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Protein

Double C2-like domain-containing protein beta

Gene

Doc2b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Calcium sensor which positively regulates SNARE-dependent fusion of vesicles with membranes. Binds phospholipids in a calcium-dependent manner and may act at the priming stage of fusion by modifying membrane curvature to stimulate fusion. Involved in calcium-triggered exocytosis in chromaffin cells and calcium-dependent spontaneous release of neurotransmitter in absence of action potentials in neuronal cells. Involved both in glucose-stimulated insulin secretion in pancreatic cells and insulin-dependent GLUT4 transport to the plasma membrane in adipocytes.4 Publications

GO - Molecular functioni

  • calcium-dependent phospholipid binding Source: UniProtKB
  • calcium ion binding Source: InterPro
  • syntaxin binding Source: UniProtKB

GO - Biological processi

  • calcium ion-regulated exocytosis of neurotransmitter Source: UniProtKB
  • positive regulation of calcium ion-dependent exocytosis Source: UniProtKB
  • positive regulation of insulin secretion Source: UniProtKB
  • positive regulation of vesicle fusion Source: UniProtKB
  • protein localization Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Calcium, Calcium/phospholipid-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Double C2-like domain-containing protein beta
Short name:
Doc2-beta
Gene namesi
Name:Doc2b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1100497. Doc2b.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • presynapse Source: GOC
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice are viable and fertile without gross abnormalities.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi157 – 1571D → N: Loss of interaction with STX4 and insulin-dependent translocation to the cell membrane; when assoicated with N-163, N-297 and N-303. 1 Publication
Mutagenesisi163 – 1631D → N: Loss of interaction with STX4 and insulin-dependent translocation to the cell membrane; when assoicated with N-157, N-297 and N-303. 1 Publication
Mutagenesisi297 – 2971D → N: Loss of interaction with STX4 and insulin-dependent translocation to the cell membrane; when assoicated with N-157, N-163 and N-303. 1 Publication
Mutagenesisi303 – 3031D → N: Loss of interaction with STX4 and insulin-dependent translocation to the cell membrane; when assoicated with N-157, N-163 and N-297. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 412412Double C2-like domain-containing protein betaPRO_0000079969Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei411 – 4111PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP70169.
PRIDEiP70169.

PTM databases

PhosphoSiteiP70169.

Expressioni

Tissue specificityi

Widely expressed. Expressed in pancreatic islet cells (at protein level).2 Publications

Gene expression databases

BgeeiP70169.
CleanExiMM_DOC2B.
GenevisibleiP70169. MM.

Interactioni

Subunit structurei

Interacts with cytoplasmic dynein light chain DYNLT1. May interact with UNC13A; the interaction mediates targeting to the plasma membrane (By similarity). Probably interacts with the SNARE (soluble N-ethylmaleimide-sensitive factor attached protein receptor) complex composed of SNAP25, STX1A and VAMP2; the interaction is calcium-dependent and competitive with SYT1. Interacts with STX4; the interaction is calcium-dependent, increased by insulin and glucose, and mediates vesicle fusion with plasma membrane in pancreatic cells and adipocytes. Interacts with STXBP3; the interaction is direct, occurs at the cell membrane and regulates glucose-stimulated insulin secretion.By similarity4 Publications

GO - Molecular functioni

  • syntaxin binding Source: UniProtKB

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000021209.

Structurei

3D structure databases

ProteinModelPortaliP70169.
SMRiP70169. Positions 125-412.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini128 – 232105C2 1PROSITE-ProRule annotationAdd
BLAST
Domaini268 – 371104C2 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 9090Mediates interaction with DYNLT1By similarityAdd
BLAST
Regioni1 – 3636Negatively regulates targeting to plasma membraneAdd
BLAST
Regioni257 – 375119Mediates interaction with STXBP3Add
BLAST

Domaini

C2 domain 1 is involved in binding calcium and phospholipids. According to PubMed:19033398, the C2 domain 2 may also play a role in the calcium-dependent targeting to membranes.

Sequence similaritiesi

Contains 2 C2 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1013. Eukaryota.
ENOG410XQXA. LUCA.
GeneTreeiENSGT00810000125376.
HOGENOMiHOG000232127.
HOVERGENiHBG051388.
InParanoidiP70169.
KOiK19917.
OMAiKLKANHT.
OrthoDBiEOG7CZK67.
TreeFamiTF351844.

