O00463 (TRAF5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TNF receptor-associated factor 5

Alternative name(s):
RING finger protein 84

Gene names

Name:	TRAF5
Synonyms:	RNF84

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	557 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. Mediates activation of NF-kappa-B and probably JNK. Seems to be involved in apoptosis.
Subunit structure	Homotrimer Probable. Heteromer with TRAF3. Associates with TNFRSF5/CD40 through interaction with TRAF3. Associates with LTBR/TNFRSF3, TNFRSF4, TNFRSF8/CD30, TNFRSF11A/RANK, TNFRSF13B/TACI, TNFRSF14, TNFRSF17, TNFRSF19/TROY, RIPK2, MAP3K14, MAP3K5, and TRAF and TNF receptor associated protein TDP2.
Subcellular location	Cytoplasm Probable.
Tissue specificity	Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon, and peripheral blood.
Domain	The MATH/TRAF domain binds to receptor cytoplasmic domains.
Sequence similarities	Belongs to the TNF receptor-associated factor family. A subfamily. Contains 1 MATH domain. Contains 1 RING-type zinc finger. Contains 2 TRAF-type zinc fingers.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from expression pattern PubMed 12761501. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype PubMed 12296995. Source: BHF-UCL positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara regulation of apoptotic process Inferred from electronic annotation. Source: InterPro signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	CD40 receptor complex Inferred from sequence or structural similarity. Source: BHF-UCL centrosome Inferred from direct assay PubMed 21399614. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell internal side of plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	signal transducer activity Inferred from electronic annotation. Source: Compara ubiquitin-protein ligase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TNFRSF14	Q92956	5	EBI-523498,EBI-1056653

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 557	557	TNF receptor-associated factor 5		PRO_0000056405
Regions
	Domain	403 – 549	147	MATH
	Zinc finger	45 – 85	41	RING-type
	Zinc finger	127 – 181	55	TRAF-type 1
	Zinc finger	182 – 239	58	TRAF-type 2
	Coiled coil	237 – 342	106	Potential
Natural variations
	Natural variant	120	1	V → G. Corresponds to variant rs3946808 [ dbSNP | Ensembl ].		VAR_052151
	Natural variant	186	1	N → H. Corresponds to variant rs2271458 [ dbSNP | Ensembl ].		VAR_020117
	Natural variant	358	1	L → V. Corresponds to variant rs2230780 [ dbSNP | Ensembl ].		VAR_052152

