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GCA grancalcin [ Homo sapiens (human) ]

Gene ID: 25801, updated on 3-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (162318763..162375396)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (162775430..162833885)
105.20220307 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. 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
  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. 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
  4. GCA links TRAF6-ULK1-dependent autophagy activation in resistant chronic myeloid leukemia. Han SH, et al. Autophagy, 2019 Dec. PMID 30929559, Free PMC Article
  5. Grancalcin (GCA) modulates Toll-like receptor 9 (TLR9) mediated signaling through its direct interaction with TLR9. Kim TW, et al. Eur J Immunol, 2016 Mar. PMID 26648480

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)

Genotypes

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
    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
    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
    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
    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
    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
    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
    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_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
    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

    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

    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

    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

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

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

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

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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