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Q14184

- DOC2B_HUMAN

UniProt

Q14184 - DOC2B_HUMAN

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Protein

Double C2-like domain-containing protein beta

Gene

DOC2B

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 4 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 (By similarity).By similarity

GO - Molecular functioni

  1. calcium-dependent phospholipid binding Source: UniProtKB
  2. transporter activity Source: InterPro

GO - Biological processi

  1. calcium ion-dependent exocytosis of neurotransmitter Source: UniProtKB
  2. positive regulation of calcium ion-dependent exocytosis Source: UniProtKB
  3. positive regulation of insulin secretion Source: UniProtKB
  4. positive regulation of vesicle fusion Source: UniProtKB
  5. 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
Synonyms:DOC2BL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:2986. DOC2B.

Subcellular locationi

Cytoplasm. Cytoplasmic granule By similarity. Cell membrane By similarity; Peripheral membrane protein By similarity
Note: Translocates to the plasma membrane in a calcium-dependent manner.By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. plasma membrane Source: UniProtKB
  3. synaptic vesicle Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27452.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 412412Double C2-like domain-containing protein betaPRO_0000079968Add
BLAST

Proteomic databases

PaxDbiQ14184.
PRIDEiQ14184.

PTM databases

PhosphoSiteiQ14184.

Expressioni

Tissue specificityi

Widely expressed with highest levels in brain and kidney. Expressed in pancreatic islet cells (at protein level).2 Publications

Gene expression databases

BgeeiQ14184.
CleanExiHS_DOC2B.
GenevestigatoriQ14184.

Organism-specific databases

HPAiHPA043168.

Interactioni

Subunit structurei

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. May interact with UNC13A; the interaction mediates targeting to the plasma membrane (By similarity). Interacts with cytoplasmic dynein light chain DYNLT1.By similarity1 Publication

Protein-protein interaction databases

BioGridi114025. 2 interactions.
IntActiQ14184. 1 interaction.
MINTiMINT-7006088.
STRINGi9606.ENSP00000343665.

Structurei

3D structure databases

ProteinModelPortaliQ14184.
SMRiQ14184. 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 DYNLT1Add
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

eggNOGiNOG247952.
HOGENOMiHOG000232127.
HOVERGENiHBG051388.
InParanoidiQ14184.
OrthoDBiEOG7CZK67.
PhylomeDBiQ14184.
TreeFamiTF351844.

Family and domain databases

Gene3Di2.60.40.150. 2 hits.
InterProiIPR000008. C2_dom.
IPR014638. Doc2.
IPR001565. Synaptotagmin.
[Graphical view]
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.

Q14184-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MTLRRRGEKA TISIQEHMAI DVCPGPIRPI KQISDYFPRF PRGLPPDAGP
60 70 80 90 100
RAAAPPDAPA RPAVAGAGRR SPSDGAREDD EDVDQLFGAY GSSPGPSPGP
110 120 130 140 150
SPARPPAKPP EDEPDADGYE SDDCTALGTL DFSLLYDQEN NALHCTITKA
160 170 180 190 200
KGLKPMDHNG LADPYVKLHL LPGASKANKL RTKTLRNTLN PTWNETLTYY
210 220 230 240 250
GITDEDMIRK TLRISVCDED KFRHNEFIGE TRVPLKKLKP NHTKTFNICL
260 270 280 290 300
EKQLPVDKTE DKSLEERGRI LISLKYSSQK QGLLVGIVRC AHLAAMDANG
310 320 330 340 350
YSDPYVKTYL RPDVDKKSKH KTAVKKKTLN PEFNEEFCYE IKHGDLAKKS
360 370 380 390 400
LEVTVWDYDI GKSNDFIGGV VLGIHAKGER LKHWFDCLKN KDKRIERWHT
410
LTSELPGAVL SD
Length:412
Mass (Da):45,949
Last modified:November 1, 1996 - v1
Checksum:i679592A874542ED3
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti209 – 2091R → L in a patient with amyotrophic lateral sclerosis. 1 Publication
VAR_065743

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D70830 mRNA. Translation: BAA11107.1.
CCDSiCCDS73934.1.
RefSeqiNP_003576.2. NM_003585.4.
UniGeneiHs.551705.

Genome annotation databases

GeneIDi8447.
KEGGihsa:8447.
UCSCiuc010vpx.1. human.

Polymorphism databases

DMDMi51701386.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D70830 mRNA. Translation: BAA11107.1 .
CCDSi CCDS73934.1.
RefSeqi NP_003576.2. NM_003585.4.
UniGenei Hs.551705.

3D structure databases

ProteinModelPortali Q14184.
SMRi Q14184. Positions 125-412.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114025. 2 interactions.
IntActi Q14184. 1 interaction.
MINTi MINT-7006088.
STRINGi 9606.ENSP00000343665.

PTM databases

PhosphoSitei Q14184.

Polymorphism databases

DMDMi 51701386.

Proteomic databases

PaxDbi Q14184.
PRIDEi Q14184.

Protocols and materials databases

DNASUi 8447.
Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 8447.
KEGGi hsa:8447.
UCSCi uc010vpx.1. human.

Organism-specific databases

CTDi 8447.
GeneCardsi GC17M000007.
HGNCi HGNC:2986. DOC2B.
HPAi HPA043168.
MIMi 604568. gene.
neXtProti NX_Q14184.
PharmGKBi PA27452.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG247952.
HOGENOMi HOG000232127.
HOVERGENi HBG051388.
InParanoidi Q14184.
OrthoDBi EOG7CZK67.
PhylomeDBi Q14184.
TreeFami TF351844.

Miscellaneous databases

GeneWikii DOC2B.
GenomeRNAii 8447.
NextBioi 31606.
PROi Q14184.
SOURCEi Search...

Gene expression databases

Bgeei Q14184.
CleanExi HS_DOC2B.
Genevestigatori Q14184.

Family and domain databases

Gene3Di 2.60.40.150. 2 hits.
InterProi IPR000008. C2_dom.
IPR014638. Doc2.
IPR001565. Synaptotagmin.
[Graphical view ]
Pfami PF00168. C2. 2 hits.
[Graphical view ]
PIRSFi PIRSF036931. Doc2. 1 hit.
PRINTSi PR00360. C2DOMAIN.
PR00399. SYNAPTOTAGMN.
SMARTi SM00239. C2. 2 hits.
[Graphical view ]
SUPFAMi SSF49562. SSF49562. 2 hits.
PROSITEi PS50004. C2. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Molecular cloning of an isoform of Doc2 having two C2-like domains."
    Sakaguchi G., Orita S., Maeda M., Igarashi H., Takai Y.
    Biochem. Biophys. Res. Commun. 217:1053-1061(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
  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: FUNCTION, INTERACTION WITH DYNLT1.
  3. "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: TISSUE SPECIFICITY.
  4. "Resequencing of 29 candidate genes in patients with familial and sporadic amyotrophic lateral sclerosis."
    Daoud H., Valdmanis P.N., Gros-Louis F., Belzil V., Spiegelman D., Henrion E., Diallo O., Desjarlais A., Gauthier J., Camu W., Dion P.A., Rouleau G.A.
    Arch. Neurol. 68:587-593(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT LEU-209.

Entry informationi

Entry nameiDOC2B_HUMAN
AccessioniPrimary (citable) accession number: Q14184
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: November 1, 1996
Last modified: October 29, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3