TRIM1 ( Kr.Xq22.3), MID2, MRX101, RNF60,
Todennäköisesti E3 ubiquitin-proteiini ligaasi, (C-I,
COS, FN3, PRYSPRY)
TRIM1 geeni
sijaitsee X-kromosomissa. Proteiini paikallistuu sytoplasmisiin
mikrotubuluksiin. Geenin vaihtoehtoisluennat johtavat kahteen
erilaiseen transkriptiin ja vastaaviin isoformeihin. C-terminaalin
perusteella luokitellaan alaryhmään C_I Tähän geeniin liittyy
proteiinin homodimerisaatio, aktivoituminen ja ligaasisaktiviteetti.
Geenin tärkeä paralogi on MID1. Geenillä lienee merktitystä
mikrotubulien stabilisoinnissa. Vaihtoehtoisin pleissauksin tulee
kaksi transkriptia, jotka koodaavat eri isoformeja.Geeniä ilmentyy kilpirauhasessa, rasvakudoksessa ja 24 muussa kudoksessa
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- https://www.ncbi.nlm.nih.gov/gene/11043
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- MID2. Muita nimiä: FXY2; RNF60; TRIM1; MRX101 Summary
- The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to microtubular structures in the cytoplasm. Alternate splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Feb 2009] Expression Ubiquitous expression in thyroid (RPKM 3.8), fat (RPKM 3.4) and 24 other tissues See more
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GeneCards Summary for MID2 Gene MID2 (Midline 2) is a
Protein Coding gene. Diseases associated with MID2 include Mental
Retardation, X-Linked 101 and X-Linked
Non-Specific Intellectual Disability. GO annotations related to
this gene include protein homodimerization activity and
ligase activity. An important paralog of this gene is MID1.
RAKENNE: Konservoidut domeenit:
Conserved Domains
(5) summary
smart00502
Location:239 → 364
Location:239 → 364
BBC; B-Box
C-terminal domain
smart00336
Location:195 → 232
Location:195 → 232
BBOX; B-Box-type
zinc finger
cd00063
Location:401 → 531
Location:401 → 531
FN3; Fibronectin
type 3 domain; One of three types of internal repeats found in the
plasma protein fibronectin. Its tenth fibronectin type III repeat
contains an RGD cell recognition sequence in a flexible loop between
2 strands. Approximately 2% of all ...
cd13739
Location:536 → 705
Location:536 → 705
SPRY_PRY_TRIM1;
PRY/SPRY domain of tripartite motif-binding protein 1 (TRIM1) or MID2
- cd16754
Location:30 → 82 - RING-HC_MID2; RING finger, HC subclass, found in midline-2 (MID2) and similar proteins
TRIM1 isoformi 1 (735 aminohappoa)
https://www.ncbi.nlm.nih.gov/protein/NP_036348.2LOCUS NP_036348 735 aa linear PRI 08-APR-2018 DEFINITION probable E3 ubiquitin-protein ligase MID2 isoform 1 [Homo sapiens]. ACCESSION NP_036348 VERSION NP_036348.2 DBSOURCE REFSEQ: accession NM_012216.3 KEYWORDS RefSeq. SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (residues 1 to 735) AUTHORS Wang L, Wu J, Yuan J, Zhu X, Wu H and Li M. TITLE Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer cell proliferation in vitro and in vivo JOURNAL Front Med 10 (1), 41-51 (2016) PUBMED 26791755 REMARK GeneRIF: overexpressed in advanced breast cancer and high overexpression is prognostic factor for poor overall survival REFERENCE 2 (residues 1 to 735) AUTHORS Gholkar AA, Senese S, Lo YC, Vides E, Contreras E, Hodara E, Capri J, Whitelegge JP and Torres JZ. TITLE The X-Linked-Intellectual-Disability-Associated Ubiquitin Ligase Mid2 Interacts with Astrin and Regulates Astrin Levels to Promote Cell Division JOURNAL Cell Rep 14 (2), 180-188 (2016) PUBMED 26748699 REMARK GeneRIF: Mid2 regulates cell division through the ubiquitination of astrin on K409, which is critical for its degradation and proper cytokinesis. REFERENCE 3 (residues 1 to 735) AUTHORS Kimura,T., Jain,A., Choi,S.W., Mandell,M.A., Schroder,K., Johansen,T. and Deretic,V. TITLE TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity JOURNAL J. Cell Biol. 210 (6), 973-989 (2015) PUBMED 26347139 REFERENCE 4 (residues 1 to 735) AUTHORS Geetha TS, Michealraj KA, Kabra M, Kaur G, Juyal RC and Thelma BK. TITLE Targeted deep resequencing identifies MID2 mutation for X-linked intellectual disability with varied disease severity in a large kindred from India JOURNAL Hum. Mutat. 