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Q14258 (TRI25_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin/ISG15 ligase TRIM25

EC=6.3.2.19
EC=6.3.2.n3
Alternative name(s):
Estrogen-responsive finger protein
RING finger protein 147
Tripartite motif-containing protein 25
Ubiquitin/ISG15-conjugating enzyme TRIM25
Zinc finger protein 147
Gene names
Name:TRIM25
Synonyms:EFP, RNF147, ZNF147
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length630 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.7 Ref.9

Catalytic activity

ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.

ATP + [ISG15] + [protein]-lysine = AMP + diphosphate + [protein]-N-ISGyllysine.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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. Ref.9 Ref.11

Subcellular location

Cytoplasm. Note: Colocalized with DDX58 at cytoplasmic perinuclear bodies. Ref.9

Tissue specificity

Ubiquitous. Ref.4

Induction

By interferons. Ref.6 Ref.7

Domain

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.

Post-translational modification

Auto-ISGylated. Ref.8

Sequence similarities

Contains 1 B30.2/SPRY domain.

Contains 1 RING-type zinc finger.

Ontologies

Keywords
   Biological processAntiviral defense
Host-virus interaction
Immunity
Innate immunity
Ubl conjugation pathway
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DomainCoiled coil
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdefense response to virus

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from direct assay PubMed 18248090. Source: UniProt

negative regulation of type I interferon production

Traceable author statement. Source: Reactome

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay PubMed 23077300. Source: UniProt

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype PubMed 23077300. Source: UniProt

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype PubMed 23077300. Source: UniProt

regulation of viral entry into host cell

Inferred from direct assay PubMed 18248090. Source: UniProt

regulation of viral release from host cell

Inferred from mutant phenotype PubMed 18248090. Source: UniProt

response to estrogen

Inferred from electronic annotation. Source: Ensembl

response to vitamin D

Inferred from electronic annotation. Source: Ensembl

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionpoly(A) RNA binding

Inferred from direct assay PubMed 22658674. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.11. Source: IntAct

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.1. Source: ProtInc

ubiquitin-protein transferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NSP034963EBI-2341129,EBI-2547442From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 630630E3 ubiquitin/ISG15 ligase TRIM25
PRO_0000056233

Regions

Domain439 – 630192B30.2/SPRY
Zinc finger13 – 5442RING-type
Region180 – 450271Interaction with influenza A virus NS1
Coiled coil217 – 30791 Potential

Amino acid modifications

Modified residue1001Phosphoserine Ref.10
Modified residue2731N6-acetyllysine Ref.12
Modified residue5671N6-acetyllysine Ref.12
Cross-link117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.8

Natural variations

Natural variant891V → G.
Corresponds to variant rs7212260 [ dbSNP | Ensembl ].
VAR_024614
Natural variant3581P → L. Ref.1 Ref.3 Ref.15
Corresponds to variant rs205498 [ dbSNP | Ensembl ].
VAR_024615

Experimental info

Mutagenesis211K → R: No effect on ISGylation. Ref.8
Mutagenesis651K → R: No effect on ISGylation. Ref.8
Mutagenesis1121K → R: No effect on ISGylation. Ref.8
Mutagenesis1171K → R: No ISGylation. Ref.8

Sequences

Sequence LengthMass (Da)Tools
Q14258 [UniParc].

Last modified November 30, 2010. Version 2.
Checksum: EB0AB353F0AD4C80

FASTA63070,973
        10         20         30         40         50         60 
MAELCPLAEE LSCSICLEPF KEPVTTPCGH NFCGSCLNET WAVQGSPYLC PQCRAVYQAR 

        70         80         90        100        110        120 
PQLHKNTVLC NVVEQFLQAD LAREPPADVW TPPARASAPS PNAQVACDHC LKEAAVKTCL 

       130        140        150        160        170        180 
VCMASFCQEH LQPHFDSPAF QDHPLQPPVR DLLRRKCSQH NRLREFFCPE HSECICHICL 

       190        200        210        220        230        240 
VEHKTCSPAS LSQASADLEA TLRHKLTVMY SQINGASRAL DDVRNRQQDV RMTANRKVEQ 

       250        260        270        280        290        300 
LQQEYTEMKA LLDASETTST RKIKEEEKRV NSKFDTIYQI LLKKKSEIQT LKEEIEQSLT 

       310        320        330        340        350        360 
KRDEFEFLEK ASKLRGISTK PVYIPEVELN HKLIKGIHQS TIDLKNELKQ CIGRLQEPTP 

       370        380        390        400        410        420 
SSGDPGEHDP ASTHKSTRPV KKVSKEEKKS KKPPPVPALP SKLPTFGAPE QLVDLKQAGL 

       430        440        450        460        470        480 
EAAAKATSSH PNSTSLKAKV LETFLAKSRP ELLEYYIKVI LDYNTAHNKV ALSECYTVAS 

       490        500        510        520        530        540 
VAEMPQNYRP HPQRFTYCSQ VLGLHCYKKG IHYWEVELQK NNFCGVGICY GSMNRQGPES 

       550        560        570        580        590        600 
RLGRNSASWC VEWFNTKISA WHNNVEKTLP STKATRVGVL LNCDHGFVIF FAVADKVHLM 

