Q14183 (DOC2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:

DOC2A

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	400 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Calcium sensor which most probably regulates fusion of vesicles with membranes. Binds calcium and phospholipids. May be involved in calcium dependent neurotransmitter release through the interaction with UNC13A. May be involved in calcium-dependent spontaneous release of neurotransmitter in absence of action potentials in neuronal cells. Regulates Ca2+-dependent secretory lysosome exocytosis in mast cells. Ref.4 Ref.5 Ref.6
Subunit structure	Interacts (via N-terminus) with UNC13A. Interacts with cytoplasmic dynein light chain DYNLT1. Interacts with UNC13D. Ref.4 Ref.5 Ref.6
Subcellular location	Lysosome By similarity. Cytoplasmic vesicle › secretory vesicle › synaptic vesicle membrane; Peripheral membrane protein Probable. Cell junction › synapse › synaptosome. Note: Colocalizes to synaptic vesicles.
Tissue specificity	Predominantly expressed in brain. Also expressed in testis. Ref.1 Ref.3
Domain	C2 domain 1 is involved in binding calcium and phospholipids By similarity.
Sequence similarities	Contains 2 C2 domains.

Ontologies

Keywords
Biological process	Exocytosis
Cellular component	Cell junction Cytoplasmic vesicle Lysosome Membrane Synapse Synaptosome
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium Calcium/phospholipid-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nervous system development Traceable author statement Ref.1. Source: ProtInc regulation of calcium ion-dependent exocytosis Inferred from mutant phenotype Ref.6. Source: UniProtKB synaptic transmission Traceable author statement Ref.1. Source: ProtInc synaptic vesicle exocytosis Inferred from electronic annotation. Source: Compara
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell neuron projection Inferred from electronic annotation. Source: UniProtKB-SubCell synaptic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium-dependent phospholipid binding Inferred from electronic annotation. Source: UniProtKB-KW 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 – 400	400	Double C2-like domain-containing protein alpha		PRO_0000079965
Regions
	Domain	91 – 195	105	C2 1
	Domain	253 – 356	104	C2 2
	Region	1 – 89	89	Interaction with UNC13D and DYNLT1
	Region	215 – 400	186	Interaction with UNC13D
Natural variations
	Natural variant	48	1	G → S. Ref.1 Ref.2 Corresponds to variant rs1140239 [ dbSNP | Ensembl ].		VAR_019656
Experimental info
	Sequence conflict	92	1	T → K in BAA06695. Ref.1
	Sequence conflict	108 – 109	2	CS → VC in BAA06695. Ref.1
	Sequence conflict	238	1	E → D in BAA06695. Ref.1
	Sequence conflict	376	1	P → R in BAA06695. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q14183 [UniParc]. Last modified June 26, 2007. Version 5. Checksum: 2E61A459AC373C6C	FASTA	400	43,959
	10 20 30 40 50 60 MRGRRGDRMT INIQEHMAIN VCPGPIRPIR QISDYFPRGP GPEGGGGGGG EAPAHLVPLA 70 80 90 100 110 120 LAPPAALLGA TTPEDGAEVD SYDSDDATAL GTLEFDLLYD RASCTLHCSI LRAKGLKPMD 130 140 150 160 170 180 FNGLADPYVK LHLLPGACKA NKLKTKTQRN TLNPVWNEDL TYSGITDDDI THKVLRIAVC 190 200 210 220 230 240 DEDKLSHNEF IGEIRVPLRR LKPSQKKHFN ICLERQVPLA SPSSMSAALR GISCYLKELE 250 260 270 280 290 300 QAEQGQGLLE ERGRILLSLS YSSRRRGLLV GILRCAHLAA MDVNGYSDPY VKTYLRPDVD 310 320 330 340 350 360 KKSKHKTCVK KKTLNPEFNE EFFYEIELST LATKTLEVTV WDYDIGKSND FIGGVSLGPG 370 380 390 400 ARGEARKHWS DCLQQPDAAL ERWHTLTSEL PPAAGALSSA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Doc2, a novel synaptic vesicle protein with two repeated C2-like domains." Orita S., Sasaki T., Naito A., Maeda M., Igarashi H., Takai Y. Biochem. Biophys. Res. Commun. 206:439-448(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-48, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-48. Tissue: Brain and Mammary gland.
[3]	"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: TISSUE SPECIFICITY.
[4]	"Role of the Doc2 alpha-Munc13-1 interaction in the neurotransmitter release process." Mochida S., Orita S., Sakaguchi G., Sasaki T., Takai Y. Proc. Natl. Acad. Sci. U.S.A. 95:11418-11422(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH UNC13A.
[5]	"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.
[6]	"Doc2 alpha and Munc13-4 regulate Ca(2+) -dependent secretory lysosome exocytosis in mast cells." Higashio H., Nishimura N., Ishizaki H., Miyoshi J., Orita S., Sakane A., Sasaki T. J. Immunol. 180:4774-4784(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH UNC13D.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D31897 mRNA. Translation: BAA06695.1. BC041769 mRNA. Translation: AAH41769.2. BC055284 mRNA. Translation: AAH55284.1. BC063436 mRNA. Translation: AAH63436.1.
IPI	IPI00455076.
PIR	JC2473.
RefSeq	NP_003577.2. NM_003586.2.
UniGene	Hs.355281.
3D structure databases
ProteinModelPortal	Q14183.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000340017.
PTM databases
PhosphoSite	Q14183.
Polymorphism databases
DMDM	150421541.
Proteomic databases
PaxDb	Q14183.
PRIDE	Q14183.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000350119; ENSP00000340017; ENSG00000149927. ENST00000564944; ENSP00000455196; ENSG00000149927. ENST00000564979; ENSP00000455624; ENSG00000149927.
GeneID	8448.
KEGG	hsa:8448.
UCSC	uc002dvn.3. human.
Organism-specific databases
CTD	8448.
GeneCards	GC16M030016.
H-InvDB	HIX0012939.
HGNC	HGNC:2985. DOC2A.
MIM	604567. gene.
neXtProt	NX_Q14183.
PharmGKB	PA27451.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG247952.
HOGENOM	HOG000232127.
HOVERGEN	HBG051388.
InParanoid	Q14183.
OMA	WNEDLMY.
OrthoDB	EOG4PRSR0.
PhylomeDB	Q14183.
Gene expression databases
ArrayExpress	Q14183.
Bgee	Q14183.
CleanEx	HS_DOC2A.
Genevestigator	Q14183.
GermOnline	ENSG00000149927. Homo sapiens.
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	8448.
NextBio	31610.
SOURCE	Search...

Entry information

Entry name

DOC2A_HUMAN

Accession

Primary (citable) accession number: Q14183
Secondary accession number(s): Q6P4G4, Q7Z5G0, Q8IVX0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 31, 2004
Last sequence update:	June 26, 2007
Last modified:	May 1, 2013
This is version 112 of the entry and version 5 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.