CAPS1_RAT
ID CAPS1_RAT Reviewed; 1289 AA.
AC Q62717;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Calcium-dependent secretion activator 1;
DE AltName: Full=Calcium-dependent activator protein for secretion 1;
DE Short=CAPS-1;
DE Short=rCAPS;
GN Name=Cadps; Synonyms=Caps, Caps1;
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], PROTEIN SEQUENCE OF 103-109; 560-595; 810-821
RP AND 1155-1183, CALCIUM-BINDING, AND TISSUE SPECIFICITY.
RX PubMed=9289490; DOI=10.1074/jbc.272.32.19637;
RA Ann K., Kowalchyk J.A., Loyet K.M., Martin T.F.J.;
RT "Novel Ca2+-binding protein (CAPS) related to UNC-31 required for Ca2+-
RT activated exocytosis.";
RL J. Biol. Chem. 272:19637-19640(1997).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=1516133; DOI=10.1016/0092-8674(92)90310-9;
RA Walent J.H., Porter B.W., Martin T.F.J.;
RT "A novel 145 kd brain cytosolic protein reconstitutes Ca(2+)-regulated
RT secretion in permeable neuroendocrine cells.";
RL Cell 70:765-775(1992).
RN [3]
RP FUNCTION.
RX PubMed=9162085; DOI=10.1074/jbc.272.22.14447;
RA Martin T.F.J., Kowalchyk J.A.;
RT "Docked secretory vesicles undergo Ca2+-activated exocytosis in a cell-free
RT system.";
RL J. Biol. Chem. 272:14447-14453(1997).
RN [4]
RP PHOSPHOINOSIDE-BINDING.
RX PubMed=9525942; DOI=10.1074/jbc.273.14.8337;
RA Loyet K.M., Kowalchyk J.A., Chaudhary A., Chen J., Prestwich G.D.,
RA Martin T.F.J.;
RT "Specific binding of phosphatidylinositol 4,5-bisphosphate to calcium-
RT dependent activator protein for secretion (CAPS), a potential
RT phosphoinositide effector protein for regulated exocytosis.";
RL J. Biol. Chem. 273:8337-8343(1998).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9697858; DOI=10.1016/s0896-6273(00)80521-8;
RA Berwin B., Floor E., Martin T.F.J.;
RT "CAPS (mammalian UNC-31) protein localizes to membranes involved in dense-
RT core vesicle exocytosis.";
RL Neuron 21:137-145(1998).
RN [6]
RP FUNCTION.
RX PubMed=9697859; DOI=10.1016/s0896-6273(00)80522-x;
RA Tandon A., Bannykh S., Kowalchyk J.A., Banerjee A., Martin T.F.J.,
RA Balch W.E.;
RT "Differential regulation of exocytosis by calcium and CAPS in semi-intact
RT synaptosomes.";
RL Neuron 21:147-154(1998).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10792045; DOI=10.1073/pnas.090359097;
RA Rupnik M., Kreft M., Sikdar S.K., Grilc S., Romih R., Zupancic G.,
RA Martin T.F.J., Zorec R.;
RT "Rapid regulated dense-core vesicle exocytosis requires the CAPS protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:5627-5632(2000).
RN [8]
RP SUBCELLULAR LOCATION, DOMAIN, PHOSPHOINOSIDE-BINDING, AND MUTAGENESIS OF
RP LYS-531; 537-TRP--ARG-540; 558-ARG--LYS-561 AND LYS-561.
RX PubMed=11927595; DOI=10.1074/jbc.m201614200;
RA Grishanin R.N., Klenchin V.A., Loyet K.M., Kowalchyk J.A., Ann K.,
RA Martin T.F.J.;
RT "Membrane association domains in Ca2+-dependent activator protein for
RT secretion mediate plasma membrane and dense-core vesicle binding required
RT for Ca2+-dependent exocytosis.";
RL J. Biol. Chem. 277:22025-22034(2002).
