EFC4B_HUMAN
ID EFC4B_HUMAN Reviewed; 731 AA.
AC Q9BSW2; B4E1X0; B9EK63;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-APR-2021, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=EF-hand calcium-binding domain-containing protein 4B;
DE AltName: Full=Calcium release-activated calcium channel regulator 2A;
DE Short=CRAC channel regulator 2A;
DE AltName: Full=Calcium release-activated channel regulator 2A;
DE AltName: Full=Ras-related protein Rab-46 {ECO:0000303|PubMed:31092558};
GN Name=CRACR2A; Synonyms=EFCAB4B, RAB46 {ECO:0000303|PubMed:31092558};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS VAL-128
RP AND LYS-154.
RC TISSUE=Brain, and Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY (ISOFORM 2).
RX PubMed=25475730; DOI=10.1016/j.bbrc.2014.11.095;
RA Wilson L.A., McKeown L., Tumova S., Li J., Beech D.J.;
RT "Expression of a long variant of CRACR2A that belongs to the Rab GTPase
RT protein family in endothelial cells.";
RL Biochem. Biophys. Res. Commun. 456:398-402(2015).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORMS 1 AND 2),
RP SUBCELLULAR LOCATION (ISOFORM 2), TISSUE SPECIFICITY (ISOFORMS 1 AND 2),
RP INTERACTION WITH VAV1 (ISOFORM 2), MUTAGENESIS OF 97-ASP--ASP-99; THR-559;
RP GLN-604; ASN-658 AND 729-CYS--GLY-731, AND ISOPRENYLATION AT CYS-729
RP (ISOFORM 2).
RX PubMed=27016526; DOI=10.1126/scisignal.aac9171;
RA Srikanth S., Kim K.D., Gao Y., Woo J.S., Ghosh S., Calmettes G., Paz A.,
RA Abramson J., Jiang M., Gwack Y.;
RT "A large Rab GTPase encoded by CRACR2A is a component of subsynaptic
RT vesicles that transmit T cell activation signals.";
RL Sci. Signal. 9:ra31-ra31(2016).
RN [6]
RP FUNCTION (ISOFORM 1), SUBCELLULAR LOCATION (ISOFORM 1), CALCIUM-BINDING
RP (ISOFORM 1), INTERACTION WITH ORAI1; ORAI2; ORAI3 AND STIM1 (ISOFORM 1),
RP AND MUTAGENESIS OF 97-ASP--ASP-99.
RX PubMed=20418871; DOI=10.1038/ncb2045;
RA Srikanth S., Jung H.J., Kim K.D., Souda P., Whitelegge J., Gwack Y.;
RT "A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that
RT stabilizes CRAC channels in T cells.";
RL Nat. Cell Biol. 12:436-446(2010).
RN [7]
RP FUNCTION (ISOFORM 2).
RX PubMed=29987160; DOI=10.4049/jimmunol.1800659;
RA Woo J.S., Srikanth S., Kim K.D., Elsaesser H., Lu J., Pellegrini M.,
RA Brooks D.G., Sun Z., Gwack Y.;
RT "CRACR2A-Mediated TCR Signaling Promotes Local Effector Th1 and Th17
RT Responses.";
RL J. Immunol. 201:1174-1185(2018).
RN [8]
RP FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), INTERACTION WITH
RP THE DYNEIN-DYNACTIN COMPLEX (ISOFORM 2), MUTAGENESIS OF ASP-63; GLU-65;
RP ASP-97 AND ASP-99, AND TISSUE SPECIFICITY (ISOFORM 2).
RX PubMed=30814157; DOI=10.1083/jcb.201806097;
RA Wang Y., Huynh W., Skokan T.D., Lu W., Weiss A., Vale R.D.;
RT "CRACR2a is a calcium-activated dynein adaptor protein that regulates
RT endocytic traffic.";
RL J. Cell Biol. 218:1619-1633(2019).
RN [9]
RP FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), INTERACTION WITH
RP DYNC1H1 (ISOFORM 2), MUTAGENESIS OF THR-559; GLN-604 AND ASN-658 (ISOFORM
RP 2), AND TISSUE SPECIFICITY (ISOFORM 2).
RX PubMed=31092558; DOI=10.1083/jcb.201810118;
RA Miteva K.T., Pedicini L., Wilson L.A., Jayasinghe I., Slip R.G.,
RA Marszalek K., Gaunt H.J., Bartoli F., Deivasigamani S., Sobradillo D.,
RA Beech D.J., McKeown L.;
RT "Rab46 integrates Ca2+ and histamine signaling to regulate selective cargo
RT release from Weibel-Palade bodies.";
RL J. Cell Biol. 218:2232-2246(2019).