35 (1), 41-44 (2014) PUBMED 24115387 REMARK GeneRIF: A novel missense mutation (c.1040G>A, p.Arg347Gln) was reported in MID2, which encodes ubiquitin ligase E3, as the likely cause of X-linked mental retardation in a large kindred. REFERENCE 5 (residues 1 to 735) AUTHORS Uchil PD, Hinz A, Siegel S, Coenen-Stass A, Pertel T, Luban J and Mothes W. TITLE TRIM protein-mediated regulation of inflammatory and innate immune signaling and its association with antiretroviral activity JOURNAL J. Virol. 87 (1), 257-272 (2013) PUBMED 23077300 REFERENCE 6 (residues 1 to 735) AUTHORS Yap MW, Nisole S, Lynch C and Stoye JP. TITLE Trim5alpha protein restricts both HIV-1 and murine leukemia virus JOURNAL Proc. Natl. Acad. Sci. U.S.A. 101 (29), 10786-10791 (2004) PUBMED 15249690 REFERENCE 7 (residues 1 to 735) AUTHORS Short KM, Hopwood B, Yi Z and Cox TC. TITLE MID1 and MID2 homo- and heterodimerise to tether the rapamycin-sensitive PP2A regulatory subunit, alpha 4, to microtubules: implications for the clinical variability of X-linked Opitz GBBB syndrome and other developmental disorders JOURNAL BMC Cell Biol. 3, 1 (2002) PUBMED 11806752 REMARK GeneRIF: MID2 coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the MID-alpha 4 complex with microtubules. REFERENCE 8 (residues 1 to 735) AUTHORS Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG and Ballabio A. TITLE The tripartite motif family identifies cell compartments JOURNAL EMBO J. 20 (9), 2140-2151 (2001) PUBMED 11331580 REFERENCE 9 (residues 1 to 735) AUTHORS Perry J, Short KM, Romer JT, Swift S, Cox TC and Ashworth A. TITLE FXY2/MID2, a gene related to the X-linked Opitz syndrome gene FXY/MID1, maps to Xq22 and encodes a FNIII domain-containing protein that associates with microtubules JOURNAL Genomics 62 (3), 385-394 (1999) PUBMED 10644436 REFERENCE 10 (residues 1 to 735) AUTHORS Buchner G, Montini E, Andolfi G, Quaderi N, Cainarca S, Messali S, Bassi MT, Ballabio A, Meroni G and Franco B. TITLE MID2, a homologue of the Opitz syndrome gene MID1: similarities in subcellular localization and differences in expression during development JOURNAL Hum. Mol. Genet. 8 (8), 1397-1407 (1999) PUBMED 10400986 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from DN997921.1, Y18880.1 and AL034399.6. This sequence is a reference standard in the RefSeqGene project. On Feb 20, 2009 this sequence version replaced NP_036348.1. Summary: The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to microtubular structures in the cytoplasm. Alternate splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Feb 2009]. Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1). Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1660805.85252.1, Y18880.