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Protein

RNA-binding E3 ubiquitin-protein ligase MEX3C

Gene

MEX3C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin ligase responsible for the post-transcriptional regulation of common HLA-A allotypes. Binds to the 3' UTR of HLA-A2 mRNA, and regulates its levels by promoting mRNA decay. RNA binding is sufficient to prevent translation, but ubiquitin ligase activity is required for mRNA degradation.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri608 – 64841RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • poly(A) RNA binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, RNA-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Names & Taxonomyi

Protein namesi
Recommended name:
RNA-binding E3 ubiquitin-protein ligase MEX3C (EC:6.3.2.-)
Alternative name(s):
RING finger and KH domain-containing protein 2
RING finger protein 194
Gene namesi
Name:MEX3C
Synonyms:RKHD2, RNF194
ORF Names:BM-013
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:28040. MEX3C.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Genetic variations in MEX3C may be associated with susceptibility to essential hypertension.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi343 – 3431G → D: Prevents RNA binding. 1 Publication

Organism-specific databases

PharmGKBiPA162395821.

Polymorphism and mutation databases

BioMutaiMEX3C.
DMDMi134047827.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 659659RNA-binding E3 ubiquitin-protein ligase MEX3CPRO_0000278782Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei88 – 881PhosphoserineCombined sources
Modified residuei537 – 5371PhosphoserineCombined sources
Modified residuei545 – 5451PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ5U5Q3.
MaxQBiQ5U5Q3.
PaxDbiQ5U5Q3.
PeptideAtlasiQ5U5Q3.
PRIDEiQ5U5Q3.

PTM databases

iPTMnetiQ5U5Q3.
PhosphoSiteiQ5U5Q3.

Expressioni

Tissue specificityi

Highest levels found in fetal brain and testis. Also expressed in thymus, salivary gland and uterus. Highly expressed in cells of the innate immune system, in particular activated NK cells. Week expression in the intestine.2 Publications

Gene expression databases

BgeeiQ5U5Q3.
CleanExiHS_MEX3C.
ExpressionAtlasiQ5U5Q3. baseline and differential.
GenevisibleiQ5U5Q3. HS.

Organism-specific databases

HPAiHPA040603.

Interactioni

Subunit structurei

Interacts with USP7, which antagonizes the ability to degrade mRNA.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
USP7Q930093EBI-2864451,EBI-302474

Protein-protein interaction databases

BioGridi119471. 51 interactions.
IntActiQ5U5Q3. 89 interactions.
MINTiMINT-8394690.
STRINGi9606.ENSP00000385610.

Structurei

3D structure databases

ProteinModelPortaliQ5U5Q3.
SMRiQ5U5Q3. Positions 326-396, 606-653.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini232 – 29362KH 1PROSITE-ProRule annotationAdd
BLAST
Domaini326 – 38762KH 2PROSITE-ProRule annotationAdd
BLAST

Domaini

Binds RNA through its KH domains.

Sequence similaritiesi

Contains 2 KH domains.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri608 – 64841RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG2113. Eukaryota.
ENOG410Y337. LUCA.
GeneTreeiENSGT00390000018714.
HOGENOMiHOG000236282.
HOVERGENiHBG071698.
InParanoidiQ5U5Q3.
KOiK15686.
OMAiRNKNGPT.
OrthoDBiEOG7D85WG.
PhylomeDBiQ5U5Q3.
TreeFamiTF315107.

Family and domain databases

Gene3Di3.30.1370.10. 2 hits.
3.30.40.10. 1 hit.
InterProiIPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF00013. KH_1. 2 hits.
[Graphical view]
SMARTiSM00322. KH. 2 hits.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF54791. SSF54791. 2 hits.
PROSITEiPS50084. KH_TYPE_1. 2 hits.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5U5Q3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPSGSSAALA LAAAPAPLPQ PPPPPPPPPP PLPPPSGGPE LEGDGLLLRE
60 70 80 90 100
RLAALGLDDP SPAEPGAPAL RAPAAAAQGQ ARRAAELSPE ERAPPGRPGA
110 120 130 140 150
PEAAELELEE DEEEGEEAEL DGDLLEEEEL EEAEEEDRSS LLLLSPPAAT
160 170 180 190 200
ASQTQQIPGG SLGSVLLPAA RFDAREAAAA AAAAGVLYGG DDAQGMMAAM
210 220 230 240 250
LSHAYGPGGC GAAAAALNGE QAALLRRKSV NTTECVPVPS SEHVAEIVGR
260 270 280 290 300
QGCKIKALRA KTNTYIKTPV RGEEPIFVVT GRKEDVAMAK REILSAAEHF
310 320 330 340 350
SMIRASRNKN GPALGGLSCS PNLPGQTTVQ VRVPYRVVGL VVGPKGATIK
360 370 380 390 400
RIQQQTHTYI VTPSRDKEPV FEVTGMPENV DRAREEIEMH IAMRTGNYIE
410 420 430 440 450
LNEENDFHYN GTDVSFEGGT LGSAWLSSNP VPPSRARMIS NYRNDSSSSL
460 470 480 490 500
GSGSTDSYFG SNRLADFSPT SPFSTGNFWF GDTLPSVGSE DLAVDSPAFD
510 520 530 540 550
SLPTSAQTIW TPFEPVNPLS GFGSDPSGNM KTQRRGSQPS TPRLSPTFPE
560 570 580 590 600
SIEHPLARRV RSDPPSTGNH VGLPIYIPAF SNGTNSYSSS NGGSTSSSPP
610 620 630 640 650
ESRRKHDCVI CFENEVIAAL VPCGHNLFCM ECANKICEKR TPSCPVCQTA

VTQAIQIHS
Length:659
Mass (Da):69,366
Last modified:March 20, 2007 - v3
Checksum:iBAFDB7AD4B331471
GO

Sequence cautioni

The sequence AAF64269.1 differs from that shown. Reason: Frameshift at positions 520 and 525. Curated
The sequence AAF64269.1 differs from that shown. Reason: Erroneous termination at position 514. Translated as Glu.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti509 – 5091I → M in AAF64269 (Ref. 4) Curated
Sequence conflicti519 – 5191L → F in AAF64269 (Ref. 4) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti412 – 4121T → P.
Corresponds to variant rs12970605 [ dbSNP | Ensembl ].
VAR_030832

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY950679 mRNA. Translation: AAY34147.1.
AC090330 Genomic DNA. No translation available.
BC041122 mRNA. Translation: AAH41122.1.
AF208855 mRNA. Translation: AAF64269.1. Sequence problems.
CCDSiCCDS11951.2.
RefSeqiNP_057710.3. NM_016626.4.
UniGeneiHs.465144.

Genome annotation databases

EnsembliENST00000406189; ENSP00000385610; ENSG00000176624.
GeneIDi51320.
KEGGihsa:51320.
UCSCiuc002lfc.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY950679 mRNA. Translation: AAY34147.1.
AC090330 Genomic DNA. No translation available.
BC041122 mRNA. Translation: AAH41122.1.
AF208855 mRNA. Translation: AAF64269.1. Sequence problems.
CCDSiCCDS11951.2.
RefSeqiNP_057710.3. NM_016626.4.
UniGeneiHs.465144.

3D structure databases

ProteinModelPortaliQ5U5Q3.
SMRiQ5U5Q3. Positions 326-396, 606-653.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119471. 51 interactions.
IntActiQ5U5Q3. 89 interactions.
MINTiMINT-8394690.
STRINGi9606.ENSP00000385610.

PTM databases

iPTMnetiQ5U5Q3.
PhosphoSiteiQ5U5Q3.

Polymorphism and mutation databases

BioMutaiMEX3C.
DMDMi134047827.

Proteomic databases

EPDiQ5U5Q3.
MaxQBiQ5U5Q3.
PaxDbiQ5U5Q3.
PeptideAtlasiQ5U5Q3.
PRIDEiQ5U5Q3.

Protocols and materials databases

DNASUi51320.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000406189; ENSP00000385610; ENSG00000176624.
GeneIDi51320.
KEGGihsa:51320.
UCSCiuc002lfc.5. human.

Organism-specific databases

CTDi51320.
GeneCardsiMEX3C.
HGNCiHGNC:28040. MEX3C.
HPAiHPA040603.
MIMi611005. gene.
neXtProtiNX_Q5U5Q3.
PharmGKBiPA162395821.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2113. Eukaryota.
ENOG410Y337. LUCA.
GeneTreeiENSGT00390000018714.
HOGENOMiHOG000236282.
HOVERGENiHBG071698.
InParanoidiQ5U5Q3.
KOiK15686.
OMAiRNKNGPT.
OrthoDBiEOG7D85WG.
PhylomeDBiQ5U5Q3.
TreeFamiTF315107.

Enzyme and pathway databases

ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

GenomeRNAii51320.
PROiQ5U5Q3.
SOURCEiSearch...

Gene expression databases

BgeeiQ5U5Q3.
CleanExiHS_MEX3C.
ExpressionAtlasiQ5U5Q3. baseline and differential.
GenevisibleiQ5U5Q3. HS.

Family and domain databases

Gene3Di3.30.1370.10. 2 hits.
3.30.40.10. 1 hit.
InterProiIPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF00013. KH_1. 2 hits.
[Graphical view]
SMARTiSM00322. KH. 2 hits.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF54791. SSF54791. 2 hits.
PROSITEiPS50084. KH_TYPE_1. 2 hits.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification and characterization of human Mex-3 proteins, a novel family of evolutionarily conserved RNA-binding proteins differentially localized to processing bodies."
    Buchet-Poyau K., Courchet J., Le Hir H., Seraphin B., Scoazec J.-Y., Duret L., Domon-Dell C., Freund J.-N., Billaud M.
    Nucleic Acids Res. 35:1289-1300(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-343, PHOSPHORYLATION.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 451-659.
    Tissue: Lung.
  4. "A novel gene expressed in human bone marrow."
    Zhao M., Song H., Li N., Peng Y., Han Z., Chen Z.
    Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 508-659.
    Tissue: Bone marrow.
  5. "Implication of chromosome 18 in hypertension by sibling pair and association analyses: putative involvement of the RKHD2 gene."
    Guzman B., Cormand B., Ribases M., Gonzalez-Nunez D., Botey A., Poch E.
    Hypertension 48:883-891(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO ESSENTIAL HYPERTENSION.
  6. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. "The RNA-binding E3 ubiquitin ligase MEX-3C links ubiquitination with MHC-I mRNA degradation."
    Cano F., Bye H., Duncan L.M., Buchet-Poyau K., Billaud M., Wills M.R., Lehner P.J.
    EMBO J. 31:3596-3606(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH USP7.
  8. "Toward a comprehensive characterization of a human cancer cell phosphoproteome."
    Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., Mohammed S.
    J. Proteome Res. 12:260-271(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-537 AND SER-545, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  9. Cited for: FUNCTION.

Entry informationi

Entry nameiMEX3C_HUMAN
AccessioniPrimary (citable) accession number: Q5U5Q3
Secondary accession number(s): A1L022, Q9NZE3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: March 20, 2007
Last modified: July 6, 2016
This is version 110 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.