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Protein

E3 ubiquitin-protein ligase TRIM8

Gene

TRIM8

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

Functioni

E3 ubiquitin-protein ligase which plays different roles in immune pathways. Participates in the activation of interferon-gamma signaling by promoting proteasomal degradation of the repressor SOCS1 (PubMed:12163497). Plays a positive role in the TNFalpha and IL-1beta signaling pathways. Mechanistically, induces the 'lys-63' polyubiquitination of MAP3K7/TAK1 component leading to the activation of NF-kappa-B (PubMed:22084099, PubMed:23152791). Modulates also STAT3 activity through negative regulation of PIAS3, either by degradation of PIAS3 through the ubiquitin-proteasome pathway or exclusion of PIAS3 from the nucleus (PubMed:20516148).4 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri15 – 56RING-typePROSITE-ProRule annotationAdd BLAST42
Zinc fingeri92 – 132B box-type 1Add BLAST41
Zinc fingeri140 – 182B box-type 2Add BLAST43

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: UniProtKB
  • transferase activity Source: UniProtKB-KW
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processImmunity, Innate immunity, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-877300 Interferon gamma signaling
UniPathwayi
UPA00143

Protein family/group databases

MoonDBiQ9BZR9 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase TRIM8 (EC:2.3.2.27)
Alternative name(s):
Glioblastoma-expressed RING finger protein
RING finger protein 27
RING-type E3 ubiquitin transferase TRIM8Curated
Tripartite motif-containing protein 8
Gene namesi
Name:TRIM8
Synonyms:GERP, RNF27
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000171206.13
HGNCiHGNC:15579 TRIM8
MIMi606125 gene
neXtProtiNX_Q9BZR9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi81603
OpenTargetsiENSG00000171206
PharmGKBiPA37983

Polymorphism and mutation databases

BioMutaiTRIM8
DMDMi18202744

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000562061 – 551E3 ubiquitin-protein ligase TRIM8Add BLAST551

Proteomic databases

EPDiQ9BZR9
MaxQBiQ9BZR9
PaxDbiQ9BZR9
PeptideAtlasiQ9BZR9
PRIDEiQ9BZR9
ProteomicsDBi79898

PTM databases

iPTMnetiQ9BZR9
PhosphoSitePlusiQ9BZR9

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiENSG00000171206 Expressed in 234 organ(s), highest expression level in oviduct epithelium
CleanExiHS_TRIM8
ExpressionAtlasiQ9BZR9 baseline and differential
GenevisibleiQ9BZR9 HS

Organism-specific databases

HPAiHPA023560
HPA023561

Interactioni

Subunit structurei

Homodimer. Interacts with SOCS1 (via) SH2 domain and SOCS box (PubMed:12163497). Interacts with HSP90AB1; prevents nucleus translocation of phosphorylated STAT3 and HSP90AB1. Interacts with MAP3K7/TAK1 (PubMed:22084099). Interacts with PIAS3 (PubMed:20516148).3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi123541, 54 interactors
IntActiQ9BZR9, 64 interactors
STRINGi9606.ENSP00000302120

Structurei

3D structure databases

ProteinModelPortaliQ9BZR9
SMRiQ9BZR9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili181 – 249Sequence analysisAdd BLAST69

Domaini

The coiled coil domain is required for homodimerization.
The region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1.By similarity

Sequence similaritiesi

Belongs to the TRIM/RBCC family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri15 – 56RING-typePROSITE-ProRule annotationAdd BLAST42
Zinc fingeri92 – 132B box-type 1Add BLAST41
Zinc fingeri140 – 182B box-type 2Add BLAST43

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITEZ Eukaryota
ENOG410ZTPN LUCA
GeneTreeiENSGT00930000150999
HOGENOMiHOG000082538
HOVERGENiHBG056254
InParanoidiQ9BZR9
KOiK12001
OMAiHPPYPRS
OrthoDBiEOG091G059M
PhylomeDBiQ9BZR9
TreeFamiTF333491

Family and domain databases

CDDicd00021 BBOX, 1 hit
Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR000315 Znf_B-box
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 8 potential isoforms that are computationally mapped.Show allAlign All

Q9BZR9-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAENWKNCFE EELICPICLH VFVEPVQLPC KHNFCRGCIG EAWAKDSGLV
60 70 80 90 100
RCPECNQAYN QKPGLEKNLK LTNIVEKFNA LHVEKPPAAL HCVFCRRGPP
110 120 130 140 150
LPAQKVCLRC EAPCCQSHVQ THLQQPSTAR GHLLVEADDV RAWSCPQHNA
160 170 180 190 200
YRLYHCEAEQ VAVCQYCCYY SGAHQGHSVC DVEIRRNEIR KMLMKQQDRL
210 220 230 240 250
EEREQDIEDQ LYKLESDKRL VEEKVNQLKE EVRLQYEKLH QLLDEDLRQT
260 270 280 290 300
VEVLDKAQAK FCSENAAQAL HLGERMQEAK KLLGSLQLLF DKTEDVSFMK
310 320 330 340 350
NTKSVKILMD RTQTCTSSSL SPTKIGHLNS KLFLNEVAKK EKQLRKMLEG
360 370 380 390 400
PFSTPVPFLQ SVPLYPCGVS SSGAEKRKHS TAFPEASFLE TSSGPVGGQY
410 420 430 440 450
GAAGTASGEG QSGQPLGPCS STQHLVALPG GAQPVHSSPV FPPSQYPNGS
460 470 480 490 500
AAQQPMLPQY GGRKILVCSV DNCYCSSVAN HGGHQPYPRS GHFPWTVPSQ
510 520 530 540 550
EYSHPLPPTP SVPQSLPSLA VRDWLDASQQ PGHQDFYRVY GQPSTKHYVT

