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TRAF4 TNF receptor associated factor 4 [ Homo sapiens (human) ]

Gene ID: 9618, updated on 11-Apr-2024

Summary

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Official Symbol
TRAF4provided by HGNC
Official Full Name
TNF receptor associated factor 4provided by HGNC
Primary source
HGNC:HGNC:12034
See related
Ensembl:ENSG00000076604 MIM:602464; AllianceGenome:HGNC:12034
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CART1; MLN62; RNF83
Summary
This gene encodes a member of the TNF receptor associated factor (TRAF) family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. The encoded protein has been shown to interact with neurotrophin receptor, p75 (NTR/NTSR1), and negatively regulate NTR induced cell death and NF-kappa B activation. This protein has been found to bind to p47phox, a cytosolic regulatory factor included in a multi-protein complex known as NAD(P)H oxidase. This protein thus, is thought to be involved in the oxidative activation of MAPK8/JNK. Alternatively spliced transcript variants have been observed but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in duodenum (RPKM 13.1), small intestine (RPKM 10.0) and 24 other tissues See more
Orthologs
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Genomic context

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Location:
17q11.2
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (28744011..28750956)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (29686797..29693739)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (27071029..27077974)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8350 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:27052063-27052786 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:27052787-27053510 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:27053511-27054234 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:27054959-27055682 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:27055683-27056406 Neighboring gene ribosomal protein L23a Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11943 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11944 Neighboring gene TLC domain containing 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:27064492-27065026 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11946 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11947 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11948 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11949 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11950 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8352 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11951 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:27070105-27071105 Neighboring gene NIMA related kinase 8 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8354 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:27074109-27075108 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr17:27087700-27088297 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:27088298-27088894 Neighboring gene family with sequence similarity 222 member B Neighboring gene uncharacterized LOC124903965 Neighboring gene ribosomal protein L31 pseudogene 58

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. TRAF4 Silencing Induces Cell Apoptosis and Improves Retinoic Acid Sensitivity in Human Neuroblastoma. Gu Y, et al. Neurochem Res, 2023 Jul. PMID 36795185
  2. TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance. Dong X, et al. Cell Death Dis, 2023 Feb 10. PMID 36765039, Free PMC Article
  3. TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling. Iyengar PV, et al. Mol Cancer Res, 2022 Oct 4. PMID 35731212, Free PMC Article
  4. High expression of TRAF4 predicts poor prognosis in tamoxifen-treated breast cancer and promotes tamoxifen resistance. Zhou J, et al. Anticancer Drugs, 2020 Jul. PMID 32304412
  5. Expression and Association of Tumor Necrosis Factor Receptor Associated Factor 4 (TRAF4) in Esophageal Squamous Cell Carcinoma. Li PC, et al. Med Sci Monit, 2019 Apr 1. PMID 30933965, Free PMC Article

See all (137) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. USP7 mediates TRAF4 deubiquitination to facilitate the malignant phenotype of ovarian cancer via the RSK4/PI3K/AKT axis.
    Title: USP7 mediates TRAF4 deubiquitination to facilitate the malignant phenotype of ovarian cancer via the RSK4/PI3K/AKT axis.
  2. De Novo PACSIN1 Gene Variant Found in Childhood Lupus and a Role for PACSIN1/TRAF4 Complex in Toll-like Receptor 7 Activation.
    Title: De Novo PACSIN1 Gene Variant Found in Childhood Lupus and a Role for PACSIN1/TRAF4 Complex in Toll-like Receptor 7 Activation.
  3. TRAF4 Silencing Induces Cell Apoptosis and Improves Retinoic Acid Sensitivity in Human Neuroblastoma.
    Title: TRAF4 Silencing Induces Cell Apoptosis and Improves Retinoic Acid Sensitivity in Human Neuroblastoma.
  4. TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance.
    Title: TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance.
  5. Stabilization of MCL-1 by E3 ligase TRAF4 confers radioresistance.
    Title: Stabilization of MCL-1 by E3 ligase TRAF4 confers radioresistance.
  6. TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling.
    Title: TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling.
  7. TRAF4 Maintains Deubiquitination of Caveolin-1 to Drive Glioblastoma Stemness and Temozolomide Resistance.
    Title: TRAF4 Maintains Deubiquitination of Caveolin-1 to Drive Glioblastoma Stemness and Temozolomide Resistance.
  8. Overexpression of TRAF4 promotes lung cancer growth and EGFR-dependent phosphorylation of ERK5.
    Title: Overexpression of TRAF4 promotes lung cancer growth and EGFR-dependent phosphorylation of ERK5.
  9. TRAF4 Promotes the Proliferation of Glioblastoma by Stabilizing SETDB1 to Activate the AKT Pathway.
    Title: TRAF4 Promotes the Proliferation of Glioblastoma by Stabilizing SETDB1 to Activate the AKT Pathway.
  10. TRAF4 hyperactivates HER2 signaling and contributes to Trastuzumab resistance in HER2-positive breast cancer.
    Title: TRAF4 hyperactivates HER2 signaling and contributes to Trastuzumab resistance in HER2-positive breast cancer.
Submit: New GeneRIF Correction See all GeneRIFs (73)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat Overexpression of the p47-phox binding domain of TRAF4 inhibits endothelial cell JNK activation by HIV-1 Tat, suggesting Tat initiates signals that enter basic signaling cassettes at the level of TRAF4 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables WW domain binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase binding IEA
Inferred from Electronic Annotation
more info
  
enables thioesterase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables transferase activity IEA
Inferred from Electronic Annotation
more info
  
enables tumor necrosis factor receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables tumor necrosis factor receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin protein ligase binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables zinc ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in innate immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of JNK cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of protein kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of canonical NF-kappaB signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in respiratory gaseous exchange by respiratory system IEA
Inferred from Electronic Annotation
more info
  
involved_in respiratory tube development IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in bicellular tight junction IEA
Inferred from Electronic Annotation
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoskeleton IEA
Inferred from Electronic Annotation
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in fibrillar center IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
part_of plasma membrane signaling receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
TNF receptor-associated factor 4
Names
MLN 62
RING finger protein 83
cysteine-rich domain associated with RING and Traf domains protein 1
cysteine-rich domain associated with ring and TRAF domain
malignant 62
metastatic lymph node gene 62 protein
tumor necrosis receptor-associated factor 4A
NP_004286.2
XP_011523806.1
XP_011523807.1
XP_011523808.1
XP_011523809.1
XP_011523810.1
XP_054173933.1
XP_054173934.1
XP_054173935.1
XP_054173936.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_004295.4 → NP_004286.2  TNF receptor-associated factor 4

    See identical proteins and their annotated locations for NP_004286.2

    Status: REVIEWED

    Source sequence(s)
    AC010761, BC001769, CR990949
    Consensus CDS
    CCDS11243.1
    UniProtKB/Swiss-Prot
    O75615, Q14848, Q2KJU4, Q2PJN8, Q9BUZ4
    UniProtKB/TrEMBL
    B4DUU9
    Related
    ENSP00000262395.5, ENST00000262395.10
    Conserved Domains (4) summary
    PLN03086
    Location:113 → 211
    PLN03086; PRLI-interacting factor K; Provisional
    cd03781
    Location:308 → 463
    MATH_TRAF4; Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF4, including the Drosophila protein DTRAF1. TRAF molecules serve as adapter ...
    pfam02176
    Location:210 → 269
    zf-TRAF; TRAF-type zinc finger
    cd16641
    Location:15 → 59
    mRING-HC-C3HC3D_TRAF4; Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) and similar proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    28744011..28750956
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011525504.4 → XP_011523806.1  TNF receptor-associated factor 4 isoform X1

    See identical proteins and their annotated locations for XP_011523806.1

    UniProtKB/TrEMBL
    B4DUU9
    Conserved Domains (3) summary
    cd00162
    Location:18 → 55
    RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
    cd03781
    Location:315 → 470
    MATH_TRAF4; Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF4, including the Drosophila protein DTRAF1. TRAF molecules serve as adapter ...
    pfam02176
    Location:217 → 276
    zf-TRAF; TRAF-type zinc finger

  2. XM_011525505.3 → XP_011523807.1  TNF receptor-associated factor 4 isoform X2

    Conserved Domains (2) summary
    cd03781
    Location:299 → 454
    MATH_TRAF4; Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF4, including the Drosophila protein DTRAF1. TRAF molecules serve as adapter ...
    pfam02176
    Location:201 → 260
    zf-TRAF; TRAF-type zinc finger

  3. XM_011525506.4 → XP_011523808.1  TNF receptor-associated factor 4 isoform X3

    See identical proteins and their annotated locations for XP_011523808.1

    Conserved Domains (2) summary
    cd03781
    Location:292 → 447
    MATH_TRAF4; Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF4, including the Drosophila protein DTRAF1. TRAF molecules serve as adapter ...
    pfam02176
    Location:194 → 253
    zf-TRAF; TRAF-type zinc finger

  4. XM_011525507.3 → XP_011523809.1  TNF receptor-associated factor 4 isoform X4

    See identical proteins and their annotated locations for XP_011523809.1

    Conserved Domains (2) summary
    cd03781
    Location:190 → 345
    MATH_TRAF4; Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF4, including the Drosophila protein DTRAF1. TRAF molecules serve as adapter ...
    pfam02176
    Location:92 → 151
    zf-TRAF; TRAF-type zinc finger

  5. XM_011525508.3 → XP_011523810.1  TNF receptor-associated factor 4 isoform X4

    See identical proteins and their annotated locations for XP_011523810.1

    Conserved Domains (2) summary
    cd03781
    Location:190 → 345
    MATH_TRAF4; Tumor Necrosis Factor Receptor (TNFR)-Associated Factor (TRAF) family, TRAF4 subfamily, TRAF domain, C-terminal MATH subdomain; composed of proteins with similarity to human TRAF4, including the Drosophila protein DTRAF1. TRAF molecules serve as adapter ...
    pfam02176
    Location:92 → 151
    zf-TRAF; TRAF-type zinc finger

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    29686797..29693739
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054317958.1 → XP_054173933.1  TNF receptor-associated factor 4 isoform X1

  2. XM_054317959.1 → XP_054173934.1  TNF receptor-associated factor 4 isoform X2

  3. XM_054317960.1 → XP_054173935.1  TNF receptor-associated factor 4 isoform X3

  4. XM_054317961.1 → XP_054173936.1  TNF receptor-associated factor 4 isoform X4

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_145751.1: Suppressed sequence

    Description
    NM_145751.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9BUZ4.1 GenPept UniProtKB/Swiss-Prot:Q9BUZ4

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