RN [9]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=14530279; DOI=10.1074/jbc.m304727200;
RA Speidel D., Varoqueaux F., Enk C., Nojiri M., Grishanin R.N.,
RA Martin T.F.J., Hofmann K., Brose N., Reim K.;
RT "A family of Ca2+-dependent activator proteins for secretion: comparative
RT analysis of structure, expression, localization, and function.";
RL J. Biol. Chem. 278:52802-52809(2003).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF GLY-476.
RX PubMed=15312653; DOI=10.1016/j.neuron.2004.07.028;
RA Grishanin R.N., Kowalchyk J.A., Klenchin V.A., Ann K., Earles C.A.,
RA Chapman E.R., Gerona R.R.L., Martin T.F.J.;
RT "CAPS acts at a prefusion step in dense-core vesicle exocytosis as a PIP2
RT binding protein.";
RL Neuron 43:551-562(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-89; SER-96 AND SER-259, AND
RP 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).
CC -!- FUNCTION: Calcium-binding protein involved in exocytosis of vesicles
CC filled with neurotransmitters and neuropeptides. Probably acts upstream
CC of fusion in the biogenesis or maintenance of mature secretory
CC vesicles. Regulates catecholamine loading of DCVs. May specifically
CC mediate the Ca(2+)-dependent exocytosis of large dense-core vesicles
CC (DCVs) and other dense-core vesicles by acting as a PtdIns(4,5)P2-
CC binding protein that acts at prefusion step following ATP-dependent
CC priming and participates in DCVs-membrane fusion. However, it may also
CC participate in small clear synaptic vesicles (SVs) exocytosis and it is
CC unclear whether its function is related to Ca(2+) triggering.
CC {ECO:0000269|PubMed:10792045, ECO:0000269|PubMed:1516133,
CC ECO:0000269|PubMed:15312653, ECO:0000269|PubMed:9162085,
CC ECO:0000269|PubMed:9697858, ECO:0000269|PubMed:9697859}.
CC -!- SUBUNIT: Interacts with the dopamine receptor DRD2 (By similarity).
CC Interacts with RASL10B (By similarity). Homodimer. {ECO:0000250,
CC ECO:0000269|PubMed:1516133}.
CC -!- INTERACTION:
CC Q62717; P32851: Stx1a; NbExp=3; IntAct=EBI-15804323, EBI-539720;
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000269|PubMed:10792045,
CC ECO:0000269|PubMed:11927595, ECO:0000269|PubMed:14530279,
CC ECO:0000269|PubMed:1516133, ECO:0000269|PubMed:9697858}. Cytoplasmic
CC vesicle, secretory vesicle, neuronal dense core vesicle membrane
CC {ECO:0000269|PubMed:10792045, ECO:0000269|PubMed:11927595,
CC ECO:0000269|PubMed:9697858}; Peripheral membrane protein {ECO:0000305}.
CC Note=Membrane-associated to vesicles. Strongly enriched in synaptic
CC fractions. Preferentially binds to dense core vesicles but not to
CC synaptic vesicles. Binds phosphoinosides, with a strong selectivity for
CC PtdIns(4,5)P2 over PtdIns(3,4,5)P3. Probably localizes to different
CC vesicles compared to CADPS2. {ECO:0000269|PubMed:10792045,
CC ECO:0000269|PubMed:11927595, ECO:0000269|PubMed:14530279,
CC ECO:0000269|PubMed:1516133, ECO:0000269|PubMed:9697858}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in neural and endocrine
CC secretory tissues. Expressed in brain, pancreas, hypothalamus,
CC pituitary and adrenal but not in heart, placenta, lung, liver, skeletal
CC muscle or kidney. In brain, it is absent from the cell body layers of
CC the hippocampus and dentate gyrus but abundant in the synaptic
CC neuropil, except for the stratum lucidum and stratum lacunosum
CC moleculare where it is not detected. In the cerebellum, it is mainly
CC detected in the glomeruli of the granule cell layer where it
CC colocalized with synaptophysin. In the olfactory bulb, it is detected
CC mainly in the glomeruli. In the adult adrenal gland, where it is
CC restricted to the medulla (at protein level).
