ID PLCH1_HUMAN Reviewed; 1693 AA. AC Q4KWH8; Q29RV9; Q4KWH9; Q68CN0; Q86XK4; Q9H9U2; Q9UPT3; DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 02-AUG-2005, sequence version 1. DT 24-JAN-2024, entry version 164. DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1 {ECO:0000305}; DE EC=3.1.4.11; DE AltName: Full=Phosphoinositide phospholipase C-eta-1; DE AltName: Full=Phospholipase C-eta-1; DE Short=PLC-eta-1; DE AltName: Full=Phospholipase C-like protein 3; DE Short=PLC-L3; GN Name=PLCH1 {ECO:0000312|HGNC:HGNC:29185}; Synonyms=KIAA1069, PLCL3; 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 [MRNA] (ISOFORMS 1 AND 3), FUNCTION, TISSUE RP SPECIFICITY, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY. RX PubMed=15702972; DOI=10.1042/bj20041677; RA Hwang J.-I., Oh Y.-S., Shin K.-J., Kim H., Ryu S.H., Suh P.-G.; RT "Molecular cloning and characterization of a novel phospholipase C, PLC- RT eta."; RL Biochem. J. 389:181-186(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 926-1693 (ISOFORM 1). RC TISSUE=Eye, and Testis; 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 216-1693 (ISOFORM 3). RC TISSUE=Brain; RX PubMed=10470851; DOI=10.1093/dnares/6.3.197; RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIV. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:197-205(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 392-1034 (ISOFORM 4). 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1470-1693 (ISOFORMS 1/2). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [8] RP INVOLVEMENT IN HPE14, VARIANT HPE14 689-ARG--LEU-1693 DEL, SUBCELLULAR RP LOCATION, AND TISSUE SPECIFICITY. RX PubMed=33820834; DOI=10.1136/jmedgenet-2020-107237; RA Drissi I., Fletcher E., Shaheen R., Nahorski M., Alhashem A.M., Lisgo S., RA Fernandez-Jaen A., Schon K., Tlili-Graiess K., Smithson S.F., Lindsay S., RA Sharpe H.J., Alkuraya F.S., Woods G.; RT "Mutations in phospholipase C eta-1 (PLCH1) are associated with RT holoprosencephaly."; RL J. Med. Genet. 59:358-365(2022). CC -!- FUNCTION: The production of the second messenger molecules CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated CC by calcium-activated phosphatidylinositol-specific phospholipase C CC enzymes. {ECO:0000269|PubMed:15702972}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- CC bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2- CC diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:33179, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:58456, CC ChEBI:CHEBI:203600; EC=3.1.4.11; CC Evidence={ECO:0000269|PubMed:15702972}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180; CC Evidence={ECO:0000305|PubMed:15702972}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00041}; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15702972, CC ECO:0000269|PubMed:33820834}. Membrane {ECO:0000269|PubMed:15702972}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=PLC-eta-1; CC IsoId=Q4KWH8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q4KWH8-2; Sequence=VSP_032901, VSP_032902; CC Name=3; Synonyms=PLC-eta-1a; CC IsoId=Q4KWH8-3; Sequence=VSP_032904, VSP_032905; CC Name=4; CC IsoId=Q4KWH8-4; Sequence=VSP_032902, VSP_032903, VSP_032906; CC -!- TISSUE SPECIFICITY: Expressed in brain and to a lower extent in lung. CC In brain, it is found in cerebrum, cerebellum and spinal cord. In CC embryo expressed in the notochord, developing spinal cord (in a ventral CC to dorsal gradient), dorsal root ganglia, cerebellum and CC dermatomyosome. {ECO:0000269|PubMed:15702972, CC ECO:0000269|PubMed:33820834}. CC -!