CRCM1_MOUSE
ID CRCM1_MOUSE Reviewed; 304 AA.
AC Q8BWG9; Q8BUD4; Q8R586;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Calcium release-activated calcium channel protein 1;
DE AltName: Full=Protein orai-1;
DE AltName: Full=Transmembrane protein 142A;
GN Name=Orai1; Synonyms=Cracm1, Tmem142a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland, and Stomach;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 16-304.
RC STRAIN=Czech II; TISSUE=Mammary gland;
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 [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP ATP2C2.
RX PubMed=23840669; DOI=10.1371/journal.pone.0067348;
RA Cross B.M., Hack A., Reinhardt T.A., Rao R.;
RT "SPCA2 regulates Orai1 trafficking and store independent Ca2+ entry in a
RT model of lactation.";
RL PLoS ONE 8:e67348-e67348(2013).
CC -!- FUNCTION: Ca(2+) release-activated Ca(2+) (CRAC) channel subunit which
CC mediates Ca(2+) influx following depletion of intracellular Ca(2+)
CC stores and channel activation by the Ca(2+) sensor, STIM1. CRAC
CC channels are the main pathway for Ca(2+) influx in T-cells and promote
CC the immune response to pathogens by activating the transcription factor
CC NFAT (By similarity). Plays a prominent role in Ca(2+) influx at the
CC basolateral membrane of mammary epithelial cells independently of the
CC Ca(2+) content of endoplasmic reticulum or Golgi stores. May mediate
CC transepithelial transport of large quantities of Ca(2+) for milk
CC secretion (PubMed:23840669) (By similarity).
CC {ECO:0000250|UniProtKB:Q96D31, ECO:0000269|PubMed:23840669}.
CC -!- ACTIVITY REGULATION: Oxidation at Cys-197 leads to inactivation of
CC channel activity. {ECO:0000250|UniProtKB:Q96D31}.
CC -!- SUBUNIT: Interacts with STIM1 and STIM2; this regulates channel
CC activity. Interacts with CALM; this may displace STIM1 and STIM2 and
CC might thereby modulate channel activity. Interacts with
CC CRACR2A/EFCAB4B; the interaction is direct and takes place in absence
CC of Ca(2+). Forms a complex with CRACR2A/EFCAB4B and STIM1 at low
CC concentration of Ca(2+), the complex dissociates at elevated Ca(2+)
CC concentrations. Interacts with SLC35G1. Interacts with UBQLN1.
CC Interacts with ADCY8; interaction is calcium store depletion
CC independent; interaction occurs in membrane raft; interaction increases
CC markedly after store depletion; positively regulates SOCE-induced
CC adenylate cyclase activity; contributes to the targeting of ADCY8 to
CC discrete regions of the plasma membrane that are shielded from other
CC calcium events (By similarity). Interacts with EFHB; the interaction
CC takes place upon Ca(2+)-store depletion (By similarity). Interacts (via
CC N- and C-termini) with ATP2C2 (via N-terminus); this interaction
CC regulates Ca(2+) influx at the plasma membrane.
CC {ECO:0000250|UniProtKB:Q96D31, ECO:0000269|PubMed:23840669}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q96D31};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q96D31}. Basolateral
CC cell membrane {ECO:0000269|PubMed:23840669}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:Q96D31}. Note=Colocalizes with STIM1 at
CC the cell membrane. {ECO:0000250|UniProtKB:Q96D31}.
CC -!- TISSUE SPECIFICITY: Expressed in lactating mammary epithelium (at
CC protein level). {ECO:0000269|PubMed:23840669}.
CC -!- PTM: N-glycosylated. N-glycosylation inhibits channel activity.
CC {ECO:0000250|UniProtKB:Q96D31}.
CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q96D31}.
CC -!- PTM: Cys-197 is oxidated, leading to inactivation of channel activity.
CC {ECO:0000250|UniProtKB:Q96D31}.
CC -!- SIMILARITY: Belongs to the Orai family. {ECO:0000305}.
CC -!- CAUTION: According to a report, ORAI1 has been shown to colocalize with
CC UBQLN1 in the autophagosome as a target for autophagic degradation;
CC ORAI1 is however not an autophagosomal protein.
CC {ECO:0000250|UniProtKB:Q96D31}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH23149.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK052573; BAC35045.1; -; mRNA.
DR EMBL; AK085755; BAC39533.1; -; mRNA.
DR EMBL; BC023149; AAH23149.1; ALT_INIT; mRNA.
DR CCDS; CCDS39261.1; -.
DR RefSeq; NP_780632.1; NM_175423.3.
DR AlphaFoldDB; Q8BWG9; -.
