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

    Gene ID: 84766, updated on 14-Nov-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, Nov 2024]
    Expression
    Broad expression in salivary gland (RPKM 9.7), colon (RPKM 7.2) and 16 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CRACR2A in Genome Data Viewer
    Location:
    12p13.32
    Exon count:
    27
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (3615328..3753109, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (3621867..3761227, complement)
    RS_2024_09 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 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. 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
    2. 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
    3. 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
    4. A large Rab GTPase family in a small GTPase world. Srikanth S, et al. Small GTPases, 2017 Jan 2. PMID 27221160, Free PMC Article
    5. A large Rab GTPase encoded by CRACR2A is a component of subsynaptic vesicles that transmit T cell activation signals. Srikanth S, et al. Sci Signal, 2016 Mar 22. PMID 27016526, Free PMC Article

    See all (35) 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)

    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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables GTP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables GTPase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables GTPase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables GTPase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    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 T-helper 1 cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    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 endosomal transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of JNK cascade IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of calcium ion transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein localization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to histamine IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in store-operated calcium entry IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in vesicle-mediated transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in Golgi membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in Weibel-Palade body IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in immunological synapse IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    located_in microtubule organizing center IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in microtubule organizing center IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in specific granule lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in trans-Golgi network membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    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_2024_08

    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

    Gene LinkOut

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