Mistä johtuu maksan ( hepar, levern,the liver) erittäin hyvä kyky regeneroitua?

 PubMed tietueesta löytyy  viime vuodelta asiasta artikkeli.  Vyöhykkeisen maksaregeneraation paikallinen ( tilavuudellinen)  ja ajallinen ohjelma akuutin vaurion jälkeisessä tilassa.  

Tällä hetkellä minua kiinnostaa se genominen varustus, mikä piilee   maksakudoksen soluissa.

https://pubmed.ncbi.nlm.nih.gov/35659879/ '

2022 Jun 2;29(6):973-989.e10.

doi: 10.1016/j.stem.2022.04.008.

The spatiotemporal program of zonal liver regeneration following acute injury

Shani Ben-Moshe  ¹ , Tamar Veg  ¹ , Rita Manco  ¹ , Stav Dan  ¹ , Delfina Papinutti  ¹ , Aviezer Lifshitz  ² , Aleksandra A Kolodziejczyk  ³ , Keren Bahar Halpern  ¹ , Eran Elinav  ⁴ , Shalev Itzkovitz  ⁵

Affiliations

• PMID: 35659879
• DOI: 10.1016/j.stem.2022.04.008

Free article

Suomennosta  tiivistelmästä (*): Maksalla on merkittävä kyky regeneroitua nopeasti akuutin vyöhykkeisen vaurion jälkeen.  Tämän  tutkimuksessa lähestytään prosessia  yksittäisen solun avulla ottaen huomioon, miten  maksasolutyypit ovat  paikallisesti heterogeenisiä. Tutkittava kohde on  koe-eläimen   hiiren maksan regeneraation dynamiikka  akuutin asetaminofeenistä  (APAP) johtuneen myrkytyksen jälkeen. Tutkijat  havaitsivat, että  hepatosyytit (maksasolut)  alkoivat proliferoitua koko maksalohkon alueella luoden  mitoottista painetta, mikä vaaditaan, jotta  nekroottinen  kuoleutunut) perisentraalinen vyöhyke täyttyisi  soluista nopeasti uudelleen. Eräs hepatosyyttialaryhmä asettui  regeneroituvaan rintamaan säätäen   ohimenevästi  ylös fetaalispesifisiä geenejä ( mukaanluettuna  geenit Afp ja Cdh17) ohjelmoituessaan  uudelleen  perisentraalisessa  tilassaan. Endoteeliset vyöhykesolut, maksan  tähtisolut (HSC) ja makrofagipopulaatiot osallistuvat  eri tavoin  immuunirekrytointiin,proliferaatioon ja matriksin uudelleen muodostamiseen. Tutkijat  havaitsivat  myeloisten solujen  massiivin ja ohimenevän  infiltroitumisen ; lymfosyyttien runsaudella  kuitenkin säilyi stabiliteettinsa,mikä  täsmääkin  antigeenien esittämiessä  tapahtuneeseen yleiseen  laskevaan suuntaukseen. Tämä tutkimus antaa resursseja vyöhykkeisen maksaregeneraation  koordinoitujen  ohjelmien käsittämiseen. 

 (*) Abstract

The liver carries a remarkable ability to regenerate rapidly after acute zonal damage. Single-cell approaches are necessary to study this process, given the spatial heterogeneity of liver cell types. Here, we use spatially resolved single-cell RNA sequencing (scRNA-seq) to study the dynamics of mouse liver regeneration after acute acetaminophen (APAP) intoxication. We find that hepatocytes proliferate throughout the liver lobule, creating the mitotic pressure required to repopulate the necrotic pericentral zone rapidly. A subset of hepatocytes located at the regenerating front transiently upregulate fetal-specific genes, including Afp and Cdh17, as they reprogram to a pericentral state. Zonated endothelial, hepatic stellate cell (HSC), and macrophage populations are differentially involved in immune recruitment, proliferation, and matrix remodeling. We observe massive transient infiltration of myeloid cells, yet stability of lymphoid cell abundance, in accordance with a global decline in antigen presentation. Our study provides a resource for understanding the coordinated programs of zonal liver regeneration.

