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    GCC2 GRIP and coiled-coil domain containing 2 [ Homo sapiens (human) ]

    Gene ID: 9648, updated on 5-May-2024

    Summary

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    Official Symbol
    GCC2provided by HGNC
    Official Full Name
    GRIP and coiled-coil domain containing 2provided by HGNC
    Primary source
    HGNC:HGNC:23218
    See related
    Ensembl:ENSG00000135968 MIM:612711; AllianceGenome:HGNC:23218
    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
    REN53; GCC185; RANBP2L4
    Summary
    The protein encoded by this gene is a peripheral membrane protein localized to the trans-Golgi network. It is sensitive to brefeldin A. This encoded protein contains a GRIP domain which is thought to be used in targeting. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]
    Expression
    Ubiquitous expression in gall bladder (RPKM 11.9), thyroid (RPKM 11.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    2q12.3
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (108449206..108509415)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (108909826..108970093)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (109065662..109125871)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene sulfotransferase family 1C member 4 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:109019914-109020414 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:109020415-109020915 Neighboring gene small integral membrane protein 12 pseudogene 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr2:109064602-109065584 and GRCh37_chr2:109065585-109066566 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:109066652-109067152 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:109067153-109067653 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16343 Neighboring gene 2q12.3 distal recombination region Neighboring gene GCC2 antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 7983 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11849 Neighboring gene LIM zinc finger domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16344 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:109191556-109192512 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16345 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:109210352-109211551 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16346 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16347 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16348 Neighboring gene NANOG hESC enhancer GRCh37_chr2:109225689-109226190 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16349 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:109252737-109253311 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16350 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:109271409-109272023 Neighboring gene Sharpr-MPRA regulatory region 6630 Neighboring gene LIMS1 antisense RNA 1 Neighboring gene cytochrome c oxidase subunit 7B, mitochondrial-like

    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. Protein flexibility is required for vesicle tethering at the Golgi. Cheung PY, et al. Elife, 2015 Dec 14. PMID 26653856, Free PMC Article
    2. GCC185 plays independent roles in Golgi structure maintenance and AP-1-mediated vesicle tethering. Brown FC, et al. J Cell Biol, 2011 Sep 5. PMID 21875948, Free PMC Article
    3. Multiple Rab GTPase binding sites in GCC185 suggest a model for vesicle tethering at the trans-Golgi. Hayes GL, et al. Mol Biol Cell, 2009 Jan. PMID 18946081, Free PMC Article
    4. Mammalian GRIP domain proteins differ in their membrane binding properties and are recruited to distinct domains of the TGN. Derby MC, et al. J Cell Sci, 2004 Nov 15. PMID 15522892
    5. Golgi-endosome transport mediated by M6PR facilitates release of antisense oligonucleotides from endosomes. Liang XH, et al. Nucleic Acids Res, 2020 Feb 20. PMID 31840180, Free PMC Article

    See all (66) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The co-localization of M6PR and of GCC2 with ASOs is influenced by the PS modifications, which have been shown to enhance the affinity of ASOs for proteins, suggesting that localization of these proteins to LEs is mediated by ASO-protein interactions. Reduction of M6PR levels also decreased PS-ASO activity in mouse cells and in livers of mice treated subcutaneously with PS-ASO, indicating a conserved mechanism.
      Title: Golgi-endosome transport mediated by M6PR facilitates release of antisense oligonucleotides from endosomes.
    2. In light of existing report suggesting critical role of Nef-GCC185 interaction reveals valuable mechanistic insights affecting specific protein transport pathway in docking of late endosome derived Rab9 bearing transport vesicle at TGN elucidating role of Nef during viral pathogenesis.
      Title: HIV-1 Nef binds with human GCC185 protein and regulates mannose 6 phosphate receptor recycling.
    3. These unexpected features support a model in which GCC185 collapses onto the Golgi surface, perhaps by binding to Rab GTPases, to mediate vesicle tethering.
      Title: Protein flexibility is required for vesicle tethering at the Golgi.
    4. Deletion of the ARL4A-interacting region of GCC185 results in inability to maintain Golgi structure and modulate endosome-to-Golgi transport.
      Title: ARL4A acts with GCC185 to modulate Golgi complex organization.
    5. Two distinct domains of GCC185 are needed either for Golgi structure maintenance or transport vesicle tethering. The domain needed for vesicle tethering binds to the clathrin adaptor AP-1.
      Title: GCC185 plays independent roles in Golgi structure maintenance and AP-1-mediated vesicle tethering.
    6. Study demonstrates that Golgi recruitment of endogenous GCC185 does not involve Rab6A/A' and Arl1.
      Title: The localization of the Golgin GCC185 is independent of Rab6A/A' and Arl1.
    7. Results show that GCC185 contains at least six binding sites for as many as 14 different Rab GTPases across its entire length.
      Title: Multiple Rab GTPase binding sites in GCC185 suggest a model for vesicle tethering at the trans-Golgi.
    8. Rab and Arl GTPase family members cooperate in the localization of GCC2.
      Title: Rab and Arl GTPase family members cooperate in the localization of the golgin GCC185.
    9. GCC2 is required for endosome-to-Golgi transport and maintenance of Golgi structure.
      Title: The trans-Golgi network golgin, GCC185, is required for endosome-to-Golgi transport and maintenance of Golgi structure.
    10. The ability of the four mammalian GRIP domain proteins, p230, golgin-97, GCC88, and GCC185 to interact is reported.
      Title: The trans-Golgi network GRIP-domain proteins form alpha-helical homodimers.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    Phenotypes