- DISEASE: Holoprosencephaly 14 (HPE14) [MIM:619895]: An autosomal CC recessive form of holoprosencephaly, a structural anomaly of the brain CC in which the developing forebrain fails to correctly separate into CC right and left hemispheres. Holoprosencephaly is genetically CC heterogeneous and associated with several distinct facies and CC phenotypic variability. In its most severe form (alobar CC holoprosencephaly), the forebrain consists of a single ventricle, and CC midbrain structures may be malformed as well. In the most extreme CC cases, anophthalmia or cyclopia is evident along with a congenital CC absence of the mature nose. In milder forms (semilobar or lobar CC holoprosencephaly), rudimentary midline structures are present. The CC less severe form features facial dysmorphism characterized by ocular CC hypertelorism, defects of the upper lip and/or nose, and absence of the CC olfactory nerves or corpus callosum. {ECO:0000269|PubMed:33820834}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=BAB14129.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AY691170; AAW22607.1; -; mRNA. DR EMBL; AY691171; AAW22608.1; -; mRNA. DR EMBL; BC043248; AAH43248.2; -; mRNA. DR EMBL; BC113950; AAI13951.1; -; mRNA. DR EMBL; AB028992; BAA83021.1; -; mRNA. DR EMBL; AK022610; BAB14129.1; ALT_INIT; mRNA. DR EMBL; CR749869; CAH18710.1; -; mRNA. DR CCDS; CCDS46939.1; -. [Q4KWH8-1] DR CCDS; CCDS46940.1; -. [Q4KWH8-3] DR RefSeq; NP_001124432.1; NM_001130960.1. [Q4KWH8-1] DR RefSeq; NP_001124433.1; NM_001130961.1. [Q4KWH8-3] DR RefSeq; NP_055811.1; NM_014996.2. DR RefSeq; XP_016861418.1; XM_017005929.1. DR AlphaFoldDB; Q4KWH8; -. DR SMR; Q4KWH8; -. DR BioGRID; 116651; 72. DR IntAct; Q4KWH8; 25. DR MINT; Q4KWH8; -. DR STRING; 9606.ENSP00000345988; -. DR SwissLipids; SLP:000000940; -. DR CarbonylDB; Q4KWH8; -. DR GlyGen; Q4KWH8; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q4KWH8; -. DR PhosphoSitePlus; Q4KWH8; -. DR BioMuta; PLCH1; -. DR DMDM; 121947010; -. DR EPD; Q4KWH8; -. DR jPOST; Q4KWH8; -. DR MassIVE; Q4KWH8; -. DR MaxQB; Q4KWH8; -. DR PaxDb; 9606-ENSP00000345988; -. DR PeptideAtlas; Q4KWH8; -. DR ProteomicsDB; 62214; -. [Q4KWH8-1] DR ProteomicsDB; 62215; -. [Q4KWH8-2] DR ProteomicsDB; 62216; -. [Q4KWH8-3] DR ProteomicsDB; 62217; -. [Q4KWH8-4] DR Pumba; Q4KWH8; -. DR Antibodypedia; 46750; 96 antibodies from 24 providers. DR DNASU; 23007; -. DR Ensembl; ENST00000334686.6; ENSP00000335469.6; ENSG00000114805.18. [Q4KWH8-2] DR Ensembl; ENST00000340059.11; ENSP00000345988.7; ENSG00000114805.18. [Q4KWH8-1] DR Ensembl; ENST00000447496.6; ENSP00000402759.2; ENSG00000114805.18. [Q4KWH8-3] DR Ensembl; ENST00000494598.5; ENSP00000419100.1; ENSG00000114805.18. [Q4KWH8-4] DR GeneID; 23007; -. DR KEGG; hsa:23007; -. DR UCSC; uc062pff.1; human. [Q4KWH8-1] DR AGR; HGNC:29185; -. DR CTD; 23007; -. DR DisGeNET; 23007; -. DR GeneCards; PLCH1; -. DR HGNC; HGNC:29185; PLCH1. DR HPA; ENSG00000114805; Tissue enhanced (lymphoid tissue, retina, testis). DR MalaCards; PLCH1; -. DR MIM; 612835; gene. DR MIM; 619895; phenotype. DR neXtProt; NX_Q4KWH8; -. DR OpenTargets; ENSG00000114805; -. DR Orphanet; 93925; Alobar holoprosencephaly. DR PharmGKB; PA128394595; -. DR VEuPathDB; HostDB:ENSG00000114805; -. DR eggNOG; KOG0169; Eukaryota. DR GeneTree; ENSGT00940000157185; -. DR HOGENOM; CLU_002738_0_1_1; -. DR InParanoid; Q4KWH8; -. DR OrthoDB; 2900494at2759; -. DR PhylomeDB; Q4KWH8; -. DR TreeFam; TF313216; -. DR BRENDA; 3.1.4.11; 2681. DR PathwayCommons; Q4KWH8; -. DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol. DR SignaLink; Q4KWH8; -. DR BioGRID-ORCS; 23007; 11 hits in 1157 CRISPR screens. DR ChiTaRS; PLCH1; human. DR GenomeRNAi; 23007; -. DR Pharos; Q4KWH8; Tbio. DR PRO; PR:Q4KWH8; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q4KWH8; Protein. DR Bgee; ENSG00000114805; Expressed in bronchial epithelial cell and 134 other cell types or tissues. DR ExpressionAtlas; Q4KWH8; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0050429; F:calcium-dependent phospholipase C activity; IDA:MGI. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IBA:GO_Central. DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IDA:MGI. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IBA:GO_Central. DR CDD; cd00275; C2_PLC_like; 1. DR CDD; cd16220; EFh_PI-PLCeta1; 1. DR CDD; cd08632; PI-PLCc_eta1; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.10.238.10; EF-hand; 2. DR Gene3D; 3.20.20.190; Phosphatidylinositol (PI) phosphodiesterase; 2. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR001192; PI-PLC_fam. DR InterPro; IPR028392; PLC-eta1_cat. DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl. DR InterPro; IPR015359; PLC_EF-hand-like. DR InterPro; IPR046972; PLCeta1_EF. DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom. DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y. DR PANTHER; PTHR10336:SF51; 1-PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE PHOSPHODIESTERASE ETA-1; 1. DR PANTHER; PTHR10336; PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C FAMILY PROTEIN; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF09279; EF-hand_like; 1. DR Pfam; PF16457; PH_12; 1. DR Pfam; PF00388; PI-PLC-X; 1. DR Pfam; PF00387; PI-PLC-Y; 1. DR PRINTS; PR00390; PHPHLIPASEC. DR SMART; SM00239; C2; 1. DR SMART; SM00054; EFh; 2. DR SMART; SM00233; PH; 1. DR SMART; SM00148; PLCXc; 1. DR SMART; SM00149; PLCYc; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF51695; PLC-like phosphodiesterases; 1. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS00018; EF_HAND_1; 1. DR PROSITE; PS50222; EF_HAND_2; 3. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1. DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1. DR Genevisible; Q4KWH8; HS. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Cytoplasm; Disease variant; KW Holoprosencephaly; Hydrolase; Lipid degradation; Lipid metabolism; KW Membrane; Metal-binding; Reference proteome; Repeat; Transducer. FT CHAIN 1..1693 FT /note="1-phosphatidylinositol 4,5-bisphosphate FT phosphodiesterase eta-1" FT /id="PRO_0000329007" FT DOMAIN 20..128 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 142..177 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 178..214 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 226..246 FT /note="EF-hand 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 299..444 FT /note="PI-PLC X-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT DOMAIN 601..714 FT /note="PI-PLC Y-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271" FT DOMAIN 715..843 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT REGION 526..585 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 992..1014 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1052..1089 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1300..1329 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1578..1613 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 530..544 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 562..577 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1052..1084 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1300..1316 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 314 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT ACT_SITE 358 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT BINDING 155 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 157 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 159 