UN13A_RAT
ID UN13A_RAT Reviewed; 1735 AA.
AC Q62768;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Protein unc-13 homolog A {ECO:0000305};
DE AltName: Full=Munc13-1;
GN Name=Unc13a {ECO:0000312|RGD:619722}; Synonyms=Unc13h1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=7559667; DOI=10.1074/jbc.270.42.25273;
RA Brose N., Hofmann K., Hata Y., Suedhof T.C.;
RT "Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel
RT family of C2-domain proteins.";
RL J. Biol. Chem. 270:25273-25280(1995).
RN [2]
RP INTERACTION WITH SYNTAXIN 1.
RX PubMed=8999968; DOI=10.1074/jbc.272.4.2520;
RA Betz A., Okamoto M., Benseler F., Brose N.;
RT "Direct interaction of the rat unc-13 homologue Munc13-1 with the N
RT terminus of syntaxin.";
RL J. Biol. Chem. 272:2520-2526(1997).
RN [3]
RP INTERACTION WITH DOC2A.
RX PubMed=9195900; DOI=10.1074/jbc.272.26.16081;
RA Orita S., Naito A., Sakaguchi G., Maeda M., Igarashi H., Sasaki T.,
RA Takai Y.;
RT "Physical and functional interactions of Doc2 and Munc13 in Ca2+-dependent
RT exocytotic machinery.";
RL J. Biol. Chem. 272:16081-16084(1997).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-567.
RX PubMed=9697857; DOI=10.1016/s0896-6273(00)80520-6;
RA Betz A., Ashery U., Rickmann M., Augustin I., Neher E., Suedhof T.C.,
RA Rettig J., Brose N.;
RT "Munc13-1 is a presynaptic phorbol ester receptor that enhances
RT neurotransmitter release.";
RL Neuron 21:123-136(1998).
RN [5]
RP INTERACTION WITH DOC2A.
RX PubMed=9736751; DOI=10.1073/pnas.95.19.11418;
RA Mochida S., Orita S., Sakaguchi G., Sasaki T., Takai Y.;
RT "Role of the Doc2 alpha-Munc13-1 interaction in the neurotransmitter
RT release process.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:11418-11422(1998).
RN [6]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9895278; DOI=10.1042/bj3370363;
RA Augustin I., Betz A., Herrmann C., Jo T., Brose N.;
RT "Differential expression of two novel Munc13 proteins in rat brain.";
RL Biochem. J. 337:363-371(1999).
RN [7]
RP FUNCTION, AND INTERACTION WITH RIMS1.
RX PubMed=11343654; DOI=10.1016/s0896-6273(01)00272-0;
RA Betz A., Thakur P., Junge H.J., Ashery U., Rhee J.S., Scheuss V.,
RA Rosenmund C., Rettig J., Brose N.;
RT "Functional interaction of the active zone proteins Munc13-1 and RIM1 in
RT synaptic vesicle priming.";
RL Neuron 30:183-196(2001).
RN [8]
RP FUNCTION.
RX PubMed=11792326; DOI=10.1016/s0092-8674(01)00635-3;
RA Rhee J.S., Betz A., Pyott S., Reim K., Varoqueaux F., Augustin I.,
RA Hesse D., Suedhof T.C., Takahashi M., Rosenmund C., Brose N.;
RT "Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter
RT release is mediated by Munc13s and not by PKCs.";
RL Cell 108:121-133(2002).
RN [9]
RP INTERACTION WITH BSN, AND IDENTIFICATION IN A COMPLEX WITH ERC2 AND RIMS1.
