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    GGA2 golgi associated, gamma adaptin ear containing, ARF binding protein 2 [ Homo sapiens (human) ]

    Gene ID: 23062, updated on 2-Nov-2024

    Summary

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    Official Symbol
    GGA2provided by HGNC
    Official Full Name
    golgi associated, gamma adaptin ear containing, ARF binding protein 2provided by HGNC
    Primary source
    HGNC:HGNC:16064
    See related
    Ensembl:ENSG00000103365 MIM:606005; AllianceGenome:HGNC:16064
    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
    VEAR
    Summary
    This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous coat proteins that regulate the trafficking of proteins between the trans-Golgi network and the lysosome. These proteins share an amino-terminal VHS domain which mediates sorting of the mannose 6-phosphate receptors at the trans-Golgi network. They also contain a carboxy-terminal region with homology to the ear domain of gamma-adaptins. This family member may play a significant role in cargo molecules regulation and clathrin-coated vesicle assembly. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in lymph node (RPKM 28.0), thyroid (RPKM 15.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GGA2 in Genome Data Viewer
    Location:
    16p12.2
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (23463542..23524359, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (23739620..23800145, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (23474863..23521815, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene component of oligomeric golgi complex 7 Neighboring gene RN7SK pseudogene 23 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:23435589-23436134 Neighboring gene uncharacterized LOC124903667 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10580 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10581 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:23511811-23512473 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:23515779-23516280 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:23516281-23516780 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7277 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7276 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7278 Neighboring gene cyclin Y like 7 (pseudogene) Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10582 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:23549327-23549828 Neighboring gene glutamyl-tRNA synthetase 2, mitochondrial Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:23549829-23550328 Neighboring gene SUB1 pseudogene 4 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:23567356-23568000 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10583 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:23568645-23569289 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:23569290-23569933 Neighboring gene ubiquitin family 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 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. Vear, a novel Golgi-associated protein with VHS and gamma-adaptin "ear" domains. Poussu A, et al. J Biol Chem, 2000 Mar 10. PMID 10702286
    2. The role of cargo proteins in GGA recruitment. Hirst J, et al. Traffic, 2007 May. PMID 17451558, Free PMC Article
    3. Crystal structure of GGA2 VHS domain and its implication in plasticity in the ligand binding pocket. Zhu G, et al. FEBS Lett, 2003 Feb 27. PMID 12606052
    4. Specific depletion of GGA2 causes cathepsin D missorting in HeLa cells. Hida T, et al. Arch Histol Cytol, 2007 Dec. PMID 18431031
    5. Integrative Genomic Analyses Identifies GGA2 as a Cooperative Driver of EGFR-Mediated Lung Tumorigenesis. O'Farrell H, et al. J Thorac Oncol, 2019 Apr. PMID 30578931, Free PMC Article

