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Protein

E3 ubiquitin/ISG15 ligase TRIM25

Gene

TRIM25

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

Functioni

Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase. Involved in innate immune defense against viruses by mediating ubiquitination of DDX58. Mediates 'Lys-63'-linked polyubiquitination of the DDX58 N-terminal CARD-like region which is crucial for triggering the cytosolic signal transduction that leads to the production of interferons in response to viral infection. Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway. Mediates estrogen action in various target organs. Mediates the ubiquitination and subsequent proteasomal degradation of ZFHX3 (PubMed:22452784).4 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication
ATP + [ISG15] + [protein]-lysine = AMP + diphosphate + [protein]-N-ISGyllysine.1 Publication

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 fingeri13 – 54RING-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

GO - Biological processi

  • defense response to virus Source: UniProtKB-KW
  • ERAD pathway Source: ParkinsonsUK-UCL
  • innate immune response Source: UniProtKB
  • interferon-gamma-mediated signaling pathway Source: Reactome
  • negative regulation of type I interferon production Source: Reactome
  • negative regulation of viral entry into host cell Source: Ensembl
  • negative regulation of viral release from host cell Source: Ensembl
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • protein monoubiquitination Source: ParkinsonsUK-UCL
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
  • regulation of viral entry into host cell Source: UniProtKB
  • regulation of viral release from host cell Source: UniProtKB
  • response to estrogen Source: UniProtKB
  • response to vitamin D Source: Ensembl
  • translesion synthesis Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Ligase, Transferase

Keywords - Biological processi

Antiviral defense, Host-virus interaction, Immunity, Innate immunity, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000121060-MONOMER.
BRENDAi2.3.2.B10. 2681.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-168928. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
R-HSA-5656169. Termination of translesion DNA synthesis.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-877300. Interferon gamma signaling.
R-HSA-918233. TRAF3-dependent IRF activation pathway.
R-HSA-933541. TRAF6 mediated IRF7 activation.
R-HSA-933542. TRAF6 mediated NF-kB activation.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin/ISG15 ligase TRIM25 (EC:6.3.2.n31 Publication)
Alternative name(s):
Estrogen-responsive finger protein
RING finger protein 147
RING-type E3 ubiquitin transferase (EC:2.3.2.271 Publication)
Tripartite motif-containing protein 25
Ubiquitin/ISG15-conjugating enzyme TRIM25
Zinc finger protein 147
Gene namesi
Name:TRIM25
Synonyms:EFP, RNF147, ZNF147
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:12932. TRIM25.

Subcellular locationi

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi21K → R: No effect on ISGylation. 1 Publication1
Mutagenesisi65K → R: No effect on ISGylation. 1 Publication1
Mutagenesisi112K → R: No effect on ISGylation. 1 Publication1
Mutagenesisi117K → R: No ISGylation. 1 Publication1

Organism-specific databases

DisGeNETi7706.
OpenTargetsiENSG00000121060.
PharmGKBiPA37519.

Polymorphism and mutation databases

BioMutaiTRIM25.
DMDMi313104033.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000562331 – 630E3 ubiquitin/ISG15 ligase TRIM25Add BLAST630

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei91PhosphothreonineCombined sources1
Modified residuei100PhosphoserineCombined sources1
Cross-linki117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)1 Publication
Modified residuei273N6-acetyllysineCombined sources1
Modified residuei278PhosphotyrosineCombined sources1
Modified residuei567N6-acetyllysineCombined sources1

Post-translational modificationi

Auto-ISGylated.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ14258.
MaxQBiQ14258.
PaxDbiQ14258.
PeptideAtlasiQ14258.
PRIDEiQ14258.

PTM databases

iPTMnetiQ14258.
PhosphoSitePlusiQ14258.
SwissPalmiQ14258.

Expressioni

Tissue specificityi

Expressed in breast tumors (at protein level). Ubiquitous.2 Publications

Inductioni

By interferons.2 Publications

Gene expression databases

BgeeiENSG00000121060.
CleanExiHS_TRIM25.
ExpressionAtlasiQ14258. baseline and differential.
GenevisibleiQ14258. HS.

Organism-specific databases

HPAiHPA005909.

Interactioni

Subunit structurei

Interacts (via SPRY domain) with DDX58 (via CARD domain). Interacts (via coiled coil) with influenza A virus NS1 protein; this interaction specifically inhibits TRIM25 multimerization and TRIM25-mediated DDX58 CARD ubiquitination, thereby suppressing DDX58 signal transduction. Interacts with ZFHX3.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
F1BA495EBI-2341129,EBI-9687469From a different organism.
DDX58O957864EBI-2341129,EBI-995350
NSP034963EBI-2341129,EBI-2547442From a different organism.