RX PubMed=12163476; DOI=10.1083/jcb.200202083;
RA Ohtsuka T., Takao-Rikitsu E., Inoue E., Inoue M., Takeuchi M.,
RA Matsubara K., Deguchi-Tawarada M., Satoh K., Morimoto K., Nakanishi H.,
RA Takai Y.;
RT "Cast: a novel protein of the cytomatrix at the active zone of synapses
RT that forms a ternary complex with RIM1 and Munc13-1.";
RL J. Cell Biol. 158:577-590(2002).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=12871971; DOI=10.1074/jbc.m303203200;
RA Sheu L., Pasyk E.A., Ji J., Huang X., Gao X., Varoqueaux F., Brose N.,
RA Gaisano H.Y.;
RT "Regulation of insulin exocytosis by Munc13-1.";
RL J. Biol. Chem. 278:27556-27563(2003).
RN [11]
RP INTERACTION WITH BSN.
RX PubMed=14734538; DOI=10.1083/jcb.200307101;
RA Takao-Rikitsu E., Mochida S., Inoue E., Deguchi-Tawarada M., Inoue M.,
RA Ohtsuka T., Takai Y.;
RT "Physical and functional interaction of the active zone proteins, CAST,
RT RIM1, and Bassoon, in neurotransmitter release.";
RL J. Cell Biol. 164:301-311(2004).
RN [12]
RP DOMAIN, AND MUTAGENESIS OF GLN-1190; LEU-1279; ILE-1364; VAL-1603 AND
RP ASP-1655.
RX PubMed=16271475; DOI=10.1016/j.cub.2005.10.055;
RA Stevens D.R., Wu Z.-X., Matti U., Junge H.J., Schirra C., Becherer U.,
RA Wojcik S.M., Brose N., Rettig J.;
RT "Identification of the minimal protein domain required for priming activity
RT of Munc13-1.";
RL Curr. Biol. 15:2243-2248(2005).
RN [13]
RP INTERACTION WITH RIMS2.
RX PubMed=16052212; DOI=10.1038/sj.emboj.7600753;
RA Dulubova I., Lou X., Lu J., Huryeva I., Alam A., Schneggenburger R.,
RA Suedhof T.C., Rizo J.;
RT "A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity?";
RL EMBO J. 24:2839-2850(2005).
RN [14]
RP INTERACTION WITH RIMS1, AND MUTAGENESIS OF THR-22; TYR-23; VAL-64; HIS-119
RP AND ILE-121.
RX PubMed=16704978; DOI=10.1074/jbc.m601421200;
RA Andrews-Zwilling Y.S., Kawabe H., Reim K., Varoqueaux F., Brose N.;
RT "Binding to Rab3A-interacting molecule RIM regulates the presynaptic
RT recruitment of Munc13-1 and ubMunc13-2.";
RL J. Biol. Chem. 281:19720-19731(2006).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239; SER-241; SER-244 AND
RP SER-255, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [16]
RP STRUCTURE BY NMR OF 567-616.
RX PubMed=15667202; DOI=10.1021/bi0476127;
RA Shen N., Guryev O., Rizo J.;
RT "Intramolecular occlusion of the diacylglycerol-binding site in the C1
RT domain of munc13-1.";
RL Biochemistry 44:1089-1096(2005).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.44 ANGSTROMS) OF 1-128, AND X-RAY CRYSTALLOGRAPHY
RP (1.78 ANGSTROMS) OF 2-150 IN COMPLEX WITH RIMS2.
RX PubMed=16732694; DOI=10.1371/journal.pbio.0040192;
RA Lu J., Machius M., Dulubova I., Dai H., Suedhof T.C., Tomchick D.R.,
RA Rizo J.;
RT "Structural basis for a Munc13-1 homodimer to Munc13-1/RIM heterodimer
RT switch.";
RL PLoS Biol. 4:1159-1172(2006).
CC -!- FUNCTION: Plays a role in vesicle maturation during exocytosis as a
CC target of the diacylglycerol second messenger pathway. Involved in
CC neurotransmitter release by acting in synaptic vesicle priming prior to
CC vesicle fusion and participates in the activity-dependent refilling of
CC readily releasable vesicle pool (RRP). Essential for synaptic vesicle
CC maturation in most excitatory/glutamatergic but not inhibitory/GABA-
CC mediated synapses. Facilitates neuronal dense core vesicles fusion as
CC well as controls the location and efficiency of their synaptic release
CC (By similarity). Also involved in secretory granule priming in insulin
CC secretion. Plays a role in dendrite formation by melanocytes (By
CC similarity). {ECO:0000250|UniProtKB:Q4KUS2,
CC ECO:0000250|UniProtKB:Q9UPW8, ECO:0000269|PubMed:11343654,
CC ECO:0000269|PubMed:11792326, ECO:0000269|PubMed:9697857}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with the N-termini of STX1A and/or STX1B1 and DOC2A
CC (PubMed:8999968, PubMed:9195900, PubMed:9736751). Interacts with BSN
CC (PubMed:12163476, PubMed:14734538). Interacts with RIMS1 which recruits
CC UNC13A to the active zone (PubMed:11343654, PubMed:16704978). Forms
CC homodimers via its first C2 domain. Also interacts via this domain with
CC the zinc finger domain of RIMS2 (PubMed:16052212, PubMed:16732694).
CC Part of a complex consisting of ERC2, RIMS1 and UNC13A
CC (PubMed:12163476). Also part of a complex consisting of UNC13A, RIMS2
CC and RAB3A. Interacts with FBXO45 (via SRY domain); leading to the
CC degradation of UNC13A by the proteasome (By similarity).
CC {ECO:0000250|UniProtKB:Q4KUS2, ECO:0000269|PubMed:11343654,
CC ECO:0000269|PubMed:12163476, ECO:0000269|PubMed:14734538,
CC ECO:0000269|PubMed:16052212, ECO:0000269|PubMed:16704978,
CC ECO:0000269|PubMed:16732694, ECO:0000269|PubMed:8999968,
CC ECO:0000269|PubMed:9195900, ECO:0000269|PubMed:9736751}.
CC -!- INTERACTION:
CC Q62768; Q9JIS1: Rims2; NbExp=4; IntAct=EBI-15584670, EBI-6972631;
CC Q62768; Q62768: Unc13a; NbExp=4; IntAct=EBI-15584670, EBI-15584670;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane
CC protein. Presynaptic cell membrane {ECO:0000269|PubMed:7559667};
CC Peripheral membrane protein. Presynaptic active zone
CC {ECO:0000269|PubMed:7559667}. Note=Translocated to the plasma membrane
CC in response to phorbol ester binding.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q62768-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q62768-2; Sequence=VSP_011382;
CC Name=3;
CC IsoId=Q62768-3; Sequence=VSP_011383;
CC -!- TISSUE SPECIFICITY: Expressed in brain, with highest levels in the
CC olfactory bulb, striatum, cerebral cortex, hippocampus and cerebellum.
CC Also expressed in pancreatic islet cells. {ECO:0000269|PubMed:12871971,
CC ECO:0000269|PubMed:7559667, ECO:0000269|PubMed:9895278}.
CC -!- DEVELOPMENTAL STAGE: First detected at birth, after which expression
CC level is steadily increasing until it reaches a plateau at P15.
CC {ECO:0000269|PubMed:9895278}.
CC -!- DOMAIN: The C2 domains are not involved in calcium-dependent
CC phospholipid binding. {ECO:0000269|PubMed:16271475}.
CC -!- DOMAIN: The C-terminal region containing both MHD domains and the third
CC C2 domain is required for synaptic vesicle priming activity.
CC {ECO:0000269|PubMed:16271475}.
CC -!- SIMILARITY: Belongs to the unc-13 family. {ECO:0000305}.
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DR EMBL; U24070; AAC52266.1; -; mRNA.
DR PIR; A57607; A57607.
DR RefSeq; NP_074052.1; NM_022861.1. [Q62768-1]
DR PDB; 1Y8F; NMR; -; A=567-616.
DR PDB; 2CJS; X-ray; 1.78 A; A/B=2-150.
DR PDB; 2CJT; X-ray; 1.44 A; A/B/C/D=1-128.
DR PDB; 2KDU; NMR; -; B=458-492.
DR PDB; 3SWH; X-ray; 2.65 A; A/B=1148-1407, A/B=1453-1531.
DR PDB; 4Y21; X-ray; 2.90 A; A=942-1407, A=1453-1523.
DR PDB; 5UE8; X-ray; 3.35 A; A/B=529-1407, A/B=1452-1531.
DR PDB; 5UF7; X-ray; 2.90 A; A=942-1407, A=1453-1531.
DR PDB; 6A30; X-ray; 2.79 A; A=944-1407, A=1453-1523.
DR PDB; 6NYC; X-ray; 1.89 A; A=675-820.
DR PDB; 6NYT; X-ray; 1.37 A; A=675-820.
DR PDB; 7T7X; EM; 10.00 A; A=529-755, A=1401-1407, A=1452-1665.
DR PDB; 7T81; EM; 10.00 A; A/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y=529-755, A/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y=1401-1407, A/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y=1452-1665.
DR PDBsum; 1Y8F; -.
DR PDBsum; 2CJS; -.
DR PDBsum; 2CJT; -.
DR PDBsum; 2KDU; -.
DR PDBsum; 3SWH; -.
DR PDBsum; 4Y21; -.
DR PDBsum; 5UE8; -.
DR PDBsum; 5UF7; -.
DR PDBsum; 6A30; -.
DR PDBsum; 6NYC; -.
DR PDBsum; 6NYT; -.
DR PDBsum; 7T7X; -.
DR PDBsum; 7T81; -.
DR AlphaFoldDB; Q62768; -.
DR BMRB; Q62768; -.
DR SMR; Q62768; -.
DR BioGRID; 249207; 1.
DR CORUM; Q62768; -.
DR DIP; DIP-29191N; -.
DR IntAct; Q62768; 3.
DR CarbonylDB; Q62768; -.
DR iPTMnet; Q62768; -.
DR PhosphoSitePlus; Q62768; -.
DR SwissPalm; Q62768; -.
DR PaxDb; Q62768; -.
DR PRIDE; Q62768; -.
DR GeneID; 64829; -.
DR KEGG; rno:64829; -.
DR CTD; 23025; -.
DR RGD; 619722; Unc13a.
DR eggNOG; KOG1011; Eukaryota.
DR InParanoid; Q62768; -.
DR OrthoDB; 117172at2759; -.
DR PhylomeDB; Q62768; -.
DR EvolutionaryTrace; Q62768; -.
DR PRO; PR:Q62768; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0044305; C:calyx of Held; ISO:RGD.
DR GO; GO:0060076; C:excitatory synapse; IDA:BHF-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0005798; C:Golgi-associated vesicle; IDA:UniProtKB.
DR GO; GO:0031594; C:neuromuscular junction; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098793; C:presynapse; ISO:RGD.
DR GO; GO:0048786; C:presynaptic active zone; IDA:UniProtKB.
DR GO; GO:0098831; C:presynaptic active zone cytoplasmic component; IDA:SynGO.
DR GO; GO:0042734; C:presynaptic membrane; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0097060; C:synaptic membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030672; C:synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0043195; C:terminal bouton; HDA:ParkinsonsUK-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005516; F:calmodulin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0019992; F:diacylglycerol binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0019904; F:protein domain specific binding; IDA:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0000149; F:SNARE binding; IDA:RGD.
DR GO; GO:0030507; F:spectrin binding; IPI:RGD.
DR GO; GO:0019905; F:syntaxin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0017075; F:syntaxin-1 binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0050435; P:amyloid-beta metabolic process; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0061789; P:dense core granule priming; IGI:SynGO-UCL.
DR GO; GO:0060384; P:innervation; ISO:RGD.
DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:RGD.
DR GO; GO:0007528; P:neuromuscular junction development; ISO:RGD.
DR GO; GO:0099011; P:neuronal dense core vesicle exocytosis; ISS:UniProtKB.
DR GO; GO:0007269; P:neurotransmitter secretion; IDA:RGD.
DR GO; GO:1903861; P:positive regulation of dendrite extension; ISO:RGD.
DR GO; GO:1900451; P:positive regulation of glutamate receptor signaling pathway; ISO:RGD.
DR GO; GO:0001956; P:positive regulation of neurotransmitter secretion; ISO:RGD.
DR GO; GO:0031915; P:positive regulation of synaptic plasticity; ISO:RGD.
DR GO; GO:0099525; P:presynaptic dense core vesicle exocytosis; ISO:RGD.
DR GO; GO:1902991; P:regulation of amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; ISO:RGD.
DR GO; GO:0010807; P:regulation of synaptic vesicle priming; IDA:UniProtKB.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; ISO:RGD.
DR GO; GO:0016081; P:synaptic vesicle docking; ISO:RGD.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0016188; P:synaptic vesicle maturation; ISO:RGD.
DR GO; GO:0016082; P:synaptic vesicle priming; IDA:RGD.
DR CDD; cd00029; C1; 1.
DR CDD; cd04027; C2B_Munc13; 1.
DR Gene3D; 2.60.40.150; -; 3.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR010439; MUN_dom.
DR InterPro; IPR014770; Munc13_1.
DR InterPro; IPR014772; Munc13_dom-2.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR027080; Unc-13.
DR InterPro; IPR037302; Unc-13_C2B.
DR InterPro; IPR027082; Unc13A.
DR PANTHER; PTHR10480; PTHR10480; 1.
DR PANTHER; PTHR10480:SF1; PTHR10480:SF1; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00168; C2; 3.
DR Pfam; PF06292; MUN; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00239; C2; 3.
DR SMART; SM01145; DUF1041; 1.
DR SUPFAM; SSF49562; SSF49562; 3.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50004; C2; 3.
DR PROSITE; PS51258; MHD1; 1.
DR PROSITE; PS51259; MHD2; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell membrane;
KW Cell projection; Coiled coil; Cytoplasm; Differentiation; Exocytosis;
KW Membrane; Metal-binding; Phosphoprotein; Reference proteome; Repeat;
KW Synapse; Zinc; Zinc-finger.
FT CHAIN 1..1735
FT /note="Protein unc-13 homolog A"
FT /id="PRO_0000188574"
FT DOMAIN 1..97
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 672..796
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1106..1249
FT /note="MHD1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00587"
FT DOMAIN 1358..1525
FT /note="MHD2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00588"
FT DOMAIN 1558..1685
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT ZN_FING 566..616
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 185..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 319..370
FT /evidence="ECO:0000255"
FT COMPBIAS 203..224
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 253..276
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 277..317
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 318..369
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 427..455
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 580
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 583
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 597
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 600
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 608
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 616
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 705
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 705
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 711
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 757
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 757
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 759
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 759
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 776
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 244
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 1434..1456
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_011382"
FT VAR_SEQ 1541..1559
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_011383"
FT MUTAGEN 22
FT /note="T->I: No effect on binding to RIMS1."
FT /evidence="ECO:0000269|PubMed:16704978"
FT MUTAGEN 23
FT /note="Y->N: No effect on binding to RIMS1."
FT /evidence="ECO:0000269|PubMed:16704978"
FT MUTAGEN 64
FT /note="V->M: No effect on binding to RIMS1."
FT /evidence="ECO:0000269|PubMed:16704978"
FT MUTAGEN 119
FT /note="H->R: No effect on binding to RIMS1."
FT /evidence="ECO:0000269|PubMed:16704978"
FT MUTAGEN 121
FT /note="I->N: Abolishes binding to RIMS1."
FT /evidence="ECO:0000269|PubMed:16704978"
FT MUTAGEN 567
FT /note="H->K: Loss of phorbol-ester binding."
