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Q14183

- DOC2A_HUMAN

UniProt

Q14183 - DOC2A_HUMAN

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Protein

Double C2-like domain-containing protein alpha

Gene

DOC2A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- 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

  1. calcium-dependent phospholipid binding Source: UniProtKB-KW
  2. transporter activity Source: InterPro

GO - Biological processi

  1. nervous system development Source: ProtInc
  2. regulation of calcium ion-dependent exocytosis Source: UniProtKB
  3. synaptic transmission Source: ProtInc
  4. synaptic vesicle exocytosis Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Exocytosis

Keywords - Ligandi

Calcium, 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
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:2985. DOC2A.

Subcellular locationi

Lysosome By similarity. Cytoplasmic vesiclesecretory vesiclesynaptic vesicle membrane Curated; Peripheral membrane protein Curated. Cell junctionsynapsesynaptosome
Note: Colocalizes to synaptic vesicles.

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. lysosome Source: UniProtKB-KW
  3. membrane Source: UniProtKB-KW
  4. neuron projection Source: UniProtKB-KW
  5. synaptic vesicle Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27451.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 400400Double C2-like domain-containing protein alphaPRO_0000079965Add
BLAST

Proteomic databases

MaxQBiQ14183.
PaxDbiQ14183.
PRIDEiQ14183.

PTM databases

PhosphoSiteiQ14183.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ14183.
CleanExiHS_DOC2A.
ExpressionAtlasiQ14183. baseline.
GenevestigatoriQ14183.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi114026. 8 interactions.
STRINGi9606.ENSP00000340017.

Structurei

Secondary structure

1
400
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi92 – 1009
Turni101 – 1044
Beta strandi105 – 11511
Beta strandi127 – 1359
Helixi139 – 1413
Beta strandi142 – 1443
Beta strandi155 – 1628
Helixi167 – 1726
Beta strandi174 – 1818
Beta strandi190 – 1978
Helixi198 – 2003
Beta strandi207 – 2126

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4MJJX-ray2.00A81-217[»]
ProteinModelPortaliQ14183.
SMRiQ14183. Positions 55-393.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini91 – 195105C2 1PROSITE-ProRule annotationAdd
BLAST
Domaini253 – 356104C2 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 8989Interaction with UNC13D and DYNLT1Add
BLAST
Regioni215 – 400186Interaction with UNC13DAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 2 C2 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG247952.
GeneTreeiENSGT00760000119081.
HOGENOMiHOG000232127.
HOVERGENiHBG051388.
InParanoidiQ14183.
OMAiDYFPRLG.
PhylomeDBiQ14183.
TreeFamiTF351844.

Family and domain databases

Gene3Di2.60.40.150. 2 hits.
InterProiIPR000008. C2_dom.
IPR014638. Doc2.
IPR001565. Synaptotagmin.
[Graphical view]
PfamiPF00168. C2. 2 hits.
[Graphical view]
PIRSFiPIRSF036931. Doc2. 1 hit.
PRINTSiPR00360. C2DOMAIN.
PR00399. SYNAPTOTAGMN.
SMARTiSM00239. C2. 2 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 2 hits.
PROSITEiPS50004. C2. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti92 – 921T → K in BAA06695. (PubMed:7826360)Curated
Sequence conflicti108 – 1092CS → VC in BAA06695. (PubMed:7826360)Curated
Sequence conflicti238 – 2381E → D in BAA06695. (PubMed:7826360)Curated
Sequence conflicti376 – 3761P → R in BAA06695. (PubMed:7826360)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti48 – 481G → S.2 Publications
Corresponds to variant rs1140239 [ dbSNP | Ensembl ].
VAR_019656

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 118118Missing in isoform 2. 1 PublicationVSP_056977Add
BLAST
Alternative sequencei271 – 28111GILRCAHLAAM → PEARCGQEIQA in isoform 2. 1 PublicationVSP_056978Add
BLAST
Alternative sequencei282 – 400119Missing in isoform 2. 1 PublicationVSP_056979Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
PIRiJC2473.
RefSeqiNP_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.
XP_006721160.1. XM_006721097.1.
XP_006721161.1. XM_006721098.1.
UniGeneiHs.355281.

