Reviewed, UniProtKB/Swiss-Prot Q13114 (TRAF3_HUMAN)

Names and origin

Protein names

Recommended name:
    TNF receptor-associated factor 3
Alternative name(s):
    CD40 receptor-associated factor 1
      Short name=CRAF1
    CD40-binding protein
      Short name=CD40BP
    LMP1-associated protein
    LAP1
    CAP-1

Gene names

Name:	TRAF3
Synonyms:	CAP1, CRAF1

Organism

Homo sapiens (Human) [Complete 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	568 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. Seems to be involved in activation of NF-kappa-B and JNK and in apoptosis. Is regulated by TANK/ITRAF which competes with TNFRSF5/CD40 for binding. Seems to play a role T-cell dependent immune responses.
Subunit structure	Homotrimer Probable. Heteromer with TRAF5 By similarity. Binds to TNFRSF5/CD40. Associates with LTBR/TNFRSF3, TNFRSF4, TNFRSF8/CD30, TNFRSF17/BCMA and EDAR, MAP3K5, MAP3K14, and TRAF-interacting protein TRIP and TRAF and TNF receptor associated protein TTRAP. Binds to TANK/ITRAF and TRAF3IP1. Interacts with TICAM1 By similarity. Interacts with OTUD5. Ref.1 Ref.2 Ref.3 Ref.4 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27
Subcellular location	Cytoplasm Probable.
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	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis Traceable author statement. Source: ProtInc signal transduction Ref.3 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Ref.4 Ref.18 Ref.21 Ref.29 Inferred from physical interaction. Source: IntAct signal transducer activity Ref.1 Ref.3 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CD40	P25942	3	EBI-357631,EBI-525714
EDA2R	Q9HAV5	1	EBI-357631,EBI-526033
EDAR	Q9UNE0	1	EBI-357631,EBI-529289
TANK	Q92844	1	EBI-357631,EBI-356349
TNFRSF14	Q92956	1	EBI-357631,EBI-1056653
TRAF3IP1	Q6PCT1	4	EBI-357631,EBI-1104484

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 568

568

TNF receptor-associated factor 3

PRO_0000056401

Regions

Domain

415 – 560

146

MATH

Zinc finger

68 – 77

10

RING-type

Zinc finger

135 – 190

56

TRAF-type 1

Zinc finger

191 – 249

59

TRAF-type 2

Coiled coil

267 – 338

72

Potential

Natural variations

Natural variant

129

1

M → T: dbSNP rs1131877. Ref.1 Ref.3

VAR_052149

Experimental info

Sequence conflict

134

1

Missing in AAA56753. Ref.4

Sequence conflict

218 – 242

25

Missing in AAA68195. Ref.3

Sequence conflict

339

1

P → S in AAA68195. Ref.3

Sequence conflict

405

1

R → G in AAA56753. Ref.4

Secondary structure

1

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568

Helix Strand Turn

Details...

Turn

54 – 56

3

Beta strand

59 – 62

4

Beta strand

67 – 69

3

Helix

74 – 81

8

Turn

89 – 91

3

Turn

97 – 99

3

Turn

365 – 373

9

Helix

374 – 410

37

Beta strand

414 – 423

10

Helix

425 – 433

9

Beta strand

445 – 448

4

Beta strand

456 – 459

4

Helix

464 – 466

3

Turn

467 – 469

3

Beta strand

470 – 475

6

Turn

481 – 484

4

Beta strand

494 – 498

5

Beta strand

502 – 504

3

Beta strand

508 – 512

5

Beta strand

521 – 523

3

Beta strand

525 – 528

4

Beta strand

533 – 539

7

Helix

540 – 543

4

Beta strand

544 – 546

3

Beta strand

551 – 559

9

Sequences

	Sequence		Length	Mass (Da)
	Q13114-1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 9456E440C0A90FBF	FASTA	568	64,490
	10 20 30 40 50 60 MESSKKMDSP GALQTNPPLK LHTDRSAGTP VFVPEQGGYK EKFVKTVEDK YKCEKCHLVL 70 80 90 100 110 120 CSPKQTECGH RFCESCMAAL LSSSSPKCTA CQESIVKDKV FKDNCCKREI LALQIYCRNE 130 140 150 160 170 180 SRGCAEQLML GHLLVHLKND CHFEELPCVR PDCKEKVLRK DLRDHVEKAC KYREATCSHC 190 200 210 220 230 240 KSQVPMIALQ KHEDTDCPCV VVSCPHKCSV QTLLRSELSA HLSECVNAPS TCSFKRYGCV 250 260 270 280 290 300 FQGTNQQIKA HEASSAVQHV NLLKEWSNSL EKKVSLLQNE SVEKNKSIQS LHNQICSFEI 310 320 330 340 350 360 EIERQKEMLR NNESKILHLQ RVIDSQAEKL KELDKEIRPF RQNWEEADSM KSSVESLQNR 370 380 390 400 410 420 VTELESVDKS AGQVARNTGL LESQLSRHDQ MLSVHDIRLA DMDLRFQVLE TASYNGVLIW 430 440 450 460 470 480 KIRDYKRRKQ EAVMGKTLSL YSQPFYTGYF GYKMCARVYL NGDGMGKGTH LSLFFVIMRG 490 500 510 520 530 540 EYDALLPWPF KQKVTLMLMD QGSSRRHLGD AFKPDPNSSS FKKPTGEMNI ASGCPVFVAQ 550 560 TVLENGTYIK DDTIFIKVIV DTSDLPDP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Involvement of CRAF1, a relative of TRAF, in CD40 signaling." Cheng G., Cleary A.M., Ye Z.S., Hong D.I., Lederman S., Baltimore D. Science 267:1494-1498(1995) [PubMed: 7533327] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH TNFRSF5, VARIANT THR-129.
[2]	"The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family." Mosialos G., Birkenbach M., Yalamanchili R., VanArsdale T., Ware C., Kieff E. Cell 80:389-399(1995) [PubMed: 7859281] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, INTERACTION WITH EBV LMP-1. Tissue: Lymphoma.
[3]	"A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40." Sato T., Irie S., Reed J.C. FEBS Lett. 358:113-118(1995) [PubMed: 7530216] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH TNFRSF5, VARIANT THR-129. Tissue: Fetal brain.
[4]	"A novel RING finger protein interacts with the cytoplasmic domain of CD40." Hu H.M., O'Rourke K., Boguski M.S., Dixit V.M. J. Biol. Chem. 269:30069-30072(1994) [PubMed: 7527023] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH TNFRSF5.
[5]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Fetal brain.
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[7]	"A single gene for human TRAF-3 at chromosome 14q32.3 encodes a variety of mRNA species by alternative polyadenylation, mRNA splicing and transcription initiation." van Eyndhoven W.G., Frank D., Kalachikov S., Cleary A.M., Hong D.I., Cho E., Nasr S., Perez A.J., Mackus W.J.M., Cayanis E., Wellington S., Fischer S.G., Warburton D., Lederman S. Mol. Immunol. 35:1189-1206(1998) [PubMed: 10199393] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 536-568.
[8]	"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: 11384837] [Abstract] Cited for: REVIEW.
[9]	"Tumor necrosis factor receptor-associated factors (TRAFs)." Bradley J.R., Pober J.S. Oncogene 20:6482-6491(2001) [PubMed: 11607847] [Abstract] Cited for: REVIEW.
[10]	"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: 10764746] [Abstract] Cited for: INTERACTION WITH TTRAP.
[11]	"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: 9718306] [Abstract] Cited for: INTERACTION WITH TNFRSF5 AND TRAF5.
[12]	"4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB." Arch R.H., Thompson C.B. Mol. Cell. Biol. 18:558-565(1998) [PubMed: 9418902] [Abstract] Cited for: INTERACTION WITH TNFRSF4 AND TNFRSF9.
[13]	"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: 9488716] [Abstract] Cited for: INTERACTION WITH TNFRSF4.
[14]	"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: 9774460] [Abstract] Cited for: INTERACTION WITH TNFRSF11A.
[15]	"Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand." Kwon B., Yu K.-Y., Ni J., Yu G.-L., Jang I.-K., Kim Y.-J., Xing L., Liu D., Wang S.-X., Kwon B.S. J. Biol. Chem. 274:6056-6061(1999) [PubMed: 10037686] [Abstract] Cited for: INTERACTION WITH TNFRSF18. Tissue: T-cell.
[16]	"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: 10809768] [Abstract] Cited for: INTERACTION WITH TNFRSF19.
[17]	"MIP-T3, a novel protein linking tumor necrosis factor receptor-associated factor 3 to the microtubule network." Ling L., Goeddel D.V. J. Biol. Chem. 275:23852-23860(2000) [PubMed: 10791955] [Abstract] Cited for: INTERACTION WITH TRAF3IP1.
[18]	"The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A." Kumar A., Eby M.T., Sinha S., Jasmin A., Chaudhary P.M. J. Biol. Chem. 276:2668-2677(2001) [PubMed: 11035039] [Abstract] Cited for: INTERACTION WITH EDAR.
[19]	"TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase." Hatzoglou A., Roussel J., Bourgeade M.-F., Rogier E., Madry C., Inoue J., Devergne O., Tsapis A. J. Immunol. 165:1322-1330(2000) [PubMed: 10903733] [Abstract] Cited for: INTERACTION WITH TNFRSF17.
[20]	"Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily." Boucher L.-M., Marengere L.E., Lu Y., Thukral S., Mak T.W. Biochem. Biophys. Res. Commun. 233:592-600(1997) [PubMed: 9168896] [Abstract] Cited for: INTERACTION WITH TNFRSF8.
[21]	"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: 9162022] [Abstract] Cited for: INTERACTION WITH TNFRSF14.
[22]	"TRAF5, an activator of NF-kappaB and putative signal transducer for the lymphotoxin-beta receptor." Nakano H., Oshima H., Chung W., Williams-Abbott L., Ware C.F., Yagita H., Okumura K. J. Biol. Chem. 271:14661-14664(1996) [PubMed: 8663299] [Abstract] Cited for: INTERACTION WITH LTBR.
[23]	"I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction." Rothe M., Xiong J., Shu H.-B., Williamson K., Goddard A., Goeddel D.V. Proc. Natl. Acad. Sci. U.S.A. 93:8241-8246(1996) [PubMed: 8710854] [Abstract] Cited for: INTERACTION WITH TANK.
[24]	"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: 9275204] [Abstract] Cited for: INTERACTION WITH MAP3K14.
[25]	"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: 9774977] [Abstract] Cited for: INTERACTION WITH MAP3K5.
[26]	"Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1)." Hoeflich K.P., Yeh W.C., Yao Z., Mak T.W., Woodgett J.R. Oncogene 18:5814-5820(1999) [PubMed: 10523862] [Abstract] Cited for: INTERACTION WITH MAP3K5.
[27]	"DUBA: a deubiquitinase that regulates type I interferon production." Kayagaki N., Phung Q., Chan S., Chaudhari R., Quan C., O'Rourke K.M., Eby M., Pietras E., Cheng G., Bazan J.F., Zhang Z., Arnott D., Dixit V.M. Science 318:1628-1632(2007) [PubMed: 17991829] [Abstract] Cited for: INTERACTION WITH OTUD5.
[28]	"Molecular basis for CD40 signaling mediated by TRAF3." Ni C.Z., Welsh K., Leo E., Chiou C.K., Wu H., Reed J.C., Ely K.R. Proc. Natl. Acad. Sci. U.S.A. 97:10395-10399(2000) [PubMed: 10984535] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 341-568, X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 341-568 IN COMPLEX WITH TNFRSF5.
[29]	"Downstream regulator TANK binds to the CD40 recognition site on TRAF3." Li C., Ni C.Z., Havert M.L., Cabezas E., He J., Kaiser D., Reed J.C., Satterthwait A.C., Cheng G., Ely K.R. Structure 10:403-411(2002) [PubMed: 12005438] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 377-568 IN COMPLEX WITH TANK, X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 377-568 IN COMPLEX WITH TNFRSF5.
[30]	"Solution structure of the zinc finger, C3HC4 type (RING finger) domain of TNF receptor-associated factor 3." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2008) to the PDB data bank Cited for: STRUCTURE BY NMR OF 43-101.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U21092 mRNA. Translation: AAC50112.1.
U19260 mRNA. Translation: AAA65732.1.
L38509 mRNA. Translation: AAA68195.1.
U15637 mRNA. Translation: AAA56753.1.
BX247977 mRNA. Translation: CAD62311.1.
BC075087 mRNA. Translation: AAH75087.1.
BC075086 mRNA. Translation: AAH75086.1.
AF110908 mRNA. Translation: AAD29276.1.

IPI

IPI00297473.

PIR

A55960.
S68467.

RefSeq

NP_003291.2.
NP_663777.1.
NP_663778.1.

UniGene

Hs.510528

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FLK	X-ray	2.80	A/B	341-568	[»]
1FLL	X-ray	3.50	A/B	341-568	[»]
1KZZ	X-ray	3.50	A	377-568	[»]
1L0A	X-ray	2.90	A	377-568	[»]
1RF3	X-ray	3.50	A	377-568	[»]
1ZMS	X-ray	2.80	A	377-568	[»]
2ECY	NMR	-	A	43-101	[»]
2GKW	X-ray	2.70	A	377-568	[»]

SMR

Q13114. Positions 42-139, 136-198, 168-229.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6222N.

IntAct

Q13114. 8 interactions.

STRING

Q13114.

Proteomic databases

PRIDE

Q13114.

Genome annotation databases

Ensembl

ENST00000351691; ENSP00000332468; ENSG00000131323; Homo sapiens. [Genome view]
ENST00000392745; ENSP00000376500; ENSG00000131323; Homo sapiens. [Genome view]

GeneID

7187.

KEGG

hsa:7187.

UCSC

uc001ymc.1. human.

Organism-specific databases

CTD

7187.

GeneCards

GC14P102313.

HGNC

HGNC:12033. TRAF3.

HPA

HPA002933.

MIM

601896. gene.

PharmGKB

PA36710.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18962.

HOGENOM

HBG506127.

HOVERGEN

Q13114.

InParanoid

Q13114.

OMA

CKSQVPM.

OrthoDB

EOG9DBX00.

PhylomeDB

Q13114.

Gene expression databases

ArrayExpress

Q13114.

Bgee

Q13114.

CleanEx

HS_CAP1.
HS_TRAF3.

Genevestigator

Q13114.

GermOnline

ENSG00000131323. Homo sapiens.

Family and domain databases

InterPro

IPR002083. MATH.
IPR012227. TNF_recpt_TRAF.
IPR008974. TRAF-like.
IPR013322. TRAF-type.
IPR001841. Znf_RING.
IPR017907. Znf_RING_CS.
IPR001293. Znf_TRAF.
[Graphical view]

Gene3D

G3DSA:2.60.210.10. TRAF-type. 1 hit.

Pfam

PF00917. MATH. 1 hit.
[Graphical view]

PIRSF

PIRSF015614. TRAF. 1 hit.

SMART

SM00061. MATH. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]

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 Resources

NextBio

28176.

PMAP-CutDB

Q13114.

SOURCE

Search...

Entry information

Entry name

TRAF3_HUMAN

Accession

Primary (citable) accession number: Q13114
Secondary accession number(s): Q12990 , Q13076, Q13947, Q6AZX1, Q9UNL1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	October 17, 2006
Last modified:	February 9, 2010
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.