Keywords: DILI; acetaminophen; acute liver failure; damage-induced liver injury; hepatocytes; liver regeneration; liver zonation; single-cell transcriptomics; spatial transcriptomics.

Copyright © 2022 Elsevier Inc. All rights reserved. 

 The single cells clustered into 11 cell types, each exhibiting distinct marker genes (Figures 1C, 1D, and S1A; Table S2A). These cell types included hepatocytes, endothelial cells, HSCs, Kupffer cells, cholangiocytes, monocytes, macrophages, plasmocytoid dendritic cells (pDCs), conventional dendritic cells (cDCs), B cells and a cluster of T and NK cells. The Visium dataset included mice livers taken at 24, 48, and 72 h after APAP injection, two mice from each time point (Figure S2).

Highlights

• Spatiotemporal liver cell atlas of zonal regeneration following acute APAP injury
• New pericentral hepatocytes express onco-fetal genes while zonally reprogramming
• Nonparenchymal cells exhibit zone-specific cues to instruct regeneration
• Global reduction in MHC-I genes may prevent induction of adaptive immunity
   
  .. Differential expression analysis between the proliferating and nonproliferating hepatocytes at distinct lobule zones revealed a decrease in hepatocyte metabolic functions in proliferating hepatocytes (Figure S3F; Table S3C). A similar decrease in hepatocyte metabolic functions in proliferating hepatocytes was recently observed upon deletion of ZNRF3 and RNF43 in hepatocytes (

  Sun et al., 2021

  ).
  .. We found that interface hepatocytes exhibited a distinct expression signature, consisting of genes that are expressed in fetal livers and in hepatocellular carcinomas yet not in adult hepatocytes (Figures 3A–3C, S4A, and S4B). These included Afp, encoding the fetal serum protein alfa feto-protein (

  Camp et al., 2017

  ;

  Kuhlmann, 1978

  ;

  Ruoslahti and Seppälä, 1979

  ); Spp1, encoding osteopontin (

  El Makarem et al., 2011

  ;

  Cabiati et al., 2017

  ;

  Wang et al., 2016

  ); and Cdh17, encoding a cadherin protein associated with activation of Wnt signaling in hepatocellular carcinomas (

  Bartolomé et al., 2014

  ;

  Liu et al., 2009; Figure 3C). Afp was exclusively expressed by interface hepatocytes and not observed in other lobule layers, yet was expressed by only a subset of interface hepatocytes, indicative of bursty expression (Figures 3C and S5A). Consistent with Cdh17 expression, interface hepatocytes exhibited elevated levels of Wnt pathway target genes such as Lgr5 and Axin2 (Zhao et al., 2019 ; Figures 3A and 3B). We used smFISH to validate the specific expression of these genes (Figure 3C), as well as of Apoa1 and Actb (Figure 3D) in the hepatocytes residing at the interface between the damaged and nondamaged zones.

   
   Ps.   HYVÄ artikkeli, suosittelen  lukijaa ottamaan originaalin netistä esiin  doi osoitteesta
  

Mitä prolidaasiin tulee.

 siitä sivuhyppy aminohappopuolelle peptidaasien ja varsinkin dipeptidaasi,tripeptidaasi-entsyymin vajeen ongelmiin, missä  dieetillä on merkitystä.  8.12. 2023.

Proliini taas on ihmisen rakenteellinen konstituelli aminohappo, sitä muodostuu koska  se on ihmisen  rakennetta. Ongelma on  sen katabolian puolella suurin.  Eräs Nobel jaettiin tästä  seudusta  (proliini, hydroxyproliini, HIF tekijän  säätely),  hypoksiavasteen   signaloinnista takavuosina. 

Hydroxyproliini  (Hyl) taas on  posttranslationaalisesti muodostuva muoto peptidien  muokkauksessa.   

Peptidien pilkkoutumisessa  pieniin osiin jää tri ja dipeptidimuotoja, ja prolinaasi pilkkoo C-terminaalista proliinia nissä XaaP dipeptideissä. 

Ravinnon gluteenissa on paljon PQ ja QP peptidejä,  ja  keliakiaa koskevasa kirjallisuudesa  on toksisista peptideista  luetteloita  qppp,pqpp qqqp jne,  Prolidaasilla on runsaasti niitä dipeptidejä joihin sillä on affiniteettia varmasti enemmn kuin qp dipeptidiin, joten luonnollisesti sellaisia jää antigeeniksi   jopa verenkiertoon asti keliakiassa ja siten  onkin paras hoito-ohje välttää gluteenia.

EGR C2H2-tyyppisten sinkkisormiproteiinien eräs alaryhmäperhe . Miten monta tähän perheeseen kuuluu? Löytyy 4 geeniä.

 Katson luetteloa GeneCards tietueesta, koska en ole aimmin tavannut tämän alaryhmän  nimitystäkään.  

C2H2  sinkkisormen omaavien  proteiinien ryhmä on suurin ja siitä voi löytää useitakin alaryhmittelyjä ajan myötä.

EGR1 (jo edellä mainittu  linkki)

https://www.genecards.org/cgi-bin/carddisp.pl?gene=EGR1&keywords=EGR 

 EGR2 (10q21.3)

Aliases for EGR2 Gene: GeneCards Symbol: EGR2 ² Early Growth Response 2 ^{2 3 5} KROX20 ^{3 4 5} E3 SUMO-Protein Transferase ERG2 ^{3 4} Early Growth Response Protein 2 ^{3 4} E3 SUMO-Protein Ligase EGR2 ^{3 4} Zinc Finger Protein Krox-20 ^{3 4} AT591 ^{3 4}  KROX-20, Drosophila, Homolog (Early Growth Response-2) ³

Early Growth Response 2 (Krox-20 Homolog, Drosophila) ²
Krox-20 Homolog, Drosophila ²
EC 2.3.2.- ⁴
CMT1D ³
CMT4E ³
EGR-2 ⁴

• The protein encoded by this gene is a transcription factor with three tandem C2H2-type zinc fingers. Defects in this gene are associated with Charcot-Marie-Tooth disease type 1D (CMT1D), Charcot-Marie-Tooth disease type 4E (CMT4E), and with Dejerine-Sottas syndrome (DSS). Multiple transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

GeneCards Summary for EGR2 Gene

EGR2 (Early Growth Response 2) is a Protein Coding gene. Diseases associated with EGR2 include Neuropathy, Congenital Hypomyelinating, 1, Autosomal Recessive and Charcot-Marie-Tooth Disease, Demyelinating, Type 1D. Among its related pathways are Signaling by NTRKs and Nuclear Events (kinase and transcription factor activation). Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and ligase activity. An important paralog of this gene is EGR3.

UniProtKB/Swiss-Prot Summary for EGR2 Gene

Sequence-specific DNA-binding transcription factor (PubMed:17717711). Plays a role in hindbrain segmentation by regulating the expression of a subset of homeobox containing genes and in Schwann cell myelination by regulating the expression of genes involved in the formation and maintenance of myelin (By similarity). Binds to two EGR2-consensus sites EGR2A (5'-CTGTAGGAG-3') and EGR2B (5'-ATGTAGGTG-3') in the HOXB3 enhancer and promotes HOXB3 transcriptional activation (By similarity). Binds to specific DNA sites located in the promoter region of HOXA4, HOXB2 and ERBB2 (By similarity). Regulates hindbrain segmentation by controlling the expression of Hox genes, such as HOXA4, HOXB3 and HOXB2, and thereby specifying odd and even rhombomeres (By similarity). Promotes the expression of HOXB3 in the rhombomere r5 in the hindbrain (By similarity). Regulates myelination in the peripheral nervous system after birth, possibly by regulating the expression of myelin proteins, such as MPZ, and by promoting the differentiation of Schwann cells (By similarity). Involved in the development of the jaw openener musculature, probably by playing a role in its innervation through trigeminal motor neurons (By similarity). May play a role in adipogenesis, possibly by regulating the expression of CEBPB (By similarity). ( EGR2_HUMAN,P11161 )

E3 SUMO-protein ligase helping SUMO1 conjugation to its coregulators NAB1 and NAB2, whose sumoylation down-regulates EGR2 transcriptional activity. ( EGR2_HUMAN,P11161 )

EGR3 (8p21.3)

Aliases for EGR3 Gene     GeneCards Symbol: EGR3 ²

Early Growth Response 3 ^{2 3 5}
PILOT ^{2 3 4 5}
Zinc Finger Protein Pilot ^{2 3 4}
Early Growth Response Protein 3 ^{3 4}
EGR-3 ^{3 4}

NCBI Gene Summary for EGR3 Gene

• This gene encodes a transcriptional regulator that belongs to the EGR family of C2H2-type zinc-finger proteins. It is an immediate-early growth response gene which is induced by mitogenic stimulation. The protein encoded by this gene participates in the transcriptional regulation of genes in controling biological rhythm. It may also play a role in a wide variety of processes including muscle development, lymphocyte development, endothelial cell growth and migration, and neuronal development. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Dec 2010]

GeneCards Summary for EGR3 Gene

EGR3 (Early Growth Response 3) is a Protein Coding gene. Diseases associated with EGR3 include Patella, Chondromalacia Of and Schizophrenia 19. Among its related pathways are Signaling by NTRKs and Nuclear Events (kinase and transcription factor activation). Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity. An important paralog of this gene is EGR2.

UniProtKB/Swiss-Prot Summary for EGR3 Gene

Probable transcription factor involved in muscle spindle development. ( EGR3_HUMAN,Q06889 )

EGR4  (2p13.2)

Aliases for EGR4 Gen      GeneCards Symbol: EGR4 ²

Early Growth Response 4 ^{2 3 5}
NGFI-C ^{2 3 5}
PAT133 ^{2 3 5}
Early Growth Response Protein 4 ^{3 4}
AT133 ^{3 4}
NGFIC ³
EGR-4 ⁴

External Ids for EGR4 Gene

• Enables DNA-binding transcription activator activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleoplasm. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

GeneCards Summary for EGR4 Gene

EGR4 (Early Growth Response 4) is a Protein Coding gene. Diseases associated with EGR4 include Schizophrenia 19 and Neuropathy, Congenital Hypomyelinating, 1, Autosomal Recessive. Among its related pathways are Signaling by NTRKs and Nuclear Events (kinase and transcription factor activation). Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity. An important paralog of this gene is EGR2.

UniProtKB/Swiss-Prot Summary for EGR4 Gene

Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-GCGGGGGCG-3' (GSG). Activates the transcription of target genes whose products are required for mitogenesis and differentiation (By similarity). ( EGR4_HUMAN,Q05215 ) 

Muistiin  8.12. 2023. Varhaiseen myeliinin metaboliaan assosioituva. 

