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Protein

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

Gene

CRACR2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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
MIMi614178 gene
neXtProtiNX_Q9BSW2

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
ProteomicsDBi78930
78931 [Q9BSW2-2]
TopDownProteomicsiQ9BSW2-1 [Q9BSW2-1]
Q9BSW2-2 [Q9BSW2-2]

PTM databases

iPTMnetiQ9BSW2
PhosphoSitePlusiQ9BSW2

Expressioni

Gene expression databases

BgeeiENSG00000130038 Expressed in 160 organ(s), highest expression level in parotid gland
CleanExiHS_EFCAB4B
ExpressionAtlasiQ9BSW2 baseline and differential
GenevisibleiQ9BSW2 HS

Organism-specific databases

HPAiHPA038686

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

Protein-protein interaction databases

BioGridi124247, 12 interactors
IntActiQ9BSW2, 41 interactors
MINTiQ9BSW2
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
OMAiWKQRSGS
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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7BXT2H7BXT2_HUMAN
EF-hand calcium-binding domain-cont...
CRACR2A
198Annotation score:
H0YFI5H0YFI5_HUMAN
EF-hand calcium-binding domain-cont...
CRACR2A
118Annotation score:

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

Cross-referencesi

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

3D structure databases

ProteinModelPortaliQ9BSW2
SMRiQ9BSW2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124247, 12 interactors
IntActiQ9BSW2, 41 interactors
MINTiQ9BSW2
STRINGi9606.ENSP00000409382

Chemistry databases

BindingDBiQ9BSW2
ChEMBLiCHEMBL3638353

PTM databases

iPTMnetiQ9BSW2
PhosphoSitePlusiQ9BSW2

Polymorphism and mutation databases

BioMutaiEFCAB4B
DMDMi74761240

Proteomic databases

MaxQBiQ9BSW2
PaxDbiQ9BSW2
PeptideAtlasiQ9BSW2
PRIDEiQ9BSW2
ProteomicsDBi78930
78931 [Q9BSW2-2]
TopDownProteomicsiQ9BSW2-1 [Q9BSW2-1]
Q9BSW2-2 [Q9BSW2-2]

Protocols and materials databases

DNASUi84766
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi84766
DisGeNETi84766
EuPathDBiHostDB:ENSG00000130038.9
GeneCardsiCRACR2A
HGNCiHGNC:28657 CRACR2A
HPAiHPA038686
MIMi614178 gene
neXtProtiNX_Q9BSW2
OpenTargetsiENSG00000130038
PharmGKBiPA144596438
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-6798695 Neutrophil degranulation

Miscellaneous databases

ChiTaRSiCRACR2A human
GenomeRNAii84766
PROiPR:Q9BSW2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130038 Expressed in 160 organ(s), highest expression level in parotid gland
CleanExiHS_EFCAB4B
ExpressionAtlasiQ9BSW2 baseline and differential
GenevisibleiQ9BSW2 HS

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
ProtoNetiSearch...

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: November 7, 2018
This is version 141 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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