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    VPS26A VPS26 retromer complex component A [ Homo sapiens (human) ]

    Gene ID: 9559, updated on 27-Nov-2024

    Summary

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    Official Symbol
    VPS26Aprovided by HGNC
    Official Full Name
    VPS26 retromer complex component Aprovided by HGNC
    Primary source
    HGNC:HGNC:12711
    See related
    Ensembl:ENSG00000122958 MIM:605506; AllianceGenome:HGNC:12711
    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
    HB58; PEP8A; VPS26; Hbeta58
    Summary
    This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis (RPKM 20.4), esophagus (RPKM 15.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See VPS26A in Genome Data Viewer
    Location:
    10q22.1
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (69124178..69174412)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (69991871..70042751)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (70883934..70934168)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105378342 Neighboring gene Sharpr-MPRA regulatory region 5024 Neighboring gene MPRA-validated peak1005 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3475 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3476 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3477 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:70812477-70812978 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:70812979-70813478 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3478 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2426 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3480 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3479 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3481 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3482 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3483 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3484 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16959 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:70828777-70829328 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16968 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:70847990-70849189 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2427 Neighboring gene serglycin Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3485 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2428 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:70884392-70884898 Neighboring gene ribosomal protein S12 pseudogene 17 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3486 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:70949649-70949852 Neighboring gene Suv3 like RNA helicase Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2429 Neighboring gene uncharacterized LOC101928994 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16991 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16994 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_16995 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3487 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3488 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:70991590-70992789 Neighboring gene hexokinase domain containing 1

    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. Mutations in VPS26A are not a frequent cause of Parkinson's disease. Koschmidder E, et al. Neurobiol Aging, 2014 Jun. PMID 24417787
    2. The Prognostic Value and the Oncogenic and Immunological Roles of Vacuolar Protein Sorting Associated Protein 26 A in Pancreatic Adenocarcinoma. Hou J, et al. Int J Mol Sci, 2023 Feb 9. PMID 36834898, Free PMC Article
    3. Image-based and biochemical assays to investigate endosomal protein sorting. Breusegem SY, et al. Methods Enzymol, 2014. PMID 24359953
    4. Model-guided microarray implicates the retromer complex in Alzheimer's disease. Small SA, et al. Ann Neurol, 2005 Dec. PMID 16315276
    5. The miRNA profile of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis. van de Bunt M, et al. PLoS One, 2013. PMID 23372846, Free PMC Article

    See all (130) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The Prognostic Value and the Oncogenic and Immunological Roles of Vacuolar Protein Sorting Associated Protein 26 A in Pancreatic Adenocarcinoma.
      Title: The Prognostic Value and the Oncogenic and Immunological Roles of Vacuolar Protein Sorting Associated Protein 26 A in Pancreatic Adenocarcinoma.
    2. Novel crosstalk between Vps26a and Nox4 signaling during neurogenesis.
      Title: Novel crosstalk between Vps26a and Nox4 signaling during neurogenesis.
    3. We investigated the modification of air pollution and diabetes association by a genetic risk score covering 63 T2D genes. Five single variants near GRB14, UBE2E2, PTPRD, VPS26A and KCNQ1 showed nominally significant interactions with PM10 (P<0.05). Our results suggest that genetic risk for T2D may modify susceptibility to air pollution through alterations in insulin sensitivity.
      Title: Air pollution and diabetes association: Modification by type 2 diabetes genetic risk score.
    4. The retromer complex is a highly conserved membrane trafficking assembly composed of three proteins - Vps26, Vps29 and Vps35, which are impaired in neurodegenerative diseases. (Review)
      Title: Retromer's Role in Endosomal Trafficking and Impaired Function in Neurodegenerative Diseases.
    5. X-ray crystallographic analysis of a 4-component complex comprising the VPS26 & VPS35 subunits of retromer, sorting nexin SNX3, & recycling signal from the divalent cation transporter DMT1-II; analysis identifies a binding site for canonical recycling signals at the interface between VPS26 & SNX3; shows cooperative interactions among the VPS subunits, SNX3 & cargo that couple signal-recognition to membrane recruitment.
      Title: Structural Mechanism for Cargo Recognition by the Retromer Complex.
    6. Mutagenesis studies coupled with coimmunoprecipitations revealed that retromer-mediated trafficking requires the Env cytoplasmic tail that we show binds directly to retromer components Vps35 and Vps26.
      Title: Retromer regulates HIV-1 envelope glycoprotein trafficking and incorporation into virions.
    7. provides molecular insights into the essential role of Vps26 and Vps35 in Rab7-mediated recruitment of the core retromer complex
      Title: Molecular insights into Rab7-mediated endosomal recruitment of core retromer: deciphering the role of Vps26 and Vps35.
    8. This study demonstrated that Genetic variability of VPS26A in parkinsonism.
      Title: Genetic variability of the retromer cargo recognition complex in parkinsonism.
    9. Mutations in the gene composing the retromer cargo recognition subunit are not a common cause of Parkinson's disease.
      Title: Genetic variation of the retromer subunits VPS26A/B-VPS29 in Parkinson's disease.
    10. Mutations in VPS26A are not a frequent cause of Parkinson's disease.
      Title: Mutations in VPS26A are not a frequent cause of Parkinson's disease.
    Submit: New GeneRIF Correction See all GeneRIFs (16)