Family and domain databases

Gene3Di2.60.40.150. 2 hits.
InterProiIPR000008. C2_dom.
IPR014638. Doc2.
IPR030534. Doc2b.
IPR001565. Synaptotagmin.
[Graphical view]
PANTHERiPTHR10024:SF204. PTHR10024:SF204. 2 hits.
PfamiPF00168. C2. 2 hits.
[Graphical view]
PIRSFiPIRSF036931. Doc2. 1 hit.
PRINTSiPR00360. C2DOMAIN.
PR00399. SYNAPTOTAGMN.
SMARTiSM00239. C2. 2 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 2 hits.
PROSITEiPS50004. C2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P70169-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTLRRRGEKA TISIQEHMAI DVCPGPIRPI KQISDYFPRF PRGLPPTAAP
60 70 80 90 100
RAPAPPDAPA RSPAASASPR SPSDGARDDD EDVDQLFGAY GASPGPSPGP
110 120 130 140 150
SPARPPAKPP EDEPDVDGYE SDDCTALGTL DFSLLYDQEN NALHCTISKA
160 170 180 190 200
KGLKPMDHNG LADPYVKLHL LPGASKANKL RTKTLRNTLN PSWNETLTYY
210 220 230 240 250
GITDEDMVRK TLRISVCDED KFRHNEFIGE TRVPLKKLKP NHTKTFSICL
260 270 280 290 300
EKQLPVDKAE DKSLEERGRI LISLKYSSQK QGLLVGIVRC AHLAAMDANG
310 320 330 340 350
YSDPYVKTYL KPDVDKKSKH KTAVKKKTLN PEFNEEFCYE IKHGDLAKKT
360 370 380 390 400
LEVTVWDYDI GKSNDFIGGV VLGINAKGER LKHWFDCLKN KDKRIERWHT
410
LTNELPGAVL SD
Length:412
Mass (Da):45,853
Last modified:July 27, 2011 - v2
Checksum:i4E94480BEDE91722
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti389 – 3891K → N in BAA12714 (PubMed:8902635).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D85037 mRNA. Translation: BAA12714.1.
AL669897 Genomic DNA. Translation: CAI26032.1.
CH466596 Genomic DNA. Translation: EDL12842.1.
BC067030 mRNA. Translation: AAH67030.1.
CCDSiCCDS25057.1.
PIRiJC4921.
RefSeqiNP_031899.2. NM_007873.3.
UniGeneiMm.5137.

Genome annotation databases

EnsembliENSMUST00000021209; ENSMUSP00000021209; ENSMUSG00000020848.
GeneIDi13447.
KEGGimmu:13447.
UCSCiuc007kev.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D85037 mRNA. Translation: BAA12714.1.
AL669897 Genomic DNA. Translation: CAI26032.1.
CH466596 Genomic DNA. Translation: EDL12842.1.
BC067030 mRNA. Translation: AAH67030.1.
CCDSiCCDS25057.1.
PIRiJC4921.
RefSeqiNP_031899.2. NM_007873.3.
UniGeneiMm.5137.

3D structure databases

ProteinModelPortaliP70169.
SMRiP70169. Positions 125-412.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000021209.

PTM databases

PhosphoSiteiP70169.

Proteomic databases

PaxDbiP70169.
PRIDEiP70169.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021209; ENSMUSP00000021209; ENSMUSG00000020848.
GeneIDi13447.
KEGGimmu:13447.
UCSCiuc007kev.1. mouse.

Organism-specific databases

CTDi8447.
MGIiMGI:1100497. Doc2b.

Phylogenomic databases

eggNOGiKOG1013. Eukaryota.
ENOG410XQXA. LUCA.
GeneTreeiENSGT00810000125376.
HOGENOMiHOG000232127.
HOVERGENiHBG051388.
InParanoidiP70169.
KOiK19917.
OMAiKLKANHT.
OrthoDBiEOG7CZK67.
TreeFamiTF351844.

Miscellaneous databases

ChiTaRSiDoc2b. mouse.
NextBioi283895.
PROiP70169.
SOURCEiSearch...

Gene expression databases

BgeeiP70169.
CleanExiMM_DOC2B.
GenevisibleiP70169. MM.

Family and domain databases

Gene3Di2.60.40.150. 2 hits.
InterProiIPR000008. C2_dom.
IPR014638. Doc2.
IPR030534. Doc2b.
IPR001565. Synaptotagmin.
[Graphical view]
PANTHERiPTHR10024:SF204. PTHR10024:SF204. 2 hits.
PfamiPF00168. C2. 2 hits.
[Graphical view]
PIRSFiPIRSF036931. Doc2. 1 hit.
PRINTSiPR00360. C2DOMAIN.
PR00399. SYNAPTOTAGMN.
SMARTiSM00239. C2. 2 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 2 hits.
PROSITEiPS50004. C2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Calcium-dependent phospholipid binding to the C2A domain of a ubiquitous form of double C2 protein (Doc2 beta)."
    Kojima T., Fukuda M., Aruga J., Mikoshiba K.
    J. Biochem. 120:671-676(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
    Tissue: Cerebellum.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain.
  5. "Doc2beta is a novel Munc18c-interacting partner and positive effector of syntaxin 4-mediated exocytosis."
    Ke B., Oh E., Thurmond D.C.
    J. Biol. Chem. 282:21786-21797(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH STXBP3, TISSUE SPECIFICITY.
  6. Cited for: INTERACTION WITH STX1A AND SNAP25.
  7. "DOC2b is a SNARE regulator of glucose-stimulated delayed insulin secretion."
    Miyazaki M., Emoto M., Fukuda N., Hatanaka M., Taguchi A., Miyamoto S., Tanizawa Y.
    Biochem. Biophys. Res. Commun. 384:461-465(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STX4.
  8. "DOC2B: a novel syntaxin-4 binding protein mediating insulin-regulated GLUT4 vesicle fusion in adipocytes."
    Fukuda N., Emoto M., Nakamori Y., Taguchi A., Miyamoto S., Uraki S., Oka Y., Tanizawa Y.
    Diabetes 58:377-384(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STX4, MUTAGENESIS OF ASP-157; ASP-163; ASP-297 AND ASP-303.
  9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.
  10. Cited for: DISRUPTION PHENOTYPE, FUNCTION.

Entry informationi

Entry nameiDOC2B_MOUSE
AccessioniPrimary (citable) accession number: P70169
Secondary accession number(s): Q5SS41, Q6NXK3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: July 27, 2011
Last modified: May 11, 2016
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.