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CRACR2A calcium release activated channel regulator 2A [ Homo sapiens (human) ]

Gene ID: 84766, updated on 5-Mar-2024

Summary

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Official Symbol
CRACR2Aprovided by HGNC
Official Full Name
calcium release activated channel regulator 2Aprovided by HGNC
Primary source
HGNC:HGNC:28657
See related
Ensembl:ENSG00000130038 MIM:614178; AllianceGenome:HGNC:28657
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
RAB46; EFCAB4B
Summary
Enables GTPase activity and calcium ion binding activity. Involved in several processes, including activation of store-operated calcium channel activity; positive regulation of JNK cascade; and store-operated calcium entry. Located in several cellular components, including Golgi apparatus; Weibel-Palade body; and immunological synapse. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Broad expression in salivary gland (RPKM 9.7), colon (RPKM 7.2) and 16 other tissues See more
Orthologs
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Genomic context

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Location:
12p13.32
Exon count:
27
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (3615328..3753109, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (3621867..3761227, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (3724494..3862275, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene protein arginine methyltransferase 8 Neighboring gene ribosomal protein S26 pseudogene 44 Neighboring gene thyroid cancer-associated transcript 155 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:3688671-3689170 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:3709097-3709922 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:3716235-3716736 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:3716737-3717236 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:3738174-3738805 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:3801592-3802218 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4141 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:3842402-3843030 Neighboring gene RNA, U6 small nuclear 174, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4142 Neighboring gene uncharacterized LOC107984495 Neighboring gene poly(ADP-ribose) polymerase family member 11 Neighboring gene OTUD4 pseudogene 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. Vigorous Physical Activity Is Associated with Lower Risk of Metastatic-Lethal Progression in Prostate Cancer and Hypomethylation in the CRACR2A Gene. Dai JY, et al. Cancer Epidemiol Biomarkers Prev, 2019 Feb. PMID 30464020, Free PMC Article
  2. A genome-wide association study identifies an association between variants in EFCAB4B gene and periodontal disease in an Italian isolated population. Bevilacqua L, et al. J Periodontal Res, 2018 Dec. PMID 30284742
  3. A large Rab GTPase family in a small GTPase world. Srikanth S, et al. Small GTPases, 2017 Jan 2. PMID 27221160, Free PMC Article
  4. Expression of a long variant of CRACR2A that belongs to the Rab GTPase protein family in endothelial cells. Wilson LA, et al. Biochem Biophys Res Commun, 2015 Jan 2. PMID 25475730, Free PMC Article
  5. Rab46 integrates Ca(2+) and histamine signaling to regulate selective cargo release from Weibel-Palade bodies. Miteva KT, et al. J Cell Biol, 2019 Jul 1. PMID 31092558, Free PMC Article

See all (32) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. These data demonstrate for the first time that a Rab GTPase, Rab46, integrates G protein and Ca(2+) signals to couple on-demand histamine signals to selective Weibel-Palade bodies (WPBs) trafficking.
    Title: Rab46 integrates Ca(2+) and histamine signaling to regulate selective cargo release from Weibel-Palade bodies.
  2. Vigorous physical activity before diagnosis is associated with epigenetic alterations of CRACR2A and prostate cancer metastatic-lethal progression.
    Title: Vigorous Physical Activity Is Associated with Lower Risk of Metastatic-Lethal Progression in Prostate Cancer and Hypomethylation in the CRACR2A Gene.
  3. There is a significant association between the EFCAB4B gene and localized periodontitis.
    Title: A genome-wide association study identifies an association between variants in EFCAB4B gene and periodontal disease in an Italian isolated population.
  4. Results show the characterization of CRACR2A protein which encodes a large Rab GTPase containing multiple functional domains contrary to small Rab GTPases. It was found to play an unexpected role in regulating intracellular signaling pathways important for T cell activation.
    Title: A large Rab GTPase family in a small GTPase world.
  5. GTP binding and prenylation of CRACR2A were associated with its localization near the Golgi and its stability
    Title: A large Rab GTPase encoded by CRACR2A is a component of subsynaptic vesicles that transmit T cell activation signals.
  6. endothelial cells contain a long variant of CRACR2A which is an EF-hand-containing Rab protein that lacks impact on CRAC channels
    Title: Expression of a long variant of CRACR2A that belongs to the Rab GTPase protein family in endothelial cells.
  7. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
    Title: Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.
  8. CRACR2A interacts directly with Orai1 and STIM1, forming a ternary complex that dissociates at elevated Ca(2+) concentrations; is a key regulator of CRAC channel-mediated SOCE
    Title: A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that stabilizes CRAC channels in T cells.
  9. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Submit: New GeneRIF Correction