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1968189 [ECO:0000348] ##Evidence-Data-END## FEATURES Location/Qualifiers source 1..735 /organism="Homo sapiens" /db_xref="taxon:9606" /chromosome="X" /map="Xq22.3" Protein 1..735 /product="probable E3 ubiquitin-protein ligase MID2 isoform 1" /EC_number="2.3.2.27" /note="tripartite motif protein 1; midin 2; probable E3 ubiquitin-protein ligase MID2; midline defect 2; RING finger protein 60; tripartite motif-containing protein 1; RING-type E3 ubiquitin transferase MID2" /calculated_mol_wt=83080 Region 30..82 /region_name="RING-HC_MID2" /note="RING finger, HC subclass, found in midline-2 (MID2) and similar proteins; cd16754" /db_xref="CDD:319668" Region 30..79 /region_name="RING-HC finger (C3HC4-type)" /note="RING-HC finger (C3HC4-type) [structural motif]" /db_xref="CDD:319668" Site order(30,33,45,47,50,53,76,79) /site_type="other" /note="Zn binding site [ion binding]" /db_xref="CDD:319668" Region 195..232 /region_name="BBOX" /note="B-Box-type zinc finger; smart00336" /db_xref="CDD:197662" Site order(195,198,218,224) /site_type="other" /note="Zn2+ binding site [ion binding]" /db_xref="CDD:237988" Region 239..364 /region_name="BBC" /note="B-Box C-terminal domain; smart00502" /db_xref="CDD:128778" Region 401..531 /region_name="FN3" /note="Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all...; cd00063" /db_xref="CDD:238020" Region 536..705 /region_name="SPRY_PRY_TRIM1" /note="PRY/SPRY domain of tripartite motif-binding protein 1 (TRIM1) or MID2; cd13739" /db_xref="CDD:293974" CDS 1..735 /gene="MID2" /gene_synonym="FXY2; MRX101; RNF60; TRIM1" /coded_by="NM_012216.3:574..2781" /note="isoform 1 is encoded by transcript variant 1" /db_xref="CCDS:CCDS14532.2" /db_xref="GeneID:11043" /db_xref="HGNC:HGNC:7096" /db_xref="MIM:300204" ORIGIN 1 mgespasvvl nasgglfslk metleseltc piclelfedp lllpcahslc fscahrilvs 61 scssgesiep itafqcptcr yvislnhrgl dglkrnvtlq niidrfqkas vsgpnspses 121 rrertyrptt amsseriacq fceqdpprda vktcitcevs ycdrclrath pnkkpftshr 181 lvepvpdthl rgitcldhen ekvnmycvsd dqlicalckl vgrhrdhqva slndrfeklk 241 qtlemnltnl vkrnselenq makliqicqq vevntamhea klmeecdelv eiiqqrkqmi 301 avkiketkvm klrklaqqva ncrqclerst vlinqaehil kendqarflq sakniaerva 361 matassqvli pdinfndafe nfaldfsrek kllegldylt apnppsiree lctashdtit 421 vhwisddefs issyelqyti ftgqanfisk swcswglwpe irkckeavsc srlagaprgl 481 ynsvdswmiv pnikqnhytv hglqsgtryi fivkainqag srnseptrlk tnsqpfkldp 541 kmthkklkis ndglqmekde sslkkshtpe rfsgtgcyga agnifidsgc hywevvmgss 601 twyaigiayk sapknewigk nasswvfsrc nsnfvvrhnn kemlvdvpph lkrlgvlldy 661 dnnmlsfydp anslhlhtfd vtfilpvcpt ftiwnkslmi lsglpapdfi dyperqecnc 721 rpqespyvsg mktch //
Artikkeleita Related articles in PubMed
TRIM1(MID2, RNF60) ja BRCA1(RNF53)
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Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer cell proliferation in vitro and in vivo. Wang L, et al. Front Med, 2016 Mar. PMID 26791755 (Suomennsota)
Midline2 (MID2) on
ubikitiiniä konjugoiva E2-entsyymi, joka linkkiytyy tuumorin
progredioitumiseen ja on uusi havaittu proteiini, joka tekee
interaktion BRCA1:n kanssa (BRCA1 on RING finger proteiini 53
RNF53, muita nimiä PPP1R53, IMP, IRIS, PSCP, FANCS,PNCA4) . Tässä
tutkimuksessa haluttiin selvittää TRIM1:n osuus rintasyövän
varhaisessa alussa. MID2 mRNA oli ylössäätynyt yli 95%:ssa
tutkituista näytteistä. MID2-ilmenemä myös lisääntyi taudin
kliinisen vaikeusasteen myötä. Analyysien perusteella MID2 on
itsenäinen prognostinen faktori. . MID2:n siRNA- hiljennys
vähensi merkitsevästi syöpäsolulinjoja in vitro ja koe-eläimen
xenokraftituumoria in vivo. MID2 voi toimia prognostisena markkerina
sekä interventiokohteena rintasyövässä.
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Midline2 (MID2) is an ubiquitin-conjugating E2 enzyme linked to tumor progression and a novel interacting partner of breast cancer 1, early-onset (BRCA1). However, the role of MID2 in breast cancer remains unknown. This study investigated the expression, prognostic value, and role of MID2 in breast cancer.
