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    SARAF store-operated calcium entry associated regulatory factor [ Homo sapiens (human) ]

    Gene ID: 51669, updated on 10-Dec-2024

    Summary

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    Official Symbol
    SARAFprovided by HGNC
    Official Full Name
    store-operated calcium entry associated regulatory factorprovided by HGNC
    Primary source
    HGNC:HGNC:28789
    See related
    Ensembl:ENSG00000133872 MIM:614768; AllianceGenome:HGNC:28789
    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
    XTP3; FOAP-7; TMEM66; HSPC035
    Summary
    Involved in regulation of store-operated calcium entry. Located in endoplasmic reticulum membrane and endoplasmic reticulum-plasma membrane contact site. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Ubiquitous expression in brain (RPKM 148.3), adrenal (RPKM 121.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SARAF in Genome Data Viewer
    Location:
    8p12
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (30063003..30083208, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (30341918..30362124, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (29920519..29940724, complement)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:29890859-29891680 Neighboring gene mitogen-activated protein kinase kinase 1 pseudogene 1 Neighboring gene RNA, U6 small nuclear 1218, pseudogene Neighboring gene MED14-independent group 3 enhancer GRCh37_chr8:29914456-29915655 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27207 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27208 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19074 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27209 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19075 Neighboring gene leptin receptor overlapping transcript like 1 Neighboring gene ribosomal protein S15a pseudogene 24 Neighboring gene membrane bound O-acyltransferase domain containing 4

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Store-operated Ca2+ entry is remodelled and controls in vitro angiogenesis in endothelial progenitor cells isolated from tumoral patients. Lodola F, et al. PLoS One, 2012. PMID 23049731, Free PMC Article
    2. Fine-tuning of store-operated calcium entry by fast and slow Ca(2+)-dependent inactivation: Involvement of SARAF. Jardín I, et al. Biochim Biophys Acta Mol Cell Res, 2018 Mar. PMID 29223474
    3. SARAF Luminal Domain Structure Reveals a Novel Domain-Swapped β-Sandwich Fold Important for SOCE Modulation. Kimberlin CR, et al. J Mol Biol, 2019 Jul 12. PMID 31082439, Free PMC Article
    4. Chemoresistant ovarian cancer enhances its migration abilities by increasing store-operated Ca(2+) entry-mediated turnover of focal adhesions. Huang HK, et al. J Biomed Sci, 2020 Feb 21. PMID 32079527, Free PMC Article
    5. MiR-30a-5p isoform -1|1 promotes the progression of gastric cancer by inhibiting TMEM66 and reducing intratumoral cytotoxic T cells. Dai Y, et al. Exp Cell Res, 2024 Jun 15. PMID 38802035

    See all (50) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MiR-30a-5p isoform -1|1 promotes the progression of gastric cancer by inhibiting TMEM66 and reducing intratumoral cytotoxic T cells.
      Title: MiR-30a-5p isoform -1|1 promotes the progression of gastric cancer by inhibiting TMEM66 and reducing intratumoral cytotoxic T cells.
    2. Reduced Ca[2+] mobilization in neonatal human platelets involves SARAF and pannexin-1.
      Title: Reduced Ca(2+) mobilization in neonatal human platelets involves SARAF and pannexin-1.
    3. Bidirectional regulation of calcium release-activated calcium (CRAC) channel by SARAF.
      Title: Bidirectional regulation of calcium release-activated calcium (CRAC) channel by SARAF.
    4. Temporal modulation of calcium sensing in hematopoietic stem cells is crucial for proper stem cell expansion and engraftment.
      Title: Temporal modulation of calcium sensing in hematopoietic stem cells is crucial for proper stem cell expansion and engraftment.
    5. Chemoresistant ovarian cancer enhances its migration abilities by increasing store-operated Ca(2+) entry-mediated turnover of focal adhesions.
      Title: Chemoresistant ovarian cancer enhances its migration abilities by increasing store-operated Ca(2+) entry-mediated turnover of focal adhesions.
    6. Y316F mutation altered the pattern of interaction between STIM1 and SARAF under resting conditions and upon Ca(2+) store depletion. Expression of the STIM1 Y316F mutant enhanced slow Ca(2+)-dependent inactivation (SCDI) as compared to STIM1 WT, an effect that was abolished by SARAF knockdown.
      Title: STIM1 phosphorylation at Y(316) modulates its interaction with SARAF and the activation of SOCE and I(CRAC).
    7. Described is the X-ray crystal structure of the SARAF luminal domain, SARAFL. This domain forms a novel 10-stranded beta-sandwich fold that includes a set of three conserved disulfide bonds, denoted the "SARAF-fold." The structure reveals a domain-swapped dimer in which the last two beta-strands (beta9 and beta10) are exchanged forming a region denoted the "SARAF luminal switch" that is essential for dimerization.
      Title: SARAF Luminal Domain Structure Reveals a Novel Domain-Swapped β-Sandwich Fold Important for SOCE Modulation.
    8. Study shows that SARAF interacted with STIM1 to limit Ca2+ influx during physiological stimulation, but interaction of SARAF with STIM1 was transient during pathological stimulation of acinar cells, resulting in sustained, toxic Ca2+ influx. Transgenic expression of SARAF in mouse pancreatic acini reduced pathologic Ca2+ influx, prevented inflammation, and reduced tissue damage in mouse models of severe pancreatitis.
      Title: Ca(2+) Influx Channel Inhibitor SARAF Protects Mice From Acute Pancreatitis.
    9. EFHB is a new store-operated Ca2+ entry regulator that modulates STIM1-SARAF interaction.
      Title: EFHB is a Novel Cytosolic Ca2+ Sensor That Modulates STIM1-SARAF Interaction.
    10. SARAF also interacts with Orai1 and TRPC1 in cells endogenously expressing STIM1 and cells with a low STIM1 expression and modulates channel function. This review focuses on the modulation by SARAF of SOCE and other forms of Ca(2+) influx mediated by Orai1 and TRPC1 in order to provide spatio-temporally regulated Ca(2+) signals.
      Title: Fine-tuning of store-operated calcium entry by fast and slow Ca(2+)-dependent inactivation: Involvement of SARAF.
    Submit: New GeneRIF Correction See all GeneRIFs (19)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of transmembrane protein 66 (TMEM66) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC8721, FLJ22274

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in calcium ion transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of store-operated calcium entry IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of store-operated calcium entry IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in endoplasmic reticulum membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum-plasma membrane contact site IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    store-operated calcium entry-associated regulatory factor
    Names
    HBV X-transactivated gene 3 protein
    HBV XAg-transactivated protein 3
    SOCE-associated regulatory factor
    testicular secretory protein Li 59
    transmembrane protein 66

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_001284239.1 → NP_001271168.1  store-operated calcium entry-associated regulatory factor isoform 2

      See identical proteins and their annotated locations for NP_001271168.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and 5' coding region which results in the use of a downstream start codon compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AC044849, AK315956, BM280420, DC359554
      Consensus CDS
      CCDS64866.1
      UniProtKB/TrEMBL
      B3KSV1
      Related
      ENSP00000441351.1, ENST00000545648.2
      Conserved Domains (1) summary
      pfam06682
      Location:2 → 167
      SARAF; SOCE-associated regulatory factor of calcium homoeostasis

    2. NM_016127.6 → NP_057211.4  store-operated calcium entry-associated regulatory factor isoform 1 precursor

      See identical proteins and their annotated locations for NP_057211.4

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC044849
      Consensus CDS
      CCDS6074.1
      UniProtKB/Swiss-Prot
      B3KQQ4, B7Z9J1, D3DSU7, H9MHJ8, H9MHJ9, Q53HE8, Q96BY9, Q9UNZ3, Q9Y683
      UniProtKB/TrEMBL
      A0A140VK59, B7Z307
      Related
      ENSP00000256255.6, ENST00000256255.11
      Conserved Domains (1) summary
      pfam06682
      Location:24 → 339
      SARAF; SOCE-associated regulatory factor of calcium homoeostasis

    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_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      30063003..30083208 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      30341918..30362124 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96BY9.1 GenPept UniProtKB/Swiss-Prot:Q96BY9

    Gene LinkOut

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

    Chemical Information
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