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 association study does not reveal major genetic determinants for anti-cytomegalovirus antibody response.
EBI GWAS Catalog
Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.
EBI GWAS Catalog
Genome-wide study of single-nucleotide polymorphisms associated with azoospermia and severe oligozoospermia.
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)

Genotypes

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

  • MGC4266, FLJ33046, FLJ33805, DKFZp686G13246

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables GTP binding IEA
Inferred from Electronic Annotation
more info
  
enables GTPase activity IEA
Inferred from Electronic Annotation
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 
Process Evidence Code Pubs
involved_in activation of store-operated calcium channel activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in adaptive immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of calcium ion transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in store-operated calcium entry IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi membrane IEA
Inferred from Electronic Annotation
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in membrane HDA PubMed 
located_in microtubule organizing center IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in specific granule lumen TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
EF-hand calcium-binding domain-containing protein 4B
Names
CRAC channel regulator 2A
CRAC regulator 2A
Ca2+ release-activated Ca2+ (CRAC) channel regulator 2A
EF-hand calcium binding domain 4B
calcium release-activated calcium channel regulator 2A
ras-related protein Rab-46

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_001144958.2 → NP_001138430.1  EF-hand calcium-binding domain-containing protein 4B isoform a

    See identical proteins and their annotated locations for NP_001138430.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).
    Source sequence(s)
    AK304017, DB214079
    Consensus CDS
    CCDS44803.1
    UniProtKB/Swiss-Prot
    B4E1X0, B9EK63, Q9BSW2
    Related
    ENSP00000409382.2, ENST00000440314.7
    Conserved Domains (3) summary
    PRK12309
    Location:33 → 113
    PRK12309; transaldolase
    cd00154
    Location:546 → 704
    Rab; Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases)
    TIGR02168
    Location:201 → 384
    SMC_prok_B; chromosome segregation protein SMC, common bacterial type

  2. NM_032680.4 → NP_116069.1  EF-hand calcium-binding domain-containing protein 4B isoform c

    See identical proteins and their annotated locations for NP_116069.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (c) has a shorter and distinct C-terminus, compared to isoform a.
    Source sequence(s)
    BC004524, DB214079
    Consensus CDS
    CCDS8522.1
    UniProtKB/Swiss-Prot
    Q9BSW2
    Related
    ENSP00000252322.1, ENST00000252322.1
    Conserved Domains (2) summary
    cl25732
    Location:201 → 370
    SMC_N; RecF/RecN/SMC N terminal domain
    cl28446
    Location:33 → 113
    PRK12309; transaldolase/EF-hand domain-containing protein; Provisional

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_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    3615328..3753109 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011521034.4 → XP_011519336.1  EF-hand calcium-binding domain-containing protein 4B isoform X1

    See identical proteins and their annotated locations for XP_011519336.1

    Conserved Domains (5) summary
    smart00175
    Location:547 → 710
    RAB; Rab subfamily of small GTPases
    cd00154
    Location:547 → 705
    Rab; Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases)
    pfam13499
    Location:55 → 109
    EF-hand_7; EF-hand domain pair
    cl08302
    Location:54 → 114
    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 ...
    cl23720
    Location:226 → 313
    RILP-like; Rab interacting lysosomal protein-like 1 and 2 (Rilpl1 and Rilpl2)

  2. XM_006719021.4 → XP_006719084.1  EF-hand calcium-binding domain-containing protein 4B isoform X1

    See identical proteins and their annotated locations for XP_006719084.1

    Conserved Domains (5) summary
    smart00175
    Location:547 → 710
    RAB; Rab subfamily of small GTPases
    cd00154
    Location:547 → 705
    Rab; Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases)
    pfam13499
    Location:55 → 109
    EF-hand_7; EF-hand domain pair
    cl08302
    Location:54 → 114
    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 ...
    cl23720
    Location:226 → 313
    RILP-like; Rab interacting lysosomal protein-like 1 and 2 (Rilpl1 and Rilpl2)