 

EGR (Early Growth Response)- domeenin omaavien C2H2-tyyppisten sinkkisormiproteiinien perheestä EGR1 geeni, rukkaa biologista kelloakin

 Esimerkki on EGR1

https://www.genecards.org/cgi-bin/carddisp.pl?gene=EGR1&keywords=EGR

Aliases for EGR1 Gene

GeneCards Symbol: EGR1 ²
Early Growth Response 1 ^{2 3 5}
NGFI-A ^{2 3 4 5}
AT225 ^{2 3 4 5}
Nerve Growth Factor-Induced Protein A ^{2 3 4}
Early Growth Response Protein 1 ^{2 3 4}
Transcription Factor ETR103 ^{2 3 4}
KROX-24 ^{2 3 5}
ZIF-268 ^{2 3 5}
G0S30 ^{2 3 5}
TIS8 ^{2 3 5}
Transcription Factor Zif268 ^{3 4}
Zinc Finger Protein Krox-24 ^{3 4}
Zinc Finger Protein 225 ^{3 4}
Zinc Finger Gene 225 ^{2 3}
ZNF225 ^{3 4}
EGR-1 ^{3 4}
225 ^{2 5}
KROX24 ⁴

NCBI Gene Summary for EGR1 Gene

• The protein encoded by this gene belongs to the EGR family of C2H2-type zinc-finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentitation and mitogenesis. Studies suggest this is a cancer suppressor gene. [provided by RefSeq, Dec 2014]

GeneCards Summary for EGR1 Gene

EGR1 (Early Growth Response 1) is a Protein Coding gene. Diseases associated with EGR1 include Ischemia and Monocytic Leukemia. Among its related pathways are PIP3 activates AKT signaling and Hepatocyte growth factor receptor signaling. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription factor binding. An important paralog of this gene is EGR3.

UniProtKB/Swiss-Prot Summary for EGR1 Gene

Transcriptional regulator (PubMed:20121949). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (By similarity). Binds double-stranded target DNA, irrespective of the cytosine methylation status (PubMed:25258363, 25999311). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation. Required for normal progress through mitosis and normal proliferation of hepatocytes after partial hepatectomy. Mediates responses to ischemia and hypoxia; regulates the expression of proteins such as IL1B and CXCL2 that are involved in inflammatory processes and development of tissue damage after ischemia. Regulates biosynthesis of luteinizing hormone (LHB) in the pituitary (By similarity). Regulates the amplitude of the expression rhythms of clock genes: BMAL1, PER2 and NR1D1 in the liver via the activation of PER1 (clock repressor) transcription. Regulates the rhythmic expression of core-clock gene BMAL1 in the suprachiasmatic nucleus (SCN) (By similarity). ( EGR1_HUMAN,P18146 )

WT-1 geeni kuuluu EGR:n kaltaisen domeenin omaavaan C2H2-tyyppiseen sinkkisormiproteiiniperheeseen.

WT-1 gene , WILMS tumor 1,(11p13) ( Huom. geeninimessä ei kuitenkaan ole kirjaimet EGR, näkyy kyllä WAGR nimi).

 Suomennosta  (*)Sinkkisormimotiiveja on neljä C-terminaalissa ja yksi P/Q pitoinen  DNA:ta sitova  motiivi N-terminaalissa. Tällä geenillä on  essentielli osuus urogenitaalisysteemin kehityksessä. Geenissä on mutaatio niillä, joille kehittyy Wilmsin tuumori. Geeni ilmentää  monimutkaisia kudosspesifisiä ja polymorfisia mallituksia, joilla on bialleeleja ja monoalleeleja expressoitumisia  eri kudosten maternaalisista tai paternaalisista alleeleista.  Multippeleita  transkriptivariantteja on kuvattu. Useissa varianteissa on näyttöä siitä, että  ensimmäisen AUG- koodin kanssa  sen raamialueessa tai  sen ylävirrassa  toimii  myös ei-AUG (CUG)  translaation aloituskodonia. On myös näyttöä siitä, että  WT1 mRNA pystyy editoitumaan ihmisessä ja rotassa   ja että tämä prosessi on kudoksiin rajoittunutta ja kehityksellisesti  säätynyttä

  https://www.genecards.org/cgi-bin/carddisp.pl?gene=WT1&keywords=WT1 

Aliases for WT1 Gene

GeneCards Symbol: WT1 ²
WT1 Transcription Factor ^{2 3 5}
WIT-2 ^{2 3 5}
NPHS4 ^{2 3 5}
WAGR ^{2 3 5}
AWT1 ^{2 3 5}
WT-1 ^{2 3 5} Wilms Tumor Protein ^{3 4} Wilms Tumor 1 ^{2 3} WT33 ^{3 4} GUD ^{3 5}

