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

Summary

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, Nov 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

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_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
Bidirectional regulation of calcium release-activated calcium (CRAC) channel by SARAF.
Title: Bidirectional regulation of calcium release-activated calcium (CRAC) channel by SARAF.
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.
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.
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).
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.
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.
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.
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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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

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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

D8S1463 (e-PCR)
- UniSTS:18505

RH66551 (e-PCR)
- UniSTS:68691

WI-20115 (e-PCR)
- UniSTS:31333

STS-W87932 (e-PCR)
- UniSTS:34480

D8S2122 (e-PCR)
- UniSTS:3825

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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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)

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
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