Q9BSW2 (EFC4B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
EF-hand calcium-binding domain-containing protein 4B

Alternative name(s):
Calcium release-activated calcium channel regulator 2A
Short name=CRAC channel regulator 2A

Gene names

Name:	EFCAB4B
Synonyms:	CRACR2A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	395 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ca2+-binding protein that plays a key role in store-operated Ca2+ 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 Ca2+ concentration. It thereby regulates CRAC channel activation, including translocation and clustering of ORAI1 and STIM1. Upon increase of cytoplasmic Ca2+ resulting from opening of CRAC channels, dissociates from ORAI1 and STIM1, thereby destabilizing the ORAI1-STIM1 complex. Ref.4
Subunit structure	Interacts with ORAI1 and STIM1; the interaction is direct and takes place in absence of Ca2+. Forms a complex with ORAI1 and STIM1 at low concentration of Ca2+, the complex dissociates at elevated Ca2+ concentrations. Interacts with ORAI2 and ORAI3. Ref.4
Subcellular location	Cytoplasm Ref.4.
Sequence similarities	Belongs to the EFCAB4 family. Contains 2 EF-hand domains.

Ontologies

Keywords
Biological process	Adaptive immunity Calcium transport Immunity Ion transport Transport
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Repeat
Ligand	Calcium Metal-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of store-operated calcium channel activity Inferred from mutant phenotype Ref.4. Source: UniProtKB positive regulation of calcium ion transport Inferred from mutant phenotype Ref.4. Source: UniProtKB store-operated calcium entry Inferred from mutant phenotype Ref.4. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from direct assay. Source: HPA nucleolus Inferred from direct assay. Source: HPA
Molecular_function	calcium ion binding Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Hoxa1	P09022	3	EBI-739773,EBI-3957603	From a different organism.
ORAI1	Q96D31	6	EBI-739773,EBI-2291476
STIM1	Q13586	3	EBI-739773,EBI-448878

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BSW2-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9BSW2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     374-395: CVGGHWPVLRAPPRSLGSEGPV → ERNKHLRDER...HPAKKKSCCG

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 395	395	EF-hand calcium-binding domain-containing protein 4B		PRO_0000283046
Regions
	Domain	54 – 82	29	EF-hand 1
	Domain	84 – 119	36	EF-hand 2
	Calcium binding	97 – 108	12	Ref.4
	Coiled coil	201 – 373	173	Potential
Natural variations
	Alternative sequence	374 – 395	22	CVGGH…SEGPV → ERNKHLRDERDICFQKNKAA KANTAASRASWKKRSGSVIG KYVDSRGILRSQSEEEEEVF GIPRRSSLGLSGYPLTEEEP GTGEPGPGGPYPRPLRRIIS VEEDPLPQLLDGGFEQPLSK CSEEEEVSDQGVQGQIPEAP PLKLTPTSPRGQPVGKEALC KEESSPSAPDRLFKIVFVGN SAVGKTSFLRRFCEDRFSPG MAATVGIDYRVKTLNVDNSQ VALQLWDTAGQERYRCITQQ FFRKADGVIVMYDLTDKQSF LSVRRWLSSVEEAVGDRVPV LLLGNKLDNEKEREVPRGLG EQLATENNLIFYECSAYSGH NTKESLLHLARFLKEQEDTV REDTIQVGHPAKKKSCCG in isoform 2.		VSP_039546
	Natural variant	7	1	R → G. Corresponds to variant rs9788233 [ dbSNP | Ensembl ].		VAR_031483
	Natural variant	98	1	A → T. Corresponds to variant rs17836273 [ dbSNP | Ensembl ].		VAR_031484
	Natural variant	128	1	A → V. Ref.3 Corresponds to variant rs242017 [ dbSNP | Ensembl ].		VAR_031485
	Natural variant	136	1	H → P. Corresponds to variant rs34088152 [ dbSNP | Ensembl ].		VAR_031486
	Natural variant	154	1	E → K. Ref.3 Corresponds to variant rs242018 [ dbSNP | Ensembl ].		VAR_031487
	Natural variant	212	1	H → Q. Corresponds to variant rs36030417 [ dbSNP | Ensembl ].		VAR_031488
Experimental info
	Mutagenesis	97 – 99	3	DAD → AAA in EF2MUT; enhanced STIM1 clustering and elevated cytoplasmic Ca2+, thereby causing cell death in T-cells. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 9A69FA0D8B769860	FASTA	395	45,592
	10 20 30 40 50 60 MAAPDGRVVS RPQRLGQGSG QGPKGSGACL HPLDSLEQKE TQEQTSGQLV MLRKAQEFFQ 70 80 90 100 110 120 TCDAEGKGFI ARKDMQRLHK ELPLSLEELE DVFDALDADG NGYLTPQEFT TGFSHFFFSQ 130 140 150 160 170 180 NNPSQEDAGE QVAQRHEEKV YLSRGDEDLG DMGEDEEAQF RMLMDRLGAQ KVLEDESDVK 190 200 210 220 230 240 QLWLQLKKEE PHLLSNFEDF LTRIISQLQE AHEEKNELEC ALKRKIAAYD EEIQHLYEEM 250 260 270 280 290 300 EQQIKSEKEQ FLLKDTERFQ ARSQELEQKL LCKEQELEQL TQKQKRLEGQ CTALHHDKHE 310 320 330 340 350 360 TKAENTKLKL TNQELARELE RTSWELQDAQ QQLESLQQEA CKLHQEKEME VYRVTESLQR 370 380 390 EKAGLLKQLD FLRCVGGHWP VLRAPPRSLG SEGPV
	Isoform 2 [UniParc]. Checksum: DE746B5B604ACC44	FASTA	731	83,193
	10 20 30 40 50 60 MAAPDGRVVS RPQRLGQGSG QGPKGSGACL HPLDSLEQKE TQEQTSGQLV MLRKAQEFFQ 70 80 90 100 110 120 TCDAEGKGFI ARKDMQRLHK ELPLSLEELE DVFDALDADG NGYLTPQEFT TGFSHFFFSQ 130 140 150 160 170 180 NNPSQEDAGE QVAQRHEEKV YLSRGDEDLG DMGEDEEAQF RMLMDRLGAQ KVLEDESDVK 190 200 210 220 230 240 QLWLQLKKEE PHLLSNFEDF LTRIISQLQE AHEEKNELEC ALKRKIAAYD EEIQHLYEEM 250 260 270 280 290 300 EQQIKSEKEQ FLLKDTERFQ ARSQELEQKL LCKEQELEQL TQKQKRLEGQ CTALHHDKHE 310 320 330 340 350 360 TKAENTKLKL TNQELARELE RTSWELQDAQ QQLESLQQEA CKLHQEKEME VYRVTESLQR 370 380 390 400 410 420 EKAGLLKQLD FLRERNKHLR DERDICFQKN KAAKANTAAS RASWKKRSGS VIGKYVDSRG 430 440 450 460 470 480 ILRSQSEEEE EVFGIPRRSS LGLSGYPLTE EEPGTGEPGP GGPYPRPLRR IISVEEDPLP 490 500 510 520 530 540 QLLDGGFEQP LSKCSEEEEV SDQGVQGQIP EAPPLKLTPT SPRGQPVGKE ALCKEESSPS 550 560 570 580 590 600 APDRLFKIVF VGNSAVGKTS FLRRFCEDRF SPGMAATVGI DYRVKTLNVD NSQVALQLWD 610 620 630 640 650 660 TAGQERYRCI TQQFFRKADG VIVMYDLTDK QSFLSVRRWL SSVEEAVGDR VPVLLLGNKL 670 680 690 700 710 720 DNEKEREVPR GLGEQLATEN NLIFYECSAY SGHNTKESLL HLARFLKEQE DTVREDTIQV 730 GHPAKKKSCC G