    See all (94) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Inactivation of the three GGA genes in HeLa cells partially compromises lysosomal enzyme sorting.
      Title: Inactivation of the three GGA genes in HeLa cells partially compromises lysosomal enzyme sorting.
    2. GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic.
      Title: GGA2 and RAB13 promote activity-dependent β1-integrin recycling.
    3. Data suggest that overexpression of GGA2 in LUAD tumors results in the accumulation of EGFR protein and increased EGFR signaling, which helps drive tumor progression.
      Title: Integrative Genomic Analyses Identifies GGA2 as a Cooperative Driver of EGFR-Mediated Lung Tumorigenesis.
    4. Study shows that reduced expression of GGA3 resultes in accumulation of endocytosed EGFR within enlarged endosomes. GGA2 interacts with EGFR cytoplasmic domain to stabilize the receptor expression and promote cell growth. Finally, GGA2 was upregulated in 30.8% of human hepatocellular carcinomas and 23.3% of colorectal cancers.
      Title: GGA2 interacts with EGFR cytoplasmic domain to stabilize the receptor expression and promote cell growth.
    5. PI4KIIIbeta interaction with the VHS domain of GGA2 affected PI4KIIIbeta localization.
      Title: Conserved role for Gga proteins in phosphatidylinositol 4-kinase localization to the trans-Golgi network.
    6. full length alpha2B-AR associated with GGA2 but not GGA1, its third intracellular loop was found to directly interact with both GGA1 and GGA2. More interestingly, further mapping of interaction domains showed that the GGA1 hinge region and the GGA2 GAE domain bound to multiple subdomains of the loop.
      Title: Regulation of α(2B)-Adrenergic Receptor Cell Surface Transport by GGA1 and GGA2.
    7. These data indicate that clathrin is required for the function of AP-1- and GGA-coated carriers at the trans-Golgi network but may be dispensable for outward traffic en route to the plasma membrane.
      Title: Clathrin terminal domain-ligand interactions regulate sorting of mannose 6-phosphate receptors mediated by AP-1 and GGA adaptors.
    8. GGA2 mediates a vital function that cannot be compensated for by GGA1and/or GGA3.
      Title: Analysis of Gga null mice demonstrates a non-redundant role for mammalian GGA2 during development.
    9. GGA overexpression causes various sorting defects as measured by recycling of CD-MPR, internalization of transferrin receptor, and the subcellular localization of proteins like Tsg101, ubiquitin, and Hrs.
      Title: Defects in cellular sorting and retroviral assembly induced by GGA overexpression.
    10. GGA2 is recruited to the trans-Golgi network independently of the other Golgi-localized, gamma-ear-containing, ARF-binding proteins and is required for the efficient sorting of lysosomal enzymes
      Title: Specific depletion of GGA2 causes cathepsin D missorting in HeLa cells.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    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 Variation Viewer (GRCh37.p13)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef Genome-wide shRNA screening identifies GGA2, which is required for HIV-1 Nef-induced downregulation of CD4 in HeLa CD4+ cells PubMed
    Pr55(Gag) gag siRNA-mediated depletion of GGA2 leads to a significant increase in particle release in an HIV-1 Gag late domain-dependent manner, while GGA2 overexpression severely reduces virus particle production by impairing Gag trafficking to the membrane PubMed
    Vpr vpr Expression of a patient-derived HIV-1 Vpr protein reveals a significant reduction in Vpr nuclear import. Vpr F72L mutation is responsible for this decreased Vpr nuclear import and the F72L mutant is co-localized with gamma-adaptin in the Golgi apparatus PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ20966, KIAA1080

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables phosphatidylinositol binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables small GTPase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables small GTPase binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in Golgi to plasma membrane protein transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in Golgi to plasma membrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intracellular protein transport NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in protein localization to cell surface IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein localization to cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in clathrin-coated vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in early endosome membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in endosome membrane TAS
    Traceable Author Statement
    more info
    		  
    is_active_in trans-Golgi network IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in trans-Golgi network IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    ADP-ribosylation factor-binding protein GGA2
    Names
    VHS domain and ear domain of gamma-adaptin
    VHS domain and ear domain-containing protein
    gamma-adaptin-related protein 2
    golgi-localized, gamma ear-containing, ARF-binding protein 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.

    mRNA and Protein(s)

    1. NM_015044.4 → NP_055859.1  ADP-ribosylation factor-binding protein GGA2

      See identical proteins and their annotated locations for NP_055859.1

      Status: REVIEWED

      Source sequence(s)
      AC008915, AF165531, DA439738
      Consensus CDS
      CCDS10611.1
      UniProtKB/Swiss-Prot
      D3DWF0, O14564, Q9NYN2, Q9UJY4, Q9UPS2
      Related
      ENSP00000311962.4, ENST00000309859.8
      Conserved Domains (4) summary
      smart00809
      Location:491 → 605
      Alpha_adaptinC2; Adaptin C-terminal domain
      cd03567
      Location:25 → 163
      VHS_GGA; VHS domain family, GGA subfamily; GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) comprise a subfamily of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins. The VHS domain has a superhelical structure similar to ...
      cd14239
      Location:227 → 315
      GAT_GGA1_GGA2; GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2
      cl21478
      Location:168 → 240
      ATP-synt_B; ATP synthase B/B' CF(0)

    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_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      23463542..23524359 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047433801.1 → XP_047289757.1  ADP-ribosylation factor-binding protein GGA2 isoform X1

    2. XM_047433802.1 → XP_047289758.1  ADP-ribosylation factor-binding protein GGA2 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      23739620..23800145 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054379851.1 → XP_054235826.1  ADP-ribosylation factor-binding protein GGA2 isoform X1

    2. XM_054379852.1 → XP_054235827.1  ADP-ribosylation factor-binding protein GGA2 isoform X2

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_138640.1: Suppressed sequence

      Description
      NM_138640.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UJY4.3 GenPept UniProtKB/Swiss-Prot:Q9UJY4

    Gene LinkOut

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

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