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    GCA grancalcin [ Homo sapiens (human) ]

    Gene ID: 25801, updated on 9-Dec-2024

    Summary

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    Official Symbol
    GCAprovided by HGNC
    Official Full Name
    grancalcinprovided by HGNC
    Primary source
    HGNC:HGNC:15990
    See related
    Ensembl:ENSG00000115271 MIM:607030; AllianceGenome:HGNC:15990
    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
    GCL
    Summary
    This gene encodes a calcium-binding protein that is abundant in neutrophils and macrophages. In the absence of divalent cation, this protein localizes to the cytosolic fraction; with magnesium alone, it partitions with the granule fraction; and in the presence of magnesium and calcium, it associates with both the granule and membrane fractions. Alternative splicing and use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Aug 2016]
    Expression
    Broad expression in bone marrow (RPKM 47.3), appendix (RPKM 18.4) and 18 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GCA in Genome Data Viewer
    Location:
    2q24.2
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (162318763..162375396)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (162775430..162833885)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (163175273..163219633)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373724 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_55125 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12062 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:163175227-163176426 Neighboring gene interferon induced with helicase C domain 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16718 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12063 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12064 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_55234 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_55244 Neighboring gene potassium voltage-gated channel subfamily H member 7 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16719 Neighboring gene uncharacterized LOC124906084 Neighboring gene RNA, 5S ribosomal pseudogene 109 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_55297 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:163568111-163568632 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16720 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16721 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16722 Neighboring gene Sharpr-MPRA regulatory region 9339 Neighboring gene KCNH7 antisense RNA 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. Isolation and characterization of grancalcin, a novel 28 kDa EF-hand calcium-binding protein from human neutrophils. Teahan CG, et al. Biochem J, 1992 Sep 1. PMID 1530588, Free PMC Article
    2. Molecular cloning and characterization of grancalcin, a novel EF-hand calcium-binding protein abundant in neutrophils and monocytes. Boyhan A, et al. J Biol Chem, 1992 Feb 15. PMID 1737748
    3. A growing family of the Ca2+-binding proteins with five EF-hand motifs. Maki M, et al. Biochem J, 1997 Dec 1. PMID 9441591, Free PMC Article
    4. Crystal structure of human grancalcin, a member of the penta-EF-hand protein family. Jia J, et al. J Mol Biol, 2000 Jul 28. PMID 10903868
    5. Biochemical characterization of the penta-EF-hand protein grancalcin and identification of L-plastin as a binding partner. Lollike K, et al. J Biol Chem, 2001 May 25. PMID 11279160

    See all (41) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. GCA activates TRAF6 ubiquitin ligase activity to induce Lys63 ubiquitination of ULK1, a crucial regulator of autophagy, resulting in its stabilization and activation. It was also highlighted the role of GCA-TRAF6-ULK1 autophagy regulatory axis in imatinib resistance.
      Title: GCA links TRAF6-ULK1-dependent autophagy activation in resistant chronic myeloid leukemia.
    2. Results indicate that heterodimerization of GCA and TLR9 is important for TLR9-mediated downstream signaling and might serve to fine tune processes against viral infection.
      Title: Grancalcin (GCA) modulates Toll-like receptor 9 (TLR9) mediated signaling through its direct interaction with TLR9.
    3. IFIH1-GCA-KCNH7 locus is not associated with genetic susceptibility to multiple sclerosis in French patients
      Title: IFIH1-GCA-KCNH7 locus is not associated with genetic susceptibility to multiple sclerosis in French patients.
    4. IFIH1 interferon induced helicase, GCA grancalcin or the potassium channel KCNH7 - are potential candidates implicated in the pathogenesis of multiple sclerosis.
      Title: IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis risk.
    5. The reported type 1 diabetes association is from a linkage disequilibrium region including three candidate genes, FAP, IFIH1 and GCA.
      Title: The association between the IFIH1 locus and type 1 diabetes.
    6. Observational study of gene-disease association. (HuGE Navigator)
      Title: Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
    7. GCA interacts with SRI in vivo and in vitro.
      Title: The PEF family proteins sorcin and grancalcin interact in vivo and in vitro.
    Submit: New GeneRIF Correction

    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)

    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 calcium ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables calcium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein heterodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in membrane fusion TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in azurophil granule lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in cytoplasm TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    grancalcin
    Names
    grancalcin, EF-hand calcium-binding protein
    grancalcin, penta-EF-hand protein

    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_001330265.1 → NP_001317194.1  grancalcin isoform a

      Status: REVIEWED

      Source sequence(s)
      AC010876
      UniProtKB/TrEMBL
      B7Z322
      Conserved Domains (2) summary
      pfam13499
      Location:140 → 195
      EF-hand_7; EF-hand domain pair
      cl08302
      Location:79 → 134
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

    2. NM_001330266.1 → NP_001317195.1  grancalcin isoform a

      Status: REVIEWED

      Source sequence(s)
      AC010876
      UniProtKB/TrEMBL
      B7Z322
      Conserved Domains (2) summary
      pfam13499
      Location:140 → 195
      EF-hand_7; EF-hand domain pair
      cl08302
      Location:79 → 134
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

