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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

ORAI3 Gene

protein-coding GIFtS: 49
GCID: GC16P030960

ORAI calcium release-activated calcium modulator 3

(Previous name: transmembrane protein 142C )
(Previous symbol: TMEM142C)

Explore 3 diseases affiliated with
ORAI3 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
ORAI Calcium Release-Activated Calcium Modulator 3¹ ²
TMEM142C¹ ² ³ ⁵
Transmembrane Protein 142C¹ ² ³
MGC13024¹
Protein Orai-3²

External Ids:	HGNC: 28185¹	Entrez Gene: 93129²	Ensembl: ENSG00000175938⁷	OMIM: 610930⁵	UniProtKB: Q9BRQ5³

Export aliases for ORAI3 gene to outside databases

Previous GC identifers: GC16P030869 GC16P030870 GC16P028524

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

UniProtKB/Swiss-Prot: ORAI3_HUMAN, Q9BRQ5

Function: Key regulator or component of store-operated Ca(2+) channel and transcription factor NFAT nuclear import (By

similarity)

summary for ORAI3:

STIM-Orai channels have recently been identified as the underlying molecular mechanism of store-operated

calcium entry (SOCE). SOCE allows rapid Ca2+ efflux from the endoplasmic reticulum (ER), following the

emptying of intracellular Ca2+ stores. STIM (sensors stromal interaction molecule) proteins, STIM1 and

STIM2, serve as ER Ca2+ sensors. They contain N'-terminal Ca2+-sensing EF-hand domains and are localized to

the tubular ER. Following Ca2+ store depletion, STIMs rapidly cluster and relocalize to the plasma

membrane-adjacent ER regions, where they oligomerize and form 'puncta'. Orai proteins, Orai1, Orai2 and

Orai3, are STIM binding partners that form the pore of the channel. Orai proteins are uniformly distributed

in the plasma membrane and exist as dimers in the resting state. STIM activation induces tetramerization of

Orai proteins and subsequent STIM-Orai colocalization, which forms the active store-operated calcium

channel.

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000016.9 NC_018927.1 NT_010393.16

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the ORAI3 gene promoter:
NF-1/L NF-1 HTF LCR-F1 NF-AT Arnt MZF-1 AREB6 CREB c-Rel
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: ORAI3 promoter sequence

Search SABiosciences Chromatin IP Primers for ORAI3

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat ORAI3

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 16p11.2 Ensembl cytogenetic band: 16p11.2 HGNC cytogenetic band: 16p11.2

ORAI3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ORAI3 gene location

GeneLoc information about chromosome 16 GeneLoc Exon Structure

GeneLoc location for GC16P030960: view genomic region (about GC identifiers)

Start:	30,960,387 bp from pter	End:	30,967,782 bp from pter
Size:	7,396 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: ORAI3_HUMAN, Q9BRQ5 (See protein sequence)

Recommended Name: Protein orai-3

Size: 295 amino acids; 31499 Da

Subunit: Interacts with EFCAB4B/CRACR2A

Subcellular location: Membrane; Multi-pass membrane protein (By similarity)

Secondary accessions: Q96BI8

Explore the universe of human proteins at neXtProt for ORAI3: NX_Q9BRQ5

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q9BRQ5

ORAI3 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_689501.1

ENSEMBL proteins:

ENSP00000322249 ENSP00000457221 ENSP00000457388 ENSP00000457025

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	Uscn Proteins for ORAI3

Gene Ontology (GO): 1 cellular component term (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0016021	integral to membrane	IEA	--

ORAI3 for ontologies About GeneDecksing

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	Uscn ELISAs and CLIAs for ORAI3

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

ORAI3 for domains About GeneDecksing

1 InterPro domain/family:

IPR012446 CRAC_channel

Graphical View of Domain Structure for InterPro Entry Q9BRQ5

ProtoNet protein and cluster: Q9BRQ5

1 Blocks protein family: IPB012446 Protein of unknown function DUF1650

UniProtKB/Swiss-Prot: ORAI3_HUMAN, Q9BRQ5

Similarity: Belongs to the Orai family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: ORAI3_HUMAN, Q9BRQ5

Function: Key regulator or component of store-operated Ca(2+) channel and transcription factor NFAT nuclear import (By

similarity)

miRNA Products:		OriGene 3'-UTR Clone: ORAI3 Browse MicroRNA Expression Plasmids
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		hsa-miR-34b* hsa-miR-1321 hsa-miR-624 hsa-miR-650 hsa-miR-449a hsa-miR-629* hsa-miR-613 hsa-miR-1827