Sequences

	Sequence		Length	Mass (Da)
	O00463 [UniParc]. Last modified November 1, 1998. Version 2. Checksum: 86EB3724CE111176	FASTA	557	64,406
	10 20 30 40 50 60 MAYSEEHKGM PCGFIRQNSG NSISLDFEPS IEYQFVERLE ERYKCAFCHS VLHNPHQTGC 70 80 90 100 110 120 GHRFCQHCIL SLRELNTVPI CPVDKEVIKS QEVFKDNCCK REVLNLYVYC SNAPGCNAKV 130 140 150 160 170 180 ILGRYQDHLQ QCLFQPVQCS NEKCREPVLR KDLKEHLSAS CQFRKEKCLY CKKDVVVINL 190 200 210 220 230 240 QNHEENLCPE YPVFCPNNCA KIILKTEVDE HLAVCPEAEQ DCPFKHYGCA VTDKRRNLQQ 250 260 270 280 290 300 HEHSALREHM RLVLEKNVQL EEQISDLHKS LEQKESKIQQ LAETIKKLEK EFKQFAQLFG 310 320 330 340 350 360 KNGSFLPNIQ VFASHIDKSA WLEAQVHQLL QMVNQQQNKF DLRPLMEAVD TVKQKITLLE 370 380 390 400 410 420 NNDQRLAVLE EETNKHDTHI NIHKAQLSKN EERFKLLEGT CYNGKLIWKV TDYKMKKREA 430 440 450 460 470 480 VDGHTVSIFS QSFYTSRCGY RLCARAYLNG DGSGRGSHLS LYFVVMRGEF DSLLQWPFRQ 490 500 510 520 530 540 RVTLMLLDQS GKKNIMETFK PDPNSSSFKR PDGEMNIASG CPRFVAHSVL ENAKNAYIKD 550 DTLFLKVAVD LTDLEDL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5)." Mizushima S., Fujita M., Ishida T., Azuma S., Kato K., Hirai M., Otsuka M., Yamamoto T., Inoue J. Gene 207:135-140(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH TNFRSF5; TNFRSF8 AND LTBR.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Testis.
[6]	"Human TNF receptor-associated factor 5 (TRAF5): cDNA cloning, expression and assignment of the TRAF5 gene to chromosome 1q32." Nakano H., Shindo M., Yamada K., Yoshida M.C., Santee S.M., Ware C.F., Jenkins N.A., Gilbert D.J., Yagita H., Copeland N.G., Okumura K. Genomics 42:26-32(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 20-557.
[7]	"The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators." Wajant H., Henkler F., Scheurich P. Cell. Signal. 13:389-400(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[8]	"Tumor necrosis factor receptor-associated factors (TRAFs)." Bradley J.R., Pober J.S. Oncogene 20:6482-6491(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[9]	"Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1." Marsters S.A., Ayres T.M., Skubatch M., Gray C.L., Rothe M., Ashkenazi A. J. Biol. Chem. 272:14029-14032(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNFRSF14.
[10]	"ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5." Hsu H., Solovyev I., Colombero A., Elliott R., Kelley M., Boyle W.J. J. Biol. Chem. 272:13471-13474(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNFRSF14.
[11]	"Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2." Song H.Y., Regnier C.H., Kirschning C.J., Goeddel D.V., Rothe M. Proc. Natl. Acad. Sci. U.S.A. 94:9792-9796(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAP3K14.
[12]	"Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation." Aizawa S., Nakano H., Ishida T., Horie R., Nagai M., Ito K., Yagita H., Okumura K., Inoue J., Watanabe T. J. Biol. Chem. 272:2042-2045(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNFRSF8.
[13]	"ASK1 is essential for JNK/SAPK activation by TRAF2." Nishitoh H., Saitoh M., Mochida Y., Takeda K., Nakano H., Rothe M., Miyazono K., Ichijo H. Mol. Cell 2:389-395(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAP3K5.
[14]	"CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization." Pullen S.S., Miller H.G., Everdeen D.S., Dang T.T., Crute J.J., Kehry M.R. Biochemistry 37:11836-11845(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNFRSF5 AND TRAF3.
[15]	"Activation of OX40 signal transduction pathways leads to tumor necrosis factor receptor-associated factor (TRAF) 2- and TRAF5-mediated NF-kappaB activation." Kawamata S., Hori T., Imura A., Takaori-Kondo A., Uchiyama T. J. Biol. Chem. 273:5808-5814(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNFRSF4.
[16]	"RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase." McCarthy J.V., Ni J., Dixit V.M. J. Biol. Chem. 273:16968-16975(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RIPK2.
[17]	"TAJ, a novel member of the tumor necrosis factor receptor family, activates the c-Jun N-terminal kinase pathway and mediates caspase-independent cell death." Eby M.T., Jasmin A., Kumar A., Sharma K., Chaudhary P.M. J. Biol. Chem. 275:15336-15342(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNFRSF19.
[18]	"The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor." Wong B.R., Josien R., Lee S.Y., Vologodskaia M., Steinman R.M., Choi Y. J. Biol. Chem. 273:28355-28359(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNFRSF11A.
[19]	"TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation." Pype S., Declercq W., Ibrahimi A., Michiels C., Van Rietschoten J.G.I., Dewulf N., de Boer M., Vandenabeele P., Huylebroeck D., Remacle J.E. J. Biol. Chem. 275:18586-18593(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TDP2.
[20]	"TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation." Xia X.-Z., Treanor J., Senaldi G., Khare S.D., Boone T., Kelley M., Theill L.E., Colombero A., Solovyev I., Lee F., McCabe S., Elliott R., Miner K., Hawkins N., Guo J., Stolina M., Yu G., Wang J. , Delaney J., Meng S.-Y., Boyle W.J., Hsu H. J. Exp. Med. 192:137-143(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNFRSF13B.
[21]	"B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1." Shu H.-B., Johnson H. Proc. Natl. Acad. Sci. U.S.A. 97:9156-9161(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNFRSF17.
[22]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB000509 mRNA. Translation: BAA25262.1. CR536557 mRNA. Translation: CAG38794.1. AL590101 Genomic DNA. Translation: CAH72434.1. CH471100 Genomic DNA. Translation: EAW93420.1. CH471100 Genomic DNA. Translation: EAW93422.1. BC029600 mRNA. Translation: AAH29600.1. U69108 mRNA. Translation: AAC51329.1.
IPI	IPI00005760.
PIR	JC6539.
RefSeq	NP_001029082.1. NM_001033910.2. NP_004610.1. NM_004619.3. NP_665702.1. NM_145759.2.
UniGene	Hs.523930.
3D structure databases
ProteinModelPortal	O00463.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00463. 17 interactions.
STRING	9606.ENSP00000261464.
PTM databases
PhosphoSite	O00463.
Proteomic databases
PaxDb	O00463.
PRIDE	O00463.
Protocols and materials databases
DNASU	7188.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261464; ENSP00000261464; ENSG00000082512. ENST00000336184; ENSP00000336825; ENSG00000082512. ENST00000367004; ENSP00000355971; ENSG00000082512.
GeneID	7188.
KEGG	hsa:7188.
UCSC	uc001hih.3. human.
Organism-specific databases
CTD	7188.
GeneCards	GC01P211499.
HGNC	HGNC:12035. TRAF5.
HPA	CAB010277. HPA008052.
MIM	602356. gene.
neXtProt	NX_O00463.
PharmGKB	PA36712.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG239194.
HOVERGEN	HBG058222.
InParanoid	O00463.
KO	K09849.
OMA	IDKSAWL.
OrthoDB	EOG4JWVD2.
PhylomeDB	O00463.
Gene expression databases
ArrayExpress	O00463.
Bgee	O00463.
CleanEx	HS_TRAF5.
Genevestigator	O00463.
GermOnline	ENSG00000082512. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit. 3.90.890.10. 1 hit.
InterPro	IPR002083. MATH. IPR013323. SIAH-type. IPR012227. TNF_rcpt--assoc_TRAF. IPR008974. TRAF-like. IPR027130. TRAF5. IPR018957. Znf_C3HC4_RING-type. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR017907. Znf_RING_CS. IPR001293. Znf_TRAF. [Graphical view]
PANTHER	PTHR10131:SF23. PTHR10131:SF23. 1 hit.
Pfam	PF00917. MATH. 1 hit. PF00097. zf-C3HC4. 1 hit. [Graphical view]
PIRSF	PIRSF015614. TRAF. 1 hit.
SMART	SM00061. MATH. 1 hit. SM00184. RING. 1 hit. [Graphical view]
SUPFAM	SSF49599. Traf_like. 3 hits.
PROSITE	PS50144. MATH. 1 hit. PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. PS50145. ZF_TRAF. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TRAF5. human.
GenomeRNAi	7188.
NextBio	28184.
SOURCE	Search...

Entry information

Entry name

TRAF5_HUMAN

Accession

Primary (citable) accession number: O00463
Secondary accession number(s): Q6FHY1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 9, 2003
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 129 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.