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

Summary

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: mouse all
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Genomic context

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_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance.
Title: TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance.
Stabilization of MCL-1 by E3 ligase TRAF4 confers radioresistance.
Title: Stabilization of MCL-1 by E3 ligase TRAF4 confers radioresistance.
TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling.
Title: TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling.
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.
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.
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.
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)

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

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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

TRAF4_282.2 (e-PCR)
- UniSTS:277843

RH16881 (e-PCR)
- UniSTS:81389

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
involved_in signal transduction	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

EC 2.3.2.27

XP_011523806.1

EC 2.3.2.27

XP_011523807.1

EC 2.3.2.27

XP_011523808.1

EC 2.3.2.27

XP_011523809.1

EC 2.3.2.27

XP_011523810.1

EC 2.3.2.27

XP_054173933.1

EC 2.3.2.27

XP_054173934.1

EC 2.3.2.27

XP_054173935.1

EC 2.3.2.27

XP_054173936.1

EC 2.3.2.27

NCBI Reference Sequences (RefSeq)

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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)

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

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

28744011..28750956

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
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

NC_060941.1 Alternate T2T-CHM13v2.0

Range

29686797..29693739

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054317958.1 → XP_054173933.1 TNF receptor-associated factor 4 isoform X1
XM_054317959.1 → XP_054173934.1 TNF receptor-associated factor 4 isoform X2
XM_054317960.1 → XP_054173935.1 TNF receptor-associated factor 4 isoform X3
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

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.