CC -!- FUNCTION: [Isoform 1]: Ca(2+)-binding protein that plays a key role in
CC store-operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC
CC channel activation. Acts as a cytoplasmic calcium-sensor that
CC facilitates the clustering of ORAI1 and STIM1 at the junctional regions
CC between the plasma membrane and the endoplasmic reticulum upon low
CC Ca(2+) concentration. It thereby regulates CRAC channel activation,
CC including translocation and clustering of ORAI1 and STIM1. Upon
CC increase of cytoplasmic Ca(2+) resulting from opening of CRAC channels,
CC dissociates from ORAI1 and STIM1, thereby destabilizing the ORAI1-STIM1
CC complex. {ECO:0000269|PubMed:20418871, ECO:0000269|PubMed:27016526}.
CC -!- FUNCTION: [Isoform 2]: Rab GTPase that mediates the trafficking of
CC Weibel-Palade bodies (WPBs) to microtubule organizing center (MTOC) in
CC endothelial cells in response to acute inflammatory stimuli
CC (PubMed:31092558). During histamine (but not thrombin) stimulation of
CC endothelial cells, the dynein-bound form induces retrograde transport
CC of a subset of WPBs along microtubules to the MTOC in a Ca(2+)-
CC independent manner and its GTPase activity is essential for this
CC function (PubMed:31092558). Ca(2+)-regulated dynein adapter protein
CC that activates dynein-mediated transport and dynein-dynactin motility
CC on microtubules and regulates endosomal trafficking of CD47
CC (PubMed:30814157). Acts as an intracellular signaling module bridging
CC two important T-cell receptor (TCR) signaling pathways, Ca(2+)-NFAT and
CC JNK, to affect T-cell activation (PubMed:27016526). In resting T-cells,
CC is predominantly localized near TGN network in a GTP-bound form, upon
CC TCR stimulation, localizes at the immunological synapse via interaction
CC with VAV1 to activate downstream Ca(2+)-NFAT and JNK signaling pathways
CC (PubMed:27016526). Plays a role in T-helper 1 (Th1) cell
CC differentiation and T-helper 17 (Th17) cell effector function
CC (PubMed:29987160). Plays a role in store-operated Ca(2+) entry (SOCE)
CC in T-cells by regulating CRAC channel activation (PubMed:27016526).
CC {ECO:0000269|PubMed:27016526, ECO:0000269|PubMed:29987160,
CC ECO:0000269|PubMed:30814157, ECO:0000269|PubMed:31092558}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with ORAI1 and STIM1; the interaction
CC is direct and takes place in absence of Ca(2+). Forms a complex with
CC ORAI1 and STIM1 at low concentration of Ca(2+), the complex dissociates
CC at elevated Ca(2+) concentrations. Interacts with ORAI2 and ORAI3.
CC {ECO:0000269|PubMed:20418871}.
CC -!- SUBUNIT: [Isoform 2]: Interacts with DYNC1H1 (PubMed:31092558).
CC Interacts with the dynein-dynactin complex in a Ca(2+)-dependent manner
CC (PubMed:30814157). Interacts with VAV1 (PubMed:27016526).
CC {ECO:0000269|PubMed:27016526, ECO:0000269|PubMed:30814157,
CC ECO:0000269|PubMed:31092558}.
