing the expression of Sema3g. Liu W, et al. J Cell Biochem, 2015 Apr. PMID 25335934
2. Effects of SEMA3G on migration and invasion of glioma cells. Zhou X, et al. Oncol Rep, 2012 Jul. PMID 22562223
3. A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation. Ishibashi R, et al. Sci Rep, 2016 May 16. PMID 27180624, Free PMC Article
4. Semaphorin, neuropilin and VEGF expression in glial tumours: SEMA3G, a prognostic marker? Karayan-Tapon L, et al. Br J Cancer, 2008 Oct 7. PMID 18781179, Free PMC Article
5. Differential endothelial transcriptomics identifies semaphorin 3G as a vascular class 3 semaphorin. Kutschera S, et al. Arterioscler Thromb Vasc Biol, 2011 Jan. PMID 20947821
   

See all (18) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Results indicate that Sema3G protein is secreted by podocytes and protects them from inflammatory kidney diseases and diabetic nephropathy.
2. Results identify Sema3g as one of the downstream effectors of PPAR-gamma, which is centrally involved in regulating endothelial cell migration.
3. overexpressed SEMA3G inhibited the migratory and invasive behavior of U251MG cancer cells
4. Identify Sema3G as a primarily endothelial cell-expressed class 3 semaphorin that controls endothelial and smooth muscle cell functions in autocrine and paracrine manners.
5. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
6. Observational study of gene-disease association. (HuGE Navigator)
7. In gliomas, SEMA3B, SEMA3G and NRP2 expressions were related to prolonged survival
8. Sema3G inhibits tumor progression from MDA-MB-435 but not from MDA-MB-231 cancer cells. It inhibits tumor angiogenesis in MDA-MB-231 cells.
   

(19)  SEMA5B, (3q21.1), Semaphorin 5B

Muita nimiä: SEMAG, SemG
https://www.ncbi.nlm.nih.gov/gene/54437

Also known as SemG; SEMAG

Summary. This gene encodes a member of the semaphorin protein family which regulates axon growth during development of the nervous system. The encoded protein has a characteristic Sema domain near the N-terminus, through which semaphorins bind to plexin, and five thrombospondin type 1 repeats in the C-terminal region of the protein. The protein product may be cleaved and exist as a secreted molecule (PMID: 19463192). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Expression. Broad expression in brain (RPKM 2.8), heart (RPKM 1.3) and 16 other tissues See more

Orthologs mouse all

Related articles in PubMed

1. Semaphorin 5B mediates synapse elimination in hippocampal neurons. O'Connor TP, et al. Neural Dev, 2009 May 23. PMID 19463192, Free PMC Article
2. Driver Gene and Novel Mutations in Asbestos-Exposed Lung Adenocarcinoma and Malignant Mesothelioma Detected by Exome Sequencing. Mäki-Nevala S, et al. Lung, 2016 Feb. PMID 26463840 Asbestos is a carcinogen linked to malignant mesothelioma (MM) and lung cancer. Some gene aberrations related to asbestos exposure are recognized, but many associated mutations remain obscure. We performed exome sequencing to determine the association of previously known mutations (driver gene mutations) with asbestos and to identify novel mutations related to asbestos exposure in lung adenocarcinoma (LAC) and MM.
3. A novel class of murine semaphorins with homology to thrombospondin is differentially expressed during early embryogenesis. Adams RH, et al. Mech Dev, 1996 Jun. PMID 8817451
4. Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations. Wu C, et al. Nat Genet, 2011 Jun 5. PMID 21642993
5. Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. Nagase T, et al. DNA Res, 2000 Apr 28. PMID 10819331
   

See all (16) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. SEMA5B could possibly serve as a candidate gene for alterations associated with asbestos exposure.
2. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
3. Observational study of gene-disease association. (HuGE Navigator)
4. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
5. Sema5B regulates the development and maintenance of synapse size and number in hippocampal neurons.
   

(20)  SEMA6C, ( 1q21.3) , Semaphorin 6C

Muita nimiä: SEMAY, m-SemaY, m-SemaY2 Semaforiinit edustavat tärkeitä molekulaarisia signaaleita keskushermostovaurion jälkeisissä soluvasteissa ja niillä voi olla tärkeä osuus neuraalisessa regeneraatiossa.

https://www.ncbi.nlm.nih.gov/gene/10500

Also known as SEMAY; m-SemaY; m-SemaY2

Summary: This gene encodes a member of the semaphorin family. Semaphorins represent important molecular signals controlling multiple aspects of the cellular response that follows CNS injury, and thus may play an important role in neural regeneration. [provided by RefSeq, May 2010]

Expression. Broad expression in testis (RPKM 9.5), heart (RPKM 5.4) and 20 other tissues See more

Orthologs mouse all

Related articles in PubMed

1. Emerging roles for semaphorins in neural regeneration. Pasterkamp RJ, et al. Brain Res Brain Res Rev, 2001 Mar. PMID 11245885
2. Identification, characterization, and functional study of the two novel human members of the semaphorin gene family. Qu X, et al. J Biol Chem, 2002 Sep 20. PMID 12110693
3. Polymorphisms in genes involved in neurodevelopment may be associated with altered brain morphology in schizophrenia: preliminary evidence. Gregório SP, et al. Psychiatry Res, 2009 Jan 30. PMID 19054571
4. Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis. Imabayashi H, et al. Exp Cell Res, 2003 Aug 1. PMID 12878157
5. Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. Nagase T, et al. DNA Res, 2001 Apr 27. PMID 11347906
   

See all (11) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene



25.2. 2019 Muistiin  lähdetietoa semaforiineista. Koska tämä on aika uusi asia minulle, otin monta  esimerkkiä ja artikkelia. poistan myöhemmin osan ja jätän vain geenilinkin PubMed.