		SwitchGear 3'UTR luciferase reporter plasmid: ORAI3 3' UTR sequence

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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ORAI3

Gene Ontology (GO): 1 molecular function term (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005515	protein binding	IPI	--

ORAI3 for ontologies About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Interactions:

Search SABiosciences Gene Network Central^TM Interacting Genes and Proteins Networks for ORAI3

STRING Interaction Network Preview (showing 4 interactants - click image to see more details)

5 Interacting proteins for ORAI3 (Q9BRQ5³ ENSP00000322249⁴) via UniProtKB, MINT, STRING, and/or I2D

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
DDX6	P26196³	I2D: score=3
ORAI1	ENSP00000328216⁴	STRING: ENSP00000328216
STIM1	ENSP00000300737⁴	STRING: ENSP00000300737
EFCAB4B	ENSP00000409382⁴	STRING: ENSP00000409382
UBC	ENSP00000344818⁴	STRING: ENSP00000344818

About this table

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Compounds for ORAI3 available from Tocris Bioscience About this table

Compound	Action	CAS #
2-APB	IP3 receptor antagonist. Also TRP channel modulator	[524-95-8]
SKF 96365 hydrochloride	STIM1-mediated Ca2+ influx inhibitor	[130495-35-1]
ML 9 hydrochloride	Myosin light chain kinase inhibitor	[105637-50-1]

Search CenterWatch for drugs/clinical trials and news about ORAI3

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for ORAI3 gene:

NM_152288.2

Unigene Cluster for ORAI3:

ORAI calcium release-activated calcium modulator 3

Hs.460617 [show with all ESTs]

Unigene Representative Sequence: BC015555

4 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000318663(uc002eac.3) ENST00000563161 ENST00000566237 ENST00000562699

miRNA Products:		OriGene 3'-UTR Clone: ORAI3 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat ORAI3
		8/24 QIAGEN miScript miRNA Assays for microRNAs that regulate ORAI3 (see all 24):
		hsa-miR-34b* hsa-miR-1321 hsa-miR-624 hsa-miR-650 hsa-miR-449a hsa-miR-629* hsa-miR-613 hsa-miR-1827

		SwitchGear 3'UTR luciferase reporter plasmid: ORAI3 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat ORAI3

Additional cDNA sequence:

AK298276.1 BC006126.1 BC015555.1 BC016150.1 BC022786.1

5 DOTS entries:

DT.408811 DT.40249054 DT.100783943 DT.95105479 DT.120669094

24/186 AceView cDNA sequences (see all 186):

BG677581 AI702473 BX384015 CK819710 BE222694 BC048811 AA515878 BU608652

AI289104 BQ574949 AW444819 AK098777 CK819711 C01878 BU185173 AI216337

BI196649 AA423891 BC059173 BQ648716 AW027088 BM680919 AL137589 BF002009

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

ORAI3 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: CAGTAGATAG

About this image

ORAI3 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Bone

Mandibular Process

Bone

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See ORAI3 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for ORAI3

SOURCE GeneReport for Unigene cluster: Hs.460617

SABiosciences Custom PCR Arrays for ORAI3

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In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ORAI3

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for ORAI3 gene from 3/18 species (see all 18) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
lizard (Anolis carolinensis)	Reptilia	ORAI3⁶	--	64(a)	1 ↔ 1	GL343220.1(1845020-1858078)
fruit fly (Drosophila melanogaster)	Insecta	olf186-F⁶	olf186-F	22(a)	1 → many	2R(13730950-13748075)
worm (Caenorhabditis elegans)	Secernentea	orai-1⁶	Protein orai	30(a)	1 → many	III(647123-654460)

ENSEMBL Gene Tree for ORAI3 (if available)
TreeFam Gene Tree for ORAI3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for ORAI3 gene

ORAI2² ORAI1²

2 SIMAP similar genes for ORAI3 using alignment to 4 protein entries: ORAI3_HUMAN (see all proteins):

ORAI2 ORAI1

ORAI3 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 16 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs191558886^1,2		--	30962618(+)	`ACTGCA/CCTCAG`	1	--	int¹		0	--	--	--	--
rs59673229^1,2	C	--	30963450(+)	`TTTTT-/TTGAGAC`	1	--	int¹		2		NA CSA	4
rs146901337^1,2	C	--	30963450(+)	`CTTTC-/TTTTTTT`	1	--	int¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for ORAI3 (30960387 - 30967782 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 2 variations for ORAI3
2 CNVs: 4942 4941

