MEX3C_HUMAN
ID MEX3C_HUMAN Reviewed; 659 AA.
AC Q5U5Q3; A1L022; Q9NZE3;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 3.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=RNA-binding E3 ubiquitin-protein ligase MEX3C;
DE EC=2.3.2.27;
DE AltName: Full=RING finger and KH domain-containing protein 2;
DE AltName: Full=RING finger protein 194;
DE AltName: Full=RING-type E3 ubiquitin transferase MEX3C {ECO:0000305};
GN Name=MEX3C; Synonyms=RKHD2, RNF194; ORFNames=BM-013;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP MUTAGENESIS OF GLY-343, AND PHOSPHORYLATION.
RX PubMed=17267406; DOI=10.1093/nar/gkm016;
RA Buchet-Poyau K., Courchet J., Le Hir H., Seraphin B., Scoazec J.-Y.,
RA Duret L., Domon-Dell C., Freund J.-N., Billaud M.;
RT "Identification and characterization of human Mex-3 proteins, a novel
RT family of evolutionarily conserved RNA-binding proteins differentially
RT localized to processing bodies.";
RL Nucleic Acids Res. 35:1289-1300(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 451-659.
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 508-659.
RC TISSUE=Bone marrow;
RA Zhao M., Song H., Li N., Peng Y., Han Z., Chen Z.;
RT "A novel gene expressed in human bone marrow.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO ESSENTIAL HYPERTENSION.
RX PubMed=17015768; DOI=10.1161/01.hyp.0000244085.52918.a0;
RA Guzman B., Cormand B., Ribases M., Gonzalez-Nunez D., Botey A., Poch E.;
RT "Implication of chromosome 18 in hypertension by sibling pair and
RT association analyses: putative involvement of the RKHD2 gene.";
RL Hypertension 48:883-891(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH USP7.
RX PubMed=22863774; DOI=10.1038/emboj.2012.218;
RA Cano F., Bye H., Duncan L.M., Buchet-Poyau K., Billaud M., Wills M.R.,
RA Lehner P.J.;
RT "The RNA-binding E3 ubiquitin ligase MEX-3C links ubiquitination with MHC-I
RT mRNA degradation.";
RL EMBO J. 31:3596-3606(2012).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-537 AND SER-545, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP FUNCTION.
RX PubMed=23446422; DOI=10.1038/nature11935;
RA Burrell R.A., McClelland S.E., Endesfelder D., Groth P., Weller M.C.,
RA Shaikh N., Domingo E., Kanu N., Dewhurst S.M., Gronroos E., Chew S.K.,
RA Rowan A.J., Schenk A., Sheffer M., Howell M., Kschischo M., Behrens A.,
RA Helleday T., Bartek J., Tomlinson I.P., Swanton C.;
RT "Replication stress links structural and numerical cancer chromosomal
RT instability.";
RL Nature 494:492-496(2013).
CC -!- FUNCTION: E3 ubiquitin ligase responsible for the post-transcriptional
CC regulation of common HLA-A allotypes. Binds to the 3' UTR of HLA-A2
CC mRNA, and regulates its levels by promoting mRNA decay. RNA binding is
CC sufficient to prevent translation, but ubiquitin ligase activity is
CC required for mRNA degradation. {ECO:0000269|PubMed:22863774,
CC ECO:0000269|PubMed:23446422}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- SUBUNIT: Interacts with USP7, which antagonizes the ability to degrade
CC mRNA. {ECO:0000269|PubMed:22863774}.
CC -!- INTERACTION:
CC Q5U5Q3; Q93009: USP7; NbExp=3; IntAct=EBI-2864451, EBI-302474;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17267406}. Nucleus
CC {ECO:0000269|PubMed:17267406}. Note=Predominantly expressed in the
CC cytoplasm and shuttles between the cytoplasm and the nucleus through
CC the CRM1 export pathway. May act as suppressor of replication stress
CC and chromosome missegregation.
CC -!- TISSUE SPECIFICITY: Highest levels found in fetal brain and testis.
CC Also expressed in thymus, salivary gland and uterus. Highly expressed
CC in cells of the innate immune system, in particular activated NK cells.
CC Week expression in the intestine. {ECO:0000269|PubMed:17267406,
CC ECO:0000269|PubMed:22863774}.
CC -!- DOMAIN: Binds RNA through its KH domains.