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 166 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 315 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 344 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 346 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 393 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 442 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 444 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 627 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 654 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 758 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 760 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 784 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 813 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 814 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 815 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT VAR_SEQ 1..18 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_032901" FT VAR_SEQ 862..881 FT /note="Missing (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_032902" FT VAR_SEQ 1000..1034 FT /note="AEDKDGRRKGKASIKDPHFLNFNKKLSSSSSALLH -> DSSFCRPTEQAKA FT EMCKVPFPRQLECVMKMEISET (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_032903" FT VAR_SEQ 1000..1002 FT /note="AED -> VQI (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10470851, FT ECO:0000303|PubMed:15702972" FT /id="VSP_032904" FT VAR_SEQ 1003..1693 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10470851, FT ECO:0000303|PubMed:15702972" FT /id="VSP_032905" FT VAR_SEQ 1035..1693 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_032906" FT VARIANT 689..1693 FT /note="Missing (in HPE14)" FT /evidence="ECO:0000269|PubMed:33820834" FT /id="VAR_087460" SQ SEQUENCE 1693 AA; 189223 MW; 00F2ADD21C4D14E6 CRC64; MADLEVYKNL SPEKVERCMS VMQSGTQMIK LKRGTKGLVR LFYLDEHRTR LRWRPSRKSE KAKILIDSIY KVTEGRQSEI FHRQAEGNFD PSCCFTIYHG NHMESLDLIT SNPEEARTWI TGLKYLMAGI SDEDSLAKRQ RTHDQWVKQT FEEADKNGDG LLNIEEIHQL MHKLNVNLPR RKVRQMFQEA DTDENQGTLT FEEFCVFYKM MSLRRDLYLL LLSYSDKKDH LTVEELAQFL KVEQKMNNVT TDYCLDIIKK FEVSEENKVK NVLGIEGFTN FMRSPACDIF NPLHHEVYQD MDQPLCNYYI ASSHNTYLTG DQLLSQSKVD MYARVLQEGC RCVEVDCWDG PDGEPVVHHG YTLTSKILFR DVVETINKHA FVKNEFPVIL SIENHCSIQQ QRKIAQYLKG IFGDKLDLSS VDTGECKQLP SPQSLKGKIL VKGKKLPYHL GDDAEEGEVS DEDSADEIED ECKFKLHYSN GTTEHQVESF IRKKLESLLK ESQIRDKEDP DSFTVRALLK ATHEGLNAHL KQSPDVKESG KKSHGRSLMT NFGKHKKTTK SRSKSYSTDD EEDTQQSTGK EGGQLYRLGR RRKTMKLCRE LSDLVVYTNS VAAQDIVDDG TTGNVLSFSE TRAHQVVQQK SEQFMIYNQK QLTRIYPSAY RIDSSNFNPL PYWNAGCQLV ALNYQSEGRM MQLNRAKFKA NGNCGYVLKP QQMCKGTFNP FSGDPLPANP KKQLILKVIS GQQLPKPPDS MFGDRGEIID PFVEVEIIGL PVDCCKDQTR VVDDNGFNPV WEETLTFTVH MPEIALVRFL VWDHDPIGRD FVGQRTVTFS SLVPGYRHVY LEGLTEASIF VHITINEIYG KWSPLILNPS YTILHFLGAT KNRQLQGLKG LFNKNPRHSS SENNSHYVRK RSIGDRILRR TASAPAKGRK KSKMGFQEMV EIKDSVSEAT RDQDGVLRRT TRSLQARPVS MPVDRNLLGA LSLPVSETAK DIEGKENSLA EDKDGRRKGK ASIKDPHFLN FNKKLSSSSS ALLHKDTSQG DTIVSTAHMS VTGEQLGMSS PRGGRTTSNA TSNCQENPCP SKSLSPKQHL APDPVVNPTQ DLHGVKIKEK GNPEDFVEGK SILSGSVLSH SNLEIKNLEG NRGKGRAATS FSLSDVSMLC SDIPDLHSTA ILQESVISHL IDNVTLTNEN EPGSSISALI GQFDETNNQA LTVVSHLHNT SVMSGHCPLP SLGLKMPIKH GFCKGKSKSS FLCSSPELIA LSSSETTKHA TNTVYETTCT PISKTKPDDD LSSKAKTAAL ESNLPGSPNT SRGWLPKSPT KGEDWETLKS CSPASSPDLT LEDVIADPTL CFNSGESSLV EIDGESENLS LTTCEYRREG TSQLASPLKL KYNQGVVEHF QRGLRNGYCK ETLRPSVPEI FNNIQDVKTQ SISYLAYQGA GFVHNHFSDS DAKMFQTCVP QQSSAQDMHV PVPKQLAHLP LPALKLPSPC KSKSLGDLTS EDIACNFESK YQCISKSFVT TGIRDKKGVT VKTKSLEPID ALTEQLRKLV SFDQEDNCQV LYSKQDANQL PRALVRKLSS RSQSRVRNIA SRAKEKQEAN KQKVPNPSNG AGVVLRNKPS APTPAVNRHS TGSYIAGYLK NTKGGGLEGR GIPEGACTAL HYGHVDQFCS DNSVLQTEPS SDDKPEIYFL LRL //