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Protein

TNF receptor-associated factor 4

Gene

TRAF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

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

EuPathDBiHostDB:ENSG00000076604.14
HGNCiHGNC:12034 TRAF4
MIMi602464 gene
neXtProtiNX_Q9BUZ4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi79148
79149 [Q9BUZ4-2]

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 Expressed in 205 organ(s), highest expression level in adult mammalian kidney
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114979, 98 interactors
DIPiDIP-40910N
IntActiQ9BUZ4, 111 interactors
MINTiQ9BUZ4
STRINGi9606.ENSP00000262395

Structurei

Secondary structure

1470
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiEGCRWTG
OrthoDBiEOG091G0GHD
PhylomeDBiQ9BUZ4
TreeFamiTF321154

Family and domain databases

CDDicd03781 MATH_TRAF4, 1 hit
Gene3Di2.60.210.10, 1 hit
3.30.40.10, 4 hits
InterProiView protein in InterPro
IPR002083 MATH/TRAF_dom
IPR012227 TNF_rcpt--assoc_TRAF
IPR008974 TRAF-like
IPR027138 TRAF4
IPR037307 TRAF4_MATH
IPR018957 Znf_C3HC4_RING-type
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
IPR001293 Znf_TRAF
PANTHERiPTHR10131:SF118 PTHR10131:SF118, 2 hits
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

This entry has 2 described isoforms and 10 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6SA91F6SA91_HUMAN
TNF receptor-associated factor 4
TRAF4
437Annotation score:
C9JJ10C9JJ10_HUMAN
TNF receptor-associated factor 4
TRAF4
182Annotation score:
A0A0C4DFM9A0A0C4DFM9_HUMAN
TNF receptor-associated factor 4
TRAF4
195Annotation score:
J9JIG0J9JIG0_HUMAN
TNF receptor-associated factor 4
TRAF4
112Annotation score:
K7ER49K7ER49_HUMAN
TNF receptor-associated factor 4
TRAF4
90Annotation score:
Q2KJU6Q2KJU6_HUMAN
TNF receptor-associated factor 4
TRAF4
144Annotation score:
K7EJG7K7EJG7_HUMAN
TNF receptor-associated factor 4
TRAF4
48Annotation score:
K7EM06K7EM06_HUMAN
TNF receptor-associated factor 4
TRAF4
53Annotation score:
J3QR87J3QR87_HUMAN
TNF receptor-associated factor 4
TRAF4
49Annotation score:
J3QS94J3QS94_HUMAN
TNF receptor-associated factor 4
TRAF4
92Annotation score:

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

Similar proteinsi

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[»]
5YC1X-ray2.51A/B/C/D/E/F290-470[»]
ProteinModelPortaliQ9BUZ4
SMRiQ9BUZ4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114979, 98 interactors
DIPiDIP-40910N
IntActiQ9BUZ4, 111 interactors
MINTiQ9BUZ4
STRINGi9606.ENSP00000262395

PTM databases

iPTMnetiQ9BUZ4
PhosphoSitePlusiQ9BUZ4

Polymorphism and mutation databases

BioMutaiTRAF4
DMDMi30580636

Proteomic databases

EPDiQ9BUZ4
MaxQBiQ9BUZ4
PaxDbiQ9BUZ4
PeptideAtlasiQ9BUZ4
PRIDEiQ9BUZ4
ProteomicsDBi79148
79149 [Q9BUZ4-2]

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
EuPathDBiHostDB:ENSG00000076604.14
GeneCardsiTRAF4
HGNCiHGNC:12034 TRAF4
HPAiHPA052377
MIMi602464 gene
neXtProtiNX_Q9BUZ4
OpenTargetsiENSG00000076604
PharmGKBiPA36711
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

SignaLinkiQ9BUZ4
SIGNORiQ9BUZ4

Miscellaneous databases

ChiTaRSiTRAF4 human
EvolutionaryTraceiQ9BUZ4
GeneWikiiTRAF4
GenomeRNAii9618
PROiPR:Q9BUZ4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000076604 Expressed in 205 organ(s), highest expression level in adult mammalian kidney
CleanExiHS_TRAF4
ExpressionAtlasiQ9BUZ4 baseline and differential
GenevisibleiQ9BUZ4 HS

Family and domain databases

CDDicd03781 MATH_TRAF4, 1 hit
Gene3Di2.60.210.10, 1 hit
3.30.40.10, 4 hits
InterProiView protein in InterPro
IPR002083 MATH/TRAF_dom
IPR012227 TNF_rcpt--assoc_TRAF
IPR008974 TRAF-like
IPR027138 TRAF4
IPR037307 TRAF4_MATH
IPR018957 Znf_C3HC4_RING-type
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
IPR001293 Znf_TRAF
PANTHERiPTHR10131:SF118 PTHR10131:SF118, 2 hits
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: November 7, 2018
This is version 174 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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