DOC2B_MOUSE
ID DOC2B_MOUSE Reviewed; 412 AA.
AC P70169; Q5SS41; Q6NXK3;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Double C2-like domain-containing protein beta;
DE Short=Doc2-beta;
GN Name=Doc2b;
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 [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Cerebellum;
RX PubMed=8902635; DOI=10.1093/oxfordjournals.jbchem.a021464;
RA Kojima T., Fukuda M., Aruga J., Mikoshiba K.;
RT "Calcium-dependent phospholipid binding to the C2A domain of a ubiquitous
RT form of double C2 protein (Doc2 beta).";
RL J. Biochem. 120:671-676(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP SUBCELLULAR LOCATION, INTERACTION WITH STXBP3, AND TISSUE SPECIFICITY.
RX PubMed=17548353; DOI=10.1074/jbc.m701661200;
RA Ke B., Oh E., Thurmond D.C.;
RT "Doc2beta is a novel Munc18c-interacting partner and positive effector of
RT syntaxin 4-mediated exocytosis.";
RL J. Biol. Chem. 282:21786-21797(2007).
RN [6]
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH STX4.
RX PubMed=19410553; DOI=10.1016/j.bbrc.2009.04.133;
RA Miyazaki M., Emoto M., Fukuda N., Hatanaka M., Taguchi A., Miyamoto S.,
RA Tanizawa Y.;
RT "DOC2b is a SNARE regulator of glucose-stimulated delayed insulin
RT secretion.";
RL Biochem. Biophys. Res. Commun. 384:461-465(2009).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STX4, AND MUTAGENESIS OF
RP ASP-157; ASP-163; ASP-297 AND ASP-303.
RX PubMed=19033398; DOI=10.2337/db08-0303;
RA Fukuda N., Emoto M., Nakamori Y., Taguchi A., Miyamoto S., Uraki S.,
RA Oka Y., Tanizawa Y.;
RT "DOC2B: a novel syntaxin-4 binding protein mediating insulin-regulated
RT GLUT4 vesicle fusion in adipocytes.";
RL Diabetes 58:377-384(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP DISRUPTION PHENOTYPE, AND 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 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:19033398,
CC ECO:0000269|PubMed:19410553, ECO:0000269|PubMed:20150444,
CC ECO:0000269|PubMed:8902635}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with cytoplasmic dynein light chain DYNLT1. May
CC interact with UNC13A; the interaction mediates targeting to the plasma
CC membrane (By similarity). Probably interacts with the SNARE (soluble N-
CC ethylmaleimide-sensitive factor attached protein receptor) complex
CC composed of SNAP25, STX1A and VAMP2; the interaction is calcium-
CC dependent and competitive with SYT1. Interacts with STX4; the
CC interaction is calcium-dependent, increased by insulin and glucose, and
CC mediates vesicle fusion with plasma membrane in pancreatic cells and
CC adipocytes. Interacts with STXBP3; the interaction is direct, occurs at
CC the cell membrane and regulates glucose-stimulated insulin secretion.
CC {ECO:0000250, ECO:0000269|PubMed:17548353, ECO:0000269|PubMed:18596155,
CC ECO:0000269|PubMed:19033398, ECO:0000269|PubMed:19410553}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasmic granule. Cell membrane;
CC Peripheral membrane protein. Note=Translocates to the plasma membrane
CC in a calcium-dependent manner.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in pancreatic islet
CC cells (at protein level). {ECO:0000269|PubMed:17548353,
CC ECO:0000269|PubMed:8902635}.
CC -!- DOMAIN: C2 domain 1 is involved in binding calcium and phospholipids.
CC According to PubMed:19033398, the C2 domain 2 may also play a role in
CC the calcium-dependent targeting to membranes.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile without gross
CC abnormalities. {ECO:0000269|PubMed:20150444}.
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DR EMBL; D85037; BAA12714.1; -; mRNA.
DR EMBL; AL669897; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466596; EDL12842.1; -; Genomic_DNA.
DR EMBL; BC067030; AAH67030.1; -; mRNA.
DR CCDS; CCDS25057.1; -.
DR PIR; JC4921; JC4921.
DR RefSeq; NP_031899.2; NM_007873.3.
DR AlphaFoldDB; P70169; -.
DR SMR; P70169; -.
DR BioGRID; 199266; 2.
DR STRING; 10090.ENSMUSP00000021209; -.
DR iPTMnet; P70169; -.
