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Q14184 (DOC2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Double C2-like domain-containing protein beta

Short name=Doc2-beta
Gene names
Name:DOC2B
Synonyms:DOC2BL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length412 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2

Subunit structure

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. Ref.2

Subcellular location

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

Tissue specificity

Widely expressed with highest levels in brain and kidney. Expressed in pancreatic islet cells (at protein level). Ref.1 Ref.3

Domain

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.

Sequence similarities

Contains 2 C2 domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 412412Double C2-like domain-containing protein beta
PRO_0000079968

Regions

Domain128 – 232105C2 1
Domain268 – 371104C2 2
Region1 – 9090Mediates interaction with DYNLT1
Region1 – 3636Negatively regulates targeting to plasma membrane By similarity
Region257 – 375119Mediates interaction with STXBP3 By similarity

Natural variations

Natural variant2091R → L in a patient with amyotrophic lateral sclerosis. Ref.4
VAR_065743

Sequences

Sequence LengthMass (Da)Tools
Q14184 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 679592A874542ED3

FASTA41245,949
        10         20         30         40         50         60 
MTLRRRGEKA TISIQEHMAI DVCPGPIRPI KQISDYFPRF PRGLPPDAGP RAAAPPDAPA 

        70         80         90        100        110        120 
RPAVAGAGRR SPSDGAREDD EDVDQLFGAY GSSPGPSPGP SPARPPAKPP EDEPDADGYE 

       130        140        150        160        170        180 
SDDCTALGTL DFSLLYDQEN NALHCTITKA KGLKPMDHNG LADPYVKLHL LPGASKANKL 

       190        200        210        220        230        240 
RTKTLRNTLN PTWNETLTYY GITDEDMIRK TLRISVCDED KFRHNEFIGE TRVPLKKLKP 

       250        260        270        280        290        300 
NHTKTFNICL EKQLPVDKTE DKSLEERGRI LISLKYSSQK QGLLVGIVRC AHLAAMDANG 

       310        320        330        340        350        360 
YSDPYVKTYL RPDVDKKSKH KTAVKKKTLN PEFNEEFCYE IKHGDLAKKS LEVTVWDYDI 

       370        380        390        400        410 
GKSNDFIGGV VLGIHAKGER LKHWFDCLKN KDKRIERWHT LTSELPGAVL SD 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D70830 mRNA. Translation: BAA11107.1.
RefSeqNP_003576.2. NM_003585.4.
UniGeneHs.551705.

3D structure databases

ProteinModelPortalQ14184.
SMRQ14184. Positions 125-412.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114025. 1 interaction.
IntActQ14184. 1 interaction.
MINTMINT-7006088.
STRING9606.ENSP00000343665.

PTM databases

PhosphoSiteQ14184.

Polymorphism databases

DMDM51701386.

Proteomic databases

PaxDbQ14184.
PRIDEQ14184.

Protocols and materials databases

DNASU8447.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID8447.
KEGGhsa:8447.
UCSCuc010vpx.1. human.

Organism-specific databases

CTD8447.
GeneCardsGC17M000007.
HGNCHGNC:2986. DOC2B.
HPAHPA043168.
MIM604568. gene.
neXtProtNX_Q14184.
PharmGKBPA27452.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG247952.
HOGENOMHOG000232127.
HOVERGENHBG051388.
InParanoidQ14184.
OrthoDBEOG7CZK67.
PhylomeDBQ14184.
TreeFamTF351844.

Gene expression databases

BgeeQ14184.
CleanExHS_DOC2B.
GenevestigatorQ14184.

Family and domain databases

Gene3D2.60.40.150. 2 hits.
InterProIPR000008. C2_dom.
IPR014638. Doc2.
IPR001565. Synaptotagmin.
[Graphical view]
PfamPF00168. C2. 2 hits.
[Graphical view]
PIRSFPIRSF036931. Doc2. 1 hit.
PRINTSPR00360. C2DOMAIN.
PR00399. SYNAPTOTAGMN.
SMARTSM00239. C2. 2 hits.
[Graphical view]
SUPFAMSSF49562. SSF49562. 2 hits.
PROSITEPS50004. C2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiDOC2B.
GenomeRNAi8447.
NextBio31606.
PROQ14184.
SOURCESearch...

Entry information

Entry nameDOC2B_HUMAN
AccessionPrimary (citable) accession number: Q14184
Entry history
Integrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM