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Protein

Double C2-like domain-containing protein beta

Gene

Doc2b

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

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

Keywordsi

LigandCalcium, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620519 Doc2b

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi15 – 20QEHMAI → YKDWAF: Prevents diacylglycerol-induced localization to the plasma membrane. Probably prevents interaction with UNC13A. 1 Publication6
Mutagenesisi158H → A: Loss of calcium-dependent binding to liposomes and altered fusion-promoting activity; when associated with A-222 and A-360. 1 Publication1
Mutagenesisi218D → N: Binds liposomes in a calcium-independent manner; when associated with N-220. 1 Publication1
Mutagenesisi220D → N: Binds liposomes in a calcium-independent manner; when associated with N-218. 1 Publication1
Mutagenesisi222F → A: Loss of calcium-dependent binding to liposomes and altered fusion-promoting activity; when associated with A-158 and A-360. 1 Publication1
Mutagenesisi237K → 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 Publication1
Mutagenesisi319K → 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 Publication1
Mutagenesisi360I → A: Loss of calcium-dependent binding to liposomes and altered fusion-promoting activity; when associated with A-158 and A-222. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000799701 – 412Double C2-like domain-containing protein betaAdd BLAST412

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei411PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiP70610

PTM databases

iPTMnetiP70610

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

GO - Molecular functioni

Structurei

Secondary structure

1412
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi129 – 137Combined sources9
Helixi138 – 140Combined sources3
Beta strandi142 – 152Combined sources11
Beta strandi164 – 172Combined sources9
Helixi176 – 178Combined sources3
Beta strandi179 – 181Combined sources3
Beta strandi192 – 199Combined sources8
Helixi204 – 209Combined sources6
Beta strandi211 – 218Combined sources8
Beta strandi226 – 234Combined sources9
Helixi235 – 237Combined sources3
Beta strandi244 – 249Combined sources6
Beta strandi266 – 277Combined sources12
Turni278 – 281Combined sources4
Beta strandi282 – 292Combined sources11
Beta strandi304 – 312Combined sources9
Beta strandi332 – 340Combined sources9
Helixi343 – 348Combined sources6
Beta strandi350 – 357Combined sources8
Beta strandi360 – 362Combined sources3
Beta strandi365 – 373Combined sources9
Helixi378 – 389Combined sources12
Beta strandi395 – 403Combined sources9

3D structure databases

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini128 – 232C2 1PROSITE-ProRule annotationAdd BLAST105
Domaini268 – 371C2 2PROSITE-ProRule annotationAdd BLAST104

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 90Mediates interaction with DYNLT1By similarityAdd BLAST90
Regioni1 – 36Negatively regulates targeting to plasma membraneBy similarityAdd BLAST36
Regioni257 – 375Mediates interaction with STXBP3By similarityAdd BLAST119

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

Keywords - Domaini

Repeat

Phylogenomic databases

HOGENOMiHOG000232127
HOVERGENiHBG051388
InParanoidiP70610
KOiK19917
PhylomeDBiP70610

Family and domain databases

Gene3Di2.60.40.150, 2 hits
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR014638 Doc2
IPR030534 Doc2b
IPR001565 Synaptotagmin
PANTHERiPTHR10024:SF204 PTHR10024:SF204, 2 hits
PfamiView protein in Pfam
PF00168 C2, 2 hits
PIRSFiPIRSF036931 Doc2, 1 hit
PRINTSiPR00360 C2DOMAIN
PR00399 SYNAPTOTAGMN
SMARTiView protein in SMART
SM00239 C2, 2 hits
PROSITEiView protein in PROSITE
PS50004 C2, 2 hits

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

Similar proteinsi

Entry informationi

Entry nameiDOC2B_RAT
AccessioniPrimary (citable) accession number: P70610
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: October 1, 2000
Last modified: March 28, 2018
This is version 119 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health