FT /evidence="ECO:0000269|PubMed:9697857"
FT MUTAGEN 1190
FT /note="Q->R: Loss of binding to STX1B and priming activity;
FT when associated with P-1279 and E-1655."
FT /evidence="ECO:0000269|PubMed:16271475"
FT MUTAGEN 1279
FT /note="L->P: Loss of binding to STX1B and priming activity;
FT when associated with R-1190 and E-1655."
FT /evidence="ECO:0000269|PubMed:16271475"
FT MUTAGEN 1364
FT /note="I->F: Loss of binding to STX1B and priming
FT activity."
FT /evidence="ECO:0000269|PubMed:16271475"
FT MUTAGEN 1603
FT /note="V->D: Loss of binding to STX1B and priming
FT activity."
FT /evidence="ECO:0000269|PubMed:16271475"
FT MUTAGEN 1655
FT /note="D->E: Loss of binding to STX1B and priming activity;
FT when associated with R-1190 and P-1279."
FT /evidence="ECO:0000269|PubMed:16271475"
FT STRAND 2..12
FT /evidence="ECO:0007829|PDB:2CJT"
FT HELIX 17..19
FT /evidence="ECO:0007829|PDB:2CJT"
FT STRAND 21..28
FT /evidence="ECO:0007829|PDB:2CJT"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:2CJT"
FT STRAND 38..42
FT /evidence="ECO:0007829|PDB:2CJT"
FT STRAND 44..53
FT /evidence="ECO:0007829|PDB:2CJT"
FT STRAND 57..66
FT /evidence="ECO:0007829|PDB:2CJT"
FT STRAND 72..81
FT /evidence="ECO:0007829|PDB:2CJT"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:2CJT"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:2CJT"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:2CJT"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:2CJT"
FT STRAND 120..128
FT /evidence="ECO:0007829|PDB:2CJT"
FT HELIX 135..150
FT /evidence="ECO:0007829|PDB:2CJS"
FT HELIX 459..478
FT /evidence="ECO:0007829|PDB:2KDU"
FT HELIX 487..490
FT /evidence="ECO:0007829|PDB:2KDU"
FT HELIX 544..558
FT /evidence="ECO:0007829|PDB:5UE8"
FT STRAND 569..572
FT /evidence="ECO:0007829|PDB:5UE8"
FT STRAND 581..583
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 590..592
FT /evidence="ECO:0007829|PDB:5UE8"
FT STRAND 594..597
FT /evidence="ECO:0007829|PDB:5UE8"
FT TURN 598..600
FT /evidence="ECO:0007829|PDB:5UE8"
FT TURN 606..608
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 609..611
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 616..627
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 630..650
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 653..661
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 666..680
FT /evidence="ECO:0007829|PDB:5UE8"
FT STRAND 689..700
FT /evidence="ECO:0007829|PDB:6NYT"
FT STRAND 712..718