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

ORAI3 for disorders           About GeneDecksing

OMIM gene information: 610930    OMIM disorders: --

3 diseases for ORAI3:    About MalaCards

estrogen-receptor negative breast cancer breast cancer retinitis

Export disorders for ORAI3 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for ORAI3 gene, integrated from 9 sources (see all 18):
(articles sorted by number of sources associating them with ORAI3)

Utopia: connect your pdf to the dynamic
world of online information

A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. (PubMed id 16582901)^{1, 2, 3} Feske S.... Rao A. (2006)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
Expression of Orai genes and I(CRAC) activation in th e human retinal pigment epithelium. (PubMed id 20607548)¹ Cordeiro S. and Strauss O. (2011)
Down-regulation of Orai3 arrests cell-cycle progressi on and induces apoptosis in breast cancer cells but not in normal breast epithe lial cells. (PubMed id 20683915)¹ Faouzi M....Ouadid-Ahidouch H. (2011)
Systematic and quantitative assessment of the ubiquiti n-modified proteome. (PubMed id 21906983)¹ Kim W....Gygi S.P. (2011)
Molecular determinants within N terminus of Orai3 pro tein that control channel activation and gating. (PubMed id 21724845)¹ Bergsmann J....Romanin C. (2011)
Differential redox regulation of ORAI ion channels: a mechanism to tune cellular calcium signaling. (PubMed id 20354224)¹ Bogeski I....Niemeyer B.A. (2010)
A novel native store-operated calcium channel encoded by Orai3: selective requirement of Orai3 versus Orai1 in estrogen receptor-pos itive versus estrogen receptor-negative breast cancer cells. (PubMed id 20395295)¹ Motiani R.K....Trebak M. (2010)
A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that stabilizes CRAC channels in T cells. (PubMed id 20418871)² Srikanth S....Gwack Y. (2010)
Molecular determinants of the coupling between STIM1 and Orai channels: differential activation of Orai1-3 channels by a STIM1 coile d-coil mutant. (PubMed id 19506081)¹ Frischauf I....Romanin C. (2009)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 93129	HGNC: 28185	AceView: FBXL19andMGC13024	Ensembl:ENSG00000175938	euGenes: HUgn93129
ECgene: ORAI3	H-InvDB: ORAI3

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for ORAI3	Pharmacogenomics, SNPs, Pathways

Intellectual Property for ORAI3 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

About This Section

Patent Information for ORAI3 gene:
Search GeneIP for patents involving ORAI3

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
In Situ Hybridization Assays from
Advanced Cell Diagnostics
About This Section


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	Gene Synthesis: Any Gene in Any Vector		Vector-based siRNA and miRNA, Ready for Transfection
	Gene Mutant Library, Variants up to 10^11		Plasmid Preparation
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GeneCards Homepage - Last full update: 18 Mar 2013 - Incrementals: 21 Mar 2013 , 15 Apr 2013 , 27 Apr 2013

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Category			VWF (GIFTS: 73) von Willebrand factor
GIFtS Group

The GeneCards human gene database gene index: 1 3 5 6 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

The GeneCards Human Gene Database

Developed at the Crown Human Genome Center, Department of Molecular Genetics, the Weizmann Institute of Science

Hot genes Disease genes ORAI3 gene at Home site.

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ORAI3 Gene

ORAI calcium release-activated calcium modulator 3

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ORAI3 Gene

ORAI calcium release-activated calcium modulator 3

Aliasesfor ORAI3 gene

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Genomic Viewsfor ORAI3 gene

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Protein Domains /Familiesfor ORAI3 gene

Functionfor ORAI3 gene

Pathways & Interactionsfor ORAI3 gene

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for ORAI3 gene

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for ORAI3 gene

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for ORAI3 gene

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for ORAI3 gene

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for ORAI3 gene

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for ORAI3 gene

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for ORAI3 gene

Transcripts
for ORAI3 gene

Expression
for ORAI3 gene

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for ORAI3 gene

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for ORAI3 gene

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for ORAI3 gene

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for ORAI3 gene