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Protein

TNF receptor-associated factor 4

Gene

TRAF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Adapter protein and signal transducer that links members of the tumor necrosis factor receptor (TNFR) family to different signaling pathways. Plays a role in the activation of NF-kappa-B and JNK, and in the regulation of cell survival and apoptosis. Regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. Required for normal skeleton development, and for normal development of the respiratory tract (By similarity). Required for activation of RPS6KB1 in response to TNF signaling. Modulates TRAF6 functions.By similarity6 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri18 – 58RING-typePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri102 – 154TRAF-type 1PROSITE-ProRule annotationAdd BLAST53
Zinc fingeri155 – 208TRAF-type 2PROSITE-ProRule annotationAdd BLAST54
Zinc fingeri209 – 266TRAF-type 3PROSITE-ProRule annotationAdd BLAST58

GO - Molecular functioni

  • DNA binding Source: ProtInc
  • identical protein binding Source: IntAct
  • thioesterase binding Source: UniProtKB
  • tumor necrosis factor receptor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: InterPro
  • WW domain binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • activation of NF-kappaB-inducing kinase activity Source: InterPro
  • apoptotic process Source: UniProtKB-KW
  • positive regulation of JNK cascade Source: UniProtKB
  • positive regulation of protein homodimerization activity Source: UniProtKB
  • positive regulation of protein kinase activity Source: UniProtKB
  • regulation of apoptotic process Source: InterPro
  • respiratory gaseous exchange Source: Ensembl
  • respiratory tube development Source: Ensembl
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionDevelopmental protein
Biological processApoptosis
LigandMetal-binding, Zinc

Enzyme and pathway databases

SignaLinkiQ9BUZ4.
SIGNORiQ9BUZ4.

Names & Taxonomyi

Protein namesi
Recommended name:
TNF receptor-associated factor 4
Alternative name(s):
Cysteine-rich domain associated with RING and Traf domains protein 1
Metastatic lymph node gene 62 protein
Short name:
MLN 62
RING finger protein 83
Gene namesi
Name:TRAF4
Synonyms:CART1, MLN62, RNF83
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:12034. TRAF4.

Subcellular locationi

GO - Cellular componenti

  • bicellular tight junction Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB-SubCell

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus, Tight junction

Pathology & Biotechi

Organism-specific databases

DisGeNETi9618.
OpenTargetsiENSG00000076604.
PharmGKBiPA36711.

Polymorphism and mutation databases

BioMutaiTRAF4.
DMDMi30580636.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000564031 – 470TNF receptor-associated factor 4Add BLAST470

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei426PhosphoserineCombined sources1

Post-translational modificationi

Polyubiquitinated, leading to its proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9BUZ4.
MaxQBiQ9BUZ4.
PaxDbiQ9BUZ4.
PeptideAtlasiQ9BUZ4.
PRIDEiQ9BUZ4.

PTM databases

iPTMnetiQ9BUZ4.
PhosphoSitePlusiQ9BUZ4.

Expressioni

Tissue specificityi

Expressed in epithelial cells of thymus, dendritic cells of lymph node, and in the basal cell layer of epithelia such as epidermis, nasopharynx, respiratory tract, salivary gland, and esophagus.2 Publications

Inductioni

Up-regulated by bacterial lipopolysaccharides (LPS) and by single-stranded CpG oligodeoxynucleotide.1 Publication

Gene expression databases

BgeeiENSG00000076604.
CleanExiHS_TRAF4.
ExpressionAtlasiQ9BUZ4. baseline and differential.
GenevisibleiQ9BUZ4. HS.

Organism-specific databases

HPAiHPA052377.

Interactioni

Subunit structurei

Homotrimer (Probable). Interacts with LTBR/TNFRSF3, NGFR/TNFRSF16, RPS6KB1 and TGFB1I1. Interacts with SMURF1. Interacts (via TRAF domain) with MAP3K4 (via kinase domain). Interacts with NCF1, TICAM1, IRAK1 and TRAF6, and is probably part of a complex containing TRAF4, NCF1, TICAM1, IRAK1 and TRAF6.Curated8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • thioesterase binding Source: UniProtKB
  • tumor necrosis factor receptor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • WW domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114979. 94 interactors.
DIPiDIP-40910N.
IntActiQ9BUZ4. 93 interactors.
MINTiMINT-107471.
STRINGi9606.ENSP00000262395.

