ID   ORAI2_HUMAN             Reviewed;         254 AA.
AC   Q96SN7; Q6IA68; Q8WY94; Q9H9Y3;
DT   16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   24-JAN-2024, entry version 147.
DE   RecName: Full=Protein orai-2;
DE   AltName: Full=CAP-binding protein complex-interacting protein 2;
DE   AltName: Full=Transmembrane protein 142B;
GN   Name=ORAI2; Synonyms=C7orf19, CBCIP2, TMEM142B; ORFNames=PP1729;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Teratocarcinoma;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12853948; DOI=10.1038/nature01782;
RA   Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA   Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA   Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA   Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA   Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA   Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA   Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA   Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA   Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA   Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA   Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA   Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA   Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA   Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA   Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA   Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA   Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA   McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA   Wilson R.K.;
RT   "The DNA sequence of human chromosome 7.";
RL   Nature 424:157-164(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 191-254.
RX   PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA   Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA   Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA   Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT   "Large-scale cDNA transfection screening for genes related to cancer
RT   development and progression.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN   [5]
RP   PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   FUNCTION.
RX   PubMed=16807233; DOI=10.1074/jbc.m604589200;
RA   Mercer J.C., Dehaven W.I., Smyth J.T., Wedel B., Boyles R.R., Bird G.S.,
RA   Putney J.W. Jr.;
RT   "Large store-operated calcium selective currents due to co-expression of
RT   Orai1 or Orai2 with the intracellular calcium sensor, Stim1.";
RL   J. Biol. Chem. 281:24979-24990(2006).
RN   [7]
RP   IDENTIFICATION.
RX   PubMed=16582901; DOI=10.1038/nature04702;
RA   Feske S., Gwack Y., Prakriya M., Srikanth S., Puppel S.-H., Tanasa B.,
RA   Hogan P.G., Lewis R.S., Daly M., Rao A.;
RT   "A mutation in Orai1 causes immune deficiency by abrogating CRAC channel
RT   function.";
RL   Nature 441:179-185(2006).
RN   [8]
RP   FUNCTION.
RX   PubMed=17452328; DOI=10.1074/jbc.m611374200;
RA   Dehaven W.I., Smyth J.T., Boyles R.R., Putney J.W. Jr.;
RT   "Calcium inhibition and calcium potentiation of orai1, orai2, and orai3
RT   calcium release-activated calcium channels.";
RL   J. Biol. Chem. 282:17548-17556(2007).
RN   [9]
RP   INTERACTION WITH CRACR2A.
RX   PubMed=20418871; DOI=10.1038/ncb2045;
RA   Srikanth S., Jung H.J., Kim K.D., Souda P., Whitelegge J., Gwack Y.;
RT   "A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that
RT   stabilizes CRAC channels in T cells.";
RL   Nat. Cell Biol. 12:436-446(2010).
CC   -!- FUNCTION: Ca(2+) release-activated Ca(2+)-like (CRAC-like) channel
CC       subunit which mediates Ca(2+) influx and increase in Ca(2+)-selective
CC       current by synergy with the Ca(2+) sensor, STIM1.
CC       {ECO:0000269|PubMed:16807233, ECO:0000269|PubMed:17452328}.
CC   -!- SUBUNIT: Interacts with CRACR2A/EFCAB4B. {ECO:0000269|PubMed:20418871}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Multi-pass membrane
CC       protein {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the Orai family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAG23755.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC       Sequence=AAP22352.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=CAG33568.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
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DR   EMBL; AK027639; BAB55256.1; -; mRNA.
DR   EMBL; AC093668; AAP22351.1; -; Genomic_DNA.
DR   EMBL; AC093668; AAP22352.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BC069270; AAH69270.1; -; mRNA.
DR   EMBL; AF258552; AAG23755.1; ALT_SEQ; mRNA.
DR   EMBL; CR457287; CAG33568.1; ALT_SEQ; mRNA.
DR   CCDS; CCDS5722.1; -.
DR   RefSeq; NP_001119812.1; NM_001126340.2.
DR   RefSeq; NP_001258747.1; NM_001271818.1.
DR   RefSeq; NP_116220.1; NM_032831.3.
DR   AlphaFoldDB; Q96SN7; -.
DR   SMR; Q96SN7; -.
DR   BioGRID; 123192; 6.
DR   DIP; DIP-48944N; -.
DR   IntAct; Q96SN7; 9.
DR   STRING; 9606.ENSP00000348752; -.
DR   BindingDB; Q96SN7; -.
DR   ChEMBL; CHEMBL4888450; -.
DR   GuidetoPHARMACOLOGY; 2965; -.
DR   iPTMnet; Q96SN7; -.
DR   PhosphoSitePlus; Q96SN7; -.
DR   BioMuta; ORAI2; -.
DR   DMDM; 74732728; -.
DR   EPD; Q96SN7; -.
DR   jPOST; Q96SN7; -.
DR   MassIVE; Q96SN7; -.
