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    GET3 guided entry of tail-anchored proteins factor 3, ATPase [ Homo sapiens (human) ]

    Gene ID: 439, updated on 2-Nov-2024

    Summary

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    Official Symbol
    GET3provided by HGNC
    Official Full Name
    guided entry of tail-anchored proteins factor 3, ATPaseprovided by HGNC
    Primary source
    HGNC:HGNC:752
    See related
    Ensembl:ENSG00000198356 MIM:601913; AllianceGenome:HGNC:752
    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
    ARSA1; ASNA1; CMD2H; TRC40; ARSA-I; ASNA-I
    Summary
    This gene represents the human homolog of the bacterial arsA gene, encoding the arsenite-stimulated ATPase component of the arsenite transporter responsible for resistance to arsenicals. This protein is also a central component of a transmembrane domain (TMD) recognition complex (TRC) that is involved in the post-translational delivery of tail-anchored (TA) proteins from the cytosol to the endoplasmic reticulum (ER). It recognizes and selectively binds the TMD of TA proteins in the cytosol, and delivers them to the ER for insertion. [provided by RefSeq, Oct 2011]
    Expression
    Ubiquitous expression in kidney (RPKM 39.3), thyroid (RPKM 34.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GET3 in Genome Data Viewer
    Location:
    19p13.13
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (12737106..12748323)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (12861599..12872815)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (12847920..12859137)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene transportin 2 Neighboring gene small nucleolar RNA, C/D box 41 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10157 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10158 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:12832661-12833279 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:12833280-12833897 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:12833898-12834516 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:12834517-12835133 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:12842300-12842847 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10160 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10161 Neighboring gene CRISPRi-FlowFISH-validated RAD23A regulatory element 1 Neighboring gene CRISPRi-FlowFISH-validated TRIR regulatory element Neighboring gene telomerase RNA component interacting RNase Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:12855878-12856378 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10165 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10166 Neighboring gene bestrophin 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:12876343-12876888 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10167 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:12881756-12882256 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:12882257-12882757 Neighboring gene hook microtubule tethering protein 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:12885288-12885968 Neighboring gene CRISPRi-FlowFISH-validated DNASE2 and PRDX2 regulatory element Neighboring gene CRISPRi-FlowFISH-validated PRDX2 regulatory element 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14077 Neighboring gene CRISPRi-FlowFISH-validated PRDX2 regulatory element 2 Neighboring gene CRISPRi-FlowFISH-validated JUNB and PRDX2 regulatory element 1 Neighboring gene CRISPRi-FlowFISH-validated JUNB and PRDX2 regulatory element 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14078 Neighboring gene microRNA 5684

    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 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. Emery-Dreifuss muscular dystrophy mutations impair TRC40-mediated targeting of emerin to the inner nuclear membrane. Pfaff J, et al. J Cell Sci, 2016 Feb 1. PMID 26675233
    2. Increased sensitivity to platinating agents and arsenite in human ovarian cancer by downregulation of ASNA1. Hemmingsson O, et al. Oncol Rep, 2009 Oct. PMID 19724867
    3. A trap mutant reveals the physiological client spectrum of TRC40. Coy-Vergara J, et al. J Cell Sci, 2019 Jul 1. PMID 31182645, Free PMC Article
    4. Asna1/TRC40-mediated membrane insertion of tail-anchored proteins. Favaloro V, et al. J Cell Sci, 2010 May 1. PMID 20375064
    5. Identification of a targeting factor for posttranslational membrane protein insertion into the ER. Stefanovic S, et al. Cell, 2007 Mar 23. PMID 17382883