CC -!- INTERACTION:
CC Q9BSW2; Q8N6D5: ANKRD29; NbExp=3; IntAct=EBI-739773, EBI-17439331;
CC Q9BSW2; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-739773, EBI-14199987;
CC Q9BSW2; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-739773, EBI-10175300;
CC Q9BSW2; Q9UJX2: CDC23; NbExp=3; IntAct=EBI-739773, EBI-396137;
CC Q9BSW2; P35638: DDIT3; NbExp=3; IntAct=EBI-739773, EBI-742651;
CC Q9BSW2; G5E9A7: DMWD; NbExp=3; IntAct=EBI-739773, EBI-10976677;
CC Q9BSW2; Q8NDB6: FAM156A; NbExp=3; IntAct=EBI-739773, EBI-749727;
CC Q9BSW2; Q9NVL1-2: FAM86C1P; NbExp=3; IntAct=EBI-739773, EBI-12845222;
CC Q9BSW2; O75344: FKBP6; NbExp=3; IntAct=EBI-739773, EBI-744771;
CC Q9BSW2; O75420: GIGYF1; NbExp=3; IntAct=EBI-739773, EBI-947774;
CC Q9BSW2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-739773, EBI-618309;
CC Q9BSW2; P42858: HTT; NbExp=9; IntAct=EBI-739773, EBI-466029;
CC Q9BSW2; O14901: KLF11; NbExp=3; IntAct=EBI-739773, EBI-948266;
CC Q9BSW2; Q15323: KRT31; NbExp=3; IntAct=EBI-739773, EBI-948001;
CC Q9BSW2; O95678: KRT75; NbExp=3; IntAct=EBI-739773, EBI-2949715;
CC Q9BSW2; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-739773, EBI-1048945;
CC Q9BSW2; Q5T3J3: LRIF1; NbExp=3; IntAct=EBI-739773, EBI-473196;
CC Q9BSW2; Q99750: MDFI; NbExp=3; IntAct=EBI-739773, EBI-724076;
CC Q9BSW2; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-739773, EBI-10172526;
CC Q9BSW2; Q13064: MKRN3; NbExp=3; IntAct=EBI-739773, EBI-2340269;
CC Q9BSW2; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-739773, EBI-945833;
CC Q9BSW2; O43482: OIP5; NbExp=3; IntAct=EBI-739773, EBI-536879;
CC Q9BSW2; Q96D31: ORAI1; NbExp=6; IntAct=EBI-739773, EBI-2291476;
CC Q9BSW2; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-739773, EBI-10171633;
CC Q9BSW2; O15160: POLR1C; NbExp=3; IntAct=EBI-739773, EBI-1055079;
CC Q9BSW2; Q9NYW8: RBAK; NbExp=3; IntAct=EBI-739773, EBI-1210429;
CC Q9BSW2; Q92753-1: RORB; NbExp=3; IntAct=EBI-739773, EBI-18560266;
CC Q9BSW2; Q8ND83: SLAIN1; NbExp=3; IntAct=EBI-739773, EBI-10269374;
CC Q9BSW2; O60504: SORBS3; NbExp=3; IntAct=EBI-739773, EBI-741237;
CC Q9BSW2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-739773, EBI-5235340;
CC Q9BSW2; Q13586: STIM1; NbExp=3; IntAct=EBI-739773, EBI-448878;
CC Q9BSW2; Q08117: TLE5; NbExp=4; IntAct=EBI-739773, EBI-717810;
CC Q9BSW2; Q08117-2: TLE5; NbExp=3; IntAct=EBI-739773, EBI-11741437;
CC Q9BSW2; Q13077: TRAF1; NbExp=3; IntAct=EBI-739773, EBI-359224;
CC Q9BSW2; O75604: USP2; NbExp=3; IntAct=EBI-739773, EBI-743272;
CC Q9BSW2; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-739773, EBI-14104088;
CC Q9BSW2; P17024: ZNF20; NbExp=3; IntAct=EBI-739773, EBI-717634;
CC Q9BSW2; Q8N720: ZNF655; NbExp=3; IntAct=EBI-739773, EBI-625509;
CC Q9BSW2; P09022: Hoxa1; Xeno; NbExp=3; IntAct=EBI-739773, EBI-3957603;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000269|PubMed:20418871}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:30814157, ECO:0000269|PubMed:31092558}. Cytoplasm,
CC cytoskeleton, microtubule organizing center
CC {ECO:0000269|PubMed:30814157, ECO:0000269|PubMed:31092558}. Cell
CC membrane {ECO:0000269|PubMed:30814157}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:27016526}. Golgi apparatus, trans-Golgi network
CC membrane {ECO:0000269|PubMed:27016526}. Vesicle
CC {ECO:0000269|PubMed:27016526}. Note=T-cell activation-induced elevation
CC of intracellular of Ca(2+) stimulates its transport toward the
CC microtubule organizing center (MTOC) (PubMed:30814157). Histamine
CC stimulation induces a trafficking to the MTOC in a GTP-binding-
CC dependent but Ca(2+)-binding-independent manner (PubMed:31092558).
