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Protein

E3 ubiquitin/ISG15 ligase TRIM25

Gene

TRIM25

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 + N6-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

  • cadherin binding Source: BHF-UCL
  • DNA-binding transcription factor activity Source: ProtInc
  • ligase activity Source: UniProtKB-KW
  • RNA binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: ParkinsonsUK-UCL
  • ubiquitin-protein transferase activity Source: Reactome
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionLigase, Transferase
Biological processAntiviral defense, Host-virus interaction, Immunity, Innate immunity, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi2.3.2.B10 2681
ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta
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 DDX58/IFIH1 signaling
UniPathwayi
UPA00143

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)
RING-type E3 ubiquitin transferase TRIM25Curated
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

EuPathDBiHostDB:ENSG00000121060.14
HGNCiHGNC:12932 TRIM25
MIMi600453 gene
neXtProtiNX_Q14258

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

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
ProteomicsDBi59953

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 Expressed in 196 organ(s), highest expression level in blood
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 with ZFHX3.2 Publications
(Microbial infection) 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.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113500, 2388 interactors
CORUMiQ14258
IntActiQ14258, 31 interactors
MINTiQ14258
STRINGi9606.ENSP00000323889

Structurei

Secondary structure

1630
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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.

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
OMAiSPAFQDH
OrthoDBiEOG091G05F6
PhylomeDBiQ14258
TreeFamiTF351086

Family and domain databases

CDDicd00021 BBOX, 1 hit
Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001870 B30.2/SPRY
IPR003879 Butyrophylin_SPRY
IPR013320 ConA-like_dom_sf
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
PfamiView protein in Pfam
PF13765 PRY, 1 hit
PF00622 SPRY, 1 hit
PF13445 zf-RING_UBOX, 1 hit
PRINTSiPR01407 BUTYPHLNCDUF
SMARTiView protein in SMART
SM00589 PRY, 1 hit
SM00184 RING, 1 hit
SM00449 SPRY, 1 hit
SUPFAMiSSF49899 SSF49899, 1 hit
PROSITEiView protein in PROSITE
PS50188 B302_SPRY, 1 hit
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 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L2W4I3L2W4_HUMAN
E3 ubiquitin/ISG15 ligase TRIM25
TRIM25
43Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02461489V → G. Corresponds to variant dbSNP:rs7212260Ensembl.1
Natural variantiVAR_024615358P → LCombined sources2 PublicationsCorresponds to variant dbSNP:rs205498Ensembl.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

Similar proteinsi

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[»]
5NT1X-ray2.82A/E/I190-379[»]
5NT2X-ray4.26A/I/N/V190-379[»]
6FLMX-ray2.01A/B/C435-630[»]
6FLNX-ray3.60A/B/E189-630[»]
ProteinModelPortaliQ14258
SMRiQ14258
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113500, 2388 interactors
CORUMiQ14258
IntActiQ14258, 31 interactors
MINTiQ14258
STRINGi9606.ENSP00000323889

PTM databases

iPTMnetiQ14258
PhosphoSitePlusiQ14258
SwissPalmiQ14258

Polymorphism and mutation databases

BioMutaiTRIM25
DMDMi313104033

Proteomic databases

EPDiQ14258
MaxQBiQ14258
PaxDbiQ14258
PeptideAtlasiQ14258
PRIDEiQ14258
ProteomicsDBi59953

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
EuPathDBiHostDB:ENSG00000121060.14
GeneCardsiTRIM25
HGNCiHGNC:12932 TRIM25
HPAiHPA005909
MIMi600453 gene
neXtProtiNX_Q14258
OpenTargetsiENSG00000121060
PharmGKBiPA37519
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ITFP Eukaryota
ENOG410XQS1 LUCA
GeneTreeiENSGT00760000118995
HOVERGENiHBG101063
InParanoidiQ14258
KOiK10652
OMAiSPAFQDH
OrthoDBiEOG091G05F6
PhylomeDBiQ14258
TreeFamiTF351086

Enzyme and pathway databases

UniPathwayi
UPA00143

BRENDAi2.3.2.B10 2681
ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta
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 DDX58/IFIH1 signaling

Miscellaneous databases

ChiTaRSiTRIM25 human
GeneWikiiTRIM25
GenomeRNAii7706
PROiPR:Q14258
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121060 Expressed in 196 organ(s), highest expression level in blood
CleanExiHS_TRIM25
ExpressionAtlasiQ14258 baseline and differential
GenevisibleiQ14258 HS

Family and domain databases

CDDicd00021 BBOX, 1 hit
Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR001870 B30.2/SPRY
IPR003879 Butyrophylin_SPRY
IPR013320 ConA-like_dom_sf
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
PfamiView protein in Pfam
PF13765 PRY, 1 hit
PF00622 SPRY, 1 hit
PF13445 zf-RING_UBOX, 1 hit
PRINTSiPR01407 BUTYPHLNCDUF
SMARTiView protein in SMART
SM00589 PRY, 1 hit
SM00184 RING, 1 hit
SM00449 SPRY, 1 hit
SUPFAMiSSF49899 SSF49899, 1 hit
PROSITEiView protein in PROSITE
PS50188 B302_SPRY, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTRI25_HUMAN
AccessioniPrimary (citable) accession number: Q14258
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: November 30, 2010
Last modified: September 12, 2018
This is version 192 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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