    See all (91) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Golgi-resident tail-anchored proteins such as the golgins golgin-84, CASP and giantin as well as the vesicle-associated membrane-protein-associated proteins VAPA and VAPB interact with TRC40.
      Title: A trap mutant reveals the physiological client spectrum of TRC40.
    2. Mutation in ASNA1 cause severe pediatric cardiomyopathy and early death.
      Title: Biallelic Variants in ASNA1, Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy.
    3. The authors conclude that the TRC40 pathway is critical for hearing and propose that otoferlin is an essential substrate of this pathway in hair cells.
      Title: Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing.
    4. Asna1/TRC40 is required at a late step of herpes simplex virus type 1 infection for efficient release of mature virions to the extracellular milieu.
      Title: Asna1/TRC40 that mediates membrane insertion of tail-anchored proteins is required for efficient release of Herpes simplex virus 1 virions.
    5. reveal unanticipated complexity in the mutual regulation of the TRC40 receptor subunits and raise the question as to the role of the excess CAML in the endoplasmic reticulum
      Title: Tail-anchored Protein Insertion in Mammals: FUNCTION AND RECIPROCAL INTERACTIONS OF THE TWO SUBUNITS OF THE TRC40 RECEPTOR.
    6. Emerin interacts with TRC40 in situ.
      Title: Emery-Dreifuss muscular dystrophy mutations impair TRC40-mediated targeting of emerin to the inner nuclear membrane.
    7. The repertoire of VAPB interactors is more diverse than previously anticipated and link VAPB to the function of ATPase complexes such as p97/FAF1 and ASNA1/transmembrane-domain recognition complex.
      Title: VAPB/ALS8 interacts with FFAT-like proteins including the p97 cofactor FAF1 and the ASNA1 ATPase.
    8. Proteins bind to TRC40 and can utilise this component for their delivery to the ER membrane.
      Title: TRC40 can deliver short secretory proteins to the Sec61 translocon.
    9. PEX19 formed a complex with the peroxisomal tail anchored protein PEX26 in the cytosol and translocated it directly to peroxisomes by a TRC40-independent class I pathway.
      Title: Tail-anchored PEX26 targets peroxisomes via a PEX19-dependent and TRC40-independent class I pathway.
    10. Results indicate calcium-modulating cyclophilin ligand (CAML) and WRB as components of the TRC40 receptor complex and a crucial mechanism for driving ER membrane insertion of TA proteins in mammalian cells.
      Title: Molecular machinery for insertion of tail-anchored membrane proteins into the endoplasmic reticulum membrane in mammalian cells.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    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

    Associated conditions

    Description Tests
    Cardiomyopathy, dilated, 2H
    MedGen: C5774296 OMIM: 620203 GeneReviews: Not available
    		not available

    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 Expression of HIV-1 Tat upregulates the abundance of arsA arsenite transporter, ATP-binding, homolog 1 (ASNA1) in the nucleoli of Jurkat T-cells 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

    Clone Names

    • MGC3821

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP hydrolysis activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables arsenite transmembrane transporter activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables membrane insertase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in arsenite transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein insertion into ER membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in tail-anchored membrane protein insertion into ER membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in tail-anchored membrane protein insertion into ER membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tail-anchored membrane protein insertion into ER membrane IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of GET complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of GET complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of GET complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    located_in cytoplasm TAS
    Traceable Author Statement
    more info
    		 PubMed 
    is_active_in endoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular exosome HDA PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    ATPase GET3
    Names
    arsA arsenite transporter, ATP-binding, homolog 1
    golgi to ER traffic 3 homolog
    transmembrane domain recognition complex 40 kDa ATPase subunit
    NP_001358417.1
    NP_001358418.1
    NP_004308.2

    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.

    Genomic

    1. NG_051267.1 RefSeqGene

      Range
      5039..15865
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001371488.1 → NP_001358417.1  ATPase GET3

      Status: REVIEWED

      Description
      Transcript Variant: Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AC018761
      Consensus CDS
      CCDS32920.1
      UniProtKB/Swiss-Prot
      A6NHP8, A8K740, O43681, Q53FC6, Q92849
      UniProtKB/TrEMBL
      B4DEE5
      Conserved Domains (1) summary
      pfam02374
      Location:37 → 340
      ArsA_ATPase; Anion-transporting ATPase

    2. NM_001371489.1 → NP_001358418.1  ATPase GET3

      Status: REVIEWED

      Description
      Transcript Variant: Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AC018761
      Consensus CDS
      CCDS32920.1
      UniProtKB/Swiss-Prot
      A6NHP8, A8K740, O43681, Q53FC6, Q92849
      UniProtKB/TrEMBL
      B4DEE5
      Related
      ENSP00000466379.1, ENST00000591090.5
      Conserved Domains (1) summary
      pfam02374
      Location:37 → 340
      ArsA_ATPase; Anion-transporting ATPase

    3. NM_004317.4 → NP_004308.2  ATPase GET3

      See identical proteins and their annotated locations for NP_004308.2

      Status: REVIEWED

      Description
      Transcript Variant: Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      BC002651, BM718941
      Consensus CDS
      CCDS32920.1
      UniProtKB/Swiss-Prot
      A6NHP8, A8K740, O43681, Q53FC6, Q92849
      UniProtKB/TrEMBL
      B4DEE5
      Related
      ENSP00000349887.3, ENST00000357332.8
      Conserved Domains (1) summary
      pfam02374
      Location:37 → 340
      ArsA_ATPase; Anion-transporting ATPase

    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_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      12737106..12748323
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      12861599..12872815
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43681.2 GenPept UniProtKB/Swiss-Prot:O43681

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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