ID GRP2_MOUSE Reviewed; 608 AA. AC Q9QUG9; O09004; Q80WC0; Q8BSC8; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 15-JAN-2008, sequence version 2. DT 24-JAN-2024, entry version 175. DE RecName: Full=RAS guanyl-releasing protein 2; DE AltName: Full=Calcium and DAG-regulated guanine nucleotide exchange factor I; DE Short=CalDAG-GEFI; DE AltName: Full=F25B3.3 kinase-like protein; GN Name=Rasgrp2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION AS A RAP ACTIVATOR. RX PubMed=9789079; DOI=10.1073/pnas.95.22.13278; RA Kawasaki H., Springett G.M., Toki S., Canales J.J., Harlan P., RA Blumenstiel J.P., Chen E.J., Bany I.A., Mochizuki N., Ashbacher A., RA Matsuda M., Housman D.E., Graybiel A.M.; RT "A Rap guanine nucleotide exchange factor enriched highly in the basal RT ganglia."; RL Proc. Natl. Acad. Sci. U.S.A. 95:13278-13283(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC STRAIN=C57BL/6J; TISSUE=Mammary gland; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 204-608 (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Embryo; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 349-608 (ISOFORM 1). RX PubMed=9341881; DOI=10.1007/s004390050562; RA Kedra D., Seroussi E., Fransson I., Trifunovic J., Clark M., RA Lagercrantz J., Blennow E., Mehlin H., Dumanski J.; RT "The germinal centre kinase gene and a novel CDC25-like gene are located in RT the vicinity of the PYGM gene on 11q13."; RL Hum. Genet. 100:611-619(1997). RN [5] RP FUNCTION. RX PubMed=10777492; DOI=10.1074/jbc.m000981200; RA Ohba Y., Mochizuki N., Yamashita S., Chan A.M., Schrader J.W., Hattori S., RA Nagashima K., Matsuda M.; RT "Regulatory proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3."; RL J. Biol. Chem. 275:20020-20026(2000). RN [6] RP TISSUE SPECIFICITY. RX PubMed=10835426; DOI=10.1074/jbc.m003414200; RA Yamashita S., Mochizuki N., Ohba Y., Tobiume M., Okada Y., Sawa H., RA Nagashima K., Matsuda M.; RT "CalDAG-GEFIII activation of Ras, R-ras, and Rap1."; RL J. Biol. Chem. 275:25488-25493(2000). RN [7] RP FUNCTION AS RAP2 ACTIVATOR. RX PubMed=10913189; DOI=10.1128/mcb.20.16.6074-6083.2000; RA Ohba Y., Mochizuki N., Matsuo K., Yamashita S., Nakaya M., Hashimoto Y., RA Hamaguchi M., Kurata T., Nagashima K., Matsuda M.; RT "Rap2 as a slowly responding molecular switch in the Rap1 signaling RT cascade."; RL Mol. Cell. Biol. 20:6074-6083(2000). RN [8] RP FUNCTION. RX PubMed=11432821; DOI=10.1093/emboj/20.13.3333; RA Ohba Y., Ikuta K., Ogura A., Matsuda J., Mochizuki N., Nagashima K., RA Kurokawa K., Mayer B.J., Maki K., Miyazaki J., Matsuda M.; RT "Requirement for C3G-dependent Rap1 activation for cell adhesion and RT embryogenesis."; RL EMBO J. 20:3333-3341(2001). RN [9] RP FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY, AND DEVELOPMENTAL RP STAGE. RX PubMed=11278453; DOI=10.1074/jbc.m008970200; RA Dupuy A.J., Morgan K., von Lintig F.C., Shen H., Acar H., Hasz D.E., RA Jenkins N.A., Copeland N.G., Boss G.R., Largaespada D.A.; RT "Activation of the Rap1 guanine nucleotide exchange gene, CalDAG-GEF I, in RT BXH-2 murine myeloid leukemia."; RL J. Biol. Chem. 276:11804-11811(2001). RN [10] RP FUNCTION. RX PubMed=12239348; DOI=10.1073/pnas.202380099; RA Eto K., Murphy R., Kerrigan S.W., Bertoni A., Stuhlmann H., Nakano T., RA Leavitt A.D., Shattil S.J.; RT "Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in RT integrin signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 99:12819-12824(2002). RN [11] RP FUNCTION IN PLATELET AGGREGATION, DISRUPTION PHENOTYPE, INTERACTION WITH RP RAP1, AND TISSUE SPECIFICITY. RX PubMed=15334074; DOI=10.1038/nm1098; RA Crittenden J.R., Bergmeier W., Zhang Y., Piffath C.L., Liang Y., RA Wagner D.D., Housman D.E., Graybiel A.M.; RT "CalDAG-GEFI integrates signaling for platelet aggregation and thrombus RT formation."; RL Nat. Med. 10:982-986(2004). RN [12] RP FUNCTION. RX PubMed=16357324; DOI=10.1182/blood-2005-07-3023; RA Bernardi B., Guidetti G.F., Campus F., Crittenden J.R., Graybiel A.M., RA Balduini C., Torti M.; RT "The small GTPase Rap1b regulates the cross talk between platelet integrin RT alpha2beta1 and integrin alphaIIbbeta3."; RL Blood 107:2728-2735(2006). RN [13] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=17492052; DOI=10.1172/jci30575; RA Bergmeier W., Goerge T., Wang H.