    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

    EBI GWAS Catalog

    Description
    Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
    EBI GWAS Catalog
    Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.
    EBI GWAS Catalog
    Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.
    EBI GWAS Catalog

    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
    Envelope surface glycoprotein gp120 env Depletion of VPS26 by siRNA increases plasma membrane expression of HIV-1 gp120/gp41 and incorporation into viral particles, indicating that VPS26 regulates gp120/gp41 trafficking in cells PubMed
    Envelope transmembrane glycoprotein gp41 env The gp41 cytoplasmic tail binds directly to retromer components VPS26 and VPS35 in HIV-1-infected cells PubMed
    env Depletion of VPS26 by siRNA increases plasma membrane expression of HIV-1 gp120/gp41 and incorporation into viral particles, indicating that VPS26 regulates gp120/gp41 trafficking in cells PubMed
    env The gp41 cytoplasmic tail determines sensitivity to VPS26 depletion in HIV-1-infected cells, and the cytoplasmic tail alone is sufficient for trafficking of Env through the retromer-containing compartment 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

    • FLJ12930

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in endocytic recycling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in intracellular protein transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of macroautophagy TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in retrograde transport, endosome to Golgi IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in retrograde transport, endosome to Golgi IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in retrograde transport, endosome to Golgi NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in early endosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in endosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endosome membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosome IDA
    Inferred from Direct Assay
    more info
    		  
    part_of retromer complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of retromer complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of retromer complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    part_of retromer, cargo-selective complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of retromer, cargo-selective complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in tubular endosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    vacuolar protein sorting-associated protein 26A
    Names
    VPS26 retromer complex comonent A
    vacuolar protein sorting 26 homolog A
    vesicle protein sorting 26A

    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_001035260.3 → NP_001030337.1  vacuolar protein sorting-associated protein 26A isoform 2

      See identical proteins and their annotated locations for NP_001030337.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an exon in the 3' coding region which results in a frameshift and early translation termination, compared to variant 1. The encoded isoform (2) has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AF054179, AL596223, BQ068008, BX647725, DA498726
      Consensus CDS
      CCDS41536.1
      UniProtKB/TrEMBL
      S4R3Q6
      Related
      ENSP00000378532.1, ENST00000395098.5
      Conserved Domains (1) summary
      pfam03643
      Location:8 → 243
      Vps26; Vacuolar protein sorting-associated protein 26

    2. NM_001318944.2 → NP_001305873.1  vacuolar protein sorting-associated protein 26A isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) includes an additional exon in the 5' region, and it thus differs in its 5' UTR and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) has a shorter and distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AK309021, AL596223, BX647725, DA498726
      UniProtKB/TrEMBL
      B4DLT1
      Conserved Domains (1) summary
      pfam03643
      Location:45 → 276
      Vps26; Vacuolar protein sorting-associated protein 26

    3. NM_001318945.2 → NP_001305874.1  vacuolar protein sorting-associated protein 26A isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) includes an additional exon in the 5' region, and it thus differs in its 5' UTR and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (4) has a shorter and distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AK297142, AL596223, BX647725, DA498726
      UniProtKB/TrEMBL
      B4DLT1
      Conserved Domains (1) summary
      pfam03643
      Location:34 → 266
      Vps26; Vacuolar protein sorting-associated protein 26

    4. NM_001318946.2 → NP_001305875.1  vacuolar protein sorting-associated protein 26A isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks an alternate exon in the 5' region, and it thus differs in its 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (5) is shorter at the N-terminus, compared to isoform 1.
      Source sequence(s)
      AF054179, AL596223, BX647725, DA498726
      UniProtKB/TrEMBL
      A8K3C1
      Conserved Domains (1) summary
      pfam03643
      Location:2 → 172
      Vps26; Vacuolar protein sorting-associated protein 26

    5. NM_004896.5 → NP_004887.2  vacuolar protein sorting-associated protein 26A isoform 1

      See identical proteins and their annotated locations for NP_004887.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AF054179, AL596223, BX647725, DA498726
      Consensus CDS
      CCDS7286.1
      UniProtKB/Swiss-Prot
      A8MZ56, B2RDD3, O75436, Q8TBH4, Q9H982
      UniProtKB/TrEMBL
      B4DLT1
      Related
      ENSP00000263559.6, ENST00000263559.11
      Conserved Domains (1) summary
      pfam03643
      Location:8 → 283
      Vps26; Vacuolar protein sorting-associated protein 26

    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_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      69124178..69174412
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      69991871..70042751
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054367220.1 → XP_054223195.1  vacuolar protein sorting-associated protein 26A isoform X1

      UniProtKB/Swiss-Prot
      A8MZ56, B2RDD3, O75436, Q8TBH4, Q9H982
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O75436.2 GenPept UniProtKB/Swiss-Prot:O75436

    Gene LinkOut

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