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Protein

Double C2-like domain-containing protein beta

Gene

Doc2b

Organism
Rattus norvegicus (Rat)
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.2 Publications

GO - Molecular functioni

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

GO - Biological processi

  • calcium ion-regulated exocytosis of neurotransmitter Source: UniProtKB
  • exocytosis Source: RGD
  • 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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620519. 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

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi15 – 206QEHMAI → YKDWAF: Prevents diacylglycerol-induced localization to the plasma membrane. Probably prevents interaction with UNC13A. 1 Publication
Mutagenesisi158 – 1581H → A: Loss of calcium-dependent binding to liposomes and altered fusion-promoting activity; when associated with A-222 and A-360. 1 Publication
Mutagenesisi218 – 2181D → N: Binds liposomes in a calcium-independent manner; when associated with N-220. 1 Publication
Mutagenesisi220 – 2201D → N: Binds liposomes in a calcium-independent manner; when associated with N-218. 1 Publication
Mutagenesisi222 – 2221F → A: Loss of calcium-dependent binding to liposomes and altered fusion-promoting activity; when associated with A-158 and A-360. 1 Publication
Mutagenesisi237 – 2371K → E: Loss of calcium-independent binding to liposomes. Loss of interaction with the SNARE complex and altered fusion-promoting activity; when associated with E-319. 1 Publication
Mutagenesisi319 – 3191K → E: Loss of calcium-independent binding to liposomes. Loss of interaction with the SNARE complex and altered fusion-promoting activity; when associated with E-237. 1 Publication
Mutagenesisi360 – 3601I → A: Loss of calcium-dependent binding to liposomes and altered fusion-promoting activity; when associated with A-158 and A-222. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 412412Double C2-like domain-containing protein betaPRO_0000079970Add
BLAST

Amino acid modifications

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

Keywords - PTMi

Phosphoprotein

Expressioni

Tissue specificityi

Expressed in brain; highly enriched in neurons.1 Publication

Interactioni

Subunit structurei

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 similarity). Interacts with cytoplasmic dynein light chain DYNLT1. 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. May interact with UNC13A; the interaction mediates targeting to the plasma membrane.By similarity4 Publications

Structurei

Secondary structure

1
412
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi129 – 1379Combined sources
Helixi138 – 1403Combined sources
Beta strandi142 – 15211Combined sources
Beta strandi164 – 1729Combined sources
Helixi176 – 1783Combined sources
Beta strandi179 – 1813Combined sources
Beta strandi192 – 1998Combined sources
Helixi204 – 2096Combined sources
Beta strandi211 – 2188Combined sources
Beta strandi226 – 2349Combined sources
Helixi235 – 2373Combined sources
Beta strandi244 – 2496Combined sources
Beta strandi266 – 27712Combined sources
Turni278 – 2814Combined sources
Beta strandi282 – 29211Combined sources
Beta strandi304 – 3129Combined sources
Beta strandi332 – 3409Combined sources
Helixi343 – 3486Combined sources
Beta strandi350 – 3578Combined sources
Beta strandi360 – 3623Combined sources
Beta strandi365 – 3739Combined sources
Helixi378 – 38912Combined sources
Beta strandi395 – 4039Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4LCVX-ray2.00A/B/C/D125-255[»]
4LDCX-ray1.26A265-412[»]
ProteinModelPortaliP70610.
SMRiP70610. Positions 127-252, 260-404.
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 membraneBy similarityAdd
BLAST
Regioni257 – 375119Mediates interaction with STXBP3By similarityAdd
BLAST

Domaini

C2 domain 1 is involved in binding calcium and phospholipids. C2 domain 2 may also play a role in the calcium-dependent targeting to membranes (By similarity).By similarity

Sequence similaritiesi

Contains 2 C2 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

HOGENOMiHOG000232127.
HOVERGENiHBG051388.
InParanoidiP70610.
KOiK19917.
PhylomeDBiP70610.

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.

P70610-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTLRRRGEKA TISIQEHMAI DVCPGPIRPI KQISDYFPRF PRGLPPTAAP
60 70 80 90 100
RASAPPDAPA RSPAATAGPR SPSDGARDDD EDVDQLFGAY GASPGPSPGP
110 120 130 140 150
SPVRPPAKPP EDEPDADGYE SDDCTALGTL DFSLLYDQEN NALHCTISKA
160 170 180 190 200
KGLKPMDHNG LADPYVKLHL LPGASKANKL RTKTLRNTLN PSWNETLTYY
210 220 230 240 250
GITDEDMIRK 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
LTNEIPGAVL SD
Length:412
Mass (Da):45,841
Last modified:October 1, 2000 - v2
Checksum:i61595BC6886F1012
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70778 mRNA. Translation: AAB47747.2.
RefSeqiNP_112404.1. NM_031142.1.
UniGeneiRn.10689.

Genome annotation databases

GeneIDi81820.
KEGGirno:81820.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70778 mRNA. Translation: AAB47747.2.
RefSeqiNP_112404.1. NM_031142.1.
UniGeneiRn.10689.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4LCVX-ray2.00A/B/C/D125-255[»]
4LDCX-ray1.26A265-412[»]
ProteinModelPortaliP70610.
SMRiP70610. Positions 127-252, 260-404.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi81820.
KEGGirno:81820.

Organism-specific databases

CTDi8447.
RGDi620519. Doc2b.

Phylogenomic databases

HOGENOMiHOG000232127.
HOVERGENiHBG051388.
InParanoidiP70610.
KOiK19917.
PhylomeDBiP70610.

Miscellaneous databases

NextBioi615739.
PROiP70610.

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. "DOC2 proteins in rat brain: complementary distribution and proposed function as vesicular adapter proteins in early stages of secretion."
    Verhage M., de Vries K.J., Roeshol H., Burbach J.P., Gispen W.H., Suedhof T.C.
    Neuron 18:453-461(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Tissue: Brain.
  2. "Interaction of Doc2 with tctex-1, a light chain of cytoplasmic dynein. Implication in dynein-dependent vesicle transport."
    Nagano F., Orita S., Sasaki T., Naito A., Sakaguchi G., Maeda M., Watanabe T., Kominami E., Uchiyama Y., Takai Y.
    J. Biol. Chem. 273:30065-30068(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DYNLT1.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  3. "Ca(2+)-induced recruitment of the secretory vesicle protein DOC2B to the target membrane."
    Groffen A.J., Brian E.C., Dudok J.J., Kampmeijer J., Toonen R.F., Verhage M.
    J. Biol. Chem. 279:23740-23747(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH UNC13A, SUBCELLULAR LOCATION, MUTAGENESIS OF 15-GLN--ILE-20.
  4. Cited for: FUNCTION, PHOSPHOLIPID-BINDING, MUTAGENESIS OF ASP-218 AND ASP-220, INTERACTION WITH STX1A AND SNAP25.
  5. Cited for: FUNCTION, PHOSPHOLIPID-BINDING, INTERACTION WITH SNARE COMPLEX, MUTAGENESIS OF HIS-158; PHE-222; LYS-237; LYS-319 AND ILE-360.
  6. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiDOC2B_RAT
AccessioniPrimary (citable) accession number: P70610
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: October 1, 2000
Last modified: May 11, 2016
This is version 109 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.