UNC13_CAEEL
ID UNC13_CAEEL Reviewed; 2155 AA.
AC P27715; O17665; Q23512; Q7YSR2; Q867Z2; Q8I095;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2004, sequence version 4.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Phorbol ester/diacylglycerol-binding protein unc-13;
DE AltName: Full=Uncoordinated protein 13;
GN Name=unc-13; ORFNames=ZK524.2;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=Bristol N2;
RX PubMed=2062851; DOI=10.1073/pnas.88.13.5729;
RA Maruyama I.N., Brenner S.;
RT "A phorbol ester/diacylglycerol-binding protein encoded by the unc-13 gene
RT of Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:5729-5733(1991).
RN [2]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1/2/6/7 AND 3).
RC STRAIN=Bristol N2;
RX PubMed=11029047; DOI=10.1091/mbc.11.10.3441;
RA Kohn R.E., Duerr J.S., McManus J.R., Duke A., Rakow T.L., Maruyama H.,
RA Moulder G., Maruyama I.N., Barstead R.J., Rand J.B.;
RT "Expression of multiple UNC-13 proteins in the Caenorhabditis elegans
RT nervous system.";
RL Mol. Biol. Cell 11:3441-3452(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [4]
RP ZINC AND PHORBOL-ESTERS BINDING.
RX PubMed=1445255; DOI=10.1042/bj2870995;
RA Ahmed S., Maruyama I.N., Kozma R., Lee J., Brenner S., Lim L.;
RT "The Caenorhabditis elegans unc-13 gene product is a phospholipid-dependent
RT high-affinity phorbol ester receptor.";
RL Biochem. J. 287:995-999(1992).
RN [5]
RP FUNCTION.
RX PubMed=17891142; DOI=10.1038/nn1981;
RA Van Buskirk C., Sternberg P.W.;
RT "Epidermal growth factor signaling induces behavioral quiescence in
RT Caenorhabditis elegans.";
RL Nat. Neurosci. 10:1300-1307(2007).
RN [6]
RP INTERACTION WITH CMD-1.
RX PubMed=17854888; DOI=10.1016/j.ceca.2007.07.008;
RA Shen X., Valencia C.A., Gao W., Cotten S.W., Dong B., Huang B.C., Liu R.;
RT "Ca(2+)/Calmodulin-binding proteins from the C. elegans proteome.";
RL Cell Calcium 43:444-456(2008).
CC -!- FUNCTION: May form part of a signal transduction pathway, transducing
CC the signal from diacylglycerol to effector functions (PubMed:2062851).
CC One such function could be the release of neurotransmitter from neurons
CC (PubMed:2062851). Probably by regulating neuronal transmission
CC downstream of lin-3 and receptor lin-23 and phospholipase plc-3 and
CC upstream of innexin unc-7 and egl-4/PKG in ALA neurons, involved in the
CC decrease in pharyngeal pumping during the quiescent state that precedes
CC each larval molt, (PubMed:17891142). {ECO:0000269|PubMed:17891142,
CC ECO:0000269|PubMed:2062851}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with cmd-1 in the presence of Ca(2+).
CC {ECO:0000269|PubMed:17854888}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=6; Synonyms=d;
CC IsoId=P27715-6; Sequence=Displayed;
CC Name=1; Synonyms=a;
CC IsoId=P27715-1; Sequence=VSP_009726, VSP_009727;
CC Name=2;
CC IsoId=P27715-2; Sequence=VSP_009726, VSP_009728;
CC Name=3;
CC IsoId=P27715-3; Sequence=VSP_004485;
CC Name=5; Synonyms=c;
CC IsoId=P27715-5; Sequence=VSP_009724, VSP_009726;
CC Name=7; Synonyms=e;
CC IsoId=P27715-7; Sequence=VSP_009726;
CC -!- DOMAIN: The phorbol ester binding activity is zinc and calcium-
CC dependent.
CC -!- DISRUPTION PHENOTYPE: Worms exhibit diverse nervous system defects.
CC {ECO:0000269|PubMed:2062851}.
CC -!- SIMILARITY: Belongs to the unc-13 family. {ECO:0000305}.
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DR EMBL; M62830; AAA93094.1; -; mRNA.
DR EMBL; U50735; AAA99780.1; -; Genomic_DNA.