CC Localizes to Golgi membrane in resting T-cells and upon its interaction
CC with VAV1, is translocated from the Golgi membrane to the immunological
CC synapse via subsynaptic vesicles (PubMed:27016526). Its localization in
CC the Golgi membrane requires isoprenylation and GTP-binding
CC (PubMed:27016526). {ECO:0000269|PubMed:27016526,
CC ECO:0000269|PubMed:30814157, ECO:0000269|PubMed:31092558}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2; Synonyms=CRACR2A-L, CRACR2A-A {ECO:0000303|PubMed:27016526};
CC IsoId=Q9BSW2-2; Sequence=Displayed;
CC Name=1; Synonyms=CRACR2A-S, CRACR2A-C {ECO:0000303|PubMed:27016526};
CC IsoId=Q9BSW2-1; Sequence=VSP_060977, VSP_060978;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in the Jurkat T-cell line.
CC {ECO:0000269|PubMed:27016526}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in endothelial cells
CC (PubMed:25475730). Expressed in Weibel-Palade bodies (which are P-
CC selectin/SELP negative) in endothelial cells (PubMed:31092558).
CC Expressed in the Jurkat T-cell line (PubMed:30814157, PubMed:27016526).
CC {ECO:0000269|PubMed:25475730, ECO:0000269|PubMed:27016526,
CC ECO:0000269|PubMed:30814157, ECO:0000269|PubMed:31092558}.
CC -!- SIMILARITY: Belongs to the EFCAB4 family. {ECO:0000305}.
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DR EMBL; AK304017; BAG64932.1; -; mRNA.
DR EMBL; AC005831; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455583; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455584; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455587; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004524; AAH04524.1; -; mRNA.
DR EMBL; BC150643; AAI50644.1; -; mRNA.
DR CCDS; CCDS44803.1; -. [Q9BSW2-2]
DR CCDS; CCDS8522.1; -. [Q9BSW2-1]
DR RefSeq; NP_001138430.1; NM_001144958.1. [Q9BSW2-2]
DR RefSeq; NP_116069.1; NM_032680.3. [Q9BSW2-1]
DR PDB; 6PSD; X-ray; 2.66 A; A/C/E/G/I/K/M/O=47-121.
DR PDBsum; 6PSD; -.
DR AlphaFoldDB; Q9BSW2; -.
DR SMR; Q9BSW2; -.
DR BioGRID; 124247; 68.
DR IntAct; Q9BSW2; 48.
DR MINT; Q9BSW2; -.
DR STRING; 9606.ENSP00000409382; -.
DR BindingDB; Q9BSW2; -.
DR ChEMBL; CHEMBL3638353; -.
DR iPTMnet; Q9BSW2; -.
DR MetOSite; Q9BSW2; -.
DR PhosphoSitePlus; Q9BSW2; -.
DR BioMuta; CRACR2A; -.
DR DMDM; 74761240; -.
DR CPTAC; CPTAC-1026; -.
DR EPD; Q9BSW2; -.
DR jPOST; Q9BSW2; -.
DR MassIVE; Q9BSW2; -.
DR MaxQB; Q9BSW2; -.
DR PaxDb; Q9BSW2; -.
DR PeptideAtlas; Q9BSW2; -.
DR PRIDE; Q9BSW2; -.
DR ProteomicsDB; 78930; -. [Q9BSW2-1]
DR ProteomicsDB; 78931; -. [Q9BSW2-2]
DR TopDownProteomics; Q9BSW2-1; -. [Q9BSW2-1]
DR TopDownProteomics; Q9BSW2-2; -. [Q9BSW2-2]
DR Antibodypedia; 22229; 186 antibodies from 30 providers.
DR DNASU; 84766; -.
DR Ensembl; ENST00000252322.1; ENSP00000252322.1; ENSG00000130038.10. [Q9BSW2-1]
DR Ensembl; ENST00000440314.7; ENSP00000409382.2; ENSG00000130038.10. [Q9BSW2-2]
DR GeneID; 84766; -.
DR KEGG; hsa:84766; -.
DR MANE-Select; ENST00000440314.7; ENSP00000409382.2; NM_001144958.2; NP_001138430.1.
DR UCSC; uc001qmj.3; human. [Q9BSW2-2]
DR CTD; 84766; -.
DR DisGeNET; 84766; -.
DR GeneCards; CRACR2A; -.
DR HGNC; HGNC:28657; CRACR2A.
DR HPA; ENSG00000130038; Tissue enhanced (bone marrow, intestine, salivary gland).
DR MIM; 614178; gene.
DR neXtProt; NX_Q9BSW2; -.
DR OpenTargets; ENSG00000130038; -.
DR PharmGKB; PA144596438; -.