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    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)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef HIV-1 Nef binds GCC2 (GCC185); the N-terminal EEEE65 acidic domain of Nef as the key region for interaction 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

    • KIAA0336

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables small GTPase binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in Golgi ribbon formation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    NOT involved_in Golgi to plasma membrane protein transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in late endosome to Golgi transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in late endosome to Golgi transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in microtubule anchoring IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in microtubule organizing center organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein localization to Golgi apparatus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein targeting to lysosome IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in recycling endosome to Golgi transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of protein exit from endoplasmic reticulum IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in retrograde transport, endosome to Golgi IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in Golgi apparatus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in membrane HDA PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in trans-Golgi network IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    GRIP and coiled-coil domain-containing protein 2
    Names
    185 kDa Golgi coiled-coil protein
    CLL-associated antigen KW-11
    CTCL tumor antigen se1-1
    GCC protein, 185-kD
    Golgi coiled-coil protein GCC185
    Ran-binding protein 2-like 4
    renal carcinoma antigen NY-REN-53

    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_001410194.1 → NP_001397123.1  GRIP and coiled-coil domain-containing protein 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC012487, AC068941
      UniProtKB/TrEMBL
      A0A8I5QJB7
      Related
      ENSP00000508981.1, ENST00000685519.1

    2. NM_181453.4 → NP_852118.2  GRIP and coiled-coil domain-containing protein 2 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the functional protein.
      Source sequence(s)
      AC012487, AC068941
      Consensus CDS
      CCDS33268.1
      UniProtKB/Swiss-Prot
      A6H8X8, O15045, Q4ZG46, Q8IWJ2, Q8TDH3, Q9H2G8
      UniProtKB/TrEMBL
      A0A8I5KW38
      Related
      ENSP00000307939.5, ENST00000309863.11
      Conserved Domains (4) summary
      COG1196
      Location:41 → 953
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      TIGR02168
      Location:700 → 1478
      SMC_prok_B; chromosome segregation protein SMC, common bacterial type
      pfam16704
      Location:1548 → 1612
      Rab_bind; Rab binding domain
      pfam01465
      Location:1613 → 1656
      GRIP; GRIP domain

    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

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      108449206..108509415
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006712870.4 → XP_006712933.1  GRIP and coiled-coil domain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      A0A8I5KW38
      Conserved Domains (4) summary
      COG1196
      Location:44 → 956
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      TIGR02168
      Location:703 → 1481
      SMC_prok_B; chromosome segregation protein SMC, common bacterial type
      pfam01465
      Location:1617 → 1659
      GRIP; GRIP domain
      pfam16704
      Location:1551 → 1615
      Rab_bind; Rab binding domain

    2. XM_006712871.2 → XP_006712934.1  GRIP and coiled-coil domain-containing protein 2 isoform X2

      See identical proteins and their annotated locations for XP_006712934.1

      UniProtKB/TrEMBL
      A0A8I5KW38, A0A8I5QJB7
      Conserved Domains (4) summary
      COG1196
      Location:17 → 852
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      TIGR02168
      Location:599 → 1377
      SMC_prok_B; chromosome segregation protein SMC, common bacterial type
      pfam01465
      Location:1513 → 1555
      GRIP; GRIP domain
      pfam16704
      Location:1447 → 1511
      Rab_bind; Rab binding domain

    3. XM_047446447.1 → XP_047302403.1  GRIP and coiled-coil domain-containing protein 2 isoform X3

    4. XM_047446448.1 → XP_047302404.1  GRIP and coiled-coil domain-containing protein 2 isoform X4

    5. XM_006712872.4 → XP_006712935.1  GRIP and coiled-coil domain-containing protein 2 isoform X5

      UniProtKB/TrEMBL
      B8ZZW2
      Conserved Domains (1) summary
      COG1196
      Location:44 → 956
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]

    6. XM_047446449.1 → XP_047302405.1  GRIP and coiled-coil domain-containing protein 2 isoform X6

      Related
      ENSP00000386997.1, ENST00000409896.1

    RNA

    1. XR_923067.3 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      108909826..108970093
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054344670.1 → XP_054200645.1  GRIP and coiled-coil domain-containing protein 2 isoform X1

    2. XM_054344671.1 → XP_054200646.1  GRIP and coiled-coil domain-containing protein 2 isoform X3

    3. XM_054344672.1 → XP_054200647.1  GRIP and coiled-coil domain-containing protein 2 isoform X4

    4. XM_054344673.1 → XP_054200648.1  GRIP and coiled-coil domain-containing protein 2 isoform X5

    5. XM_054344674.1 → XP_054200649.1  GRIP and coiled-coil domain-containing protein 2 isoform X6

    RNA

    1. XR_008486606.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8IWJ2.4 GenPept UniProtKB/Swiss-Prot:Q8IWJ2

    Gene LinkOut

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

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