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL

Protein-protein interaction databases

BioGridi113500. 94 interactors.
IntActiQ14258. 31 interactors.
STRINGi9606.ENSP00000323889.

Structurei

Secondary structure

1630
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 5Combined sources4
Helixi7 – 10Combined sources4
Turni14 – 16Combined sources3
Beta strandi17 – 19Combined sources3
Beta strandi21 – 25Combined sources5
Beta strandi31 – 33Combined sources3
Helixi34 – 43Combined sources10
Beta strandi46 – 49Combined sources4
Turni51 – 53Combined sources3
Beta strandi56 – 59Combined sources4
Helixi67 – 78Combined sources12
Helixi191 – 300Combined sources110
Helixi307 – 316Combined sources10
Helixi331 – 358Combined sources28

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4CFGX-ray2.80A/B1-630[»]
4LTBX-ray2.59A/B189-379[»]
5EYAX-ray2.40F/G1-83[»]
5FERX-ray2.34A/D1-82[»]
ProteinModelPortaliQ14258.
SMRiQ14258.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini439 – 630B30.2/SPRYPROSITE-ProRule annotationAdd BLAST192

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni180 – 450Interaction with influenza A virus NS1Add BLAST271

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili217 – 307Sequence analysisAdd BLAST91

Domaini

The RING-type zinc finger is important for ISG15 E3 ligase activity and autoISGylation. AutoISGylation negatively regulates ISG15 E3 ligase activity.
The C-terminal B30.2/SPRY domain interacts with the first N-terminal CARD domain of DDX58.

Sequence similaritiesi

Contains 1 B30.2/SPRY domain.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri13 – 54RING-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITFP. Eukaryota.
ENOG410XQS1. LUCA.
GeneTreeiENSGT00760000118995.
HOVERGENiHBG101063.
InParanoidiQ14258.
KOiK10652.
OMAiEYTEMKA.
OrthoDBiEOG091G05F6.
PhylomeDBiQ14258.
TreeFamiTF351086.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
4.10.45.10. 1 hit.
InterProiIPR001870. B30.2/SPRY.
IPR003879. Butyrophylin.
IPR013320. ConA-like_dom.
IPR006574. PRY.
IPR003877. SPRY_dom.
IPR027370. Znf-RING_LisH.
IPR000315. Znf_B-box.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF13765. PRY. 1 hit.
PF00622. SPRY. 1 hit.
PF13445. zf-RING_UBOX. 1 hit.
[Graphical view]
PRINTSiPR01407. BUTYPHLNCDUF.
SMARTiSM00589. PRY. 1 hit.
SM00184. RING. 1 hit.
SM00449. SPRY. 1 hit.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 1 hit.
PROSITEiPS50188. B302_SPRY. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q14258-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAELCPLAEE LSCSICLEPF KEPVTTPCGH NFCGSCLNET WAVQGSPYLC
60 70 80 90 100
PQCRAVYQAR PQLHKNTVLC NVVEQFLQAD LAREPPADVW TPPARASAPS
110 120 130 140 150
PNAQVACDHC LKEAAVKTCL VCMASFCQEH LQPHFDSPAF QDHPLQPPVR
160 170 180 190 200
DLLRRKCSQH NRLREFFCPE HSECICHICL VEHKTCSPAS LSQASADLEA
210 220 230 240 250
TLRHKLTVMY SQINGASRAL DDVRNRQQDV RMTANRKVEQ LQQEYTEMKA
260 270 280 290 300
LLDASETTST RKIKEEEKRV NSKFDTIYQI LLKKKSEIQT LKEEIEQSLT
310 320 330 340 350
KRDEFEFLEK ASKLRGISTK PVYIPEVELN HKLIKGIHQS TIDLKNELKQ
360 370 380 390 400
CIGRLQEPTP SSGDPGEHDP ASTHKSTRPV KKVSKEEKKS KKPPPVPALP
410 420 430 440 450
SKLPTFGAPE QLVDLKQAGL EAAAKATSSH PNSTSLKAKV LETFLAKSRP
460 470 480 490 500
ELLEYYIKVI LDYNTAHNKV ALSECYTVAS VAEMPQNYRP HPQRFTYCSQ
510 520 530 540 550
VLGLHCYKKG IHYWEVELQK NNFCGVGICY GSMNRQGPES RLGRNSASWC
560 570 580 590 600
VEWFNTKISA WHNNVEKTLP STKATRVGVL LNCDHGFVIF FAVADKVHLM
610 620 630
YKFRVDFTEA LYPAFWVFSA GATLSICSPK
Length:630
Mass (Da):70,973
Last modified:November 30, 2010 - v2
Checksum:iEB0AB353F0AD4C80
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02461489V → G.Corresponds to variant rs7212260dbSNPEnsembl.1
Natural variantiVAR_024615358P → L.Combined sources2 PublicationsCorresponds to variant rs205498dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D21205 mRNA. Translation: BAA04747.1.
AC015912 Genomic DNA. No translation available.
BC016924 mRNA. Translation: AAH16924.1.
BC042541 mRNA. Translation: AAH42541.1.
CCDSiCCDS11591.1.
PIRiA49656.
RefSeqiNP_005073.2. NM_005082.4.
UniGeneiHs.528952.