DR VEuPathDB; HostDB:ENSG00000130038; -.
DR eggNOG; KOG0078; Eukaryota.
DR GeneTree; ENSGT00440000033504; -.
DR HOGENOM; CLU_023178_0_0_1; -.
DR InParanoid; Q9BSW2; -.
DR OMA; CYQKPKN; -.
DR OrthoDB; 1184845at2759; -.
DR PhylomeDB; Q9BSW2; -.
DR TreeFam; TF329556; -.
DR PathwayCommons; Q9BSW2; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q9BSW2; -.
DR BioGRID-ORCS; 84766; 13 hits in 1078 CRISPR screens.
DR ChiTaRS; CRACR2A; human.
DR GenomeRNAi; 84766; -.
DR Pharos; Q9BSW2; Tchem.
DR PRO; PR:Q9BSW2; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9BSW2; protein.
DR Bgee; ENSG00000130038; Expressed in parotid gland and 143 other tissues.
DR ExpressionAtlas; Q9BSW2; baseline and differential.
DR Genevisible; Q9BSW2; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:0032588; C:trans-Golgi network membrane; IDA:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0033093; C:Weibel-Palade body; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IMP:UniProtKB.
DR GO; GO:0032237; P:activation of store-operated calcium channel activity; IMP:UniProtKB.
DR GO; GO:0016197; P:endosomal transport; IDA:UniProtKB.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IMP:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB.
DR GO; GO:0034776; P:response to histamine; IDA:UniProtKB.
DR GO; GO:0002115; P:store-operated calcium entry; IMP:UniProtKB.
DR GO; GO:0045063; P:T-helper 1 cell differentiation; IMP:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF13499; EF-hand_7; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00054; EFh; 2.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Calcium;
KW Calcium transport; Cell membrane; Coiled coil; Cytoplasm; Cytoskeleton;
KW Golgi apparatus; GTP-binding; Immunity; Ion transport; Lipoprotein;
KW Membrane; Metal-binding; Nucleotide-binding; Prenylation;
KW Reference proteome; Repeat; Transport.
FT CHAIN 1..731
FT /note="EF-hand calcium-binding domain-containing protein
FT 4B"
FT /id="PRO_0000283046"
FT DOMAIN 84..119
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..540
FT /note="Proline-rich domain (PRD) which mediates interaction
FT with VAV1"
FT /evidence="ECO:0000269|PubMed:27016526"
FT REGION 426..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 494..528
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 201..382
FT /evidence="ECO:0000255"
FT BINDING 97
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 99
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 101
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 103
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 108
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 552..559
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT BINDING 600..604
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT BINDING 659..661
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P63000"
FT LIPID 729
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000269|PubMed:27016526"
FT VAR_SEQ 374..395
FT /note="ERNKHLRDERDICFQKNKAAKA -> CVGGHWPVLRAPPRSLGSEGPV (in
FT isoform 1)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_060977"
FT VAR_SEQ 396..731
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_060978"
FT VARIANT 7
FT /note="R -> G (in dbSNP:rs9788233)"
FT /id="VAR_031483"
FT VARIANT 98
FT /note="A -> T (in dbSNP:rs17836273)"
FT /id="VAR_031484"
FT VARIANT 128
FT /note="A -> V (in dbSNP:rs242017)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031485"
FT VARIANT 136
FT /note="H -> P (in dbSNP:rs34088152)"
FT /id="VAR_031486"
FT VARIANT 154
FT /note="E -> K (in dbSNP:rs242018)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031487"
FT VARIANT 212
FT /note="H -> Q (in dbSNP:rs36030417)"
FT /id="VAR_031488"
FT MUTAGEN 63
FT /note="D->A: Loss of calcium-binding and interaction with
FT the dynein-dynactin complex; when associated with A-65; A-
FT 97 and A-99."
FT /evidence="ECO:0000269|PubMed:30814157"
FT MUTAGEN 65
FT /note="E->A: Loss of calcium-binding and interaction with
FT the dynein-dynactin complex; when associated with A-63; A-
FT 97 and A-99."
FT /evidence="ECO:0000269|PubMed:30814157"
FT MUTAGEN 97..99
FT /note="DAD->AAA: In EF2MUT; enhanced STIM1 clustering and
FT elevated cytoplasmic Ca2+, thereby causing cell death in T-
FT cells. Loss of calcium-binding. Can rescue JNK
FT phosphorylation when expressed in CRACR2A-depleted T-cells.
FT No effect on its localization to the Golgi membrane."
