DOC2B_RAT
ID DOC2B_RAT Reviewed; 412 AA.
AC P70610;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Double C2-like domain-containing protein beta;
DE Short=Doc2-beta;
GN Name=Doc2b;
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
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 INTERACTION WITH UNC13A, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 15-GLN--ILE-20.
RX PubMed=15033971; DOI=10.1074/jbc.m400731200;
RA Groffen A.J., Brian E.C., Dudok J.J., Kampmeijer J., Toonen R.F.,
RA Verhage M.;
RT "Ca(2+)-induced recruitment of the secretory vesicle protein DOC2B to the
RT target membrane.";
RL J. Biol. Chem. 279:23740-23747(2004).
RN [4]
RP FUNCTION, PHOSPHOLIPID-BINDING, MUTAGENESIS OF ASP-218 AND ASP-220, AND
RP INTERACTION WITH STX1A AND SNAP25.
RX PubMed=18596155; DOI=10.1523/jneurosci.0538-08.2008;
RA Friedrich R., Groffen A.J., Connell E., van Weering J.R., Gutman O.,
RA Henis Y.I., Davletov B., Ashery U.;
RT "DOC2B acts as a calcium switch and enhances vesicle fusion.";
RL J. Neurosci. 28:6794-6806(2008).
RN [5]
RP FUNCTION, PHOSPHOLIPID-BINDING, INTERACTION WITH SNARE COMPLEX, AND
RP MUTAGENESIS OF HIS-158; PHE-222; LYS-237; LYS-319 AND ILE-360.
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).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, AND IDENTIFICATION BY
RP 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 sensor which positively regulates SNARE-dependent
CC fusion of vesicles with membranes. Binds phospholipids in a calcium-
CC dependent manner and may act at the priming stage of fusion by
CC modifying membrane curvature to stimulate fusion. Involved in calcium-
CC triggered exocytosis in chromaffin cells and calcium-dependent
CC spontaneous release of neurotransmitter in absence of action potentials
CC in neuronal cells. Involved both in glucose-stimulated insulin
CC secretion in pancreatic cells and insulin-dependent GLUT4 transport to
CC the plasma membrane in adipocytes. {ECO:0000269|PubMed:18596155,
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 with STX4; the interaction is calcium-dependent,
CC increased by insulin and glucose, and mediates vesicle fusion with
CC plasma membrane in pancreatic cells and adipocytes. Interacts with
CC STXBP3; the interaction is direct, occurs at the cell membrane and
CC regulates glucose-stimulated insulin secretion (By similarity).
CC Interacts with cytoplasmic dynein light chain DYNLT1. Interacts with
CC the SNARE (soluble N-ethylmaleimide-sensitive factor attached protein
CC receptor) complex composed of SNAP25, STX1A and VAMP2; the interaction
CC is calcium-dependent and competitive with SYT1. May interact with
CC UNC13A; the interaction mediates targeting to the plasma membrane.
CC {ECO:0000250, ECO:0000269|PubMed:15033971, ECO:0000269|PubMed:18596155,
CC ECO:0000269|PubMed:20150444, ECO:0000269|PubMed:9804756}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasmic granule {ECO:0000250}.
CC Cell membrane; Peripheral membrane protein. Note=Translocates to the
CC plasma membrane in a calcium-dependent manner.
CC -!- TISSUE SPECIFICITY: Expressed in brain; highly enriched in neurons.
CC {ECO:0000269|PubMed:9115738}.
CC -!- DOMAIN: C2 domain 1 is involved in binding calcium and phospholipids.
CC C2 domain 2 may also play a role in the calcium-dependent targeting to
CC membranes (By similarity). {ECO:0000250}.
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DR EMBL; U70778; AAB47747.2; -; mRNA.
DR RefSeq; NP_112404.1; NM_031142.1.
DR PDB; 4LCV; X-ray; 2.00 A; A/B/C/D=125-255.
DR PDB; 4LDC; X-ray; 1.26 A; A=265-412.
DR PDBsum; 4LCV; -.
DR PDBsum; 4LDC; -.
DR AlphaFoldDB; P70610; -.
DR SMR; P70610; -.
DR STRING; 10116.ENSRNOP00000008429; -.
DR iPTMnet; P70610; -.
DR PRIDE; P70610; -.
DR ABCD; P70610; 1 sequenced antibody.
DR GeneID; 81820; -.
DR KEGG; rno:81820; -.
DR CTD; 8447; -.
DR RGD; 620519; Doc2b.
DR eggNOG; KOG1013; Eukaryota.
DR InParanoid; P70610; -.
DR OrthoDB; 374694at2759; -.
DR PhylomeDB; P70610; -.
DR PRO; PR:P70610; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098793; C:presynapse; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; ISO:RGD.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB.
DR GO; GO:0019905; F:syntaxin binding; ISO:RGD.
DR GO; GO:0048791; P:calcium ion-regulated exocytosis of neurotransmitter; IDA:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IEP:RGD.
DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; IDA:UniProtKB.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; IDA:UniProtKB.
DR GO; GO:0008104; P:protein localization; ISS:UniProtKB.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IBA:GO_Central.
DR GO; GO:0061669; P:spontaneous neurotransmitter secretion; ISO: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; 2.
DR PANTHER; PTHR45729:SF1; PTHR45729:SF1; 2.