-W., Crittenden J.R., Baldwin A.C.W., RA Cifuni S.M., Housman D.E., Graybiel A.M., Wagner D.D.; RT "Mice lacking the signaling molecule CalDAG-GEFI represent a model for RT leukocyte adhesion deficiency type III."; RL J. Clin. Invest. 117:1699-1707(2007). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116 AND SER-117, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116; SER-117; SER-147 AND RP SER-554, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, and RC Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: Functions as a calcium- and DAG-regulated nucleotide exchange CC factor specifically activating Rap through the exchange of bound GDP CC for GTP. May also activate other GTPases such as RRAS, RRAS2, NRAS, CC KRAS but not HRAS. Functions in aggregation of platelets and adhesion CC of T-lymphocytes and neutrophils probably through inside-out integrin CC activation. May function in the muscarinic acetylcholine receptor CC M1/CHRM1 signaling pathway. {ECO:0000269|PubMed:10777492, CC ECO:0000269|PubMed:10913189, ECO:0000269|PubMed:11278453, CC ECO:0000269|PubMed:11432821, ECO:0000269|PubMed:12239348, CC ECO:0000269|PubMed:15334074, ECO:0000269|PubMed:16357324, CC ECO:0000269|PubMed:17492052, ECO:0000269|PubMed:9789079}. CC -!- SUBUNIT: Forms a signaling complex with RAP1 and BRAF. Interacts with CC F-actin (By similarity). Interacts with RAP1. {ECO:0000250, CC ECO:0000269|PubMed:15334074}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Cell membrane CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Synapse, CC synaptosome {ECO:0000250}. Cell projection, ruffle membrane CC {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=Found CC both in the cytosol and associated with membranes. Enriched at CC juxtamembrane areas and membrane ruffles. Localizes to the cell bodies CC and axons of striatal neurons. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=CalDAG-GEF1a; CC IsoId=Q9QUG9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9QUG9-2; Sequence=VSP_030579; CC Name=3; Synonyms=CalDAG-GEF1b; CC IsoId=Q9QUG9-3; Sequence=VSP_030577, VSP_030578; CC -!- TISSUE SPECIFICITY: Detected in megakaryocytes, platelet and CC neutrophils but not in lymphocytes (at protein level). Isoform 1 and CC isoform 3 are detected in brain basal glanglia, heart, lung, spleen, CC liver and kidney interstitial cells. {ECO:0000269|PubMed:10835426, CC ECO:0000269|PubMed:11278453, ECO:0000269|PubMed:15334074}. CC -!- DEVELOPMENTAL STAGE: Expressed in embryo with higher expression between CC 15 dpc and 17 dpc. {ECO:0000269|PubMed:11278453}. CC -!- DOMAIN: The N-terminal Ras-GEF domain mediates association with F- CC actin. {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Mice have a combination of defects in leukocytes CC and platelet functions which are reminiscent of the human leukocyte CC adhesion deficiency type III syndrome (LAD3). They display bleeding CC diathesis due to a defect in platelet aggregation and are resistant to CC collagen-induced thrombosis. In parallel, they also display impaired CC response to acute inflammation associated with defects in beta-1 and CC beta-2 integrin-mediated adhesion of neutrophils. CC {ECO:0000269|PubMed:15334074, ECO:0000269|PubMed:17492052}. CC -!- MISCELLANEOUS: [Isoform 3]: The corresponding protein is not CC undetectable. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the RASGRP family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC28797.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF081193; AAC79697.1; -; mRNA. DR EMBL; U78171; AAD12742.1; -; mRNA. DR EMBL; BC051474; AAH51474.1; -; mRNA. DR EMBL; AK034683; BAC28797.1; ALT_INIT; mRNA. DR EMBL; Y12339; CAA73008.1; -; mRNA. DR CCDS; CCDS37898.1; -. [Q9QUG9-1] DR CCDS; CCDS89325.1; -. [Q9QUG9-3] DR RefSeq; NP_035372.2; NM_011242.2. [Q9QUG9-1] DR RefSeq; XP_006531748.1; XM_006531685.3. DR RefSeq; XP_006531749.1; XM_006531686.3. [Q9QUG9-1] DR RefSeq; XP_006531750.1; XM_006531687.2. [Q9QUG9-1] DR RefSeq; XP_006531751.1; XM_006531688.3. [Q9QUG9-1] DR RefSeq; XP_006531752.1; XM_006531689.3. DR RefSeq; XP_006531753.1; XM_006531690.3. [Q9QUG9-1] DR RefSeq; XP_006531754.1; XM_006531691.3. [Q9QUG9-1] DR AlphaFoldDB; Q9QUG9; -. DR BMRB; Q9QUG9; -. DR SMR; Q9QUG9; -. DR IntAct; Q9QUG9; 1. DR MINT; Q9QUG9; -. DR STRING; 10090.ENSMUSP00000109104; -. DR iPTMnet; Q9QUG9; -. DR PhosphoSitePlus; Q9QUG9; -. DR EPD; Q9QUG9; -. DR jPOST; Q9QUG9; -. DR MaxQB; Q9QUG9; -. DR PaxDb; 10090-ENSMUSP00000109104; -. DR PeptideAtlas; Q9QUG9; -. DR ProteomicsDB; 271334; -. [Q9QUG9-1] DR ProteomicsDB; 271335; -. [Q9QUG9-2] DR ProteomicsDB; 271336; -. [Q9QUG9-3] DR Antibodypedia; 2786; 150 antibodies from 27 providers. DR DNASU; 19395; -. DR Ensembl; ENSMUST00000035716.15; ENSMUSP00000041135.9; ENSMUSG00000032946.17. [Q9QUG9-1] DR Ensembl; ENSMUST00000113471.3; ENSMUSP00000109099.2; ENSMUSG00000032946.17. [Q9QUG9-3] DR Ensembl; ENSMUST00000113472.8; ENSMUSP00000109100.2; ENSMUSG00000032946.17. [Q9QUG9-3] DR Ensembl; ENSMUST00000113475.8; ENSMUSP00000109103.2; ENSMUSG00000032946.17. [Q9QUG9-3] DR Ensembl; ENSMUST00000113476.8; ENSMUSP00000109104.2; ENSMUSG00000032946.17. [Q9QUG9-1] DR Ensembl; ENSMUST00000167240.8; ENSMUSP00000129873.2; ENSMUSG00000032946.17. [Q9QUG9-1] DR GeneID; 19395; -. DR KEGG; mmu:19395; -. DR UCSC; uc008gip.1; mouse. [Q9QUG9-1] DR UCSC; uc008gir.1; mouse. [Q9QUG9-2] DR AGR; MGI:1333849; -. DR CTD; 10235; -. DR MGI; MGI:1333849; Rasgrp2. DR VEuPathDB; HostDB:ENSMUSG00000032946; -. DR eggNOG; KOG3417; Eukaryota. DR GeneTree; ENSGT00940000160483; -. DR HOGENOM; CLU_019261_1_0_1; -. DR InParanoid; Q9QUG9; -. DR OMA; HNFHESS; -. DR OrthoDB; 4260488at2759; -. DR PhylomeDB; Q9QUG9; -. DR TreeFam; TF312918; -. DR Reactome; R-MMU-354192; Integrin signaling. DR Reactome; R-MMU-392517; Rap1 signalling. DR BioGRID-ORCS; 19395; 0 hits in 75 CRISPR screens. DR PRO; PR:Q9QUG9; -. DR Proteomes; UP000000589; Chromosome 19. DR RNAct; Q9QUG9; Protein. DR Bgee; ENSMUSG00000032946; Expressed in granulocyte and 62 other cell types or tissues. DR ExpressionAtlas; Q9QUG9; baseline and differential. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:MGI. DR GO; GO:0071277; P:cellular response to calcium ion; ISO:MGI. DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central. DR CDD; cd20861; C1_RASGRP2; 1. DR CDD; cd00051; EFh; 1. DR CDD; cd00155; RasGEF; 1. DR CDD; cd06224; REM; 1. DR Gene3D; 3.30.60.20; -; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 1.10.840.10; Ras guanine-nucleotide exchange factors catalytic domain; 1. DR Gene3D; 1.20.870.10; Son of sevenless (SoS) protein Chain: S domain 1; 1. DR InterPro; IPR046349; C1-like_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR002219; PE/DAG-bd. DR InterPro; IPR008937; Ras-like_GEF. DR InterPro; IPR000651; Ras-like_Gua-exchang_fac_N. DR InterPro; IPR023578; Ras_GEF_dom_sf. DR InterPro; IPR001895; RASGEF_cat_dom. DR InterPro; IPR036964; RASGEF_cat_dom_sf. DR PANTHER; PTHR23113; GUANINE NUCLEOTIDE EXCHANGE FACTOR; 1. DR PANTHER; PTHR23113:SF16; RAS GUANYL-RELEASING PROTEIN 2; 1. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF13499; EF-hand_7; 1. DR Pfam; PF00617; RasGEF; 1. DR Pfam; PF00618; RasGEF_N; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00054; EFh; 2. DR SMART; SM00147; RasGEF; 1. DR SMART; SM00229; RasGEFN; 1. DR SUPFAM; SSF57889; Cysteine-rich domain; 1. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF48366; Ras GEF; 1. DR PROSITE; PS00018; EF_HAND_1; 2. DR PROSITE; PS50222; EF_HAND_2; 2. DR PROSITE; PS50009; RASGEF_CAT; 1. DR PROSITE; PS50212; RASGEF_NTER; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. DR Genevisible; Q9QUG9; MM. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Cell membrane; Cell projection; Cytoplasm; KW Guanine-nucleotide releasing factor; Membrane; Metal-binding; KW Phosphoprotein; Reference proteome; Repeat; Synapse; Synaptosome; Zinc; KW Zinc-finger. FT CHAIN 1..608 FT /note="RAS guanyl-releasing protein 2" FT /id="PRO_0000315609" FT DOMAIN 4..126 FT /note="N-terminal Ras-GEF" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135" FT DOMAIN 154..387 FT /note="Ras-GEF" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168" FT DOMAIN 426..461 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 463..490 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT ZN_FING 498..548 FT /note="Phorbol-ester/DAG-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226" FT REGION 382..405 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 555..596 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 556..572 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 439 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 441 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 443 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 445 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 450 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 468 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 470 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 472 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 474 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 479 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT MOD_RES 116 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 117 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 147 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 554 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 575 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P0C643" FT VAR_SEQ 125..141 FT /note="PTYKWKRQVTQRNPVEQ -> CVGAERKGHYACYTICA (in isoform FT 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_030577" FT VAR_SEQ 142..608 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_030578" FT VAR_SEQ 472..608 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_030579" FT CONFLICT 2 FT /note="T -> A (in Ref. 1; AAC79697/AAD12742)" FT /evidence="ECO:0000305" FT CONFLICT 73 FT /note="M -> V (in Ref. 1; AAC79697/AAD12742)" FT /evidence="ECO:0000305" FT CONFLICT 83 FT /note="I -> V (in Ref. 1; AAC79697/AAD12742)" FT /evidence="ECO:0000305" FT CONFLICT 99 FT /note="Q -> P (in Ref. 1; AAC79697/AAD12742)" FT /evidence="ECO:0000305" FT CONFLICT 233 FT /note="R -> K (in Ref. 1; AAC79697/AAD12742)" FT /evidence="ECO:0000305" FT CONFLICT 339 FT /note="C -> S (in Ref. 1; AAC79697/AAD12742)" FT /evidence="ECO:0000305" FT CONFLICT 542 FT /note="E -> D (in Ref. 1; AAC79697/AAD12742)" FT /evidence="ECO:0000305" FT CONFLICT 598 FT /note="S -> T (in Ref. 1; AAC79697/AAD12742)" FT /evidence="ECO:0000305" SQ SEQUENCE 608 AA; 69446 MW; 1E6F768EF00B0468 CRC64; MTSTLDLDKG CTVEELLRGC IEAFDDSGKV RDPQLVRMFL MMHPWYIPSS QLASKLLHFY QQSRKDNSNS LQMKTCHLVR YWISAFPAEF DLNPELAEQI KELKALLDQE GNRRHSSLID IESVPTYKWK RQVTQRNPVE QKKRKMSLLF DHLEPMELAE HLTYLEYRSF CKILFQDYHS FVTHGCTVDN PVLERFISLF NSVSQWVQLM ILSKPTATQR ALVITHFVHV AERLLQLQNF NTLMAVVGGL SHSSISRLKE THSHVSPDTI KLWEGLTELV TATGNYSNYR RRLAACVGFR FPILGVHLKD LVALQLALPD WLDPGRTRLN GAKMRQLFCI LEELAMVTSL RPPVQANPDL LSLLTVSLDQ YQTEDELYQL SLQREPRSKS SPTSPTSCTP PPRPPVLEEW TSVAKPKLDQ ALVAEHIEKM VESVFRNFDV DGDGHISQEE FQIIRGNFPY LSAFGDLDQN QDGCISREEM ISYFLRSSSV LGGRMGFVHN FQESNSLRPV ACRHCKALIL GIYKQGLKCR ACGVNCHKQC KERLSVECRR RAQSVSLEGS APSPSPTHTH HRAFSFSLPR PGRRSSRPPE IREEEVQSVE DGVFDIHL //