DR EMBL; U50735; AAA99781.1; -; Genomic_DNA.
DR EMBL; Z73912; CAA98147.1; -; Genomic_DNA.
DR EMBL; Z79694; CAA98147.1; JOINED; Genomic_DNA.
DR EMBL; Z92779; CAA98147.1; JOINED; Genomic_DNA.
DR EMBL; Z73912; CAD56619.2; -; Genomic_DNA.
DR EMBL; Z92779; CAD56619.2; JOINED; Genomic_DNA.
DR EMBL; Z73912; CAD90190.2; -; Genomic_DNA.
DR EMBL; Z79694; CAD90190.2; JOINED; Genomic_DNA.
DR EMBL; Z92779; CAD90190.2; JOINED; Genomic_DNA.
DR EMBL; Z73912; CAE11317.1; -; Genomic_DNA.
DR EMBL; Z79694; CAE11317.1; JOINED; Genomic_DNA.
DR EMBL; Z92779; CAE11317.1; JOINED; Genomic_DNA.
DR PIR; A41101; A41101.
DR PIR; T19295; T19295.
DR PIR; T27886; T27886.
DR RefSeq; NP_001021871.1; NM_001026700.1. [P27715-1]
DR RefSeq; NP_001021872.1; NM_001026701.1.
DR RefSeq; NP_001021873.1; NM_001026702.1. [P27715-6]
DR RefSeq; NP_001021874.1; NM_001026703.2. [P27715-7]
DR AlphaFoldDB; P27715; -.
DR SMR; P27715; -.
DR BioGRID; 37939; 9.
DR STRING; 6239.ZK524.2d; -.
DR TCDB; 1.F.1.1.3; the synaptosomal vesicle fusion pore (svf-pore) family.
DR EPD; P27715; -.
DR PaxDb; P27715; -.
DR PeptideAtlas; P27715; -.
DR PRIDE; P27715; -.
DR EnsemblMetazoa; ZK524.2a.1; ZK524.2a.1; WBGene00006752. [P27715-1]
DR EnsemblMetazoa; ZK524.2c.1; ZK524.2c.1; WBGene00006752. [P27715-5]
DR EnsemblMetazoa; ZK524.2d.1; ZK524.2d.1; WBGene00006752. [P27715-6]
DR EnsemblMetazoa; ZK524.2e.1; ZK524.2e.1; WBGene00006752. [P27715-7]
DR GeneID; 172497; -.
DR UCSC; ZK524.2e; c. elegans. [P27715-1]
DR CTD; 43841; -.
DR WormBase; ZK524.2a; CE15371; WBGene00006752; unc-13. [P27715-1]
DR WormBase; ZK524.2c; CE34624; WBGene00006752; unc-13. [P27715-5]
DR WormBase; ZK524.2d; CE34625; WBGene00006752; unc-13. [P27715-6]
DR WormBase; ZK524.2e; CE34626; WBGene00006752; unc-13. [P27715-7]
DR eggNOG; KOG1011; Eukaryota.
DR GeneTree; ENSGT00940000168389; -.
DR InParanoid; P27715; -.
DR OMA; QELWHNA; -.
DR OrthoDB; 117172at2759; -.
DR PhylomeDB; P27715; -.
DR Reactome; R-CEL-181429; Serotonin Neurotransmitter Release Cycle.
DR Reactome; R-CEL-181430; Norepinephrine Neurotransmitter Release Cycle.
DR Reactome; R-CEL-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-CEL-212676; Dopamine Neurotransmitter Release Cycle.
DR Reactome; R-CEL-264642; Acetylcholine Neurotransmitter Release Cycle.
DR PRO; PR:P27715; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00006752; Expressed in larva and 3 other tissues.
DR ExpressionAtlas; P27715; baseline and differential.
DR GO; GO:0031594; C:neuromuscular junction; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0048786; C:presynaptic active zone; IDA:WormBase.
DR GO; GO:0098831; C:presynaptic active zone cytoplasmic component; IBA:GO_Central.
DR GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IDA:WormBase.
DR GO; GO:0030672; C:synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0043195; C:terminal bouton; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0019992; F:diacylglycerol binding; IEA:InterPro.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0017075; F:syntaxin-1 binding; IBA:GO_Central.
DR GO; GO:0061789; P:dense core granule priming; IBA:GO_Central.
