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Protein

Double C2-like domain-containing protein alpha

Gene

DOC2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

GO - Biological processi

  • calcium ion-regulated exocytosis of neurotransmitter Source: GO_Central
  • chemical synaptic transmission Source: ProtInc
  • nervous system development Source: ProtInc
  • regulation of calcium ion-dependent exocytosis Source: UniProtKB
  • vesicle fusion Source: GO_Central

Keywordsi

Biological processExocytosis
LigandCalcium, Calcium/phospholipid-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Double C2-like domain-containing protein alpha
Short name:
Doc2
Short name:
Doc2-alpha
Gene namesi
Name:DOC2A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000149927.17
HGNCiHGNC:2985 DOC2A
MIMi604567 gene
neXtProtiNX_Q14183

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cytoplasmic vesicle, Lysosome, Membrane, Synapse, Synaptosome

Pathology & Biotechi

Organism-specific databases

DisGeNETi8448
OpenTargetsiENSG00000149927
PharmGKBiPA27451

Polymorphism and mutation databases

BioMutaiDOC2A
DMDMi150421541

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000799651 – 400Double C2-like domain-containing protein alphaAdd BLAST400

Proteomic databases

MaxQBiQ14183
PaxDbiQ14183
PeptideAtlasiQ14183
PRIDEiQ14183

PTM databases

iPTMnetiQ14183
PhosphoSitePlusiQ14183
SwissPalmiQ14183

Expressioni

Tissue specificityi

Predominantly expressed in brain. Also expressed in testis.2 Publications

Gene expression databases

BgeeiENSG00000149927
CleanExiHS_DOC2A
ExpressionAtlasiQ14183 baseline and differential
GenevisibleiQ14183 HS

Organism-specific databases

HPAiHPA065676

Interactioni

Subunit structurei

Interacts (via N-terminus) with UNC13A. Interacts with cytoplasmic dynein light chain DYNLT1. Interacts with UNC13D.3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114026, 9 interactors
STRINGi9606.ENSP00000340017

Structurei

Secondary structure

1400
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi92 – 100Combined sources9
Turni101 – 104Combined sources4
Beta strandi105 – 115Combined sources11
Beta strandi127 – 135Combined sources9
Helixi139 – 141Combined sources3
Beta strandi142 – 144Combined sources3
Beta strandi155 – 162Combined sources8
Helixi167 – 172Combined sources6
Beta strandi174 – 181Combined sources8
Beta strandi190 – 197Combined sources8
Helixi198 – 200Combined sources3
Beta strandi207 – 212Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4MJJX-ray2.00A81-217[»]
ProteinModelPortaliQ14183
SMRiQ14183
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini91 – 195C2 1PROSITE-ProRule annotationAdd BLAST105
Domaini253 – 356C2 2PROSITE-ProRule annotationAdd BLAST104

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 89Interaction with UNC13D and DYNLT12 PublicationsAdd BLAST89
Regioni215 – 400Interaction with UNC13D1 PublicationAdd BLAST186

Domaini

C2 domain 1 is involved in binding calcium and phospholipids.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410INTM Eukaryota
ENOG410YZ99 LUCA
GeneTreeiENSGT00810000125376
HOGENOMiHOG000232127
HOVERGENiHBG051388
InParanoidiQ14183
KOiK19916
OMAiKVERWHT
OrthoDBiEOG091G0FPP
PhylomeDBiQ14183
TreeFamiTF351844

Family and domain databases

Gene3Di2.60.40.150, 2 hits
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR014638 Doc2
IPR030535 Doc2a
IPR001565 Synaptotagmin
PANTHERiPTHR10024:SF233 PTHR10024:SF233, 1 hit
PfamiView protein in Pfam
PF00168 C2, 2 hits
PIRSFiPIRSF036931 Doc2, 1 hit
PRINTSiPR00360 C2DOMAIN
PR00399 SYNAPTOTAGMN
SMARTiView protein in SMART
SM00239 C2, 2 hits
PROSITEiView protein in PROSITE
PS50004 C2, 2 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14183-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRGRRGDRMT INIQEHMAIN VCPGPIRPIR QISDYFPRGP GPEGGGGGGG
60 70 80 90 100
EAPAHLVPLA LAPPAALLGA TTPEDGAEVD SYDSDDATAL GTLEFDLLYD
110 120 130 140 150
RASCTLHCSI LRAKGLKPMD FNGLADPYVK LHLLPGACKA NKLKTKTQRN
160 170 180 190 200
TLNPVWNEDL TYSGITDDDI THKVLRIAVC DEDKLSHNEF IGEIRVPLRR
210 220 230 240 250
LKPSQKKHFN ICLERQVPLA SPSSMSAALR GISCYLKELE QAEQGQGLLE
260 270 280 290 300
ERGRILLSLS YSSRRRGLLV GILRCAHLAA MDVNGYSDPY VKTYLRPDVD
310 320 330 340 350
KKSKHKTCVK KKTLNPEFNE EFFYEIELST LATKTLEVTV WDYDIGKSND
360 370 380 390 400
FIGGVSLGPG ARGEARKHWS DCLQQPDAAL ERWHTLTSEL PPAAGALSSA
Length:400
Mass (Da):43,959
Last modified:June 26, 2007 - v5
Checksum:i2E61A459AC373C6C
GO
Isoform 2 (identifier: Q14183-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-118: Missing.
     271-281: GILRCAHLAAM → PEARCGQEIQA
     282-400: Missing.

Note: No experimental confirmation available.
Show »
Length:163
Mass (Da):18,384
Checksum:iC2792B98A87A207D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti92T → K in BAA06695 (PubMed:7826360).Curated1
Sequence conflicti108 – 109CS → VC in BAA06695 (PubMed:7826360).Curated2
Sequence conflicti238E → D in BAA06695 (PubMed:7826360).Curated1
Sequence conflicti376P → R in BAA06695 (PubMed:7826360).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01965648G → S2 PublicationsCorresponds to variant dbSNP:rs1140239Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0569771 – 118Missing in isoform 2. 1 PublicationAdd BLAST118
Alternative sequenceiVSP_056978271 – 281GILRCAHLAAM → PEARCGQEIQA in isoform 2. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_056979282 – 400Missing in isoform 2. 1 PublicationAdd BLAST119

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31897 mRNA Translation: BAA06695.1
AK293651 mRNA Translation: BAG57103.1
AC093512 Genomic DNA No translation available.
BC041769 mRNA Translation: AAH41769.2
BC055284 mRNA Translation: AAH55284.1
BC063436 mRNA Translation: AAH63436.1
CCDSiCCDS10666.1 [Q14183-1]
PIRiJC2473
RefSeqiNP_001268991.1, NM_001282062.1 [Q14183-1]
NP_001268992.1, NM_001282063.1 [Q14183-1]
NP_001268997.1, NM_001282068.1 [Q14183-1]
NP_003577.2, NM_003586.2 [Q14183-1]
XP_011544277.1, XM_011545975.1 [Q14183-1]
XP_016879265.1, XM_017023776.1 [Q14183-1]
XP_016879266.1, XM_017023777.1 [Q14183-1]
UniGeneiHs.355281

Genome annotation databases

EnsembliENST00000350119; ENSP00000340017; ENSG00000149927 [Q14183-1]
ENST00000564944; ENSP00000455196; ENSG00000149927 [Q14183-1]
ENST00000564979; ENSP00000455624; ENSG00000149927 [Q14183-1]
ENST00000566310; ENSP00000454857; ENSG00000149927 [Q14183-2]
ENST00000616445; ENSP00000482870; ENSG00000149927 [Q14183-1]
GeneIDi8448
KEGGihsa:8448
UCSCiuc002dvn.4 human [Q14183-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDOC2A_HUMAN
AccessioniPrimary (citable) accession number: Q14183
Secondary accession number(s): B4DEJ2
, H3BNH6, Q6P4G4, Q7Z5G0, Q8IVX0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: June 26, 2007
Last modified: March 28, 2018
This is version 152 of the entry and version 5 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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