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

    Gene ID: 9618, updated on 10-Dec-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
    mouse all
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    Genomic context

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    See TRAF4 in Genome Data Viewer
    Location:
    17q11.2
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (28744011..28750956)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (29686797..29693739)
    RS_2024_09 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: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. TRAF4 overexpression is a common characteristic of human carcinomas. Camilleri-Broët S, et al. Oncogene, 2007 Jan 4. PMID 16799635
    2. TRAF4 promotes the growth and invasion of colon cancer through the Wnt/β-catenin pathway. Yang K, et al. Int J Clin Exp Pathol, 2015. PMID 25973026, Free PMC Article
    3. [TRAF4, a multifaceted protein involved in carcinoma progression]. Rousseau A, et al. Biol Aujourdhui, 2014. PMID 25840457
    4. TRAF4 enhances osteosarcoma cell proliferation and invasion by Akt signaling pathway. Yao W, et al. Oncol Res, 2014. PMID 25700355, Free PMC Article
    5. Intracellular localization and transcriptional regulation of tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4). Glauner H, et al. Eur J Biochem, 2002 Oct. PMID 12354113

    See all (147) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. [TRAF4 promotes lung cancer development by activating tyrosine kinase of EGFR].
      Title: [TRAF4 promotes lung cancer development by activating tyrosine kinase of EGFR].
    2. TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance.
      Title: TRAF4 regulates ubiquitination-modulated survivin turnover and confers radioresistance.
    3. 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.
    4. 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.
    5. 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.
    6. TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance.
      Title: TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance.
    7. Stabilization of MCL-1 by E3 ligase TRAF4 confers radioresistance.
      Title: Stabilization of MCL-1 by E3 ligase TRAF4 confers radioresistance.
    8. TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling.
      Title: TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (75)

    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

    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 signaling adaptor activity IBA
    Inferred from Biological aspect of Ancestor
    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 IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    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 cell surface receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    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_2024_08

    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

      UniProtKB/TrEMBL
      B4DUU9

    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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