S
Length:551
Mass (Da):61,489
Last modified:September 26, 2001 - v2
Checksum:i1FEF89029EB9BACB
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8Y5K0A0A2R8Y5K0_HUMAN
E3 ubiquitin-protein ligase TRIM8
TRIM8
202Annotation score:
A0A2R8Y500A0A2R8Y500_HUMAN
E3 ubiquitin-protein ligase TRIM8
TRIM8
300Annotation score:
A0A2U3TZI0A0A2U3TZI0_HUMAN
E3 ubiquitin-protein ligase TRIM8
TRIM8
393Annotation score:
A0A2R8YD00A0A2R8YD00_HUMAN
E3 ubiquitin-protein ligase TRIM8
TRIM8
194Annotation score:
A0A2R8YFP1A0A2R8YFP1_HUMAN
E3 ubiquitin-protein ligase TRIM8
TRIM8
257Annotation score:
R4GN03R4GN03_HUMAN
E3 ubiquitin-protein ligase TRIM8
TRIM8
295Annotation score:
A0A2R8Y580A0A2R8Y580_HUMAN
E3 ubiquitin-protein ligase TRIM8
TRIM8
85Annotation score:
A0A2R8YCF6A0A2R8YCF6_HUMAN
E3 ubiquitin-protein ligase TRIM8
TRIM8
116Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti174H → R in AAG53087 (PubMed:11118312).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080568445 – 551Missing Found in a patient with Coffin-Siris syndrome also carrying a likely pathogenic ARID2 mutation; unknown pathological significance. 1 PublicationAdd BLAST107

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281046 mRNA Translation: AAG53087.1
AF220034 mRNA Translation: AAG53488.1
AL391121 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW49680.1
BC021925 mRNA Translation: AAH21925.1
CCDSiCCDS31274.1
PIRiJC7562
RefSeqiNP_112174.2, NM_030912.2
UniGeneiHs.336810

Genome annotation databases

EnsembliENST00000643721; ENSP00000496301; ENSG00000171206
GeneIDi81603
KEGGihsa:81603
UCSCiuc001kvz.3 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281046 mRNA Translation: AAG53087.1
AF220034 mRNA Translation: AAG53488.1
AL391121 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW49680.1
BC021925 mRNA Translation: AAH21925.1
CCDSiCCDS31274.1
PIRiJC7562
RefSeqiNP_112174.2, NM_030912.2
UniGeneiHs.336810

3D structure databases

ProteinModelPortaliQ9BZR9
SMRiQ9BZR9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123541, 54 interactors
IntActiQ9BZR9, 64 interactors
STRINGi9606.ENSP00000302120

Protein family/group databases

MoonDBiQ9BZR9 Predicted

PTM databases

iPTMnetiQ9BZR9
PhosphoSitePlusiQ9BZR9

Polymorphism and mutation databases

BioMutaiTRIM8
DMDMi18202744

Proteomic databases

EPDiQ9BZR9
MaxQBiQ9BZR9
PaxDbiQ9BZR9
PeptideAtlasiQ9BZR9
PRIDEiQ9BZR9
ProteomicsDBi79898

Protocols and materials databases

DNASUi81603
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000643721; ENSP00000496301; ENSG00000171206
GeneIDi81603
KEGGihsa:81603
UCSCiuc001kvz.3 human

Organism-specific databases

CTDi81603
DisGeNETi81603
EuPathDBiHostDB:ENSG00000171206.13
GeneCardsiTRIM8
HGNCiHGNC:15579 TRIM8
HPAiHPA023560
HPA023561
MIMi606125 gene
neXtProtiNX_Q9BZR9
OpenTargetsiENSG00000171206
PharmGKBiPA37983
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ITEZ Eukaryota
ENOG410ZTPN LUCA
GeneTreeiENSGT00930000150999
HOGENOMiHOG000082538
HOVERGENiHBG056254
InParanoidiQ9BZR9
KOiK12001
OMAiHPPYPRS
OrthoDBiEOG091G059M
PhylomeDBiQ9BZR9
TreeFamiTF333491

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-877300 Interferon gamma signaling

Miscellaneous databases

ChiTaRSiTRIM8 human
GenomeRNAii81603
PROiPR:Q9BZR9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171206 Expressed in 234 organ(s), highest expression level in oviduct epithelium
CleanExiHS_TRIM8
ExpressionAtlasiQ9BZR9 baseline and differential
GenevisibleiQ9BZR9 HS

Family and domain databases

CDDicd00021 BBOX, 1 hit
Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR000315 Znf_B-box
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
SMARTiView protein in SMART
SM00184 RING, 1 hit
PROSITEiView protein in PROSITE
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTRIM8_HUMAN
AccessioniPrimary (citable) accession number: Q9BZR9
Secondary accession number(s): A6NI31, Q9C028
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: September 26, 2001
Last modified: November 7, 2018
This is version 159 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
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