Genome annotation databases

EnsembliENST00000350119; ENSP00000340017; ENSG00000149927.
ENST00000564944; ENSP00000455196; ENSG00000149927.
ENST00000564979; ENSP00000455624; ENSG00000149927.
ENST00000616445; ENSP00000482870; ENSG00000149927.
GeneIDi8448.
KEGGihsa:8448.
UCSCiuc002dvn.3. human.

Polymorphism databases

DMDMi150421541.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS10666.1.
PIRi JC2473.
RefSeqi NP_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.
XP_006721160.1. XM_006721097.1.
XP_006721161.1. XM_006721098.1.
UniGenei Hs.355281.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4MJJ X-ray 2.00 A 81-217 [» ]
ProteinModelPortali Q14183.
SMRi Q14183. Positions 55-393.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114026. 8 interactions.
STRINGi 9606.ENSP00000340017.

PTM databases

PhosphoSitei Q14183.

Polymorphism databases

DMDMi 150421541.

Proteomic databases

MaxQBi Q14183.
PaxDbi Q14183.
PRIDEi Q14183.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000350119 ; ENSP00000340017 ; ENSG00000149927 .
ENST00000564944 ; ENSP00000455196 ; ENSG00000149927 .
ENST00000564979 ; ENSP00000455624 ; ENSG00000149927 .
ENST00000616445 ; ENSP00000482870 ; ENSG00000149927 .
GeneIDi 8448.
KEGGi hsa:8448.
UCSCi uc002dvn.3. human.

Organism-specific databases

CTDi 8448.
GeneCardsi GC16M030016.
H-InvDB HIX0012939.
HGNCi HGNC:2985. DOC2A.
MIMi 604567. gene.
neXtProti NX_Q14183.
PharmGKBi PA27451.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG247952.
GeneTreei ENSGT00760000119081.
HOGENOMi HOG000232127.
HOVERGENi HBG051388.
InParanoidi Q14183.
OMAi DYFPRLG.
PhylomeDBi Q14183.
TreeFami TF351844.

Miscellaneous databases

GeneWikii DOC2A.
GenomeRNAii 8448.
NextBioi 31610.
PROi Q14183.
SOURCEi Search...

Gene expression databases

Bgeei Q14183.
CleanExi HS_DOC2A.
ExpressionAtlasi Q14183. baseline.
Genevestigatori Q14183.

Family and domain databases

Gene3Di 2.60.40.150. 2 hits.
InterProi IPR000008. C2_dom.
IPR014638. Doc2.
IPR001565. Synaptotagmin.
[Graphical view ]
Pfami PF00168. C2. 2 hits.
[Graphical view ]
PIRSFi PIRSF036931. Doc2. 1 hit.
PRINTSi PR00360. C2DOMAIN.
PR00399. SYNAPTOTAGMN.
SMARTi SM00239. C2. 2 hits.
[Graphical view ]
SUPFAMi SSF49562. SSF49562. 2 hits.
PROSITEi PS50004. C2. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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] (ISOFORM 1), VARIANT SER-48, TISSUE SPECIFICITY.
    Tissue: Brain.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Cerebellum.
  3. "The sequence and analysis of duplication-rich human chromosome 16."
    Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
    , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
    Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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] (ISOFORM 1), VARIANT SER-48.
    Tissue: Brain and Mammary gland.
  5. "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.
  6. "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.
  7. "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.
  8. "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.

Entry informationi

Entry nameiDOC2A_HUMAN
AccessioniPrimary (citable) accession number: Q14183
Secondary accession number(s): B4DEJ2
, H3BNH6, Q6P4G4, Q7Z5G0, Q8IVX0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: June 26, 2007
Last modified: October 29, 2014
This is version 125 of the entry and version 5 of the sequence. [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
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3