E3 ubiquitin/ISG15 ligase TRIM25 - Homo sapiens (Human)

Contribute

Send feedback

Read comments (?) or add your own

Q14258 (TRI25_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 136. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	630 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as an 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 process	Antiviral defense Host-virus interaction Immunity Innate immunity Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Coiled coil Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome negative regulation of type I interferon production Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cell junction Inferred from direct assay. Source: HPA cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA
Molecular_function	sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: ProtInc ubiquitin-protein ligase activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NS	P03496	3	EBI-2341129,EBI-2547442	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 630

630

E3 ubiquitin/ISG15 ligase TRIM25

PRO_0000056233

Regions

Domain

439 – 630

192

B30.2/SPRY

Zinc finger

13 – 54

RING-type

Region

180 – 450

271

Interaction with influenza A virus NS1

Coiled coil

217 – 307

Potential

Amino acid modifications

Modified residue

100

Phosphoserine Ref.10

Modified residue

273

N6-acetyllysine Ref.12

Modified residue

567

N6-acetyllysine Ref.12

Cross-link

117

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.8

Natural variations

Natural variant

V → G.
Corresponds to variant rs7212260 [ dbSNP | Ensembl ].

VAR_024614

Natural variant

358

P → L. Ref.1 Ref.3 Ref.15
Corresponds to variant rs205498 [ dbSNP | Ensembl ].

VAR_024615

Experimental info

Mutagenesis

K → R: No effect on ISGylation. Ref.8

Mutagenesis

K → R: No effect on ISGylation. Ref.8

Mutagenesis

112

K → R: No effect on ISGylation. Ref.8

Mutagenesis

117

K → R: No ISGylation. Ref.8

Sequences

Sequence

Length

Mass (Da)

Tools

Q14258 [UniParc].

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

FASTA

630

70,973

        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' referencesShow '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. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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, MASS SPECTROMETRY.
+	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.
IPI	IPI00029629.
PIR	A49656.
RefSeq	NP_005073.2. NM_005082.4.
UniGene	Hs.528952.
3D structure databases
ProteinModelPortal	Q14258.
SMR	Q14258. Positions 7-53, 455-615.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q14258. 17 interactions.
STRING	9606.ENSP00000323889.
PTM databases
PhosphoSite	Q14258.
Polymorphism databases
DMDM	12585547.
Proteomic databases
PaxDb	Q14258.
PeptideAtlas	Q14258.
PRIDE	Q14258.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000316881; ENSP00000323889; ENSG00000121060. ENST00000537230; ENSP00000445961; ENSG00000121060.
GeneID	7706.
KEGG	hsa:7706.
UCSC	uc002iut.3. human.
Organism-specific databases
CTD	7706.
GeneCards	GC17M054965.
HGNC	HGNC:12932. TRIM25.
HPA	HPA005909.
MIM	600453. gene.
neXtProt	NX_Q14258.
PharmGKB	PA37519.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG253760.
HOVERGEN	HBG101063.
InParanoid	Q14258.
KO	K10652.
OMA	SHINGAT.
OrthoDB	EOG42JNRQ.
PhylomeDB	Q14258.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q14258.
Bgee	Q14258.
CleanEx	HS_TRIM25.
Genevestigator	Q14258.
GermOnline	ENSG00000121060. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR001870. 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]
Pfam	PF00622. SPRY. 1 hit. [Graphical view]
PRINTS	PR01407. BUTYPHLNCDUF.
SMART	SM00589. PRY. 1 hit. SM00184. RING. 1 hit. SM00449. SPRY. 1 hit. [Graphical view]
SUPFAM	SSF49899. ConA_like_lec_gl. 1 hit.
PROSITE	PS50188. B302_SPRY. 1 hit. PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TRIM25. human.
GenomeRNAi	7706.
NextBio	29876.
SOURCE	Search...

Entry information

Entry name

TRI25_HUMAN

Accession

Primary (citable) accession number: Q14258

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 136 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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

Human chromosome 17

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents