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Protein

EF-hand calcium-binding domain-containing protein 4B

Gene

CRACR2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi97 – 108Add BLAST12

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB

GO - Biological processi

  • activation of store-operated calcium channel activity Source: UniProtKB
  • adaptive immune response Source: UniProtKB-KW
  • neutrophil degranulation Source: Reactome
  • positive regulation of calcium ion transport Source: UniProtKB
  • store-operated calcium entry Source: UniProtKB

Keywordsi

Biological processAdaptive immunity, Calcium transport, Immunity, Ion transport, Transport
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-6798695. Neutrophil degranulation.

Names & Taxonomyi

Protein namesi
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
Calcium release-activated channel regulator 2A
Gene namesi
Name:CRACR2A
Synonyms:EFCAB4B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000130038.9.
HGNCiHGNC:28657. CRACR2A.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi97 – 99DAD → AAA in EF2MUT; enhanced STIM1 clustering and elevated cytoplasmic Ca2+, thereby causing cell death in T-cells. 1 Publication3

Organism-specific databases

DisGeNETi84766.
OpenTargetsiENSG00000130038.
PharmGKBiPA144596438.

Chemistry databases

ChEMBLiCHEMBL3638353.

Polymorphism and mutation databases

BioMutaiEFCAB4B.
DMDMi74761240.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002830461 – 395EF-hand calcium-binding domain-containing protein 4BAdd BLAST395

Proteomic databases

MaxQBiQ9BSW2.
PaxDbiQ9BSW2.
PeptideAtlasiQ9BSW2.
PRIDEiQ9BSW2.
TopDownProteomicsiQ9BSW2-1. [Q9BSW2-1]
Q9BSW2-2. [Q9BSW2-2]

PTM databases

iPTMnetiQ9BSW2.
PhosphoSitePlusiQ9BSW2.

Expressioni

Gene expression databases

BgeeiENSG00000130038.
CleanExiHS_EFCAB4B.
ExpressionAtlasiQ9BSW2. baseline and differential.
GenevisibleiQ9BSW2. HS.

Organism-specific databases

HPAiHPA038685.
HPA038686.

Interactioni

Subunit structurei

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 ORAI3.1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi124247. 12 interactors.
IntActiQ9BSW2. 34 interactors.
MINTiMINT-1455075.
STRINGi9606.ENSP00000409382.

Chemistry databases

BindingDBiQ9BSW2.

Structurei

3D structure databases

ProteinModelPortaliQ9BSW2.
SMRiQ9BSW2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 82EF-hand 1PROSITE-ProRule annotationAdd BLAST29
Domaini84 – 119EF-hand 2PROSITE-ProRule annotationAdd BLAST36

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili201 – 373Sequence analysisAdd BLAST173

Sequence similaritiesi

Belongs to the EFCAB4 family.Curated

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiENOG410IFG3. Eukaryota.
ENOG410YP84. LUCA.
GeneTreeiENSGT00440000033504.
HOGENOMiHOG000112335.
HOVERGENiHBG107143.
InParanoidiQ9BSW2.
KOiK17199.
OMAiEQPLSKC.
OrthoDBiEOG091G0CBJ.
PhylomeDBiQ9BSW2.
TreeFamiTF329556.

Family and domain databases

InterProiView protein in InterPro
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
PfamiView protein in Pfam
PF13499. EF-hand_7. 1 hit.
SMARTiView protein in SMART
SM00054. EFh. 2 hits.
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiView protein in PROSITE
PS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BSW2-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAAPDGRVVS RPQRLGQGSG QGPKGSGACL HPLDSLEQKE TQEQTSGQLV
60 70 80 90 100
MLRKAQEFFQ TCDAEGKGFI ARKDMQRLHK ELPLSLEELE DVFDALDADG
110 120 130 140 150
NGYLTPQEFT TGFSHFFFSQ NNPSQEDAGE QVAQRHEEKV YLSRGDEDLG
160 170 180 190 200
DMGEDEEAQF RMLMDRLGAQ KVLEDESDVK QLWLQLKKEE PHLLSNFEDF
210 220 230 240 250
LTRIISQLQE AHEEKNELEC ALKRKIAAYD EEIQHLYEEM EQQIKSEKEQ
260 270 280 290 300
FLLKDTERFQ ARSQELEQKL LCKEQELEQL TQKQKRLEGQ CTALHHDKHE
310 320 330 340 350
TKAENTKLKL TNQELARELE RTSWELQDAQ QQLESLQQEA CKLHQEKEME
360 370 380 390
VYRVTESLQR EKAGLLKQLD FLRCVGGHWP VLRAPPRSLG SEGPV
Length:395
Mass (Da):45,592
Last modified:June 1, 2001 - v1
Checksum:i9A69FA0D8B769860
GO
Isoform 2 (identifier: Q9BSW2-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:731
Mass (Da):83,193
Checksum:iDE746B5B604ACC44
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0314837R → G. Corresponds to variant dbSNP:rs9788233Ensembl.1
Natural variantiVAR_03148498A → T. Corresponds to variant dbSNP:rs17836273Ensembl.1
Natural variantiVAR_031485128A → V1 PublicationCorresponds to variant dbSNP:rs242017Ensembl.1
Natural variantiVAR_031486136H → P. Corresponds to variant dbSNP:rs34088152Ensembl.1
Natural variantiVAR_031487154E → K1 PublicationCorresponds to variant dbSNP:rs242018Ensembl.1
Natural variantiVAR_031488212H → Q. Corresponds to variant dbSNP:rs36030417Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_039546374 – 395CVGGH…SEGPV → ERNKHLRDERDICFQKNKAA KANTAASRASWKKRSGSVIG KYVDSRGILRSQSEEEEEVF GIPRRSSLGLSGYPLTEEEP GTGEPGPGGPYPRPLRRIIS VEEDPLPQLLDGGFEQPLSK CSEEEEVSDQGVQGQIPEAP PLKLTPTSPRGQPVGKEALC KEESSPSAPDRLFKIVFVGN SAVGKTSFLRRFCEDRFSPG MAATVGIDYRVKTLNVDNSQ VALQLWDTAGQERYRCITQQ FFRKADGVIVMYDLTDKQSF LSVRRWLSSVEEAVGDRVPV LLLGNKLDNEKEREVPRGLG EQLATENNLIFYECSAYSGH NTKESLLHLARFLKEQEDTV REDTIQVGHPAKKKSCCG in isoform 2. 1 PublicationAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS44803.1. [Q9BSW2-2]
CCDS8522.1. [Q9BSW2-1]
RefSeqiNP_001138430.1. NM_001144958.1. [Q9BSW2-2]
NP_116069.1. NM_032680.3. [Q9BSW2-1]
UniGeneiHs.504534.

Genome annotation databases

EnsembliENST00000252322; ENSP00000252322; ENSG00000130038. [Q9BSW2-1]
ENST00000440314; ENSP00000409382; ENSG00000130038. [Q9BSW2-2]
GeneIDi84766.
KEGGihsa:84766.
UCSCiuc001qmj.3. human. [Q9BSW2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiEFC4B_HUMAN
AccessioniPrimary (citable) accession number: Q9BSW2
Secondary accession number(s): B4E1X0, B9EK63
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: June 1, 2001
Last modified: September 27, 2017
This is version 136 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families