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 3D-structure; Calcium; Calcium/phospholipid-binding; Cell membrane;
KW Cytoplasm; Membrane; Metal-binding; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..412
FT /note="Double C2-like domain-containing protein beta"
FT /id="PRO_0000079970"
FT DOMAIN 126..250
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 1..90
FT /note="Mediates interaction with DYNLT1"
FT /evidence="ECO:0000250"
FT REGION 1..36
FT /note="Negatively regulates targeting to plasma membrane"
FT /evidence="ECO:0000250"
FT REGION 38..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 257..375
FT /note="Mediates interaction with STXBP3"
FT /evidence="ECO:0000250"
FT COMPBIAS 43..57
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 157
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 163
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 218
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 220
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 297
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 297
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 303
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 357
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 357
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 359
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 359
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 365
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 15..20
FT /note="QEHMAI->YKDWAF: Prevents diacylglycerol-induced
FT localization to the plasma membrane. Probably prevents
FT interaction with UNC13A."
FT /evidence="ECO:0000269|PubMed:15033971"
FT MUTAGEN 158
FT /note="H->A: Loss of calcium-dependent binding to liposomes
FT and altered fusion-promoting activity; when associated with
FT A-222 and A-360."
FT /evidence="ECO:0000269|PubMed:20150444"
FT MUTAGEN 218
FT /note="D->N: Binds liposomes in a calcium-independent
FT manner; when associated with N-220."
FT /evidence="ECO:0000269|PubMed:18596155"
FT MUTAGEN 220
FT /note="D->N: Binds liposomes in a calcium-independent
FT manner; when associated with N-218."
FT /evidence="ECO:0000269|PubMed:18596155"
FT MUTAGEN 222
FT /note="F->A: Loss of calcium-dependent binding to liposomes
FT and altered fusion-promoting activity; when associated with
FT A-158 and A-360."
FT /evidence="ECO:0000269|PubMed:20150444"
FT MUTAGEN 237
FT /note="K->E: Loss of calcium-independent binding to
FT liposomes. Loss of interaction with the SNARE complex and
FT altered fusion-promoting activity; when associated with E-
FT 319."
FT /evidence="ECO:0000269|PubMed:20150444"
FT MUTAGEN 319
FT /note="K->E: Loss of calcium-independent binding to
FT liposomes. Loss of interaction with the SNARE complex and
FT altered fusion-promoting activity; when associated with E-
FT 237."
FT /evidence="ECO:0000269|PubMed:20150444"
FT MUTAGEN 360
FT /note="I->A: Loss of calcium-dependent binding to liposomes
FT and altered fusion-promoting activity; when associated with
FT A-158 and A-222."
FT /evidence="ECO:0000269|PubMed:20150444"
FT STRAND 129..137
FT /evidence="ECO:0007829|PDB:4LCV"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:4LCV"
FT STRAND 142..152
FT /evidence="ECO:0007829|PDB:4LCV"
FT STRAND 164..172
FT /evidence="ECO:0007829|PDB:4LCV"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:4LCV"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:4LCV"
FT STRAND 192..199
FT /evidence="ECO:0007829|PDB:4LCV"
FT HELIX 204..209
FT /evidence="ECO:0007829|PDB:4LCV"
FT STRAND 211..218
FT /evidence="ECO:0007829|PDB:4LCV"
FT STRAND 226..234
FT /evidence="ECO:0007829|PDB:4LCV"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:4LCV"
FT STRAND 244..249
FT /evidence="ECO:0007829|PDB:4LCV"
FT STRAND 266..277
FT /evidence="ECO:0007829|PDB:4LDC"
FT TURN 278..281
FT /evidence="ECO:0007829|PDB:4LDC"
FT STRAND 282..292
FT /evidence="ECO:0007829|PDB:4LDC"
FT STRAND 304..312
FT /evidence="ECO:0007829|PDB:4LDC"
FT STRAND 332..340
FT /evidence="ECO:0007829|PDB:4LDC"
FT HELIX 343..348
FT /evidence="ECO:0007829|PDB:4LDC"
FT STRAND 350..357
FT /evidence="ECO:0007829|PDB:4LDC"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:4LDC"
FT STRAND 365..373
FT /evidence="ECO:0007829|PDB:4LDC"
FT HELIX 378..389
FT /evidence="ECO:0007829|PDB:4LDC"
FT STRAND 395..403
FT /evidence="ECO:0007829|PDB:4LDC"
SQ SEQUENCE 412 AA; 45841 MW; 61595BC6886F1012 CRC64;
MTLRRRGEKA TISIQEHMAI DVCPGPIRPI KQISDYFPRF PRGLPPTAAP RASAPPDAPA
RSPAATAGPR SPSDGARDDD EDVDQLFGAY GASPGPSPGP SPVRPPAKPP EDEPDADGYE
SDDCTALGTL DFSLLYDQEN NALHCTISKA KGLKPMDHNG LADPYVKLHL LPGASKANKL
RTKTLRNTLN PSWNETLTYY GITDEDMIRK TLRISVCDED KFRHNEFIGE TRVPLKKLKP
NHTKTFSICL EKQLPVDKAE DKSLEERGRI LISLKYSSQK QGLLVGIVRC AHLAAMDANG
YSDPYVKTYL KPDVDKKSKH KTAVKKKTLN PEFNEEFCYE IKHGDLAKKT LEVTVWDYDI
GKSNDFIGGV VLGINAKGER LKHWFDCLKN KDKRIERWHT LTNEIPGAVL SD
