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Q14183 (DOC2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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 alpha

Short name=Doc2
Short name=Doc2-alpha
Gene names
Name:DOC2A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length400 AA.
Sequence statusComplete.
Protein existenceEvidence 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 vesiclesecretory vesiclesynaptic vesicle membrane; Peripheral membrane protein Probable. Cell junctionsynapsesynaptosome. 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 400400Double C2-like domain-containing protein alpha
PRO_0000079965

Regions

Domain91 – 195105C2 1
Domain253 – 356104C2 2
Region1 – 8989Interaction with UNC13D and DYNLT1
Region215 – 400186Interaction with UNC13D

Natural variations

Natural variant481G → S. Ref.1 Ref.2
Corresponds to variant rs1140239 [ dbSNP | Ensembl ].
VAR_019656

Experimental info

Sequence conflict921T → K in BAA06695. Ref.1
Sequence conflict108 – 1092CS → VC in BAA06695. Ref.1
Sequence conflict2381E → D in BAA06695. Ref.1
Sequence conflict3761P → R in BAA06695. Ref.1

Secondary structure

..................... 400
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q14183 [UniParc].

Last modified June 26, 2007. Version 5.
Checksum: 2E61A459AC373C6C

FASTA40043,959
        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 

« Hide

References

« Hide '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.
PIRJC2473.
RefSeqNP_001268991.1. NM_001282062.1.
NP_001268992.1. NM_001282063.1.
NP_001268997.1. NM_001282068.1.
NP_003577.2. NM_003586.2.
XP_005255692.1. XM_005255635.2.
UniGeneHs.355281.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4MJJX-ray2.00A81-217[»]
ProteinModelPortalQ14183.
SMRQ14183. Positions 55-393.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114026. 1 interaction.
STRING9606.ENSP00000340017.

PTM databases

PhosphoSiteQ14183.

Polymorphism databases

DMDM150421541.

Proteomic databases

PaxDbQ14183.
PRIDEQ14183.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000350119; ENSP00000340017; ENSG00000149927.
ENST00000564944; ENSP00000455196; ENSG00000149927.
ENST00000564979; ENSP00000455624; ENSG00000149927.
GeneID8448.
KEGGhsa:8448.
UCSCuc002dvn.3. human.

Organism-specific databases

CTD8448.
GeneCardsGC16M030016.
H-InvDBHIX0012939.
HGNCHGNC:2985. DOC2A.
MIM604567. gene.
neXtProtNX_Q14183.
PharmGKBPA27451.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG247952.
HOGENOMHOG000232127.
HOVERGENHBG051388.
InParanoidQ14183.
OMADYFPRLG.
PhylomeDBQ14183.
TreeFamTF351844.

Gene expression databases

ArrayExpressQ14183.
BgeeQ14183.
CleanExHS_DOC2A.
GenevestigatorQ14183.

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

GeneWikiDOC2A.
GenomeRNAi8448.
NextBio31610.
PROQ14183.
SOURCESearch...

Entry information

Entry nameDOC2A_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 120 of the entry and version 5 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 16

Human chromosome 16: entries, gene names and cross-references to MIM