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Q9BSW2 (EFC4B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length395 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Hoxa1P090223EBI-739773,EBI-3957603From a different organism.
ORAI1Q96D316EBI-739773,EBI-2291476
STIM1Q135863EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 395395EF-hand calcium-binding domain-containing protein 4B
PRO_0000283046

Regions

Domain54 – 8229EF-hand 1
Domain84 – 11936EF-hand 2
Calcium binding97 – 10812 Ref.4
Coiled coil201 – 373173 Potential

Natural variations

Alternative sequence374 – 39522CVGGH…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 variant71R → G.
Corresponds to variant rs9788233 [ dbSNP | Ensembl ].
VAR_031483
Natural variant981A → T.
Corresponds to variant rs17836273 [ dbSNP | Ensembl ].
VAR_031484
Natural variant1281A → V. Ref.3
Corresponds to variant rs242017 [ dbSNP | Ensembl ].
VAR_031485
Natural variant1361H → P.
Corresponds to variant rs34088152 [ dbSNP | Ensembl ].
VAR_031486
Natural variant1541E → K. Ref.3
Corresponds to variant rs242018 [ dbSNP | Ensembl ].
VAR_031487
Natural variant2121H → Q.
Corresponds to variant rs36030417 [ dbSNP | Ensembl ].
VAR_031488

Experimental info

Mutagenesis97 – 993DAD → AAA in EF2MUT; enhanced STIM1 clustering and elevated cytoplasmic Ca2+, thereby causing cell death in T-cells. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 9A69FA0D8B769860

FASTA39545,592
        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 

« Hide

Isoform 2 [UniParc].

Checksum: DE746B5B604ACC44
Show »

FASTA73183,193

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS44803.1. [Q9BSW2-2]
CCDS8522.1. [Q9BSW2-1]
RefSeqNP_001138430.1. NM_001144958.1. [Q9BSW2-2]
NP_116069.1. NM_032680.3. [Q9BSW2-1]
UniGeneHs.504534.

3D structure databases

ProteinModelPortalQ9BSW2.
SMRQ9BSW2. Positions 55-116.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124247. 4 interactions.
IntActQ9BSW2. 7 interactions.
MINTMINT-1455075.
STRING9606.ENSP00000409382.

PTM databases

PhosphoSiteQ9BSW2.

Polymorphism databases

DMDM74761240.

Proteomic databases

MaxQBQ9BSW2.
PaxDbQ9BSW2.
PRIDEQ9BSW2.

Protocols and materials databases

DNASU84766.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252322; ENSP00000252322; ENSG00000130038. [Q9BSW2-1]
ENST00000440314; ENSP00000409382; ENSG00000130038. [Q9BSW2-2]
GeneID84766.
KEGGhsa:84766.
UCSCuc001qmj.2. human. [Q9BSW2-1]
uc010sen.1. human. [Q9BSW2-2]

Organism-specific databases

CTD84766.
GeneCardsGC12M003725.
HGNCHGNC:28657. EFCAB4B.
HPAHPA038686.
MIM614178. gene.
neXtProtNX_Q9BSW2.
PharmGKBPA144596438.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1100.
HOGENOMHOG000112335.
HOVERGENHBG107143.
InParanoidQ9BSW2.
KOK17199.
OMAEQPLSKC.
OrthoDBEOG7NW68N.
PhylomeDBQ9BSW2.
TreeFamTF329556.

Gene expression databases

ArrayExpressQ9BSW2.
BgeeQ9BSW2.
CleanExHS_EFCAB4B.
GenevestigatorQ9BSW2.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
SMARTSM00054. EFh. 2 hits.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi84766.
NextBio74911.
PROQ9BSW2.
SOURCESearch...

Entry information

Entry nameEFC4B_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM