CRACR2A
entrez
84766
canonical
uniprot
Q9BSW2
canonical
ensembl
ENSG00000130038
resolver
ensp
ENSP00000252322
resolver
ensp
ENSP00000409382
resolver
ensp
ENSP00000563505
resolver
ensp
ENSP00000714065
resolver
genesymbol
CRACR2A
resolver
genesymbol_syn
EFCAB4B
resolver
genesymbol_syn
RAB46
resolver
hgnc
HGNC:28657
resolver
uniprot
B4E1X0
resolver
uniprot
B9EK63
resolver
uniprot_entry
EFC4B_HUMAN
resolver
uniprot_sec
B4E1X0
resolver
uniprot_sec
B9EK63
resolver
amino_acid_sequence
MAAPDGRVVSRPQRLGQGSGQGPKGSGACLHPLDSLEQKETQEQTSGQLVMLRKAQEFFQTCDAEGKGFIARKDMQRLHKELPLSLEELEDVFDALDADGNGYLTPQEFTTGFSHFFFSQNNPSQEDAGEQVAQRHEEKVYLSRGDEDLGDMGEDEEAQFRMLMDRLGAQKVLEDESDVKQLWLQLKKEEPHLLSNFEDFLTRIISQLQEAHEEKNELECALKRKIAAYDEEIQHLYEEMEQQIKSEKEQFLLKDTERFQARSQELEQKLLCKEQELEQLTQKQKRLEGQCTALHHDKHETKAENTKLKLTNQELARELERTSWELQDAQQQLESLQQEACKLHQEKEMEVYRVTESLQREKAGLLKQLDFLRERNKHLRDERDICFQKNKAAKANTAASRASWKKRSGSVIGKYVDSRGILRSQSEEEEEVFGIPRRSSLGLSGYPLTEEEPGTGEPGPGGPYPRPLRRIISVEEDPLPQLLDGGFEQPLSKCSEEEEVSDQGVQGQIPEAPPLKLTPTSPRGQPVGKEALCKEESSPSAPDRLFKIVFVGNSAVGKTSFLRRFCEDRFSPGMAATVGIDYRVKTLNVDNSQVALQLWDTAGQERYRCITQQFFRKADGVIVMYDLTDKQSFLSVRRWLSSVEEAVGDRVPVLLLGNKLDNEKEREVPRGLGEQLATENNLIFYECSAYSGHNTKESLLHLARFLKEQEDTVREDTIQVGHPAKKKSCCG
uniprot
proteins
ec_number
3.6.5.2
uniprot
proteins
function
FUNCTION: [Isoform 1]: 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, ECO:0000269|PubMed:27016526}.; FUNCTION: [Isoform 2]: Rab GTPase that mediates the trafficking of Weibel-Palade bodies (WPBs) to microtubule organizing center (MTOC) in endothelial cells in response to acute inflammatory stimuli (PubMed:31092558). During histamine (but not thrombin) stimulation of endothelial cells, the dynein-bound form induces retrograde transport of a subset of WPBs along microtubules to the MTOC in a Ca(2+)-independent manner and its GTPase activity is essential for this function (PubMed:31092558). Ca(2+)-regulated dynein adapter protein that activates dynein-mediated transport and dynein-dynactin motility on microtubules and regulates endosomal trafficking of CD47 (PubMed:30814157). Acts as an intracellular signaling module bridging two important T-cell receptor (TCR) signaling pathways, Ca(2+)-NFAT and JNK, to affect T-cell activation (PubMed:27016526). In resting T-cells, is predominantly localized near TGN network in a GTP-bound form, upon TCR stimulation, localizes at the immunological synapse via interaction with VAV1 to activate downstream Ca(2+)-NFAT and JNK signaling pathways (PubMed:27016526). Plays a role in T-helper 1 (Th1) cell differentiation and T-helper 17 (Th17) cell effector function (PubMed:29987160). Plays a role in store-operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC channel activation (PubMed:27016526). {ECO:0000269|PubMed:27016526, ECO:0000269|PubMed:29987160, ECO:0000269|PubMed:30814157, ECO:0000269|PubMed:31092558}.
uniprot
proteins
mass_dalton
83193
uniprot
proteins
mutagenesis
MUTAGEN 63; /note="D->A: Loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with A-65; A-97 and A-99."; /evidence="ECO:0000269|PubMed:30814157"; MUTAGEN 65; /note="E->A: Loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with A-63; A-97 and A-99."; /evidence="ECO:0000269|PubMed:30814157"; MUTAGEN 97..99; /note="DAD->AAA: In EF2MUT; enhanced STIM1 clustering and elevated cytoplasmic Ca2+, thereby causing cell death in T-cells. Loss of calcium-binding. Can rescue JNK phosphorylation when expressed in CRACR2A-depleted T-cells. No effect on its localization to the Golgi membrane."; /evidence="ECO:0000269|PubMed:20418871, ECO:0000269|PubMed:27016526, ECO:0000269|PubMed:31092558"; MUTAGEN 97; /note="D->A: Loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with A-63; A-65 and A-99."; /evidence="ECO:0000269|PubMed:30814157"; MUTAGEN 99; /note="D->A: Loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with A-63; A-65 and A-97."; /evidence="ECO:0000269|PubMed:30814157"; MUTAGEN 559; /note="T->N: GDP-binding mutant with reduced GTPase activity and protein stability. Reduced ability to activate JNK signaling pathway. Failure to localize to the microtubule organizing center and Golgi apparatus membrane, instead shows a predominant localization to the cytoplasm."; /evidence="ECO:0000269|PubMed:27016526, ECO:0000269|PubMed:31092558"; MUTAGEN 604; /note="Q->L: GTP-binding mutant with reduced GTPase activity but increased protein stability. Increased ability to activate JNK signaling pathway. No effect on its localization to the microtubule organizing center or Golgi apparatus membrane."; /evidence="ECO:0000269|PubMed:27016526, ECO:0000269|PubMed:31092558"; MUTAGEN 658; /note="N->I: GTP/GDP-binding defective mutant with reduced GTPase activity and protein stability. Failure to localize to the microtubule organizing center and Golgi apparatus membrane, instead shows a predominant localization to the cytoplasm."; /evidence="ECO:0000269|PubMed:27016526, ECO:0000269|PubMed:31092558"; MUTAGEN 729..731; /note="Missing: Failure to localize to the Golgi membrane."; /evidence="ECO:0000269|PubMed:27016526
uniprot
proteins
protein_family
EFCAB4 family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
20418871
uniprot
proteins
pubmed
25475730
uniprot
proteins
pubmed
27016526
uniprot
proteins
pubmed
29987160
uniprot
proteins
pubmed
30814157
uniprot
proteins
pubmed
31092558
uniprot
proteins
sequence_length
731
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm {ECO:0000269|PubMed:20418871}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:30814157, ECO:0000269|PubMed:31092558}. Cytoplasm, cytoskeleton, microtubule organizing center {ECO:0000269|PubMed:30814157, ECO:0000269|PubMed:31092558}. Cell membrane {ECO:0000269|PubMed:30814157}. Golgi apparatus membrane {ECO:0000269|PubMed:27016526}. Golgi apparatus, trans-Golgi network membrane {ECO:0000269|PubMed:27016526}. Vesicle {ECO:0000269|PubMed:27016526}. Note=T-cell activation-induced elevation of intracellular of Ca(2+) stimulates its transport toward the microtubule organizing center (MTOC) (PubMed:30814157). Histamine stimulation induces a trafficking to the MTOC in a GTP-binding-dependent but Ca(2+)-binding-independent manner (PubMed:31092558). Localizes to Golgi membrane in resting T-cells and upon its interaction with VAV1, is translocated from the Golgi membrane to the immunological synapse via subsynaptic vesicles (PubMed:27016526). Its localization in the Golgi membrane requires isoprenylation and GTP-binding (PubMed:27016526). {ECO:0000269|PubMed:27016526, ECO:0000269|PubMed:30814157, ECO:0000269|PubMed:31092558}.
uniprot
proteins