       610        620        630 
YKFRVDFTEA LYPAFWVFSA GATLSICSPK 

« Hide

References

« Hide 'large scale' references
[1]"Genomic binding-site cloning reveals an estrogen-responsive gene that encodes a RING finger protein."
Inoue S., Orimo A., Hosoi T., Kondo S., Toyoshima H., Kondo T., Ikegami A., Ouchi Y., Orimo H., Muramatsu M.
Proc. Natl. Acad. Sci. U.S.A. 90:11117-11121(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LEU-358.
Tissue: Placenta.
[2]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
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], VARIANT LEU-358.
Tissue: Lymph.
[4]"Systemic distribution of estrogen-responsive finger protein (Efp) in human tissues."
Shimada N., Suzuki T., Inoue S., Kato K., Imatani A., Sekine H., Ohara S., Shimosegawa T., Sasano H.
Mol. Cell. Endocrinol. 218:147-153(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[5]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"A ubiquitin E3 ligase Efp is up-regulated by interferons and conjugated with ISG15."
Nakasato N., Ikeda K., Urano T., Horie-Inoue K., Takeda S., Inoue S.
Biochem. Biophys. Res. Commun. 351:540-546(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, FUNCTION.
[7]"The interferon-inducible ubiquitin-protein isopeptide ligase (E3) EFP also functions as an ISG15 E3 ligase."
Zou W., Zhang D.-E.
J. Biol. Chem. 281:3989-3994(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A ISG15 E3 LIGASE, INDUCTION.
[8]"Negative regulation of ISG15 E3 ligase EFP through its autoISGylation."
Zou W., Wang J., Zhang D.-E.
Biochem. Biophys. Res. Commun. 354:321-327(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ISGYLATION AT LYS-117, MUTAGENESIS OF LYS-21; LYS-65; LYS-112 AND LYS-117, AUTOISGYLATION.
[9]"TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity."
Gack M.U., Shin Y.C., Joo C.H., Urano T., Liang C., Sun L., Takeuchi O., Akira S., Chen Z., Inoue S., Jung J.U.
Nature 446:916-920(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS AN UBIQUITIN LIGASE, SUBCELLULAR LOCATION, INTERACTION WITH DDX58.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I."
Gack M.U., Albrecht R.A., Urano T., Inn K.-S., Huang I.-C., Carnero E., Farzan M., Inoue S., Jung J.U., Garcia-Sastre A.
Cell Host Microbe 5:439-449(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH INFLUENZA VIRUS PROTEIN NS1.
[12]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-273 AND LYS-567, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"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].
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-358, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Web resources

Wikipedia

TRIM25 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D21205 mRNA. Translation: BAA04747.1.
AC015912 Genomic DNA. No translation available.
BC016924 mRNA. Translation: AAH16924.1.
BC042541 mRNA. Translation: AAH42541.1.
CCDSCCDS11591.1.
PIRA49656.
RefSeqNP_005073.2. NM_005082.4.
UniGeneHs.528952.

3D structure databases

ProteinModelPortalQ14258.
SMRQ14258. Positions 7-53, 190-360, 436-628.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113500. 51 interactions.
IntActQ14258. 17 interactions.
STRING9606.ENSP00000323889.

PTM databases

PhosphoSiteQ14258.

Polymorphism databases

DMDM313104033.

Proteomic databases

MaxQBQ14258.
PaxDbQ14258.
PeptideAtlasQ14258.
PRIDEQ14258.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000316881; ENSP00000323889; ENSG00000121060.
ENST00000537230; ENSP00000445961; ENSG00000121060.
GeneID7706.
KEGGhsa:7706.
UCSCuc002iut.3. human.

Organism-specific databases

CTD7706.
GeneCardsGC17M054965.
HGNCHGNC:12932. TRIM25.
HPAHPA005909.
MIM600453. gene.
neXtProtNX_Q14258.
PharmGKBPA37519.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG253760.
HOVERGENHBG101063.
InParanoidQ14258.
KOK10652.
OMAEANSTRK.
OrthoDBEOG7CG6ZK.
PhylomeDBQ14258.
TreeFamTF351086.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ14258.
BgeeQ14258.
CleanExHS_TRIM25.
GenevestigatorQ14258.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR001870. B30.2/SPRY.
IPR003879. Butyrophylin.
IPR008985. ConA-like_lec_gl_sf.
IPR006574. PRY.
IPR018355. SPla/RYanodine_receptor_subgr.
IPR003877. SPRY_rcpt.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamPF13765. PRY. 1 hit.
PF00622. SPRY. 1 hit.
[Graphical view]
PRINTSPR01407. BUTYPHLNCDUF.
SMARTSM00589. PRY. 1 hit.
SM00184. RING. 1 hit.
SM00449. SPRY. 1 hit.
[Graphical view]
SUPFAMSSF49899. SSF49899. 1 hit.
PROSITEPS50188. B302_SPRY. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTRIM25. human.
GeneWikiTRIM25.
GenomeRNAi7706.
NextBio29876.
PROQ14258.
SOURCESearch...

Entry information

Entry nameTRI25_HUMAN
AccessionPrimary (citable) accession number: Q14258
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: November 30, 2010
Last modified: July 9, 2014
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM