DOC2A_RAT
ID DOC2A_RAT Reviewed; 403 AA.
AC P70611;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Double C2-like domain-containing protein alpha;
DE Short=Doc2-alpha;
GN Name=Doc2a;
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], AND TISSUE SPECIFICITY.
RX PubMed=9115738; DOI=10.1016/s0896-6273(00)81245-3;
RA Verhage M., de Vries K.J., Roeshol H., Burbach J.P., Gispen W.H.,
RA Suedhof T.C.;
RT "DOC2 proteins in rat brain: complementary distribution and proposed
RT function as vesicular adapter proteins in early stages of secretion.";
RL Neuron 18:453-461(1997).
RN [2]
RP INTERACTION WITH DYNLT1.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=9804756; DOI=10.1074/jbc.273.46.30065;
RA Nagano F., Orita S., Sasaki T., Naito A., Sakaguchi G., Maeda M.,
RA Watanabe T., Kominami E., Uchiyama Y., Takai Y.;
RT "Interaction of Doc2 with tctex-1, a light chain of cytoplasmic dynein.
RT Implication in dynein-dependent vesicle transport.";
RL J. Biol. Chem. 273:30065-30068(1998).
RN [3]
RP SUBCELLULAR LOCATION, 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).
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 (By similarity). {ECO:0000250}.
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. Interacts with UNC13D (By
CC 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:0000269|PubMed:18354201}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain. Also found in
CC non-neural tissues. Expressed in RBL-2H3 mast cell line.
CC {ECO:0000269|PubMed:18354201, ECO:0000269|PubMed:9115738}.
CC -!- DOMAIN: C2 domain 1 is involved in binding calcium and phospholipids.
CC {ECO:0000250}.
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DR EMBL; U70779; AAB47748.1; -; mRNA.
DR RefSeq; NP_075226.1; NM_022937.2.
DR RefSeq; XP_006230397.1; XM_006230335.3.
DR RefSeq; XP_006230398.1; XM_006230336.1.
DR RefSeq; XP_006230399.1; XM_006230337.3.
DR RefSeq; XP_006230401.1; XM_006230339.3.
DR RefSeq; XP_006230402.1; XM_006230340.1.
DR RefSeq; XP_006230403.1; XM_006230341.3.
DR RefSeq; XP_008758140.1; XM_008759918.2.
DR RefSeq; XP_017445177.1; XM_017589688.1.
DR RefSeq; XP_017445178.1; XM_017589689.1.
DR AlphaFoldDB; P70611; -.
DR SMR; P70611; -.
DR STRING; 10116.ENSRNOP00000027022; -.
DR iPTMnet; P70611; -.
DR PhosphoSitePlus; P70611; -.
DR PaxDb; P70611; -.
DR PRIDE; P70611; -.
DR Ensembl; ENSRNOT00000027022; ENSRNOP00000027022; ENSRNOG00000019920.
DR GeneID; 65031; -.
DR KEGG; rno:65031; -.
DR UCSC; RGD:620518; rat.
DR CTD; 8448; -.
DR RGD; 620518; Doc2a.
DR eggNOG; KOG1013; Eukaryota.
DR GeneTree; ENSGT00940000159141; -.
DR HOGENOM; CLU_023008_3_0_1; -.
DR InParanoid; P70611; -.
DR OMA; SPMTVRK; -.
DR OrthoDB; 374694at2759; -.
DR PhylomeDB; P70611; -.
DR TreeFam; TF351844; -.
DR PRO; PR:P70611; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000019920; Expressed in frontal cortex and 14 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0098850; C:extrinsic component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0098793; C:presynapse; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0061669; P:spontaneous neurotransmitter secretion; ISO:RGD.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; IEP:RGD.
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 1: Evidence at protein level;
KW Calcium; Calcium/phospholipid-binding; Cytoplasmic vesicle; Exocytosis;
KW Lysosome; Membrane; Metal-binding; Reference proteome; Repeat; Synapse;
KW Synaptosome.
FT CHAIN 1..403
FT /note="Double C2-like domain-containing protein alpha"
FT /id="PRO_0000079967"
FT DOMAIN 92..214
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 254..387
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..92
FT /note="Interaction with UNC13D and DYNLT1"
FT /evidence="ECO:0000250"
FT REGION 218..403
FT /note="Interaction with UNC13D"
FT /evidence="ECO:0000250"
FT BINDING 123
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 129
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 184
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 285
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 285
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 291
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 345
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 345
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
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 353
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
SQ SEQUENCE 403 AA; 44590 MW; 24EECA95486FF673 CRC64;
MRGRRGDRMT INIQEHMAIN VCPGPIRPIR QISDYFPRRG PGPEGGGGGR GFGEAPAHLA
PLALAPPAAL LGATTPDDGA EVDSYDSDDT TALGTLEFDL LYDQASCMLH CRILRAKGLK
PMDFNGLADP YVKLHLLPGA CKANKLKTKT QRNTLNPVWN EELTYSGITD DDITHKVLRI
SVCDEDKLSH NEFIGEIRVP LRRLKPSQKK HFNICLERQV PLPSPSSMSA ALRGISCYLK
ELEQAEQGPG LLEERGRILL SLSYSSRRHG LLVGIVRCAH LAAMDVNGYS DPYVKTYLRP
DVDKKSKHKT CVKKKTLNPE FNEEFFYEME LSTLATKTLE VTVWDYDIGK SNDFIGGVSL
GPGARGEAQK HWRDCLHQPD TAVERWHTLT SELPPAAGAL PLA