FT /evidence="ECO:0007829|PDB:6NYT"
FT STRAND 721..724
FT /evidence="ECO:0007829|PDB:6NYT"
FT STRAND 735..744
FT /evidence="ECO:0007829|PDB:6NYT"
FT STRAND 746..748
FT /evidence="ECO:0007829|PDB:5UE8"
FT STRAND 750..757
FT /evidence="ECO:0007829|PDB:6NYT"
FT HELIX 762..767
FT /evidence="ECO:0007829|PDB:6NYT"
FT TURN 768..770
FT /evidence="ECO:0007829|PDB:6NYT"
FT STRAND 774..784
FT /evidence="ECO:0007829|PDB:6NYT"
FT HELIX 785..787
FT /evidence="ECO:0007829|PDB:6NYT"
FT STRAND 790..797
FT /evidence="ECO:0007829|PDB:6NYT"
FT STRAND 810..818
FT /evidence="ECO:0007829|PDB:6NYT"
FT HELIX 828..843
FT /evidence="ECO:0007829|PDB:5UE8"
FT TURN 844..850
FT /evidence="ECO:0007829|PDB:5UE8"
FT TURN 869..871
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 872..880
FT /evidence="ECO:0007829|PDB:5UE8"
FT TURN 881..883
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 886..897
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 898..900
FT /evidence="ECO:0007829|PDB:5UE8"
FT STRAND 901..903
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 906..920
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 932..936
FT /evidence="ECO:0007829|PDB:5UE8"
FT HELIX 945..961
FT /evidence="ECO:0007829|PDB:6A30"
FT HELIX 964..967
FT /evidence="ECO:0007829|PDB:6A30"
FT HELIX 973..995
FT /evidence="ECO:0007829|PDB:6A30"
FT HELIX 1006..1026
FT /evidence="ECO:0007829|PDB:6A30"
FT HELIX 1028..1035
FT /evidence="ECO:0007829|PDB:6A30"
FT STRAND 1039..1041
FT /evidence="ECO:0007829|PDB:4Y21"
FT STRAND 1051..1053
FT /evidence="ECO:0007829|PDB:4Y21"
FT HELIX 1059..1077
FT /evidence="ECO:0007829|PDB:6A30"
FT TURN 1078..1082
FT /evidence="ECO:0007829|PDB:6A30"
FT TURN 1087..1089
FT /evidence="ECO:0007829|PDB:6A30"
FT HELIX 1092..1118
FT /evidence="ECO:0007829|PDB:6A30"
FT HELIX 1123..1140
FT /evidence="ECO:0007829|PDB:6A30"
FT TURN 1141..1143
FT /evidence="ECO:0007829|PDB:6A30"
FT HELIX 1145..1148
FT /evidence="ECO:0007829|PDB:6A30"
FT HELIX 1159..1187
FT /evidence="ECO:0007829|PDB:3SWH"
FT STRAND 1192..1195
FT /evidence="ECO:0007829|PDB:3SWH"
FT HELIX 1201..1218
FT /evidence="ECO:0007829|PDB:3SWH"
FT HELIX 1224..1256
FT /evidence="ECO:0007829|PDB:3SWH"
FT STRAND 1257..1260
FT /evidence="ECO:0007829|PDB:6A30"
FT HELIX 1263..1285
FT /evidence="ECO:0007829|PDB:3SWH"
FT TURN 1286..1290
FT /evidence="ECO:0007829|PDB:3SWH"
FT HELIX 1293..1320
FT /evidence="ECO:0007829|PDB:3SWH"
FT HELIX 1322..1337
FT /evidence="ECO:0007829|PDB:3SWH"
FT HELIX 1353..1378
