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EF-hand calcium-binding domain-containing protein 4B (Calcium release-activated calcium channel regulator 2A) (CRAC channel regulator 2A) (Calcium release-activated channel regulator 2A)

 EFC4B_HUMAN             Reviewed;         395 AA.
Q9BSW2; B4E1X0; B9EK63;
03-APR-2007, integrated into UniProtKB/Swiss-Prot.
01-JUN-2001, sequence version 1.
12-SEP-2018, entry version 140.
RecName: Full=EF-hand calcium-binding domain-containing protein 4B;
AltName: Full=Calcium release-activated calcium channel regulator 2A;
Short=CRAC channel regulator 2A;
AltName: Full=Calcium release-activated channel regulator 2A;
Name=CRACR2A; Synonyms=EFCAB4B;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Trachea;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16541075; DOI=10.1038/nature04569;
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
Kucherlapati R., Weinstock G., Gibbs R.A.;
"The finished DNA sequence of human chromosome 12.";
Nature 440:346-351(2006).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
VAL-128 AND LYS-154.
TISSUE=Brain, and Muscle;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
FUNCTION, SUBCELLULAR LOCATION, CALCIUM-BINDING, INTERACTION WITH
ORAI1; ORAI2; ORAI3 AND STIM1, AND MUTAGENESIS OF 97-ASP--ASP-99.
PubMed=20418871; DOI=10.1038/ncb2045;
Srikanth S., Jung H.J., Kim K.D., Souda P., Whitelegge J., Gwack Y.;
"A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that
stabilizes CRAC channels in T cells.";
Nat. Cell Biol. 12:436-446(2010).
-!- FUNCTION: Ca(2+)-binding protein that plays a key role in store-
operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC channel
activation. Acts as a cytoplasmic calcium-sensor that facilitates
the clustering of ORAI1 and STIM1 at the junctional regions
between the plasma membrane and the endoplasmic reticulum upon low
Ca(2+) concentration. It thereby regulates CRAC channel
activation, including translocation and clustering of ORAI1 and
STIM1. Upon increase of cytoplasmic Ca(2+) resulting from opening
of CRAC channels, dissociates from ORAI1 and STIM1, thereby
destabilizing the ORAI1-STIM1 complex.
{ECO:0000269|PubMed:20418871}.
-!- SUBUNIT: Interacts with ORAI1 and STIM1; the interaction is direct
and takes place in absence of Ca(2+). Forms a complex with ORAI1
and STIM1 at low concentration of Ca(2+), the complex dissociates
at elevated Ca(2+) concentrations. Interacts with ORAI2 and ORAI3.
{ECO:0000269|PubMed:20418871}.
-!- INTERACTION:
Q08117:AES; NbExp=3; IntAct=EBI-739773, EBI-717810;
Q9UJX2:CDC23; NbExp=3; IntAct=EBI-739773, EBI-396137;
Q8NDB6:FAM156A; NbExp=6; IntAct=EBI-739773, EBI-749727;
P09022:Hoxa1 (xeno); NbExp=3; IntAct=EBI-739773, EBI-3957603;
Q13064:MKRN3; NbExp=3; IntAct=EBI-739773, EBI-2340269;
Q7Z3S9:NOTCH2NL; NbExp=3; IntAct=EBI-739773, EBI-945833;
Q96D31:ORAI1; NbExp=6; IntAct=EBI-739773, EBI-2291476;
Q13586:STIM1; NbExp=3; IntAct=EBI-739773, EBI-448878;
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20418871}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q9BSW2-1; Sequence=Displayed;
Name=2;
IsoId=Q9BSW2-2; Sequence=VSP_039546;
Note=No experimental confirmation available.;
-!- SIMILARITY: Belongs to the EFCAB4 family. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; AK304017; BAG64932.1; -; mRNA.
EMBL; AC005831; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC006207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC004524; AAH04524.1; -; mRNA.
EMBL; BC150643; AAI50644.1; -; mRNA.
CCDS; CCDS44803.1; -. [Q9BSW2-2]
CCDS; CCDS8522.1; -. [Q9BSW2-1]
RefSeq; NP_001138430.1; NM_001144958.1. [Q9BSW2-2]
RefSeq; NP_116069.1; NM_032680.3. [Q9BSW2-1]
UniGene; Hs.504534; -.
ProteinModelPortal; Q9BSW2; -.
SMR; Q9BSW2; -.
BioGrid; 124247; 12.
IntAct; Q9BSW2; 41.
MINT; Q9BSW2; -.
STRING; 9606.ENSP00000409382; -.
BindingDB; Q9BSW2; -.
ChEMBL; CHEMBL3638353; -.
iPTMnet; Q9BSW2; -.
PhosphoSitePlus; Q9BSW2; -.
BioMuta; EFCAB4B; -.
DMDM; 74761240; -.
MaxQB; Q9BSW2; -.
PaxDb; Q9BSW2; -.
PeptideAtlas; Q9BSW2; -.
PRIDE; Q9BSW2; -.
ProteomicsDB; 78930; -.
ProteomicsDB; 78931; -. [Q9BSW2-2]
TopDownProteomics; Q9BSW2-1; -. [Q9BSW2-1]
TopDownProteomics; Q9BSW2-2; -. [Q9BSW2-2]
DNASU; 84766; -.
Ensembl; ENST00000252322; ENSP00000252322; ENSG00000130038. [Q9BSW2-1]
Ensembl; ENST00000440314; ENSP00000409382; ENSG00000130038. [Q9BSW2-2]
GeneID; 84766; -.
KEGG; hsa:84766; -.
UCSC; uc001qmj.3; human. [Q9BSW2-1]
CTD; 84766; -.
DisGeNET; 84766; -.
EuPathDB; HostDB:ENSG00000130038.9; -.
GeneCards; CRACR2A; -.
HGNC; HGNC:28657; CRACR2A.
HPA; HPA038686; -.
MIM; 614178; gene.
neXtProt; NX_Q9BSW2; -.
OpenTargets; ENSG00000130038; -.
PharmGKB; PA144596438; -.
eggNOG; ENOG410IFG3; Eukaryota.
eggNOG; ENOG410YP84; LUCA.
GeneTree; ENSGT00440000033504; -.
HOGENOM; HOG000112335; -.
HOVERGEN; HBG107143; -.
InParanoid; Q9BSW2; -.
KO; K17199; -.
OMA; EQPLSKC; -.
OrthoDB; EOG091G0CBJ; -.
PhylomeDB; Q9BSW2; -.
TreeFam; TF329556; -.
Reactome; R-HSA-6798695; Neutrophil degranulation.
ChiTaRS; CRACR2A; human.
GenomeRNAi; 84766; -.
PRO; PR:Q9BSW2; -.
Proteomes; UP000005640; Chromosome 12.
Bgee; ENSG00000130038; Expressed in 160 organ(s), highest expression level in parotid gland.
CleanEx; HS_EFCAB4B; -.
ExpressionAtlas; Q9BSW2; baseline and differential.
Genevisible; Q9BSW2; HS.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0016020; C:membrane; HDA:UniProtKB.
GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
GO; GO:0032237; P:activation of store-operated calcium channel activity; IMP:UniProtKB.
GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome.
GO; GO:0051928; P:positive regulation of calcium ion transport; IMP:UniProtKB.
GO; GO:0002115; P:store-operated calcium entry; IMP:UniProtKB.
InterPro; IPR011992; EF-hand-dom_pair.
InterPro; IPR018247; EF_Hand_1_Ca_BS.
InterPro; IPR002048; EF_hand_dom.
Pfam; PF13499; EF-hand_7; 1.
SMART; SM00054; EFh; 2.
SUPFAM; SSF47473; SSF47473; 1.
