SYT7_HUMAN
ID SYT7_HUMAN Reviewed; 403 AA.
AC O43581; F5GZC2; F5GZU9; F5H126; F5H1N2; F5H6C1; Q08AH6;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 3.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Synaptotagmin-7 {ECO:0000305};
DE AltName: Full=IPCA-7;
DE AltName: Full=Prostate cancer-associated protein 7;
DE AltName: Full=Synaptotagmin VII;
DE Short=SytVII;
GN Name=SYT7 {ECO:0000312|HGNC:HGNC:11514}; Synonyms=PCANAP7;
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] (ISOFORM 1), AND VARIANT ASN-332.
RX PubMed=9615227; DOI=10.1006/geno.1998.5291;
RA Cooper P.R., Nowak N.J., Higgins M.J., Church D.M., Shows T.B.;
RT "Transcript mapping of the human chromosome 11q12-q13.1 gene-rich region
RT identifies several newly described conserved genes.";
RL Genomics 49:419-429(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [5]
RP FUNCTION.
RX PubMed=11342594; DOI=10.1084/jem.193.9.1097;
RA Caler E.V., Chakrabarti S., Fowler K.T., Rao S., Andrews N.W.;
RT "The Exocytosis-regulatory protein synaptotagmin VII mediates cell invasion
RT by Trypanosoma cruzi.";
RL J. Exp. Med. 193:1097-1104(2001).
RN [6]
RP ALTERNATIVE SPLICING.
RX PubMed=12071850; DOI=10.1042/bj20011877;
RA Fukuda M., Ogata Y., Saegusa C., Kanno E., Mikoshiba K.;
RT "Alternative splicing isoforms of synaptotagmin VII in the mouse, rat and
RT human.";
RL Biochem. J. 365:173-180(2002).
RN [7]
RP FUNCTION.
RX PubMed=15811535; DOI=10.1016/j.molbiopara.2005.01.016;
RA Chakrabarti S., Andrade L.O., Andrews N.W.;
RT "Trypanosoma cruzi invades synaptotagmin VII-deficient cells by a PI-3
RT kinase independent pathway.";
RL Mol. Biochem. Parasitol. 141:125-128(2005).
RN [8]
RP DOMAIN.
RX PubMed=22966849; DOI=10.1021/bi3007115;
RA Brandt D.S., Coffman M.D., Falke J.J., Knight J.D.;
RT "Hydrophobic contributions to the membrane docking of synaptotagmin 7 C2A
RT domain: mechanistic contrast between isoforms 1 and 7.";
RL Biochemistry 51:7654-7664(2012).
RN [9]
RP DOMAIN.
RX PubMed=25437758; DOI=10.1021/bi5012223;
RA Vasquez J.K., Chantranuvatana K., Giardina D.T., Coffman M.D., Knight J.D.;
RT "Lateral diffusion of proteins on supported lipid bilayers: additive
RT friction of synaptotagmin 7 C2A-C2B tandem domains.";
RL Biochemistry 53:7904-7913(2014).
RN [10]
RP DOMAIN.
RX PubMed=26322740; DOI=10.1021/acs.biochem.5b00421;
RA Osterberg J.R., Chon N.L., Boo A., Maynard F.A., Lin H., Knight J.D.;
RT "Membrane docking of the synaptotagmin 7 C2A domain: electron paramagnetic
RT resonance measurements show contributions from two membrane binding
RT loops.";
RL Biochemistry 54:5684-5695(2015).
RN [11]
RP DOMAIN.
RX PubMed=26333120; DOI=10.1021/acs.biochem.5b00422;
RA Chon N.L., Osterberg J.R., Henderson J., Khan H.M., Reuter N., Knight J.D.,
RA Lin H.;
RT "Membrane docking of the synaptotagmin 7 C2A Domain: computation reveals
RT interplay between electrostatic and hydrophobic contributions.";
RL Biochemistry 54:5696-5711(2015).
RN [12]
RP STRUCTURE BY NMR OF 132-259.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first C2 domain of synaptotagmin VII.";
RL Submitted (JUN-2006) to the PDB data bank.
CC -!- FUNCTION: Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of
CC secretory and synaptic vesicles through Ca(2+) and phospholipid binding
CC to the C2 domain (By similarity). Ca(2+) induces binding of the C2-
CC domains to phospholipid membranes and to assembled SNARE-complexes;
CC both actions contribute to triggering exocytosis (By similarity). SYT7
CC binds Ca(2+) with high affinity and slow kinetics compared to other
CC synaptotagmins (By similarity). Involved in Ca(2+)-triggered lysosomal
CC exocytosis, a major component of the plasma membrane repair
CC (PubMed:11342594). Ca(2+)-regulated delivery of lysosomal membranes to
CC the cell surface is also involved in the phagocytic uptake of particles
CC by macrophages (By similarity). Ca(2+)-triggered lysosomal exocytosis
CC also plays a role in bone remodeling by regulating secretory pathways
CC in osteoclasts and osteoblasts (By similarity). In case of infection,
CC involved in participates cell invasion by Trypanosoma cruzi via Ca(2+)-
CC triggered lysosomal exocytosis (PubMed:11342594, PubMed:15811535).
CC Involved in cholesterol transport from lysosome to peroxisome by
CC promoting membrane contacts between lysosomes and peroxisomes: probably
CC acts by promoting vesicle fusion by binding phosphatidylinositol-4,5-
CC bisphosphate on peroxisomal membranes (By similarity). Acts as a key
CC mediator of synaptic facilitation, a process also named short-term
CC synaptic potentiation: synaptic facilitation takes place at synapses
CC with a low initial release probability and is caused by influx of
CC Ca(2+) into the axon terminal after spike generation, increasing the
CC release probability of neurotransmitters (By similarity). Probably
CC mediates synaptic facilitation by directly increasing the probability
CC of release (By similarity). May also contribute to synaptic
CC facilitation by regulating synaptic vesicle replenishment, a process
CC required to ensure that synaptic vesicles are ready for the arrival of
CC the next action potential: SYT7 is required for synaptic vesicle
CC replenishment by acting as a sensor for Ca(2+) and by forming a complex
CC with calmodulin (By similarity). Also acts as a regulator of Ca(2+)-
CC dependent insulin and glucagon secretion in beta-cells (By similarity).
CC Triggers exocytosis by promoting fusion pore opening and fusion pore
CC expansion in chromaffin cells (By similarity). Also regulates the
CC secretion of some non-synaptic secretory granules of specialized cells
CC (By similarity). {ECO:0000250|UniProtKB:Q62747,
CC ECO:0000250|UniProtKB:Q9R0N7, ECO:0000269|PubMed:11342594,
CC ECO:0000269|PubMed:15811535}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds 3 Ca(2+) ions per C2 domain. {ECO:0000255|PROSITE-
CC ProRule:PRU00041};
CC -!- SUBUNIT: Homodimer. Can also form heterodimers with SYT6, SYT9 and
CC SYT10. Interacts with calmodulin (CALM1, CALM2 or CALM3). Interacts
CC with CD63; required for localization to lysosomes. Interacts with APP
CC (By similarity). {ECO:0000250|UniProtKB:Q9R0N7}.
CC -!- INTERACTION:
CC O43581; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-10184345, EBI-747107;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q62747};
CC Single-pass membrane protein {ECO:0000255}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q9R0N7}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC membrane {ECO:0000250|UniProtKB:Q9R0N7}; Single-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q9R0N7};
CC Single-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle,
CC phagosome membrane {ECO:0000250|UniProtKB:Q9R0N7}; Single-pass membrane
CC protein {ECO:0000255}. Peroxisome membrane
CC {ECO:0000250|UniProtKB:Q9R0N7}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000250|UniProtKB:Q62747}; Single-pass membrane protein
CC {ECO:0000255}. Note=Localization to lysosomes is dependent on N-
CC terminal palmitoylation and interaction with CD63.
CC {ECO:0000250|UniProtKB:Q9R0N7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=O43581-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43581-2; Sequence=VSP_045991;
CC Name=3;
CC IsoId=O43581-3; Sequence=VSP_058233;
CC Name=4;
CC IsoId=O43581-4; Sequence=VSP_058234;
CC Name=5;
CC IsoId=O43581-5; Sequence=VSP_058231;
CC Name=6; Synonyms=Synaptotagmin VIIbeta {ECO:0000303|PubMed:12071850},
CC Syt7beta {ECO:0000305};
CC IsoId=O43581-6; Sequence=VSP_058232;
CC -!- TISSUE SPECIFICITY: Expressed in a variety of adult and fetal tissues.
CC -!- DOMAIN: The C2 domains bind Ca(2+) and membranes. Binding to membranes
CC involves Ca(2+)-dependent phospholipid binding. Compared to other
CC members of the family, the C2 domains of SYT7 dock and insert into
CC cellular membranes in response to intracellular Ca(2+) concentrations
CC that are lower than those required for other synaptotagmins
CC (PubMed:22966849). The two C2 domains bind independently to planar
CC membranes, without interdomain cooperativity (PubMed:25437758).