DR PhosphoSitePlus; P70169; -.
DR MaxQB; P70169; -.
DR PaxDb; P70169; -.
DR PeptideAtlas; P70169; -.
DR PRIDE; P70169; -.
DR ProteomicsDB; 279795; -.
DR ABCD; P70169; 1 sequenced antibody.
DR Antibodypedia; 71704; 73 antibodies from 19 providers.
DR DNASU; 13447; -.
DR Ensembl; ENSMUST00000021209; ENSMUSP00000021209; ENSMUSG00000020848.
DR GeneID; 13447; -.
DR KEGG; mmu:13447; -.
DR UCSC; uc007kev.1; mouse.
DR CTD; 8447; -.
DR MGI; MGI:1100497; Doc2b.
DR VEuPathDB; HostDB:ENSMUSG00000020848; -.
DR eggNOG; KOG1013; Eukaryota.
DR GeneTree; ENSGT00940000156758; -.
DR HOGENOM; CLU_023008_3_0_1; -.
DR InParanoid; P70169; -.
DR OMA; HCTINRA; -.
DR OrthoDB; 374694at2759; -.
DR PhylomeDB; P70169; -.
DR TreeFam; TF351844; -.
DR BioGRID-ORCS; 13447; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Doc2b; mouse.
DR PRO; PR:P70169; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P70169; protein.
DR Bgee; ENSMUSG00000020848; Expressed in subiculum and 127 other tissues.
DR Genevisible; P70169; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IDA:MGI.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; ISS:UniProtKB.
DR GO; GO:0019905; F:syntaxin binding; IPI:UniProtKB.
DR GO; GO:0048791; P:calcium ion-regulated exocytosis of neurotransmitter; IMP:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IBA:GO_Central.
DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; ISS:UniProtKB.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:UniProtKB.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; ISS:UniProtKB.
DR GO; GO:0008104; P:protein localization; IMP:UniProtKB.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IBA:GO_Central.
DR GO; GO:0061669; P:spontaneous neurotransmitter secretion; IDA:MGI.
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; Cell membrane; Cytoplasm; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..412
FT /note="Double C2-like domain-containing protein beta"
FT /id="PRO_0000079969"
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 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:0000269|PubMed:17548353"
FT COMPBIAS 43..62
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:21183079"
FT MUTAGEN 157
FT /note="D->N: Loss of interaction with STX4 and insulin-
FT dependent translocation to the cell membrane; when
FT associated with N-163, N-297 and N-303."
FT /evidence="ECO:0000269|PubMed:19033398"
FT MUTAGEN 163
FT /note="D->N: Loss of interaction with STX4 and insulin-
FT dependent translocation to the cell membrane; when
FT associated with N-157, N-297 and N-303."
FT /evidence="ECO:0000269|PubMed:19033398"
FT MUTAGEN 297
FT /note="D->N: Loss of interaction with STX4 and insulin-
FT dependent translocation to the cell membrane; when
FT associated with N-157, N-163 and N-303."
FT /evidence="ECO:0000269|PubMed:19033398"
FT MUTAGEN 303
FT /note="D->N: Loss of interaction with STX4 and insulin-
FT dependent translocation to the cell membrane; when
FT associated with N-157, N-163 and N-297."
FT /evidence="ECO:0000269|PubMed:19033398"
FT CONFLICT 389
FT /note="K -> N (in Ref. 1; BAA12714)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 412 AA; 45853 MW; 4E94480BEDE91722 CRC64;
MTLRRRGEKA TISIQEHMAI DVCPGPIRPI KQISDYFPRF PRGLPPTAAP RAPAPPDAPA
RSPAASASPR SPSDGARDDD EDVDQLFGAY GASPGPSPGP SPARPPAKPP EDEPDVDGYE
SDDCTALGTL DFSLLYDQEN NALHCTISKA KGLKPMDHNG LADPYVKLHL LPGASKANKL
RTKTLRNTLN PSWNETLTYY GITDEDMVRK TLRISVCDED KFRHNEFIGE TRVPLKKLKP
NHTKTFSICL EKQLPVDKAE DKSLEERGRI LISLKYSSQK QGLLVGIVRC AHLAAMDANG
YSDPYVKTYL KPDVDKKSKH KTAVKKKTLN PEFNEEFCYE IKHGDLAKKT LEVTVWDYDI
GKSNDFIGGV VLGINAKGER LKHWFDCLKN KDKRIERWHT LTNELPGAVL SD