CC {ECO:0000269|PubMed:14530279, ECO:0000269|PubMed:9289490,
CC ECO:0000269|PubMed:9697858}.
CC -!- DOMAIN: The PH domain is essential for regulated exocytosis and binds
CC phospholipids and plasma membrane. It however does not mediate binding
CC to DCVs. {ECO:0000269|PubMed:11927595}.
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; U16802; AAB88635.1; -; mRNA.
DR PIR; I84505; I84505.
DR RefSeq; NP_037351.1; NM_013219.1.
DR PDB; 6A68; X-ray; 2.90 A; A=859-1036.
DR PDBsum; 6A68; -.
DR AlphaFoldDB; Q62717; -.
DR SMR; Q62717; -.
DR BioGRID; 247806; 5.
DR DIP; DIP-58640N; -.
DR IntAct; Q62717; 3.
DR MINT; Q62717; -.
DR STRING; 10116.ENSRNOP00000012153; -.
DR iPTMnet; Q62717; -.
DR PhosphoSitePlus; Q62717; -.
DR jPOST; Q62717; -.
DR PaxDb; Q62717; -.
DR PRIDE; Q62717; -.
DR GeneID; 26989; -.
DR KEGG; rno:26989; -.
DR CTD; 8618; -.
DR RGD; 708573; Cadps.
DR eggNOG; KOG3543; Eukaryota.
DR InParanoid; Q62717; -.
DR OrthoDB; 138870at2759; -.
DR PRO; PR:Q62717; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0031045; C:dense core granule; IDA:ParkinsonsUK-UCL.
DR GO; GO:0098674; C:extrinsic component of neuronal dense core vesicle membrane; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0098793; C:presynapse; IDA:SynGO.
DR GO; GO:0005509; F:calcium ion binding; IDA:RGD.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:WormBase.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0050432; P:catecholamine secretion; ISO:RGD.
DR GO; GO:0006887; P:exocytosis; IBA:GO_Central.
DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; IMP:RGD.
DR GO; GO:0045921; P:positive regulation of exocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0099525; P:presynaptic dense core vesicle exocytosis; ISO:RGD.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0045055; P:regulated exocytosis; TAS:RGD.
DR GO; GO:0016082; P:synaptic vesicle priming; ISO:RGD.
DR GO; GO:0016050; P:vesicle organization; ISO:RGD.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR033227; CAPS.
DR InterPro; IPR010439; MUN_dom.
DR InterPro; IPR014770; Munc13_1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR12166; PTHR12166; 2.
DR Pfam; PF06292; MUN; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM01145; DUF1041; 1.
DR SMART; SM00233; PH; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS51258; MHD1; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cytoplasmic vesicle; Direct protein sequencing;
KW Exocytosis; Lipid-binding; Membrane; Metal-binding; Phosphoprotein;
KW Protein transport; Reference proteome; Synapse; Transport.
FT CHAIN 1..1289
FT /note="Calcium-dependent secretion activator 1"
FT /id="PRO_0000053866"
FT DOMAIN 378..493
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 519..622
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 916..1047
FT /note="MHD1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00587"
FT REGION 1..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 788..1065
FT /note="Interaction with DRD2"
FT /evidence="ECO:0000250"
FT REGION 1113..1289
FT /note="Mediates targeting and association with DCVs"
FT REGION 1264..1289
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TJ1"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 476
FT /note="G->E: Loss of function."
FT /evidence="ECO:0000269|PubMed:15312653"
FT MUTAGEN 531
FT /note="K->E: No effect."
FT /evidence="ECO:0000269|PubMed:11927595"
FT MUTAGEN 537..540
FT /note="WKKR->SQKE: Affects PtdIns(4,5)P2-binding, plasma
FT membrane-association but not binding to DCVs."
FT /evidence="ECO:0000269|PubMed:11927595"
FT MUTAGEN 558..561
FT /note="REKK->DEEE: Affects PtdIns(4,5)P2-binding, plasma
FT membrane-association but not binding to DCVs."
FT /evidence="ECO:0000269|PubMed:11927595"
FT MUTAGEN 561
FT /note="K->E: Affects PtdIns(4,5)P2-binding, plasma
FT membrane-association but not binding to DCVs."
FT /evidence="ECO:0000269|PubMed:11927595"
FT HELIX 869..921
FT /evidence="ECO:0007829|PDB:6A68"
FT HELIX 933..944
FT /evidence="ECO:0007829|PDB:6A68"
FT TURN 947..951
FT /evidence="ECO:0007829|PDB:6A68"
FT HELIX 953..981
FT /evidence="ECO:0007829|PDB:6A68"
FT HELIX 982..984
FT /evidence="ECO:0007829|PDB:6A68"
FT HELIX 1001..1015
FT /evidence="ECO:0007829|PDB:6A68"
SQ SEQUENCE 1289 AA; 146266 MW; 2ADAEA35FB20BCDD CRC64;
MLDPSSSEEE SDEILEEESG KEVLGSAASG ARLSPSRTNE GSAGSAGMGG SGAGAGVGAG
GGGGSGASSG GGAGGLQPSS RAGGGRPSSP SPSVVSEKEK EELERLQKEE EERKKRLQLY
VFVMRCIAYP FNAKQPTDMA RRPRKISKQQ LQTVKDRFQA FLNGETQIVA DEAFMNAVQS
YYEVFLKSDR VARMVQSGGC SANDSREVFK KHIEKRVRSL PEIDGLSKET VLSSWMAKFD
AIYRGEEDPR KQQARMTASA ASELILSKEQ LYEMFQNILG IKKFEHQLLY NACQLDNPDE
QAAQIRRELD GRLQMADQIA RERKFPKFVS KEMENMYIEE LKSSVNLLMA NLESMPVSKG
GEFKLQKLKR SHNASIIDMG EESENQLSKS DVLLSFSLEV VIMEVQGLKS LAPNRIVYCT
MEVEGGEKLQ TDQAEASKPT WGTQGDFSTT HALPAVKVKL FTESTGVLAL EDKELGRVIL
HPTPNSPKQS EWHKMTVSKN CPDQDLKIKL AVRMDKPQNM KHSGYLWTIG KNVWKRWKKR
FFVLVQVSQY TFAMCSYREK KAEPQELLQL DGYTVDYTDP QPGLEGGRAF FNAVKEGDTV
IFASDDEQDR ILWVQAMYRA TGQSHKPVPP TQVQKLKPRA ETCLSMDAPI SQFYADRAQK
HGMDEFISSN PCNFDHASLF EMVQRLTLDH RLNDSYSCLG WFSPGQVFVL DEYCARNGVR
GCHRHLCYLR DLLERAENGA MIDPTLLHYS FAFCASHVHG NRPDGIGTVT VEEKERFEEI
KERLRVLLEN QITHFRYCFP FGRPEGALKA TLSLLERVLM KDIVTPVPQE EVKTVIRKCL
EQAALVNYSR LSEYAKIEEN VGRLITPAKK LEDTIRLAEL VIEVLQQNEE HHAEAFAWWS
DLMVEHAETF LSLFAVDMDA ALEVQPPDTW DSFPLFQLLN DFLRTDYNLC NGKFHKHLQD
LFAPLVVRYV DLMESSIAQS IHRGFERESW EPVNNGSGTS EDLFWKLDAL QTFIRDLHWP
EEEFGKHLEQ RLKLMASDMI ESCVKRTRIA FEVKLQKTSR STDFRVPQSI CTMFNVMVDA
KAQSTKLCSM EMGQEHQYHS KIDELIEETV KEMITLLVAK FVTILEGVLA KLSRYDEGTL
FSSFLSFTVK AASKYVDVPK PGMDVADAYV TFVRHSQDVL RDKVNEEMYI ERLFDQWYNS
SMNVICTWLT DRMDLQLHIY QLKTLIRMVK KTYRDFRLQG VLDSTLNSKT YETIRNRLTV
EERTASVSEG GGLQGISMKD SDEEDEEDD