• (*)This gene encodes a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a small subset of patients with Wilms tumor. This gene exhibits complex tissue-specific and polymorphic imprinting pattern, with biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues. Multiple transcript variants have been described. In several variants, there is evidence for the use of a non-AUG (CUG) translation initiation codon upstream of, and in-frame with the first AUG. Authors of PMID:7926762 also provide evidence that WT1 mRNA undergoes RNA editing in human and rat, and that this process is tissue-restricted and developmentally regulated. [provided by RefSeq, Mar 2015]

CIViC Summary for WT1 Gene

Suomennosta (**) (**) Geeni WT1 on  kasvannaista vaimentava geeni ja  assosioituu Wilmsin tuumorin kehittymiseen. Siitä tuumorista johtuukin geenin nimi:  "geeni Wilmsintuumori ykkönen".  Toistumiseen on tusnistettu akuutissa myeloisessa leukemiassa (AML) mutaatioita WT1- geenin  eksoneissa 7 ja 9 ja on  havaittu tämän seikan  (WT1 geeni +) liittyvän huonompaan ennusteeseen ja kemoterapiaresistenssiin.

• WT1 is a tumor suppressor gene associated with the development of Wilms' Tumor, from which it was named. Mutations in exon 7 and 9 of WT1 have been recurrently identified in acute myeloid leukemia and associated with poorer prognosis and chemotherapy resistance.

GeneCards Summary for WT1 Gene

WT1 (WT1 Transcription Factor) is a Protein Coding gene. Diseases associated with WT1 include Wilms Tumor 1 and Denys-Drash Syndrome. Among its related pathways are Mammalian disorder of sexual development and Nervous system development. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and sequence-specific DNA binding. An important paralog of this gene is EGR1.

UniProtKB/Swiss-Prot Summary for WT1 Gene

 Suomennosta (***)  Geeni WT1 koodaa   transkriptiotekijää, joka on solun kehityksesssä ja solun elossaåpysymisesä  tärkeässä osassa. Se tunnistaa  DNA-sekvenssin, johon se kiinnittyy: Tämä DNA-sekvenssi on  5prim-GCG(T/G)GGGCG-3prim.  Se myös säätelee useitten kohdegeenien  ilmentymistä, Näiten kohdegeenien joukossa mainitaan myös EPO, erytropoietiinigeeni. Kuten aiemmin mainittu tällä  transkriptiotekijällä WT1  on essentielli merkitys  virtsatiejärjestelmän ja  sukupuolielinten järjestelmän kehityksessä.Tämä  transkriptiotekijä on sekä tuumorisuppressiivinen( kasvannaista vaimentava) että  onkogeeninen ( syöpää kehkeyttävä)  kasvannaisen muodostumisessa.  Funktio saattaa olla isoformispesifinen,  Sellaiset isoformit, joilta puuttuu KTS-motiivi, voivat  toimia transkriptiofaktoreina saattavat sitoutua  lähettiRNA:han ja niillä on osuutta joko  mRNA-aineenvaihdunnassa tai ne  vaikuttavat pleissaukseen (jossa  esi-mRNA, prekursori mRNA ,trimmataan, pilkotaan introneista,  varsinaiseksi  mRNAmuodoksi). Lisätietoa pleissauksesta:  https://www.wikidoc.org/index.php/Splicing_(genetics) .WT1 geenin  isoformi 1 omaa  matalahkoa affiniteettia DNA:han ja voi sitoa RNA:ta. (Yksinkertainen esimerkki  pleissauksesta. Kun vauva syntyy, sillä on liitteenä napanuora plasenta ja ne leikataan irti ja napatyvi  PYSSLATAAN  siistiKSI ja vauva on valmis  kapaloitavaksi ja annetavaksi äidin syliin jne,  Precursor mRNA = "nascent"  , pre-mRNA   ja pyslattu mRNA  on funktiovalmista).   Vert. DNA:n korjauksessa vastaavat   funktiota  kohentavat manipulaatiot ovat  lähinnä  "trimmausta".