DR BMRB; Q8BWG9; -.
DR SMR; Q8BWG9; -.
DR BioGRID; 224640; 5.
DR STRING; 10090.ENSMUSP00000113097; -.
DR ChEMBL; CHEMBL4295887; -.
DR GlyGen; Q8BWG9; 1 site.
DR iPTMnet; Q8BWG9; -.
DR PhosphoSitePlus; Q8BWG9; -.
DR SwissPalm; Q8BWG9; -.
DR EPD; Q8BWG9; -.
DR MaxQB; Q8BWG9; -.
DR PaxDb; Q8BWG9; -.
DR PRIDE; Q8BWG9; -.
DR ProteomicsDB; 285263; -.
DR Antibodypedia; 73527; 485 antibodies from 38 providers.
DR DNASU; 109305; -.
DR Ensembl; ENSMUST00000051016; ENSMUSP00000058169; ENSMUSG00000049686.
DR Ensembl; ENSMUST00000121652; ENSMUSP00000113097; ENSMUSG00000049686.
DR GeneID; 109305; -.
DR KEGG; mmu:109305; -.
DR UCSC; uc008zmy.1; mouse.
DR CTD; 84876; -.
DR MGI; MGI:1925542; Orai1.
DR VEuPathDB; HostDB:ENSMUSG00000049686; -.
DR eggNOG; KOG4298; Eukaryota.
DR GeneTree; ENSGT00390000015354; -.
DR HOGENOM; CLU_062509_1_1_1; -.
DR InParanoid; Q8BWG9; -.
DR OMA; ADHDYPR; -.
DR OrthoDB; 1197243at2759; -.
DR PhylomeDB; Q8BWG9; -.
DR TreeFam; TF313576; -.
DR BioGRID-ORCS; 109305; 1 hit in 76 CRISPR screens.
DR ChiTaRS; Orai1; mouse.
DR PRO; PR:Q8BWG9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8BWG9; protein.
DR Bgee; ENSMUSG00000049686; Expressed in granulocyte and 201 other tissues.
DR ExpressionAtlas; Q8BWG9; baseline and differential.
DR Genevisible; Q8BWG9; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:MGI.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0044853; C:plasma membrane raft; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IPI:MGI.
DR GO; GO:0005262; F:calcium channel activity; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0015279; F:store-operated calcium channel activity; ISS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0070509; P:calcium ion import; IDA:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:MGI.
DR GO; GO:0061180; P:mammary gland epithelium development; IMP:MGI.
DR GO; GO:0045762; P:positive regulation of adenylate cyclase activity; ISS:UniProtKB.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISS:UniProtKB.
DR GO; GO:0051924; P:regulation of calcium ion transport; ISO:MGI.
DR GO; GO:0002115; P:store-operated calcium entry; IGI:MGI.
DR Gene3D; 1.20.140.140; -; 1.
DR InterPro; IPR012446; CRAC_channel.
DR InterPro; IPR038350; Orai_sf.
DR PANTHER; PTHR31501; PTHR31501; 1.
DR Pfam; PF07856; Orai-1; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Calcium; Calcium channel; Calcium transport;
KW Calmodulin-binding; Cell membrane; Glycoprotein; Immunity; Ion channel;
KW Ion transport; Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..304
FT /note="Calcium release-activated calcium channel protein 1"
FT /id="PRO_0000234382"
FT TOPO_DOM 1..89
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 90..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..121
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..175
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 197..237
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..304
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 72..92
FT /note="Interaction with STIM1"
FT /evidence="ECO:0000250"
FT REGION 275..295
FT /note="Interaction with STIM1"
FT /evidence="ECO:0000250"
FT MOD_RES 298
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96D31"
FT CARBOHYD 225
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 16
FT /note="L -> F (in Ref. 2; AAH23149)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 304 AA; 33062 MW; 9743395B63D2E41F CRC64;
MHPEPAPPPS HSNPELPVSG GSSTSGSRRS RRRSGDGEPS GAPPLPPPPP AVSYPDWIGQ
SYSEVMSLNE HSMQALSWRK LYLSRAKLKA SSRTSALLSG FAMVAMVEVQ LDTDHDYPPG
LLIVFSACTT VLVAVHLFAL MISTCILPNI EAVSNVHNLN SVKESPHERM HRHIELAWAF
STVIGTLLFL AEVVLLCWVK FLPLKRQAGQ PSPTKPPAES VIVANHSDSS GITPGEAAAI
ASTAIMVPCG LVFIVFAVHF YRSLVSHKTD RQFQELNELA EFARLQDQLD HRGDHSLTPG
THYA