DR GO; GO:0007528; P:neuromuscular junction development; IBA:GO_Central.
DR GO; GO:0060282; P:positive regulation of oocyte development; IGI:UniProtKB.
DR GO; GO:0099525; P:presynaptic dense core vesicle exocytosis; IBA:GO_Central.
DR GO; GO:0046662; P:regulation of oviposition; IMP:WormBase.
DR GO; GO:0043051; P:regulation of pharyngeal pumping; IMP:WormBase.
DR GO; GO:0007283; P:spermatogenesis; IGI:UniProtKB.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IBA:GO_Central.
DR GO; GO:0016081; P:synaptic vesicle docking; IBA:GO_Central.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; IMP:WormBase.
DR GO; GO:0016188; P:synaptic vesicle maturation; IBA:GO_Central.
DR GO; GO:0016082; P:synaptic vesicle priming; IBA:GO_Central.
DR CDD; cd00029; C1; 1.
DR CDD; cd04027; C2B_Munc13; 1.
DR Gene3D; 2.60.40.150; -; 3.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR010439; MUN_dom.
DR InterPro; IPR014770; Munc13_1.
DR InterPro; IPR014772; Munc13_dom-2.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR027080; Unc-13.
DR InterPro; IPR037302; Unc-13_C2B.
DR PANTHER; PTHR10480; PTHR10480; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00168; C2; 3.
DR Pfam; PF06292; MUN; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00239; C2; 3.
DR SMART; SM01145; DUF1041; 1.
DR SUPFAM; SSF49562; SSF49562; 3.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50004; C2; 3.
DR PROSITE; PS51258; MHD1; 1.
DR PROSITE; PS51259; MHD2; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Calmodulin-binding; Metal-binding;
KW Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..2155
FT /note="Phorbol ester/diacylglycerol-binding protein unc-13"
FT /id="PRO_0000188583"
FT DOMAIN 1..114
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1140..1268
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1552..1695
FT /note="MHD1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00587"
FT DOMAIN 1798..1954
FT /note="MHD2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00588"
FT DOMAIN 1969..2097
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT ZN_FING 693..742
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 1034..1084
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 173..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 330..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..572
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 652..718
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 812..839
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..216
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 217..261
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 262..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 382..459
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 534..558
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 652..693
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1173
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1173
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1244
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT VAR_SEQ 1..341
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_009724"
FT VAR_SEQ 1..15
