DOC2B_HUMAN
ID DOC2B_HUMAN Reviewed; 412 AA.
AC Q14184; A0A087WZX8;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Double C2-like domain-containing protein beta;
DE Short=Doc2-beta;
GN Name=DOC2B {ECO:0000312|HGNC:HGNC:2986};
GN Synonyms=DOC2BL {ECO:0000312|HGNC:HGNC:2986};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=8554557; DOI=10.1006/bbrc.1995.2876;
RA Sakaguchi G., Orita S., Maeda M., Igarashi H., Takai Y.;
RT "Molecular cloning of an isoform of Doc2 having two C2-like domains.";
RL Biochem. Biophys. Res. Commun. 217:1053-1061(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, AND INTERACTION WITH DYNLT1.
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 [5]
RP 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 VARIANT LEU-209.
RX PubMed=21220648; DOI=10.1001/archneurol.2010.351;
RA Daoud H., Valdmanis P.N., Gros-Louis F., Belzil V., Spiegelman D.,
RA Henrion E., Diallo O., Desjarlais A., Gauthier J., Camu W., Dion P.A.,
RA Rouleau G.A.;
RT "Resequencing of 29 candidate genes in patients with familial and sporadic
RT amyotrophic lateral sclerosis.";
RL Arch. Neurol. 68:587-593(2011).
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 (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:9804756}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with the SNARE (soluble N-ethylmaleimide-sensitive
CC factor attached protein receptor) complex composed of SNAP25, STX1A and
CC VAMP2; the interaction is calcium-dependent and competitive with SYT1.
CC Interacts with STX4; the interaction is calcium-dependent, increased by
CC insulin and glucose, and mediates vesicle fusion with plasma membrane
CC in pancreatic cells and adipocytes. Interacts with STXBP3; the
CC interaction is direct, occurs at the cell membrane and regulates
CC glucose-stimulated insulin secretion. May interact with UNC13A; the
CC interaction mediates targeting to the plasma membrane (By similarity).
CC Interacts with cytoplasmic dynein light chain DYNLT1. {ECO:0000250,
CC ECO:0000269|PubMed:9804756}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasmic granule {ECO:0000250}.
CC Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC Note=Translocates to the plasma membrane in a calcium-dependent manner.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in brain and
CC kidney. Expressed in pancreatic islet cells (at protein level).
CC {ECO:0000269|PubMed:17548353, ECO:0000269|PubMed:8554557}.
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}.
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; D70830; BAA11107.1; -; mRNA.
DR EMBL; AC108004; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC240565; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF511233; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90677.1; -; Genomic_DNA.
DR CCDS; CCDS73934.1; -.
DR RefSeq; NP_003576.2; NM_003585.4.
DR AlphaFoldDB; Q14184; -.
DR SMR; Q14184; -.
DR BioGRID; 114025; 9.
DR IntAct; Q14184; 3.
DR MINT; Q14184; -.
DR STRING; 9606.ENSP00000482950; -.
DR iPTMnet; Q14184; -.
DR PhosphoSitePlus; Q14184; -.
DR BioMuta; DOC2B; -.
DR DMDM; 51701386; -.
DR MassIVE; Q14184; -.
DR PaxDb; Q14184; -.
DR PeptideAtlas; Q14184; -.
DR PRIDE; Q14184; -.
DR ProteomicsDB; 59902; -.
DR Antibodypedia; 71704; 73 antibodies from 19 providers.
DR DNASU; 8447; -.
DR Ensembl; ENST00000613549.3; ENSP00000482950.1; ENSG00000272636.4.
DR GeneID; 8447; -.
DR KEGG; hsa:8447; -.
DR MANE-Select; ENST00000613549.3; ENSP00000482950.1; NM_003585.5; NP_003576.2.
DR UCSC; uc010vpx.3; human.
DR CTD; 8447; -.
DR DisGeNET; 8447; -.
DR GeneCards; DOC2B; -.
DR HGNC; HGNC:2986; DOC2B.
DR HPA; ENSG00000272636; Tissue enhanced (brain, retina).
DR MIM; 604568; gene.
DR neXtProt; NX_Q14184; -.
DR OpenTargets; ENSG00000272636; -.
DR PharmGKB; PA27452; -.
DR VEuPathDB; HostDB:ENSG00000272636; -.
DR eggNOG; KOG1013; Eukaryota.
DR GeneTree; ENSGT00940000156758; -.
DR InParanoid; Q14184; -.
DR OMA; HCTINRA; -.
DR OrthoDB; 374694at2759; -.
DR PhylomeDB; Q14184; -.
DR TreeFam; TF351844; -.
DR PathwayCommons; Q14184; -.
DR SignaLink; Q14184; -.
DR BioGRID-ORCS; 8447; 5 hits in 303 CRISPR screens.
DR ChiTaRS; DOC2B; human.
DR GeneWiki; DOC2B; -.
DR GenomeRNAi; 8447; -.
DR Pharos; Q14184; Tbio.
DR PRO; PR:Q14184; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q14184; protein.
DR Bgee; ENSG00000272636; Expressed in right hemisphere of cerebellum and 99 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS: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; IEA:Ensembl.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; ISS:UniProtKB.
DR GO; GO:0019905; F:syntaxin binding; IEA:Ensembl.
DR GO; GO:0048791; P:calcium ion-regulated exocytosis of neurotransmitter; ISS: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; ISS:UniProtKB.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; ISS: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; IBA:GO_Central.
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_0000079968"
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:0000269|PubMed:9804756"
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:0000250|UniProtKB:P70169"
FT VARIANT 209
FT /note="R -> L (in a patient with amyotrophic lateral
FT sclerosis; dbSNP:rs369343321)"
FT /evidence="ECO:0000269|PubMed:21220648"
FT /id="VAR_065743"
FT CONFLICT 247
FT /note="S -> N (in Ref. 1; BAA11107)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 412 AA; 45922 MW; 8D8D2BB3FE77F3E5 CRC64;
MTLRRRGEKA TISIQEHMAI DVCPGPIRPI KQISDYFPRF PRGLPPDAGP RAAAPPDAPA
RPAVAGAGRR SPSDGAREDD EDVDQLFGAY GSSPGPSPGP SPARPPAKPP EDEPDADGYE
SDDCTALGTL DFSLLYDQEN NALHCTITKA KGLKPMDHNG LADPYVKLHL LPGASKANKL
RTKTLRNTLN PTWNETLTYY GITDEDMIRK TLRISVCDED KFRHNEFIGE TRVPLKKLKP
NHTKTFSICL EKQLPVDKTE DKSLEERGRI LISLKYSSQK QGLLVGIVRC AHLAAMDANG
YSDPYVKTYL RPDVDKKSKH KTAVKKKTLN PEFNEEFCYE IKHGDLAKKS LEVTVWDYDI
GKSNDFIGGV VLGIHAKGER LKHWFDCLKN KDKRIERWHT LTSELPGAVL SD