PROSITE; PS00018; EF_HAND_1; 1.
PROSITE; PS50222; EF_HAND_2; 1.
1: Evidence at protein level;
Adaptive immunity; Alternative splicing; Calcium; Calcium transport;
Coiled coil; Complete proteome; Cytoplasm; Immunity; Ion transport;
Metal-binding; Polymorphism; Reference proteome; Repeat; Transport.
CHAIN 1 395 EF-hand calcium-binding domain-containing
protein 4B.
/FTId=PRO_0000283046.
DOMAIN 54 82 EF-hand 1. {ECO:0000255|PROSITE-
ProRule:PRU00448}.
DOMAIN 84 119 EF-hand 2. {ECO:0000255|PROSITE-
ProRule:PRU00448}.
CA_BIND 97 108
COILED 201 373 {ECO:0000255}.
VAR_SEQ 374 395 CVGGHWPVLRAPPRSLGSEGPV -> ERNKHLRDERDICFQ
KNKAAKANTAASRASWKKRSGSVIGKYVDSRGILRSQSEEE
EEVFGIPRRSSLGLSGYPLTEEEPGTGEPGPGGPYPRPLRR
IISVEEDPLPQLLDGGFEQPLSKCSEEEEVSDQGVQGQIPE
APPLKLTPTSPRGQPVGKEALCKEESSPSAPDRLFKIVFVG
NSAVGKTSFLRRFCEDRFSPGMAATVGIDYRVKTLNVDNSQ
VALQLWDTAGQERYRCITQQFFRKADGVIVMYDLTDKQSFL
SVRRWLSSVEEAVGDRVPVLLLGNKLDNEKEREVPRGLGEQ
LATENNLIFYECSAYSGHNTKESLLHLARFLKEQEDTVRED
TIQVGHPAKKKSCCG (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_039546.
VARIANT 7 7 R -> G (in dbSNP:rs9788233).
/FTId=VAR_031483.
VARIANT 98 98 A -> T (in dbSNP:rs17836273).
/FTId=VAR_031484.
VARIANT 128 128 A -> V (in dbSNP:rs242017).
{ECO:0000269|PubMed:15489334}.
/FTId=VAR_031485.
VARIANT 136 136 H -> P (in dbSNP:rs34088152).
/FTId=VAR_031486.
VARIANT 154 154 E -> K (in dbSNP:rs242018).
{ECO:0000269|PubMed:15489334}.
/FTId=VAR_031487.
VARIANT 212 212 H -> Q (in dbSNP:rs36030417).
/FTId=VAR_031488.
MUTAGEN 97 99 DAD->AAA: In EF2MUT; enhanced STIM1
clustering and elevated cytoplasmic Ca2+,
thereby causing cell death in T-cells.
{ECO:0000269|PubMed:20418871}.
SEQUENCE 395 AA; 45592 MW; 9A69FA0D8B769860 CRC64;
MAAPDGRVVS RPQRLGQGSG QGPKGSGACL HPLDSLEQKE TQEQTSGQLV MLRKAQEFFQ
TCDAEGKGFI ARKDMQRLHK ELPLSLEELE DVFDALDADG NGYLTPQEFT TGFSHFFFSQ
NNPSQEDAGE QVAQRHEEKV YLSRGDEDLG DMGEDEEAQF RMLMDRLGAQ KVLEDESDVK
QLWLQLKKEE PHLLSNFEDF LTRIISQLQE AHEEKNELEC ALKRKIAAYD EEIQHLYEEM
EQQIKSEKEQ FLLKDTERFQ ARSQELEQKL LCKEQELEQL TQKQKRLEGQ CTALHHDKHE
TKAENTKLKL TNQELARELE RTSWELQDAQ QQLESLQQEA CKLHQEKEME VYRVTESLQR
EKAGLLKQLD FLRCVGGHWP VLRAPPRSLG SEGPV


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