CC -!- DISEASE: Note=Genetic variations in MEX3C may be associated with
CC susceptibility to essential hypertension.
CC {ECO:0000269|PubMed:17015768}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF64269.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF64269.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY950679; AAY34147.1; -; mRNA.
DR EMBL; AC090330; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC041122; AAH41122.1; -; mRNA.
DR EMBL; AF208855; AAF64269.1; ALT_SEQ; mRNA.
DR CCDS; CCDS11951.2; -.
DR RefSeq; NP_057710.3; NM_016626.4.
DR PDB; 5WWW; X-ray; 1.80 A; A=221-306.
DR PDB; 5WWX; X-ray; 2.00 A; A=320-396.
DR PDB; 5WWZ; X-ray; 2.50 A; A/B/C=320-396.
DR PDB; 5ZI6; X-ray; 2.20 A; A/B/C/D/E/F/G/H=605-659.
DR PDBsum; 5WWW; -.
DR PDBsum; 5WWX; -.
DR PDBsum; 5WWZ; -.
DR PDBsum; 5ZI6; -.
DR AlphaFoldDB; Q5U5Q3; -.
DR SMR; Q5U5Q3; -.
DR BioGRID; 119471; 78.
DR IntAct; Q5U5Q3; 93.
DR MINT; Q5U5Q3; -.
DR STRING; 9606.ENSP00000385610; -.
DR iPTMnet; Q5U5Q3; -.
DR PhosphoSitePlus; Q5U5Q3; -.
DR BioMuta; MEX3C; -.
DR DMDM; 134047827; -.
DR EPD; Q5U5Q3; -.
DR jPOST; Q5U5Q3; -.
DR MassIVE; Q5U5Q3; -.
DR MaxQB; Q5U5Q3; -.
DR PaxDb; Q5U5Q3; -.
DR PeptideAtlas; Q5U5Q3; -.
DR PRIDE; Q5U5Q3; -.
DR ProteomicsDB; 65230; -.
DR Antibodypedia; 22729; 143 antibodies from 31 providers.
DR DNASU; 51320; -.
DR Ensembl; ENST00000406189.4; ENSP00000385610.3; ENSG00000176624.12.
DR GeneID; 51320; -.
DR KEGG; hsa:51320; -.
DR MANE-Select; ENST00000406189.4; ENSP00000385610.3; NM_016626.5; NP_057710.3.
DR UCSC; uc002lfc.5; human.
DR CTD; 51320; -.
DR DisGeNET; 51320; -.
DR GeneCards; MEX3C; -.
DR HGNC; HGNC:28040; MEX3C.
DR HPA; ENSG00000176624; Tissue enhanced (testis).
DR MIM; 611005; gene.
DR neXtProt; NX_Q5U5Q3; -.
DR OpenTargets; ENSG00000176624; -.
DR PharmGKB; PA162395821; -.
DR VEuPathDB; HostDB:ENSG00000176624; -.
DR eggNOG; KOG2113; Eukaryota.
DR GeneTree; ENSGT00940000160973; -.
DR InParanoid; Q5U5Q3; -.
DR OMA; MSNYRND; -.
DR OrthoDB; 814376at2759; -.
DR PhylomeDB; Q5U5Q3; -.
DR TreeFam; TF315107; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; Q5U5Q3; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q5U5Q3; -.
DR BioGRID-ORCS; 51320; 24 hits in 1068 CRISPR screens.
DR ChiTaRS; MEX3C; human.
DR GenomeRNAi; 51320; -.
DR Pharos; Q5U5Q3; Tbio.
DR PRO; PR:Q5U5Q3; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q5U5Q3; protein.
DR Bgee; ENSG00000176624; Expressed in sperm and 196 other tissues.
DR ExpressionAtlas; Q5U5Q3; baseline and differential.
DR Genevisible; Q5U5Q3; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:FlyBase.
DR GO; GO:0003415; P:chondrocyte hypertrophy; IEA:Ensembl.
DR GO; GO:0097009; P:energy homeostasis; IEA:Ensembl.
DR GO; GO:0045598; P:regulation of fat cell differentiation; IEA:Ensembl.
DR Gene3D; 3.30.1370.10; -; 2.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF00013; KH_1; 2.
DR SMART; SM00322; KH; 2.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF54791; SSF54791; 2.