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Trachea.
[2]	"The finished DNA sequence of human chromosome 12." 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. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS VAL-128 AND LYS-154. Tissue: Brain and Muscle.
[4]	"A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that stabilizes CRAC channels in T cells." Srikanth S., Jung H.J., Kim K.D., Souda P., Whitelegge J., Gwack Y. Nat. Cell Biol. 12:436-446(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, CALCIUM-BINDING, INTERACTION WITH ORAI1; ORAI2; ORAI3 AND STIM1, MUTAGENESIS OF 97-ASP--ASP-99.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK304017 mRNA. Translation: BAG64932.1. AC005831 Genomic DNA. No translation available. AC006207 Genomic DNA. No translation available. BC004524 mRNA. Translation: AAH04524.1. BC150643 mRNA. Translation: AAI50644.1.
IPI	IPI00013398. IPI00884187.
RefSeq	NP_001138430.1. NM_001144958.1. NP_116069.1. NM_032680.3.
UniGene	Hs.504534.
3D structure databases
HSSP	HSSP built from PDB template 2A4J based on UniProtKB P41208.
ProteinModelPortal	Q9BSW2.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BSW2. 7 interactions.
MINT	MINT-1455075.
STRING	9606.ENSP00000409382.
PTM databases
PhosphoSite	Q9BSW2.
Polymorphism databases
DMDM	74761240.
Proteomic databases
PaxDb	Q9BSW2.
PRIDE	Q9BSW2.
Protocols and materials databases
DNASU	84766.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000252322; ENSP00000252322; ENSG00000130038. ENST00000440314; ENSP00000409382; ENSG00000130038.
GeneID	84766.
KEGG	hsa:84766.
UCSC	uc001qmj.2. human. uc010sen.1. human.
Organism-specific databases
CTD	84766.
GeneCards	GC12M003724.
HGNC	HGNC:28657. EFCAB4B.
HPA	HPA038686.
MIM	614178. gene.
neXtProt	NX_Q9BSW2.
PharmGKB	PA144596438.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1100.
HOGENOM	HOG000112335.
HOVERGEN	HBG107143.
InParanoid	Q9BSW2.
OMA	EQPLSKC.
OrthoDB	EOG4XWFZC.
PhylomeDB	Q9BSW2.
Gene expression databases
ArrayExpress	Q9BSW2.
Bgee	Q9BSW2.
CleanEx	HS_EFCAB4B.
Genevestigator	Q9BSW2.
Family and domain databases
Gene3D	1.10.238.10. 1 hit.
InterPro	IPR011992. EF-hand-like_dom. IPR018247. EF_Hand_1_Ca_BS. IPR002048. EF_hand_dom. [Graphical view]
SMART	SM00054. EFh. 2 hits. [Graphical view]
PROSITE	PS00018. EF_HAND_1. 1 hit. PS50222. EF_HAND_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	84766.
NextBio	74911.
SOURCE	Search...

Entry information

Entry name

EFC4B_HUMAN

Accession

Primary (citable) accession number: Q9BSW2
Secondary accession number(s): B4E1X0, B9EK63

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 3, 2007
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.