Transcription factor that plays an important role in cellular development and cell survival (PubMed:7862533). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3' (PubMed:7862533, 17716689, 25258363).<<<<<<< Regulates the expression of numerous target genes, including EPO. Plays an essential role for development of the urogenital system. It has a tumor suppressor as well as an oncogenic role in tumor formation. Function may be isoform-specific: isoforms lacking the KTS motif may act as transcription factors (PubMed:15520190). Isoforms containing the KTS motif may bind mRNA and play a role in mRNA metabolism or splicing (PubMed:16934801). Isoform 1 has lower affinity for DNA, and can bind RNA (PubMed:19123921). ( WT1_HUMAN,P19544 ) https://pubmed.ncbi.nlm.nih.gov/19123921/Investigating the effects of the same point mutations on DNA binding indicates that there are similarities and differences in the contributions of zinc fingers 2 and 3 to the DNA and RNA binding activities of WT1.

Protein attributes for WT1 Gene           Size: 449 amino acids

Quaternary structure:

• Homodimer.
  Interacts with WTIP.
  Interacts with actively translating polysomes.
  Detected in nuclear ribonucleoprotein (mRNP) particles.
  Interacts with HNRNPU via the zinc-finger region.
  Interacts with U2AF2.
  Interacts with CITED2 (By similarity).
  Interacts with ZNF224 via the zinc-finger region.
  Interacts with WTAP and SRY.
  Interacts with AMER1.
  Interacts with RBM4.

Miscellaneous:

• Presence of the KTS motif hinders interactions between DNA and zinc-finger 4.

Three dimensional structures from PDB (representative) and AlphaFold (predicted) for WT1

Lisäys: Sinkkisormiproteiinien joukossa  nämä kuuluvat C2H2- ryhmään ja  alaryhmä on tarkennettuna seuraavasti:

 

Gene Families for WT1 Gene

HGNC:

• Zinc fingers C2H2-type

Human Protein Atlas (HPA):

• Cancer-related genes
• Disease related genes
• Human disease related genes
• Predicted intracellular proteins
• Transcription factors

Protein Domains for WT1 Gene

InterPro:

• Znf_C2H2_type
• Znf_C2H2_sf
• Wilms_tumour_N

Blocks:

• C2H2-type zinc finger signature
• Wilm's tumour protein signature

Suggested Antigen Peptide Sequences for WT1 Gene

GenScript: Design optimal peptide antigens:

• Wilms tumor 1 (A0FJ57_HUMAN)
• Wilms tumor 1 (A0FJ58_HUMAN)
• WT1 protein (A8MN20_HUMAN)
• cDNA FLJ35849 fis, clone TESTI2006940, highly similar to Wilms' tumor protein (WT33) (B3KSA5_HUMAN)
• WT1 protein (Q6LBI3_HUMAN)
• See All 9 »
• 
  

Graphical View of Domain Structure for InterPro Entry

P19544

UniProtKB/Swiss-Prot:

WT1_HUMAN :

• Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers. Starting from the N-terminus, the second zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine, 5-formylcytosine or 5-carboxylcytosine.
• Belongs to the EGR C2H2-type zinc-finger protein family.

Domain:

• Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers. Starting from the N-terminus, the second zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine, 5-formylcytosine or 5-carboxylcytosine.
• The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Family:

• Belongs to the EGR C2H2-type zinc-finger protein family.

Genes that share domains with WT1: view