FT /evidence="ECO:0007829|PDB:3SWH"
FT HELIX 1381..1402
FT /evidence="ECO:0007829|PDB:3SWH"
FT STRAND 1454..1456
FT /evidence="ECO:0007829|PDB:3SWH"
FT STRAND 1458..1461
FT /evidence="ECO:0007829|PDB:4Y21"
FT HELIX 1472..1487
FT /evidence="ECO:0007829|PDB:3SWH"
FT HELIX 1488..1490
FT /evidence="ECO:0007829|PDB:3SWH"
FT HELIX 1495..1499
FT /evidence="ECO:0007829|PDB:3SWH"
FT HELIX 1502..1513
FT /evidence="ECO:0007829|PDB:3SWH"
FT TURN 1516..1518
FT /evidence="ECO:0007829|PDB:6A30"
SQ SEQUENCE 1735 AA; 196356 MW; BFE7D0467D258900 CRC64;
MSLLCVGVKK AKFDGAQEKF NTYVTLKVQN VKSTTIAVRG SQPSWEQDFM FEINRLDLGL
TVEVWNKGLI WDTMVGTVWI PLRTIRQSNE EGPGEWLTLD SQAIMADSEI CGTKDPTFHR
ILLDAHFELP LDIPEEEARY WAKKLEQLNA MRDQDEYSFQ DQQDKPLPVP SSQCCNWNYF
GWGEQNDDPD SAVDDRDSDY RSETSNSIPP PYYTTSQPNA SVHQYSVRPP PLGSRESYSD
SMHSYEEFSE PRALSPTGSS RYASSGELSQ GSSQLSEDFD PDEHSLQGSE LDDERDRDSY
HSCHSSVSYH KDSPRWDQDE EDLEDLEDLE DEELPEEEEL EEEELEEEEE LEEEELELEE
EEEVPDDLAS YTQQEDTTVA EPKEFKRISF PTAAPQKEDK VSAVPIEAPD VSKGIPKAAT
PEEKAAAECA QEAEPPKSEE SFRSREAEEG QEGQDAMSRA KANWLRAFNK VRMQLQEARG
EGEMSKSLWF KGGPGGGLII IDSMPDIRKR KPIPLVSDLA MSLVQSRKAG ITSALASSTL
NNEELKNHVY KKTLQALIYP ISCTTPHNFE VWTATTPTYC YECEGLLWGI ARQGMRCTEC
GVKCHEKCQD LLNADCLQRA AEKSSKHGAE DRTQNIIMVL KDRMKIRERN KPEIFELIQE
VFAVTKSAHT QQMKAVKQSV LDGTSKWSAK ISITVVCAQG LQAKDKTGSS DPYVTVQVGK
TKKRTKTIYG NLNPVWEENF HFECHNSSDR IKVRVLDEDD DIKSRVKQRF KRESDDFLGQ
TIIEVRTLSG EMDVWYNLDK RTDKSAVSGA IRLHISVEIK GEEKVAPYHV QYTCLHENLF
HFVTDVQNNG VVKIPDAKGD DAWKVYYDET AQEIVDEFAM RYGVESIYQA MTHFACLSSK
YMCPGVPAVM STLLANINAY YAHTTASTNV SASDRFAASN FGKERFVKLL DQLHNSLRID
LSMYRNNFPA SSPERLQDLK STVDLLTSIT FFRMKVQELQ SPPRASQVVK DCVKACLNST
YEYIFNNCHE LYGREYQTDP AKKGEVPPEE QGPSIKNLDF WSKLITLIVS IIEEDKNSYT
PCLNQFPQEL NVGKISAEVM WSLFAQDMKY AMEEHDKHRL CKSADYMNLH FKVKWLYNEY
VAELPTFKDR VPEYPAWFEP FVIQWLDENE EVSRDFLHGA LERDKKDGFQ QTSEHALFSC
SVVDVFSQLN QSFEIIKKLE CPDPQIVGHY MRRFAKTISN VLLQYADIVS KDFASYCSKE
KEKVPCILMN NTQQLRVQLE KMFEAMGGKE LDAEASGTLK ELQVKLNNVL DELSHVFATS
FQPHIEECVR QMGDILSQVK GTGNVPASAC SSVAQDADNV LQPIMDLLDS NLTLFAKICE
KTVLKRVLKE LWKLVMNTME RTIVLPPLTD QTMIGTLLRK HGKGLEKGRV KLPSHSDGTQ
MIFNAAKELG QLSKLKDHMV REEAKSLTPK QCAVVELALD TIKQYFHAGG VGLKKTFLEK
SPDLQSLRYA LSLYTQATDL LIKTFVQTQS AQVHGGKGTR FTLSEDVCPE MGSGVEDPVG
EVSVHVELFT HPGTGEQKVT VKVVAANDLK WQTSGIFRPF IEVNIVGPQL SDKKRKFATK
SKNNSWAPKY NESFQFSLSA DAGPECYELQ VCVKDYCFAR EDRTVELAVL QLRELAQRGS
AACWLPLGRR IHMDDTGLTV LRILSQRSND EVAKEFVKLK SDTRSAEEGG AAPAP