Genome annotation databases

EnsembliENST00000316881; ENSP00000323889; ENSG00000121060.
ENST00000537230; ENSP00000445961; ENSG00000121060.
GeneIDi7706.
KEGGihsa:7706.
UCSCiuc002iut.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

TRIM25 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D21205 mRNA. Translation: BAA04747.1.
AC015912 Genomic DNA. No translation available.
BC016924 mRNA. Translation: AAH16924.1.
BC042541 mRNA. Translation: AAH42541.1.
CCDSiCCDS11591.1.
PIRiA49656.
RefSeqiNP_005073.2. NM_005082.4.
UniGeneiHs.528952.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4CFGX-ray2.80A/B1-630[»]
4LTBX-ray2.59A/B189-379[»]
5EYAX-ray2.40F/G1-83[»]
5FERX-ray2.34A/D1-82[»]
ProteinModelPortaliQ14258.
SMRiQ14258.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113500. 94 interactors.
IntActiQ14258. 31 interactors.
STRINGi9606.ENSP00000323889.

PTM databases

iPTMnetiQ14258.
PhosphoSitePlusiQ14258.
SwissPalmiQ14258.

Polymorphism and mutation databases

BioMutaiTRIM25.
DMDMi313104033.

Proteomic databases

EPDiQ14258.
MaxQBiQ14258.
PaxDbiQ14258.
PeptideAtlasiQ14258.
PRIDEiQ14258.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000316881; ENSP00000323889; ENSG00000121060.
ENST00000537230; ENSP00000445961; ENSG00000121060.
GeneIDi7706.
KEGGihsa:7706.
UCSCiuc002iut.4. human.

Organism-specific databases

CTDi7706.
DisGeNETi7706.
GeneCardsiTRIM25.
HGNCiHGNC:12932. TRIM25.
HPAiHPA005909.
MIMi600453. gene.
neXtProtiNX_Q14258.
OpenTargetsiENSG00000121060.
PharmGKBiPA37519.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ITFP. Eukaryota.
ENOG410XQS1. LUCA.
GeneTreeiENSGT00760000118995.
HOVERGENiHBG101063.
InParanoidiQ14258.
KOiK10652.
OMAiEYTEMKA.
OrthoDBiEOG091G05F6.
PhylomeDBiQ14258.
TreeFamiTF351086.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000121060-MONOMER.
BRENDAi2.3.2.B10. 2681.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-168928. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
R-HSA-5656169. Termination of translesion DNA synthesis.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-877300. Interferon gamma signaling.
R-HSA-918233. TRAF3-dependent IRF activation pathway.
R-HSA-933541. TRAF6 mediated IRF7 activation.
R-HSA-933542. TRAF6 mediated NF-kB activation.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.

Miscellaneous databases

ChiTaRSiTRIM25. human.
GeneWikiiTRIM25.
GenomeRNAii7706.
PROiQ14258.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121060.
CleanExiHS_TRIM25.
ExpressionAtlasiQ14258. baseline and differential.
GenevisibleiQ14258. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
4.10.45.10. 1 hit.
InterProiIPR001870. B30.2/SPRY.
IPR003879. Butyrophylin.
IPR013320. ConA-like_dom.
IPR006574. PRY.
IPR003877. SPRY_dom.
IPR027370. Znf-RING_LisH.
IPR000315. Znf_B-box.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF13765. PRY. 1 hit.
PF00622. SPRY. 1 hit.
PF13445. zf-RING_UBOX. 1 hit.
[Graphical view]
PRINTSiPR01407. BUTYPHLNCDUF.
SMARTiSM00589. PRY. 1 hit.
SM00184. RING. 1 hit.
SM00449. SPRY. 1 hit.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 1 hit.
PROSITEiPS50188. B302_SPRY. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTRI25_HUMAN
AccessioniPrimary (citable) accession number: Q14258
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: November 30, 2010
Last modified: November 30, 2016
This is version 173 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.