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_004485"
FT VAR_SEQ 609..947
FT /note="Missing (in isoform 1, isoform 2, isoform 5 and
FT isoform 7)"
FT /evidence="ECO:0000303|PubMed:2062851"
FT /id="VSP_009726"
FT VAR_SEQ 987..989
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000305"
FT /id="VSP_009727"
FT VAR_SEQ 1629..1647
FT /note="VDKADNFPQTSEHTKFSNS -> CRQADTSHKHQNTQILEH (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:2062851"
FT /id="VSP_009728"
FT CONFLICT 157
FT /note="I -> V (in Ref. 1; AAA93094)"
FT /evidence="ECO:0000305"
FT CONFLICT 1873
FT /note="I -> N (in Ref. 1; AAA93094)"
FT /evidence="ECO:0000305"
FT CONFLICT 1990
FT /note="V -> A (in Ref. 1; AAA93094)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2155 AA; 245231 MW; B660C5926F1D26A2 CRC64;
MDDVGDYNDD QLSDGMSMRL LCITIKKARL QGAVDEFNSY VTVKLQTVKS TTVAVRGNLP
CWEQEFIFET NRPDDGMVLE LWAKGVLWDK LIGVHYMPLS EIRYSNAAGS GQWLQMDHEL
ETRNGQTVGT RGPTGHNLLT DVRFELPFDV QGHDEDIQSR LLALNGLIEH DQLGPNNHHR
APFNHSGLSE DSDYTSDVSV PVNHHQLHPN SSAHQYESHL HPHRTRQLLH TREGAASYED
EEDAYHARHQ PESDDYNHQD TYDQHSSYYN DEYAPSGSSS QYQRQGYQDQ DQQHQNIYED
TVTPVREFGE SAVPPAASSS RRQFDQVYGY ASSSEERYDT PMSSGRLPRD EPILEHSEPE
YVYDQNGYPE EDNYGINPTY SEDHFEGQTN DYSTTHQEPN DFRNDYNSSY QREYWNESEP
LSYNSRPPNG HIRTGANTWR EPSTSSRPTS SQAWNYQDDT HQYDEVDRGS RVSFTRTPSV
DRTDRPSESG GGFYDEMSES GRPGRPDSHH NWRYDSIQEE DNEKDNWKQH VEGYEEGQEE
KQKDNQKPND HSAASPQDHY HRSDSTAQQD FGNNIVRQTI QEEEEKRNYQ ELWHNAYKRV
CADLGIKSSQ ASLVATTGGT LLQNLFLYRP KLAPAGHGAT ASQFQSPAGA TRFYANHNNN
NNNVSKNELD STTETPPDPS RTPSTSSMNP VPSLAVPMSP GPYLNSDPPS PVSPNPQIKR
SIYRIKESYE DRNGGRERIY TTNLVSVYLE KMKPPDELEE GSSGSMRETQ NEIKNGTQLH
NAESNIFFPQ DSVPKSISYN AGNLKNTSIT TSKTSSAITN HSSLPPQPPS KPASRDSDPM
KQLLTFSKSF KKVRRVRSAM PRRRKRKRVK IKKSRSCPIL WKTEKTPHPM KSKSMTCIRI
PKKTVIAPLR KEIKIVRMKP PAARCESDSK AHKKKNLLDV YKDMGKSTVL DGNGSSAANA
FYKSIDAAPN MNVARTKTSI PLVSELVLKT MATKRAQAGL ANAARTTFSD TELKTHVYKK
TLQALIYPIS ATTPHNFATT TFQTPTFCYE CEGLLWGLAR QGLRCTQCQV KVHDKCRELL
SADCLQRAAE KSTKHGEADR TQSLVNVIRD RMKIQEQNKP EVFQMIRTVF DVDENIQKET
LKTVKASILE GSSKWSAKIT LTVLCAQGLI AKDKTGKSDP YVTAQVGKTK RRTRTIHQEL
NPVWNEKFHF ECHNSTDRIK VRVWDEDNDL KSKLRQKLTR ESDDFLGQTV IEVRTLSGEM
DVWYNLEKRT DKSAVSGAIR LHINVEIKGE EKLAPYHVQY TCLHEHLFAA HCVDEEVKLP
KVRGEDSWKV CFQETGQEIA EEFAMRYGIE SIYQAMTHFA CLCTRYMCAG VPAVLSTLLA
NINAYYAHTT ATSAVSAPDR FAASNFGKER FVKLLDQLHN SLRIDLSAYR NHFPSSSPAK
LQDLKSTVDL LTSITFFRMK VLELASPPRA STVVRECAKA CMQQTYQLMF ESCAEQFPIL
DTSVQFWYEF IDYIMRVIEE DQKNYTPALN QFPQELNVGN LSAETLWSMY KNDLKMALEE
HAQKKRCKTP EYMNLYFKVK GFYFKYVADL STYKSSIPEF PAWFIPFVMD WLNENDEHSM
DILRNAYNVD KADNFPQTSE HTKFSNSVVD VFTQLNAALK LLKQMDCPNP EVAADMMKRF
SKTLNKVLLA YADMVQKDFP KFAHDEKLAC ILMNNVQQLR VQLEKIYETM GGAELDEHIG
QVLTVLQKKL NSVLDRLSAE FVTTLEPHIH EQTIKLGMLL VKIKGPQLQK TQVQPEADAV
LEPLMDLLEG SLRRYADQCE KTVLKYILKE LWKITIVNME KRVVLPPLSD KALLKQLPNA
KIGDVTKLMS TNIQSIKGMN SVKDMMDMAR ESEKSLTPRQ CTVLDCALDA IKDSFHASGK
GLKKSFFEKS PELQSLKYAL SLYTQTTEQL IKTFITSQRQ QDLPSQEQPV GEVSVQVDLF
SHPGTGEQKV TVKILAANDL RWQTSSAFKP FVEVHLVGPH LSDKKRKWST KTKAGNWAPK
FNETFHFFLG NEGEPEHYEL MFQVKDYCFA RDDRVVGVGV LQLSSVVDQA GSCAMWVQLG
TRLHIDETGL ILLRILSQRQ TDEVAKDFVR LKTECRYETE TVMAASASSQ NINRT