Structurei

Secondary structure

1470
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi123 – 126Combined sources4
Turni127 – 132Combined sources6
Beta strandi142 – 144Combined sources3
Helixi150 – 155Combined sources6
Turni156 – 158Combined sources3
Beta strandi192 – 194Combined sources3
Beta strandi196 – 198Combined sources3
Beta strandi201 – 203Combined sources3
Helixi204 – 213Combined sources10
Beta strandi215 – 220Combined sources6
Beta strandi229 – 231Combined sources3
Turni232 – 234Combined sources3
Helixi235 – 240Combined sources6
Beta strandi243 – 245Combined sources3
Helixi286 – 301Combined sources16
Beta strandi309 – 314Combined sources6
Helixi317 – 326Combined sources10
Beta strandi337 – 340Combined sources4
Beta strandi345 – 351Combined sources7
Helixi356 – 358Combined sources3
Turni359 – 361Combined sources3
Beta strandi362 – 370Combined sources9
Helixi375 – 377Combined sources3
Beta strandi386 – 390Combined sources5
Turni396 – 398Combined sources3
Beta strandi404 – 408Combined sources5
Helixi415 – 417Combined sources3
Helixi427 – 431Combined sources5
Beta strandi434 – 441Combined sources8
Helixi442 – 445Combined sources4
Turni446 – 450Combined sources5
Beta strandi455 – 462Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EODNMR-A190-248[»]
2YUCNMR-A102-164[»]
3ZJBX-ray1.84A/B/C283-470[»]
4K8UX-ray2.30A/B/C281-470[»]
4M4EX-ray2.60A/B/C292-466[»]
ProteinModelPortaliQ9BUZ4.
SMRiQ9BUZ4.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BUZ4.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini307 – 462MATHPROSITE-ProRule annotationAdd BLAST156

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili277 – 309Sequence analysisAdd BLAST33

Domaini

The coiled coil domain mediates homo- and hetero-oligomerization.By similarity
The MATH/TRAF domain binds to receptor cytoplasmic domains.By similarity

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri18 – 58RING-typePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri102 – 154TRAF-type 1PROSITE-ProRule annotationAdd BLAST53
Zinc fingeri155 – 208TRAF-type 2PROSITE-ProRule annotationAdd BLAST54
Zinc fingeri209 – 266TRAF-type 3PROSITE-ProRule annotationAdd BLAST58

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0297. Eukaryota.
ENOG410Z7YX. LUCA.
GeneTreeiENSGT00550000074359.
HOGENOMiHOG000004841.
HOVERGENiHBG103438.
InParanoidiQ9BUZ4.
KOiK09848.
OrthoDBiEOG091G0GHD.
PhylomeDBiQ9BUZ4.
TreeFamiTF321154.

Family and domain databases

Gene3Di2.60.210.10. 1 hit.
3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiView protein in InterPro
IPR002083. MATH/TRAF_dom.
IPR013323. SIAH-type.
IPR012227. TNF_rcpt--assoc_TRAF.
IPR008974. TRAF-like.
IPR027138. TRAF4.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
IPR001293. Znf_TRAF.
PANTHERiPTHR10131:SF92. PTHR10131:SF92. 1 hit.
PfamiView protein in Pfam
PF00097. zf-C3HC4. 1 hit.
PF02176. zf-TRAF. 2 hits.
PIRSFiPIRSF015614. TRAF. 1 hit.
SMARTiView protein in SMART
SM00061. MATH. 1 hit.
SM00184. RING. 1 hit.
SUPFAMiSSF49599. SSF49599. 3 hits.
PROSITEiView protein in PROSITE
PS50144. MATH. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS50145. ZF_TRAF. 3 hits.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BUZ4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPGFDYKFLE KPKRRLLCPL CGKPMREPVQ VSTCGHRFCD TCLQEFLSEG
60 70 80 90 100
VFKCPEDQLP LDYAKIYPDP ELEVQVLGLP IRCIHSEEGC RWSGPLRHLQ
110 120 130 140 150
GHLNTCSFNV IPCPNRCPMK LSRRDLPAHL QHDCPKRRLK CEFCGCDFSG
160 170 180 190 200
EAYESHEGMC PQESVYCENK CGARMMRRLL AQHATSECPK RTQPCTYCTK
210 220 230 240 250
EFVFDTIQSH QYQCPRLPVA CPNQCGVGTV AREDLPGHLK DSCNTALVLC
260 270 280 290 300
PFKDSGCKHR CPKLAMARHV EESVKPHLAM MCALVSRQRQ ELQELRRELE
310 320 330 340 350
ELSVGSDGVL IWKIGSYGRR LQEAKAKPNL ECFSPAFYTH KYGYKLQVSA
360 370 380 390 400
FLNGNGSGEG THLSLYIRVL PGAFDNLLEW PFARRVTFSL LDQSDPGLAK
410 420 430 440 450
PQHVTETFHP DPNWKNFQKP GTWRGSLDES SLGFGYPKFI SHQDIRKRNY
460 470
VRDDAVFIRA AVELPRKILS
Length:470
Mass (Da):53,543
Last modified:June 1, 2001 - v1
Checksum:iA3F57E0E1081AB88
GO
Isoform 2 (identifier: Q9BUZ4-2) [UniParc]FASTAAdd to basket
Also known as: TRAF4 variant 5

The sequence of this isoform differs from the canonical sequence as follows:
     157-428: Missing.

Show »
Length:198
Mass (Da):22,841
Checksum:i1571EDE9630E7398
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025805173A → T1 PublicationCorresponds to variant dbSNP:rs35932778Ensembl.1
Natural variantiVAR_052150178R → G1 PublicationCorresponds to variant dbSNP:rs1044066Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_007403157 – 428Missing in isoform 2. 2 PublicationsAdd BLAST272

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80200 mRNA. Translation: CAA56491.1.
AF082185 mRNA. Translation: AAC32376.1.
AY937224 mRNA. Translation: AAY16990.1.
DQ323999 Genomic DNA. Translation: ABC40750.1.
AC010761 Genomic DNA. No translation available.
BC001769 mRNA. Translation: AAH01769.1.
CCDSiCCDS11243.1. [Q9BUZ4-1]
PIRiI38026.
RefSeqiNP_004286.2. NM_004295.3. [Q9BUZ4-1]
UniGeneiHs.8375.

Genome annotation databases

EnsembliENST00000262395; ENSP00000262395; ENSG00000076604. [Q9BUZ4-1]
GeneIDi9618.
KEGGihsa:9618.
UCSCiuc002hcq.2. human. [Q9BUZ4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80200 mRNA. Translation: CAA56491.1.
AF082185 mRNA. Translation: AAC32376.1.
AY937224 mRNA. Translation: AAY16990.1.
DQ323999 Genomic DNA. Translation: ABC40750.1.
AC010761 Genomic DNA. No translation available.
BC001769 mRNA. Translation: AAH01769.1.
CCDSiCCDS11243.1. [Q9BUZ4-1]
PIRiI38026.
RefSeqiNP_004286.2. NM_004295.3. [Q9BUZ4-1]
UniGeneiHs.8375.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EODNMR-A190-248[»]
2YUCNMR-A102-164[»]
3ZJBX-ray1.84A/B/C283-470[»]
4K8UX-ray2.30A/B/C281-470[»]
4M4EX-ray2.60A/B/C292-466[»]
ProteinModelPortaliQ9BUZ4.
SMRiQ9BUZ4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114979. 94 interactors.
DIPiDIP-40910N.
IntActiQ9BUZ4. 93 interactors.
MINTiMINT-107471.
STRINGi9606.ENSP00000262395.

PTM databases

iPTMnetiQ9BUZ4.
PhosphoSitePlusiQ9BUZ4.

Polymorphism and mutation databases

BioMutaiTRAF4.
DMDMi30580636.

Proteomic databases

EPDiQ9BUZ4.
MaxQBiQ9BUZ4.
PaxDbiQ9BUZ4.
PeptideAtlasiQ9BUZ4.
PRIDEiQ9BUZ4.

Protocols and materials databases

DNASUi9618.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262395; ENSP00000262395; ENSG00000076604. [Q9BUZ4-1]
GeneIDi9618.
KEGGihsa:9618.
UCSCiuc002hcq.2. human. [Q9BUZ4-1]

Organism-specific databases

CTDi9618.
DisGeNETi9618.
GeneCardsiTRAF4.
HGNCiHGNC:12034. TRAF4.
HPAiHPA052377.
MIMi602464. gene.
neXtProtiNX_Q9BUZ4.
OpenTargetsiENSG00000076604.
PharmGKBiPA36711.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0297. Eukaryota.
ENOG410Z7YX. LUCA.
GeneTreeiENSGT00550000074359.
HOGENOMiHOG000004841.
HOVERGENiHBG103438.
InParanoidiQ9BUZ4.
KOiK09848.
OrthoDBiEOG091G0GHD.
PhylomeDBiQ9BUZ4.
TreeFamiTF321154.

Enzyme and pathway databases

SignaLinkiQ9BUZ4.
SIGNORiQ9BUZ4.

Miscellaneous databases

ChiTaRSiTRAF4. human.
EvolutionaryTraceiQ9BUZ4.
GeneWikiiTRAF4.
GenomeRNAii9618.
PROiQ9BUZ4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000076604.
CleanExiHS_TRAF4.
ExpressionAtlasiQ9BUZ4. baseline and differential.
GenevisibleiQ9BUZ4. HS.

Family and domain databases

Gene3Di2.60.210.10. 1 hit.
3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiView protein in InterPro
IPR002083. MATH/TRAF_dom.
IPR013323. SIAH-type.
IPR012227. TNF_rcpt--assoc_TRAF.
IPR008974. TRAF-like.
IPR027138. TRAF4.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
IPR001293. Znf_TRAF.
PANTHERiPTHR10131:SF92. PTHR10131:SF92. 1 hit.
PfamiView protein in Pfam
PF00097. zf-C3HC4. 1 hit.
PF02176. zf-TRAF. 2 hits.
PIRSFiPIRSF015614. TRAF. 1 hit.
SMARTiView protein in SMART
SM00061. MATH. 1 hit.
SM00184. RING. 1 hit.
SUPFAMiSSF49599. SSF49599. 3 hits.
PROSITEiView protein in PROSITE
PS50144. MATH. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS50145. ZF_TRAF. 3 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiTRAF4_HUMAN
AccessioniPrimary (citable) accession number: Q9BUZ4
Secondary accession number(s): O75615
, Q14848, Q2KJU4, Q2PJN8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 9, 2003
Last sequence update: June 1, 2001
Last modified: March 15, 2017
This is version 158 of the entry and version 1 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 chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.