DR PROSITE; PS50084; KH_TYPE_1; 2.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..659
FT /note="RNA-binding E3 ubiquitin-protein ligase MEX3C"
FT /id="PRO_0000278782"
FT DOMAIN 232..293
FT /note="KH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 326..387
FT /note="KH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT ZN_FING 608..648
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 513..569
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 15..38
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 105..136
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 522..547
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 537
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 545
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 412
FT /note="T -> P (in dbSNP:rs12970605)"
FT /id="VAR_030832"
FT MUTAGEN 343
FT /note="G->D: Prevents RNA binding."
FT /evidence="ECO:0000269|PubMed:17267406"
FT CONFLICT 509
FT /note="I -> M (in Ref. 4; AAF64269)"
FT /evidence="ECO:0000305"
FT CONFLICT 519
FT /note="L -> F (in Ref. 4; AAF64269)"
FT /evidence="ECO:0000305"
FT HELIX 221..226
FT /evidence="ECO:0007829|PDB:5WWW"
FT STRAND 232..237
FT /evidence="ECO:0007829|PDB:5WWW"
FT HELIX 241..248
FT /evidence="ECO:0007829|PDB:5WWW"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:5WWW"
FT HELIX 253..262
FT /evidence="ECO:0007829|PDB:5WWW"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:5WWW"
FT STRAND 276..282
FT /evidence="ECO:0007829|PDB:5WWW"
FT HELIX 283..304
FT /evidence="ECO:0007829|PDB:5WWW"
FT STRAND 327..332
FT /evidence="ECO:0007829|PDB:5WWX"
FT HELIX 335..337
FT /evidence="ECO:0007829|PDB:5WWX"
FT HELIX 338..342
FT /evidence="ECO:0007829|PDB:5WWX"
FT HELIX 344..346
FT /evidence="ECO:0007829|PDB:5WWX"
FT HELIX 347..356
FT /evidence="ECO:0007829|PDB:5WWX"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:5WWX"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:5WWZ"
FT STRAND 369..375
FT /evidence="ECO:0007829|PDB:5WWX"
FT HELIX 377..395
FT /evidence="ECO:0007829|PDB:5WWX"
FT TURN 609..611
FT /evidence="ECO:0007829|PDB:5ZI6"
FT STRAND 612..615
FT /evidence="ECO:0007829|PDB:5ZI6"
FT STRAND 618..621
FT /evidence="ECO:0007829|PDB:5ZI6"
FT HELIX 630..638
FT /evidence="ECO:0007829|PDB:5ZI6"
FT STRAND 639..641
FT /evidence="ECO:0007829|PDB:5ZI6"
FT TURN 645..647
FT /evidence="ECO:0007829|PDB:5ZI6"
FT STRAND 652..656
FT /evidence="ECO:0007829|PDB:5ZI6"
SQ SEQUENCE 659 AA; 69366 MW; BAFDB7AD4B331471 CRC64;
MPSGSSAALA LAAAPAPLPQ PPPPPPPPPP PLPPPSGGPE LEGDGLLLRE RLAALGLDDP
SPAEPGAPAL RAPAAAAQGQ ARRAAELSPE ERAPPGRPGA PEAAELELEE DEEEGEEAEL
DGDLLEEEEL EEAEEEDRSS LLLLSPPAAT ASQTQQIPGG SLGSVLLPAA RFDAREAAAA
AAAAGVLYGG DDAQGMMAAM LSHAYGPGGC GAAAAALNGE QAALLRRKSV NTTECVPVPS
SEHVAEIVGR QGCKIKALRA KTNTYIKTPV RGEEPIFVVT GRKEDVAMAK REILSAAEHF
SMIRASRNKN GPALGGLSCS PNLPGQTTVQ VRVPYRVVGL VVGPKGATIK RIQQQTHTYI
VTPSRDKEPV FEVTGMPENV DRAREEIEMH IAMRTGNYIE LNEENDFHYN GTDVSFEGGT
LGSAWLSSNP VPPSRARMIS NYRNDSSSSL GSGSTDSYFG SNRLADFSPT SPFSTGNFWF
GDTLPSVGSE DLAVDSPAFD SLPTSAQTIW TPFEPVNPLS GFGSDPSGNM KTQRRGSQPS
TPRLSPTFPE SIEHPLARRV RSDPPSTGNH VGLPIYIPAF SNGTNSYSSS NGGSTSSSPP
ESRRKHDCVI CFENEVIAAL VPCGHNLFCM ECANKICEKR TPSCPVCQTA VTQAIQIHS