    3. NM_001330267.1 → NP_001317196.1  grancalcin isoform a

      Status: REVIEWED

      Source sequence(s)
      AC010876
      UniProtKB/TrEMBL
      B7Z322
      Conserved Domains (2) summary
      pfam13499
      Location:140 → 195
      EF-hand_7; EF-hand domain pair
      cl08302
      Location:79 → 134
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

    4. NM_001330268.1 → NP_001317197.1  grancalcin isoform c

      Status: REVIEWED

      Source sequence(s)
      AC010876
      UniProtKB/TrEMBL
      B7Z322
      Conserved Domains (2) summary
      pfam13499
      Location:151 → 206
      EF-hand_7; EF-hand domain pair
      cl08302
      Location:90 → 145
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

    5. NM_001330270.2 → NP_001317199.1  grancalcin isoform d

      Status: REVIEWED

      Source sequence(s)
      AC010876
      Consensus CDS
      CCDS82527.1
      UniProtKB/TrEMBL
      B7Z322, H7BXD5
      Conserved Domains (2) summary
      pfam13499
      Location:106 → 161
      EF-hand_7; EF-hand domain pair
      cl08302
      Location:45 → 100
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

    6. NM_001330271.2 → NP_001317200.1  grancalcin isoform d

      Status: REVIEWED

      Source sequence(s)
      AC010876, AK295413, BI760070
      Consensus CDS
      CCDS82527.1
      UniProtKB/TrEMBL
      B7Z322, H7BXD5
      Related
      ENSP00000233612.4, ENST00000233612.8
      Conserved Domains (2) summary
      pfam13499
      Location:106 → 161
      EF-hand_7; EF-hand domain pair
      cl08302
      Location:45 → 100
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

    7. NM_012198.5 → NP_036330.1  grancalcin isoform b

      See identical proteins and their annotated locations for NP_036330.1

      Status: REVIEWED

      Source sequence(s)
      AC010876, BC005214, M81637
      Consensus CDS
      CCDS2218.1
      UniProtKB/Swiss-Prot
      B2R5X3, P28676, Q53TB5, Q59EP3
      UniProtKB/TrEMBL
      B7Z322
      Related
      ENSP00000394842.2, ENST00000437150.7
      Conserved Domains (1) summary
      cd16186
      Location:53 → 217
      EFh_PEF_grancalcin; Penta-EF hand, calcium binding motifs, found in grancalcin

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      162318763..162375396
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006712398.5 → XP_006712461.1  grancalcin isoform X1

      Conserved Domains (2) summary
      pfam13499
      Location:151 → 206
      EF-hand_7; EF-hand domain pair
      cl08302
      Location:90 → 145
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

    2. XM_006712400.5 → XP_006712463.1  grancalcin isoform X2

      Conserved Domains (2) summary
      cd15897
      Location:68 → 96
      EFh_PEF; EF-hand motif [structural motif]
      cl25352
      Location:68 → 224
      EFh_PEF; The penta-EF hand (PEF) family

    3. XM_047443881.1 → XP_047299837.1  grancalcin isoform X2

    4. XM_047443882.1 → XP_047299838.1  grancalcin isoform X2

    5. XM_005246446.4 → XP_005246503.1  grancalcin isoform X3

      UniProtKB/TrEMBL
      B7Z322
      Conserved Domains (2) summary
      pfam13499
      Location:125 → 180
      EF-hand_7; EF-hand domain pair
      cl08302
      Location:64 → 119
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

    6. XM_017003767.2 → XP_016859256.1  grancalcin isoform X4

      UniProtKB/TrEMBL
      B7Z322
      Conserved Domains (2) summary
      pfam13499
      Location:106 → 161
      EF-hand_7; EF-hand domain pair
      cl08302
      Location:45 → 100
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

    7. XM_011510926.3 → XP_011509228.1  grancalcin isoform X4

      UniProtKB/TrEMBL
      B7Z322
      Conserved Domains (2) summary
      pfam13499
      Location:106 → 161
      EF-hand_7; EF-hand domain pair
      cl08302
      Location:45 → 100
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

    8. XM_011510928.3 → XP_011509230.1  grancalcin isoform X5

      UniProtKB/TrEMBL
      H7C2Z6
      Related
      ENSP00000408620.1, ENST00000414723.1
      Conserved Domains (1) summary
      cl08302
      Location:1 → 52
      EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      162775430..162833885
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054341305.1 → XP_054197280.1  grancalcin isoform X1

    2. XM_054341306.1 → XP_054197281.1  grancalcin isoform X2

    3. XM_054341307.1 → XP_054197282.1  grancalcin isoform X2

    4. XM_054341308.1 → XP_054197283.1  grancalcin isoform X2

    5. XM_054341309.1 → XP_054197284.1  grancalcin isoform X3

      UniProtKB/TrEMBL
      B7Z322

    6. XM_054341310.1 → XP_054197285.1  grancalcin isoform X4

      UniProtKB/TrEMBL
      B7Z322

    7. XM_054341311.1 → XP_054197286.1  grancalcin isoform X4

      UniProtKB/TrEMBL
      B7Z322

    8. XM_054341312.1 → XP_054197287.1  grancalcin isoform X5

      UniProtKB/TrEMBL
      H7C2Z6
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P28676.2 GenPept UniProtKB/Swiss-Prot:P28676

    Gene LinkOut

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