CC Moreover, SYT7 C2 domains insert more deeply into membranes compared to
CC other synaptotagmins (PubMed:26322740, PubMed:26333120).
CC {ECO:0000269|PubMed:22966849, ECO:0000269|PubMed:25437758,
CC ECO:0000269|PubMed:26322740, ECO:0000269|PubMed:26333120}.
CC -!- PTM: Palmitoylated at its vesicular N-terminus; palmitoylation is
CC required for localization to lysosome and phagocytosis in macrophages.
CC {ECO:0000250|UniProtKB:Q9R0N7}.
CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform.
CC {ECO:0000269|PubMed:12071850}.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB92667.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF038535; AAB92667.1; ALT_FRAME; mRNA.
DR EMBL; AP002754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003108; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003559; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW73956.1; -; Genomic_DNA.
DR EMBL; BC125170; AAI25171.1; -; mRNA.
DR EMBL; BC125171; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS31577.1; -. [O43581-1]
DR CCDS; CCDS58139.1; -. [O43581-2]
DR CCDS; CCDS73298.1; -. [O43581-6]
DR RefSeq; NP_001238994.1; NM_001252065.1. [O43581-2]
DR RefSeq; NP_001287702.1; NM_001300773.1. [O43581-6]
DR RefSeq; NP_004191.2; NM_004200.3. [O43581-1]
DR RefSeq; XP_005274440.1; XM_005274383.4.
DR RefSeq; XP_005274442.1; XM_005274385.4. [O43581-4]
DR PDB; 2D8K; NMR; -; A=132-259.
DR PDBsum; 2D8K; -.
DR AlphaFoldDB; O43581; -.
DR SMR; O43581; -.
DR BioGRID; 114525; 14.
DR CORUM; O43581; -.
DR ELM; O43581; -.
DR IntAct; O43581; 5.
DR MINT; O43581; -.
DR iPTMnet; O43581; -.
DR PhosphoSitePlus; O43581; -.
DR BioMuta; SYT7; -.
DR EPD; O43581; -.
DR jPOST; O43581; -.
DR MassIVE; O43581; -.
DR MaxQB; O43581; -.
DR PaxDb; O43581; -.
DR PeptideAtlas; O43581; -.
DR PRIDE; O43581; -.
DR ProteomicsDB; 24992; -.
DR ProteomicsDB; 25136; -.
DR ProteomicsDB; 25521; -.
DR ProteomicsDB; 25708; -.
DR ProteomicsDB; 27141; -.
DR ProteomicsDB; 49062; -. [O43581-1]
DR Antibodypedia; 2220; 272 antibodies from 33 providers.
DR DNASU; 9066; -.
DR Ensembl; ENST00000263846.8; ENSP00000263846.4; ENSG00000011347.10. [O43581-1]
DR Ensembl; ENST00000535826.5; ENSP00000437720.1; ENSG00000011347.10. [O43581-5]
DR Ensembl; ENST00000539008.6; ENSP00000439694.1; ENSG00000011347.10. [O43581-3]
DR Ensembl; ENST00000540677.5; ENSP00000444201.1; ENSG00000011347.10. [O43581-2]
DR Ensembl; ENST00000542670.5; ENSP00000444019.1; ENSG00000011347.10. [O43581-4]
DR Ensembl; ENST00000542836.5; ENSP00000444568.1; ENSG00000011347.10. [O43581-6]
DR GeneID; 9066; -.
DR KEGG; hsa:9066; -.
DR MANE-Select; ENST00000539008.6; ENSP00000439694.1; NM_001365809.2; NP_001352738.1. [O43581-3]
DR UCSC; uc001nrv.4; human. [O43581-1]
DR UCSC; uc001nrx.2; human.
DR UCSC; uc058cdk.1; human.
DR UCSC; uc058cdl.1; human.
DR UCSC; uc058cdm.1; human.
DR CTD; 9066; -.
DR DisGeNET; 9066; -.
DR GeneCards; SYT7; -.
DR HGNC; HGNC:11514; SYT7.
DR HPA; ENSG00000011347; Tissue enhanced (brain, liver, salivary gland).
DR MIM; 604146; gene.
DR neXtProt; NX_O43581; -.
DR OpenTargets; ENSG00000011347; -.
DR PharmGKB; PA36295; -.
DR VEuPathDB; HostDB:ENSG00000011347; -.
DR eggNOG; KOG1028; Eukaryota.
DR GeneTree; ENSGT00940000157180; -.
DR HOGENOM; CLU_023008_7_2_1; -.
DR InParanoid; O43581; -.
DR OMA; QNHEANS; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; O43581; -.
DR TreeFam; TF315600; -.
DR PathwayCommons; O43581; -.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR SignaLink; O43581; -.
DR BioGRID-ORCS; 9066; 10 hits in 1067 CRISPR screens.
DR ChiTaRS; SYT7; human.
DR EvolutionaryTrace; O43581; -.
DR GeneWiki; SYT7; -.
DR GenomeRNAi; 9066; -.
DR Pharos; O43581; Tbio.
DR PRO; PR:O43581; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O43581; protein.
DR Bgee; ENSG00000011347; Expressed in islet of Langerhans and 114 other tissues.
DR ExpressionAtlas; O43581; baseline and differential.
DR Genevisible; O43581; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0031045; C:dense core granule; IEA:Ensembl.
DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0008021; C:synaptic vesicle; ISS:UniProtKB.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0030276; F:clathrin binding; IBA:GO_Central.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR GO; GO:0000149; F:SNARE binding; IBA:GO_Central.
DR GO; GO:0019905; F:syntaxin binding; IEA:Ensembl.
DR GO; GO:1990927; P:calcium ion regulated lysosome exocytosis; ISS:UniProtKB.
DR GO; GO:0048791; P:calcium ion-regulated exocytosis of neurotransmitter; ISS:UniProtKB.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; IBA:GO_Central.
DR GO; GO:0071277; P:cellular response to calcium ion; IBA:GO_Central.
DR GO; GO:0006909; P:phagocytosis; ISS:UniProtKB.
DR GO; GO:0090385; P:phagosome-lysosome fusion; ISS:UniProtKB.
DR GO; GO:0001778; P:plasma membrane repair; ISS:UniProtKB.
DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; IEA:Ensembl.
DR GO; GO:0046850; P:regulation of bone remodeling; ISS:UniProtKB.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IBA:GO_Central.
DR GO; GO:0014059; P:regulation of dopamine secretion; IBA:GO_Central.
DR GO; GO:0070092; P:regulation of glucagon secretion; ISS:UniProtKB.
DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:1990926; P:short-term synaptic potentiation; ISS:UniProtKB.
DR GO; GO:0036465; P:synaptic vesicle recycling; ISS:UniProtKB.
DR GO; GO:0090119; P:vesicle-mediated cholesterol transport; ISS:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR CDD; cd08386; C2A_Synaptotagmin-7; 1.
DR CDD; cd08405; C2B_Synaptotagmin-7; 1.
DR Gene3D; 2.60.40.150; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037732; C2A_Synaptotagmin-7.
DR InterPro; IPR037741; C2B_Synaptotagmin-7.
DR InterPro; IPR001565; Synaptotagmin.
DR InterPro; IPR015427; Synaptotagmin7.
DR PANTHER; PTHR10024:SF358; PTHR10024:SF358; 2.
DR Pfam; PF00168; C2; 2.
DR PRINTS; PR00360; C2DOMAIN.
DR PRINTS; PR00399; SYNAPTOTAGMN.
DR SMART; SM00239; C2; 2.
DR SUPFAM; SSF49562; SSF49562; 2.