  3. XM_047429736.1 → XP_047285692.1  EF-hand calcium-binding domain-containing protein 4B isoform X1

  4. XM_011521036.4 → XP_011519338.1  EF-hand calcium-binding domain-containing protein 4B isoform X1

    See identical proteins and their annotated locations for XP_011519338.1

    Conserved Domains (5) summary
    smart00175
    Location:547 → 710
    RAB; Rab subfamily of small GTPases
    cd00154
    Location:547 → 705
    Rab; Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases)
    pfam13499
    Location:55 → 109
    EF-hand_7; EF-hand domain pair
    cl08302
    Location:54 → 114
    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 ...
    cl23720
    Location:226 → 313
    RILP-like; Rab interacting lysosomal protein-like 1 and 2 (Rilpl1 and Rilpl2)

  5. XM_047429738.1 → XP_047285694.1  EF-hand calcium-binding domain-containing protein 4B isoform X2

  6. XM_047429737.1 → XP_047285693.1  EF-hand calcium-binding domain-containing protein 4B isoform X2

  7. XM_011521038.3 → XP_011519340.1  EF-hand calcium-binding domain-containing protein 4B isoform X4

    See identical proteins and their annotated locations for XP_011519340.1

    Conserved Domains (2) summary
    smart00175
    Location:308 → 471
    RAB; Rab subfamily of small GTPases
    cd00154
    Location:308 → 466
    Rab; Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases)

  8. XM_011521037.3 → XP_011519339.1  EF-hand calcium-binding domain-containing protein 4B isoform X4

    See identical proteins and their annotated locations for XP_011519339.1

    Conserved Domains (2) summary
    smart00175
    Location:308 → 471
    RAB; Rab subfamily of small GTPases
    cd00154
    Location:308 → 466
    Rab; Ras-related in brain (Rab) family of small guanosine triphosphatases (GTPases)

  9. XM_047429739.1 → XP_047285695.1  EF-hand calcium-binding domain-containing protein 4B isoform X3

  10. XM_047429744.1 → XP_047285700.1  EF-hand calcium-binding domain-containing protein 4B isoform X6

  11. XM_047429742.1 → XP_047285698.1  EF-hand calcium-binding domain-containing protein 4B isoform X6

  12. XM_047429741.1 → XP_047285697.1  EF-hand calcium-binding domain-containing protein 4B isoform X5

  13. XM_047429740.1 → XP_047285696.1  EF-hand calcium-binding domain-containing protein 4B isoform X5

  14. XM_047429743.1 → XP_047285699.1  EF-hand calcium-binding domain-containing protein 4B isoform X6

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    3621867..3761227 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054373575.1 → XP_054229550.1  EF-hand calcium-binding domain-containing protein 4B isoform X1

  2. XM_054373574.1 → XP_054229549.1  EF-hand calcium-binding domain-containing protein 4B isoform X1

  3. XM_054373576.1 → XP_054229551.1  EF-hand calcium-binding domain-containing protein 4B isoform X1

  4. XM_054373577.1 → XP_054229552.1  EF-hand calcium-binding domain-containing protein 4B isoform X1

  5. XM_054373578.1 → XP_054229553.1  EF-hand calcium-binding domain-containing protein 4B isoform X1

  6. XM_054373580.1 → XP_054229555.1  EF-hand calcium-binding domain-containing protein 4B isoform X2

  7. XM_054373579.1 → XP_054229554.1  EF-hand calcium-binding domain-containing protein 4B isoform X2

  8. XM_054373583.1 → XP_054229558.1  EF-hand calcium-binding domain-containing protein 4B isoform X4

  9. XM_054373582.1 → XP_054229557.1  EF-hand calcium-binding domain-containing protein 4B isoform X4

  10. XM_054373581.1 → XP_054229556.1  EF-hand calcium-binding domain-containing protein 4B isoform X3

  11. XM_054373589.1 → XP_054229564.1  EF-hand calcium-binding domain-containing protein 4B isoform X6

  12. XM_054373587.1 → XP_054229562.1  EF-hand calcium-binding domain-containing protein 4B isoform X6

  13. XM_054373585.1 → XP_054229560.1  EF-hand calcium-binding domain-containing protein 4B isoform X5

  14. XM_054373586.1 → XP_054229561.1  EF-hand calcium-binding domain-containing protein 4B isoform X5

  15. XM_054373584.1 → XP_054229559.1  EF-hand calcium-binding domain-containing protein 4B isoform X5

  16. XM_054373588.1 → XP_054229563.1  EF-hand calcium-binding domain-containing protein 4B isoform X6

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001144959.1: Suppressed sequence

    Description
    NM_001144959.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9BSW2.2 GenPept UniProtKB/Swiss-Prot:Q9BSW2

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