DR   MaxQB; Q96SN7; -.
DR   PaxDb; 9606-ENSP00000348752; -.
DR   PeptideAtlas; Q96SN7; -.
DR   ProteomicsDB; 78130; -.
DR   Antibodypedia; 31061; 194 antibodies from 28 providers.
DR   DNASU; 80228; -.
DR   Ensembl; ENST00000356387.6; ENSP00000348752.2; ENSG00000160991.17.
DR   Ensembl; ENST00000403646.8; ENSP00000385489.3; ENSG00000160991.17.
DR   Ensembl; ENST00000473939.2; ENSP00000417928.1; ENSG00000160991.17.
DR   Ensembl; ENST00000478730.7; ENSP00000418140.1; ENSG00000160991.17.
DR   Ensembl; ENST00000495936.7; ENSP00000420178.2; ENSG00000160991.17.
DR   Ensembl; ENST00000498661.6; ENSP00000418464.2; ENSG00000160991.17.
DR   Ensembl; ENST00000611770.5; ENSP00000478113.1; ENSG00000160991.17.
DR   GeneID; 80228; -.
DR   KEGG; hsa:80228; -.
DR   MANE-Select; ENST00000495936.7; ENSP00000420178.2; NM_001126340.3; NP_001119812.1.
DR   UCSC; uc003uzj.3; human.
DR   AGR; HGNC:21667; -.
DR   CTD; 80228; -.
DR   DisGeNET; 80228; -.
DR   GeneCards; ORAI2; -.
DR   HGNC; HGNC:21667; ORAI2.
DR   HPA; ENSG00000160991; Tissue enhanced (pituitary).
DR   MIM; 610929; gene.
DR   neXtProt; NX_Q96SN7; -.
DR   OpenTargets; ENSG00000160991; -.
DR   PharmGKB; PA162398454; -.
DR   VEuPathDB; HostDB:ENSG00000160991; -.
DR   eggNOG; KOG4298; Eukaryota.
DR   GeneTree; ENSGT00390000015354; -.
DR   InParanoid; Q96SN7; -.
DR   OMA; SGHTGWQ; -.
DR   OrthoDB; 2905973at2759; -.
DR   PhylomeDB; Q96SN7; -.
DR   TreeFam; TF313576; -.
DR   PathwayCommons; Q96SN7; -.
DR   Reactome; R-HSA-139853; Elevation of cytosolic Ca2+ levels.
DR   Reactome; R-HSA-5578775; Ion homeostasis.
DR   Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR   SignaLink; Q96SN7; -.
DR   BioGRID-ORCS; 80228; 13 hits in 1150 CRISPR screens.
DR   ChiTaRS; ORAI2; human.
DR   GeneWiki; ORAI2; -.
DR   GenomeRNAi; 80228; -.
DR   Pharos; Q96SN7; Tchem.
DR   PRO; PR:Q96SN7; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q96SN7; Protein.
DR   Bgee; ENSG00000160991; Expressed in renal medulla and 188 other cell types or tissues.
DR   ExpressionAtlas; Q96SN7; baseline and differential.
DR   GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0015279; F:store-operated calcium channel activity; IBA:GO_Central.
DR   GO; GO:0002115; P:store-operated calcium entry; IBA:GO_Central.
DR   Gene3D; 1.20.140.140; Calcium release-activated calcium channel protein Orai; 1.
DR   InterPro; IPR012446; CRAC_channel.
DR   InterPro; IPR038350; Orai_sf.
DR   PANTHER; PTHR31501; CALCIUM RELEASE-ACTIVATED CALCIUM CHANNEL PROTEIN 1; 1.
DR   PANTHER; PTHR31501:SF5; PROTEIN ORAI-2; 1.
DR   Pfam; PF07856; Orai-1; 1.
DR   Genevisible; Q96SN7; HS.
PE   1: Evidence at protein level;
KW   Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..254
FT                   /note="Protein orai-2"
FT                   /id="PRO_0000234391"
FT   TRANSMEM        66..83
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        94..114
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        148..168
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        196..216
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   VARIANT         15
FT                   /note="A -> P (in dbSNP:rs34947403)"
FT                   /id="VAR_053543"
SQ   SEQUENCE   254 AA;  28570 MW;  D53CD2376F48E23C CRC64;
     MSAELNVPID PSAPACPEPG HKGMDYRDWV RRSYLELVTS NHHSVQALSW RKLYLSRAKL
     KASSRTSALL SGFAMVAMVE VQLETQYQYP RPLLIAFSAC TTVLVAVHLF ALLISTCILP
     NVEAVSNIHN LNSISESPHE RMHPYIELAW GFSTVLGILL FLAEVVLLCW IKFLPVDARR
     QPGPPPGPGS HTGWQAALVS TIIMVPVGLI FVVFTIHFYR SLVRHKTERH NREIEELHKL
     KVQLDGHERS LQVL
//