DR PROSITE; PS50004; C2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Calmodulin-binding;
KW Cell membrane; Cell projection; Cytoplasmic vesicle; Exocytosis;
KW Lipoprotein; Lysosome; Membrane; Metal-binding; Palmitate; Peroxisome;
KW Phosphoprotein; Reference proteome; Repeat; Synapse; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..403
FT /note="Synaptotagmin-7"
FT /id="PRO_0000183957"
FT TOPO_DOM 1..16
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..403
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 135..255
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 266..399
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 53..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 166
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 166
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 172
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 297
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 297
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 303
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 357
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 357
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 359
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 359
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 359
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 362
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 365
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q9R0N7"
FT BINDING 365
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0N7"
FT MOD_RES 58
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0N7"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0N7"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62747"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0N7"
FT VAR_SEQ 71
FT /note="I -> INGTLLSGAKVAAAAGLAVEREGRLGEKPAPVPPPGEDALRSGGAAP
FT SEPGSGGKAGRGRWRTVQSHLAAGKLNLS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045991"
FT VAR_SEQ 71
FT /note="I -> INDLDRDFWNNNESTVQQKWSSYPPKEFILNISPYAPYGDPRLSLNG
FT TLLSGAKVAAAAGLAVEREGRLGEKPAPVPPPGEDALRSGGAAPSEPGSGGKAGRGRWR
FT TVQSHLAAGKLNLS (in isoform 5)"
FT /id="VSP_058231"
FT VAR_SEQ 71
FT /note="I -> INDLDRDFWNNNESTVQQKWSSYPPKEFILNISPYAPYGDPRLSL
FT (in isoform 6)"
FT /id="VSP_058232"
FT VAR_SEQ 72
FT /note="K -> NDLDRDFWNNNESTVQQKWSSYPPKEFILNISPYAPYGDPRLSLNGT
FT LLSGAKVAAAAGLAVEREGRLGEKPAPVPPPGEDALRSGGAAPSEPGSGGKAGRGRWRT
FT VQSHLAAGKLNLSNFEDSTLSTATTLESIPSSTGEPKCQRPRTLMRQQSLQQPLSQHQR
FT GRQPSQPTTSQSLGQLQAHMASAPGPNPRAYGRGQARQGTSAGSKYRAAGGRSRSNPGS
FT WDHVVGQIRNRGLDMKSFLEGRMVVLSLVLGLSEQDDFANIPDLQNPGTQQNQNAQGDK
FT R (in isoform 3)"
FT /id="VSP_058233"
FT VAR_SEQ 72
FT /note="K -> NDLDRDFWNNNESTVQQKWSSYPPKEFILNISPYAPYGDPRLSLNFE
FT DSTLSTATTLESIPSSTGEPKCQRPRTLMRQQSLQQPLSQHQRGRQPSQPTTSQSLGQL
FT QAHMASAPGPNPRAYGRGQARQGTSAGSKYRAAGGRSRSNPGSWDHVVGQIRNRGLDMK
FT SFLEGRMVVLSLVLGLSEQDDFANIPDLQNPGTQQNQNAQGDKR (in isoform
FT 4)"
FT /id="VSP_058234"
FT VARIANT 332
FT /note="I -> N (in dbSNP:rs407740)"
FT /evidence="ECO:0000269|PubMed:9615227"
FT /id="VAR_052241"
FT CONFLICT 154
FT /note="V -> L (in Ref. 1; AAB92667)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="E -> K (in Ref. 1; AAB92667)"
FT /evidence="ECO:0000305"
FT STRAND 138..145
FT /evidence="ECO:0007829|PDB:2D8K"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:2D8K"
FT STRAND 152..161
FT /evidence="ECO:0007829|PDB:2D8K"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:2D8K"
FT STRAND 173..181
FT /evidence="ECO:0007829|PDB:2D8K"
FT STRAND 184..188
FT /evidence="ECO:0007829|PDB:2D8K"
FT STRAND 202..206
FT /evidence="ECO:0007829|PDB:2D8K"
FT HELIX 211..214
FT /evidence="ECO:0007829|PDB:2D8K"
FT STRAND 217..225
FT /evidence="ECO:0007829|PDB:2D8K"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:2D8K"
FT STRAND 233..241
FT /evidence="ECO:0007829|PDB:2D8K"
FT TURN 242..244
FT /evidence="ECO:0007829|PDB:2D8K"
FT STRAND 251..255
FT /evidence="ECO:0007829|PDB:2D8K"
SQ SEQUENCE 403 AA; 45501 MW; C9BFB26D298EDBE4 CRC64;
MYRDPEAASP GAPSRDVLLV SAIITVSLSV TVVLCGLCHW CQRKLGKRYK NSLETVGTPD
SGRGRSEKKA IKLPAGGKAV NTAPVPGQTP HDESDRRTEP RSSVSDLVNS LTSEMLMLSP
GSEEDEAHEG CSRENLGRIQ FSVGYNFQES TLTVKIMKAQ ELPAKDFSGT SDPFVKIYLL
PDKKHKLETK VKRKNLNPHW NETFLFEGFP YEKVVQRILY LQVLDYDRFS RNDPIGEVSI
PLNKVDLTQM QTFWKDLKPC SDGSGSRGEL LLSLCYNPSA NSIIVNIIKA RNLKAMDIGG
TSDPYVKVWL MYKDKRVEKK KTVTMKRNLN PIFNESFAFD IPTEKLRETT IIITVMDKDK
LSRNDVIGKI YLSWKSGPGE VKHWKDMIAR PRQPVAQWHQ LKA
