DOC2A_MOUSE
ID DOC2A_MOUSE Reviewed; 405 AA.
AC Q7TNF0;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Double C2-like domain-containing protein alpha;
DE Short=Doc2-alpha;
GN Name=Doc2a;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [2]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18354201; DOI=10.4049/jimmunol.180.7.4774;
RA Higashio H., Nishimura N., Ishizaki H., Miyoshi J., Orita S., Sakane A.,
RA Sasaki T.;
RT "Doc2 alpha and Munc13-4 regulate Ca(2+) -dependent secretory lysosome
RT exocytosis in mast cells.";
RL J. Immunol. 180:4774-4784(2008).
RN [3]
RP FUNCTION.
RX PubMed=20150444; DOI=10.1126/science.1183765;
RA Groffen A.J., Martens S., Diez Arazola R., Cornelisse L.N., Lozovaya N.,
RA de Jong A.P., Goriounova N.A., Habets R.L., Takai Y., Borst J.G., Brose N.,
RA McMahon H.T., Verhage M.;
RT "Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter
RT release.";
RL Science 327:1614-1618(2010).
CC -!- FUNCTION: Calcium sensor which most probably regulates fusion of
CC vesicles with membranes. Binds calcium and phospholipids. May be
CC involved in calcium dependent neurotransmitter release through the
CC interaction with UNC13A. May be involved in calcium-dependent
CC spontaneous release of neurotransmitter in absence of action potentials
CC in neuronal cells. Regulates Ca(2+)-dependent secretory lysosome
CC exocytosis in mast cells. {ECO:0000269|PubMed:18354201,
CC ECO:0000269|PubMed:20150444}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts (via N-terminus) with UNC13A. Interacts with
CC cytoplasmic dynein light chain DYNLT1 (By similarity). Interacts with
CC UNC13D (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}. Synapse, synaptosome {ECO:0000250}. Lysosome
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Brain and mast cells.
CC {ECO:0000269|PubMed:18354201}.
CC -!- DOMAIN: C2 domain 1 is involved in binding calcium and phospholipids.
CC {ECO:0000250}.
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DR EMBL; BC055768; AAH55768.1; -; mRNA.
DR CCDS; CCDS21847.1; -.
DR RefSeq; NP_034199.1; NM_010069.1.
DR RefSeq; XP_017177455.1; XM_017321966.1.
DR RefSeq; XP_017177456.1; XM_017321967.1.
DR RefSeq; XP_017177457.1; XM_017321968.1.
DR RefSeq; XP_017177458.1; XM_017321969.1.
DR RefSeq; XP_017177459.1; XM_017321970.1.
DR RefSeq; XP_017177460.1; XM_017321971.1.
DR AlphaFoldDB; Q7TNF0; -.
DR SMR; Q7TNF0; -.
DR BioGRID; 199265; 1.
DR STRING; 10090.ENSMUSP00000070119; -.
DR iPTMnet; Q7TNF0; -.
DR PhosphoSitePlus; Q7TNF0; -.
DR PaxDb; Q7TNF0; -.
DR PRIDE; Q7TNF0; -.
DR ProteomicsDB; 277485; -.
DR Antibodypedia; 26947; 134 antibodies from 24 providers.
DR DNASU; 13446; -.
DR Ensembl; ENSMUST00000064110; ENSMUSP00000070119; ENSMUSG00000052301.
DR GeneID; 13446; -.
DR KEGG; mmu:13446; -.
DR UCSC; uc009jtb.1; mouse.
DR CTD; 8448; -.
DR MGI; MGI:109446; Doc2a.
DR VEuPathDB; HostDB:ENSMUSG00000052301; -.
DR eggNOG; KOG1013; Eukaryota.
DR GeneTree; ENSGT00940000159141; -.
DR HOGENOM; CLU_023008_3_0_1; -.
DR InParanoid; Q7TNF0; -.
DR OMA; SPMTVRK; -.
DR OrthoDB; 374694at2759; -.
DR PhylomeDB; Q7TNF0; -.
DR TreeFam; TF351844; -.
DR BioGRID-ORCS; 13446; 2 hits in 74 CRISPR screens.
DR PRO; PR:Q7TNF0; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q7TNF0; protein.
DR Bgee; ENSMUSG00000052301; Expressed in ventromedial nucleus of hypothalamus and 100 other tissues.
DR ExpressionAtlas; Q7TNF0; baseline and differential.
DR Genevisible; Q7TNF0; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0098850; C:extrinsic component of synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IEA:UniProtKB-KW.
DR GO; GO:0006887; P:exocytosis; IBA:GO_Central.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IMP:UniProtKB.
DR GO; GO:0061669; P:spontaneous neurotransmitter secretion; IDA:MGI.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; IEA:Ensembl.
DR Gene3D; 2.60.40.150; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR014638; Doc2.
DR InterPro; IPR030535; Doc2a/b.
DR InterPro; IPR043566; Rabphilin/DOC2/Noc2.
DR InterPro; IPR001565; Synaptotagmin.
DR PANTHER; PTHR45729; PTHR45729; 1.
DR PANTHER; PTHR45729:SF1; PTHR45729:SF1; 1.
DR Pfam; PF00168; C2; 2.
DR PIRSF; PIRSF036931; Doc2; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR PRINTS; PR00399; SYNAPTOTAGMN.
DR SMART; SM00239; C2; 2.
DR SUPFAM; SSF49562; SSF49562; 2.
DR PROSITE; PS50004; C2; 2.
PE 2: Evidence at transcript level;
KW Calcium; Calcium/phospholipid-binding; Cytoplasmic vesicle; Exocytosis;
KW Lysosome; Membrane; Metal-binding; Reference proteome; Repeat; Synapse;
KW Synaptosome.
FT CHAIN 1..405
FT /note="Double C2-like domain-containing protein alpha"
FT /id="PRO_0000079966"
FT DOMAIN 94..216
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 256..389
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..94
FT /note="Interaction with UNC13D and DYNLT1"
FT /evidence="ECO:0000250"
FT REGION 34..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 220..405
FT /note="Interaction with UNC13D"
FT /evidence="ECO:0000250"
FT BINDING 125
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 131
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 186
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 188
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 287
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 287
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 293
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 347
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 347
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 349
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 349
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 355
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
SQ SEQUENCE 405 AA; 44609 MW; B9EDCC03C977CCE7 CRC64;
MRGRRGDRMT INIQEHMAIN VCPGPIRPIR QISDYFPRRG PGPEGGGGGG GTGCGEAPAH
LAPLALAPPA ALLGATTPDD GAEVDSYDSD DTTALGTLEF DLLYDQASCM LHCRILRAKG
LKPMDFNGLA DPYVKLHLLP GACKANKLKT KTQRNTLNPV WNEELTYSGI TDDDITHKVL
RISVCDEDKL SHNEFIGEIR VPLRRLKPSQ KKHFNICLER QVPLPSPSSM SAALRGISCY
LKELEQAEQG PGLLEERGRI LLSLSYSSRR HGLLVGIVRC AHLAAMDVNG YSDPYVKTYL
RPDVDKKSKH KTCVKKKTLN PEFNEEFFYE IELSTLATKT LEVTVWDYDI GKSNDFIGGV
SLGPGARGEA QKHWNDCLHQ PDTALERWHT LTSELPPAAG AYPLA