FT /evidence="ECO:0000269|PubMed:20418871,
FT ECO:0000269|PubMed:27016526, ECO:0000269|PubMed:31092558"
FT MUTAGEN 97
FT /note="D->A: Loss of calcium-binding and interaction with
FT the dynein-dynactin complex; when associated with A-63; A-
FT 65 and A-99."
FT /evidence="ECO:0000269|PubMed:30814157"
FT MUTAGEN 99
FT /note="D->A: Loss of calcium-binding and interaction with
FT the dynein-dynactin complex; when associated with A-63; A-
FT 65 and A-97."
FT /evidence="ECO:0000269|PubMed:30814157"
FT MUTAGEN 559
FT /note="T->N: GDP-binding mutant with reduced GTPase
FT activity and protein stability. Reduced ability to activate
FT JNK signaling pathway. Failure to localize to the
FT microtubule organizing center and Golgi apparatus membrane,
FT instead shows a predominant localization to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:27016526,
FT ECO:0000269|PubMed:31092558"
FT MUTAGEN 604
FT /note="Q->L: GTP-binding mutant with reduced GTPase
FT activity but increased protein stability. Increased ability
FT to activate JNK signaling pathway. No effect on its
FT localization to the microtubule organizing center or Golgi
FT apparatus membrane."
FT /evidence="ECO:0000269|PubMed:27016526,
FT ECO:0000269|PubMed:31092558"
FT MUTAGEN 658
FT /note="N->I: GTP/GDP-binding defective mutant with reduced
FT GTPase activity and protein stability. Failure to localize
FT to the microtubule organizing center and Golgi apparatus
FT membrane, instead shows a predominant localization to the
FT cytoplasm."
FT /evidence="ECO:0000269|PubMed:27016526,
FT ECO:0000269|PubMed:31092558"
FT MUTAGEN 729..731
FT /note="Missing: Failure to localize to the Golgi membrane."
FT /evidence="ECO:0000269|PubMed:27016526"
FT CONFLICT 424
FT /note="S -> SS (in Ref. 4 and 5)"
FT /evidence="ECO:0000305"
FT HELIX 48..62
FT /evidence="ECO:0007829|PDB:6PSD"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:6PSD"
FT HELIX 74..77
FT /evidence="ECO:0007829|PDB:6PSD"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:6PSD"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:6PSD"
FT HELIX 86..96
FT /evidence="ECO:0007829|PDB:6PSD"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:6PSD"
FT HELIX 106..117
FT /evidence="ECO:0007829|PDB:6PSD"
SQ SEQUENCE 731 AA; 83193 MW; DE746B5B604ACC44 CRC64;
MAAPDGRVVS RPQRLGQGSG QGPKGSGACL HPLDSLEQKE TQEQTSGQLV MLRKAQEFFQ
TCDAEGKGFI ARKDMQRLHK ELPLSLEELE DVFDALDADG NGYLTPQEFT TGFSHFFFSQ
NNPSQEDAGE QVAQRHEEKV YLSRGDEDLG DMGEDEEAQF RMLMDRLGAQ KVLEDESDVK
QLWLQLKKEE PHLLSNFEDF LTRIISQLQE AHEEKNELEC ALKRKIAAYD EEIQHLYEEM
EQQIKSEKEQ FLLKDTERFQ ARSQELEQKL LCKEQELEQL TQKQKRLEGQ CTALHHDKHE
TKAENTKLKL TNQELARELE RTSWELQDAQ QQLESLQQEA CKLHQEKEME VYRVTESLQR
EKAGLLKQLD FLRERNKHLR DERDICFQKN KAAKANTAAS RASWKKRSGS VIGKYVDSRG
ILRSQSEEEE EVFGIPRRSS LGLSGYPLTE EEPGTGEPGP GGPYPRPLRR IISVEEDPLP
QLLDGGFEQP LSKCSEEEEV SDQGVQGQIP EAPPLKLTPT SPRGQPVGKE ALCKEESSPS
APDRLFKIVF VGNSAVGKTS FLRRFCEDRF SPGMAATVGI DYRVKTLNVD NSQVALQLWD
TAGQERYRCI TQQFFRKADG VIVMYDLTDK QSFLSVRRWL SSVEEAVGDR VPVLLLGNKL
DNEKEREVPR GLGEQLATEN NLIFYECSAY SGHNTKESLL HLARFLKEQE DTVREDTIQV
GHPAKKKSCC G
