Q14184 (DOC2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Double C2-like domain-containing protein beta
Short name=Doc2-beta

Gene names

Name:	DOC2B
Synonyms:	DOC2BL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	412 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium Calcium/phospholipid-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium ion-dependent exocytosis of neurotransmitter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of calcium ion-dependent exocytosis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of insulin secretion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of vesicle fusion Inferred from sequence or structural similarity. Source: UniProtKB protein localization Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB microtubule cytoskeleton Inferred from direct assay. Source: HPA plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB synaptic vesicle Inferred from electronic annotation. Source: InterPro
Molecular_function	calcium-dependent phospholipid binding Inferred from sequence or structural similarity. Source: UniProtKB transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 412	412	Double C2-like domain-containing protein beta		PRO_0000079968
Regions
	Domain	128 – 232	105	C2 1
	Domain	268 – 371	104	C2 2
	Region	1 – 90	90	Mediates interaction with DYNLT1
	Region	1 – 36	36	Negatively regulates targeting to plasma membrane By similarity
	Region	257 – 375	119	Mediates interaction with STXBP3 By similarity
Natural variations
	Natural variant	209	1	R → L in a patient with amyotrophic lateral sclerosis. Ref.4		VAR_065743

Sequences

	Sequence		Length	Mass (Da)
	Q14184 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 679592A874542ED3	FASTA	412	45,949
	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

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.
IPI	IPI00020684.
RefSeq	NP_003576.2. NM_003585.3.
UniGene	Hs.551705.
3D structure databases
ProteinModelPortal	Q14184.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000343665.
PTM databases
PhosphoSite	Q14184.
Polymorphism databases
DMDM	51701386.
Proteomic databases
PaxDb	Q14184.
PRIDE	Q14184.
Protocols and materials databases
DNASU	8447.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000343572; ENSP00000343665; ENSG00000187939. ENST00000496357; ENSP00000417238; ENSG00000187939.
GeneID	8447.
KEGG	hsa:8447.
UCSC	uc010vpx.1. human.
Organism-specific databases
CTD	8447.
GeneCards	GC17M000007.
HGNC	HGNC:2986. DOC2B.
HPA	HPA043168.
MIM	604568. gene.
neXtProt	NX_Q14184.
PharmGKB	PA27452.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG247952.
HOGENOM	HOG000232127.
HOVERGEN	HBG051388.
InParanoid	Q14184.
OrthoDB	EOG4Z0B5S.
Gene expression databases
Bgee	Q14184.
CleanEx	HS_DOC2B.
Genevestigator	Q14184.
Family and domain databases
InterPro	IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR020477. C2_dom. IPR018029. C2_membr_targeting. IPR014638. Doc2. IPR001565. Synaptotagmin. [Graphical view]
Pfam	PF00168. C2. 2 hits. [Graphical view]
PIRSF	PIRSF036931. Doc2. 1 hit.
PRINTS	PR00360. C2DOMAIN. PR00399. SYNAPTOTAGMN.
SMART	SM00239. C2. 2 hits. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 2 hits.
PROSITE	PS50004. C2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8447.
NextBio	31606.
SOURCE	Search...

Entry information

Entry name

DOC2B_HUMAN

Accession

Primary (citable) accession number: Q14184

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 31, 2004
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.