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The expression of MID2 mRNA and protein was significantly upregulated in breast cancer tissue and established cell lines compared with that in normal breast epithelial cells and paired adjacent non-tumor tissue (P < 0.001). Immunohistochemical analysis demonstrated that MID2 was overexpressed in 272 of 284 (95.8%) paraffinembedded, archived breast cancer tissue. Moreover, MID2 expression increased with advanced clinical stage (P < 0.001). High MID2 expression was significantly associated with advanced clinical stages and T, N, and M staging (all P < 0.05). Univariate and multivariate analyses indicated that high MID2 expression was an independent prognostic factor..Results showed that siRNA silencing of MID2 expression significantly reduced MCF-7 and MDA-MB-231 cell proliferation in vitro and blocked the growth of MDA-MB-231 cell xenograft tumors in vivo (P < 0.05). This study indicated that MID2 may be a novel prognostic marker and interventional target in breast cancer.
TRIM1 (MID2) ja ASTRIINI
Mid2 regulates cell division through the ubiquitination of astrin on K409, which is critical for its degradation and proper cytokinesis.
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MID1 ja MID2 ovat ubikitiiniligaaseja, jotka säätelevät mikrotubulusten dynamiikkaaja joiden mutaatiot liittyvät X-kromosomiin linkkiytyneisiin kehityksellisiin häiriöihin.
Tutkijat osoittivat
tässä työssään, että ASTRIINI- niminen proteiini, joka
organisoi mikrotubuluksia, saostui tutkittaessa MID1 ja MID2
-proteiinien kanssa. ASTRIININ sijoittuminen kattaa MID1- ja
MID2- lokalisaatiokohdat jakaantumassa olevien solujen välisiltojen
mikrotubuluksissa. ASTRIININ ubikitinoi lysiiniin (K409) MID2 ja
sytokineesin aikana ASTRIINI tämän takia hajoaa normaalisti. Mutta
jos tehdään MID2-depleetio ( poisto) , ASTRIINI ehtii stabiloitua
sytokineesin kuluessa ja sytokineesi tulee puutteeliseksi, esiintyy
monitumaisia soluja ja solukuolemaa ( siis solu ei pääse
normaalisti tekemään kahta symmetristä tytärsolua) . Entä jos
ASTRIINI itse on mutatoitunut siten, että tarvitava lysiinikohta
K409 onkin muuttunut alaniiniksi, joka ei voi ubikitinoitua)
Mutatoitunutta ASTRIINIA alkaa tällöin kertyä soluun
jakaantumista yrittävien solujen väliseen mikrotubulussiltaan ja
niin sytokineesi edelleen vaikeutuu. Solut jäävät monitumaisiksi
ja kuolevat. Tulokset osoittavat, että MID2 säätelee solun
jakaantumista ubikitinoimalla ASTRIININ K409 lysiinini , mikä on
ratkaisevaa, jotta ASTRIINI hajoaisi ajoissa ja solut vapautuisivat
normaaliin sytokinetiikkaan. Nämä tulokset saattavat auttaa
selittämään, kuinka MID2-mutaatio johtaa mikrotubulusten hyvän
järjestyksen sekasortoon ja siitä johtuen signaloinnin
alavirrassa X-kromosomiin linkkiytyneeseen tautipatologiaan, joka
koskee lopulta ilmenee intelligenssin heikentymänä.
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Mid1 and Mid2 are ubiquitin ligases that regulate microtubule dynamics and whose mutation is associated with X-linked developmental disorders. We show that astrin, a microtubule-organizing protein, co-purifies with Mid1 and Mid2, has an overlapping localization with Mid1 and Mid2 at intercellular bridge microtubules, is ubiquitinated by Mid2 on lysine 409, and is degraded during cytokinesis. Mid2 depletion led to astrin stabilization during cytokinesis, cytokinetic defects, multinucleated cells, and cell death. Similarly, expression of a K409A mutant astrin in astrin-depleted cells led to the accumulation of K409A on intercellular bridge microtubules and an increase in cytokinetic defects, multinucleated cells, and cell death. These results indicate that Mid2 regulates cell division through the ubiquitination of astrin on K409, which is critical for its degradation and proper cytokinesis. These results could help explain how mutation of MID2 leads to misregulation of microtubule organization and the downstream disease pathology associated with X-linked intellectual disabilities.
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