P27715

EV
Gene name
unc-13 (ZK524.2)
Protein name
Phorbol ester/diacylglycerol-binding protein unc-13
Names
Uncoordinated protein 13
Species
Caenorhabditis elegans
KEGG Pathway
EC number
Protein Class
PROTEIN UNC-13 HOMOLOG (PTHR10480)

Descriptions

Unc13, a phorbol ester/diacylglycerol-binding protein, is a synaptic hub protein required for fast chemical synaptic transmission by directly regulating SNAREs, and its Syntaxin-interacting MUN domain is essential for Unc13 function. The C1-C2B domain N-terminally adjacent to the MUN domain inhibits Unc13 function by tightly coupled to the MUN domain, which is disinhibited by diacylglycerol (DAG) or calcium binding. The disinhibition step allows for the superpriming of synaptic vesicles. Also, the addition of flexibility to the linker between the C2B and MUN domains relieves the autoinhibited state.

Autoinhibitory domains (AIDs)

1035-1084 (C1 domain) EV

Target domain

1471-1954 (MUN domain)

Relief mechanism

Ligand binding

Assay

Deletion assay

1140-1268 (C2B domain) EV

Target domain

1471-1954 (MUN domain)

Relief mechanism

Ligand binding

Assay

Deletion assay, Mutagenesis experiment

1269-1470 (C2B-MUN linker region) EV

Target domain

1471-1954 (MUN domain)

Relief mechanism

Ligand binding

Assay

Mutagenesis experiment

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for P27715

Entry ID Method Resolution Chain Position Source
AF-P27715-F1 Predicted AlphaFoldDB

No variants for P27715

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P27715

No associated diseases with P27715

15 regional properties for P27715

Type Name Position InterPro Accession
domain Protein kinase domain 593 - 954 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 594 - 948 IPR001245
conserved_site Tyrosine-protein kinase, receptor class III, conserved site 652 - 665 IPR001824
domain Immunoglobulin subtype 34 - 122 IPR003599-1
domain Immunoglobulin subtype 135 - 206 IPR003599-2
domain Immunoglobulin subtype 220 - 310 IPR003599-3
domain Immunoglobulin subtype 322 - 414 IPR003599-4
domain Immunoglobulin-like domain 1 - 113 IPR007110-1
domain Immunoglobulin-like domain 228 - 306 IPR007110-2
domain Immunoglobulin-like domain 319 - 410 IPR007110-3
active_site Tyrosine-protein kinase, active site 814 - 826 IPR008266
domain Immunoglobulin I-set 221 - 306 IPR013098-1
domain Immunoglobulin I-set 330 - 409 IPR013098-2
binding_site Protein kinase, ATP binding site 599 - 627 IPR017441
domain Tyrosine-protein kinase, catalytic domain 593 - 950 IPR020635

Functions

Description
EC Number
Subcellular Localization
PANTHER Family PTHR10480 PROTEIN UNC-13 HOMOLOG
PANTHER Subfamily PTHR10480:SF12 UNC-13, ISOFORM E
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

8 GO annotations of cellular component

Name Definition
neuromuscular junction The junction between the axon of a motor neuron and a muscle fiber. In response to the arrival of action potentials, the presynaptic button releases molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane of the muscle fiber, leading to a change in post-synaptic potential.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
presynaptic active zone A specialized region of the plasma membrane and cell cortex of a presynaptic neuron; encompasses a region of the plasma membrane where synaptic vesicles dock and fuse, and a specialized cortical cytoskeletal matrix.
presynaptic active zone cytoplasmic component A specialized region below the presynaptic membrane, characterized by electron-dense material, a specialized cytoskeletal matrix and accumulated (associated) synaptic vesicles.
presynaptic membrane A specialized area of membrane of the axon terminal that faces the plasma membrane of the neuron or muscle fiber with which the axon terminal establishes a synaptic junction; many synaptic junctions exhibit structural presynaptic characteristics, such as conical, electron-dense internal protrusions, that distinguish it from the remainder of the axon plasma membrane.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.
synaptic vesicle membrane The lipid bilayer surrounding a synaptic vesicle.
terminal bouton Terminal inflated portion of the axon, containing the specialized apparatus necessary to release neurotransmitters. The axon terminus is considered to be the whole region of thickening and the terminal bouton is a specialized region of it.

5 GO annotations of molecular function

Name Definition
calcium ion binding Binding to a calcium ion (Ca2+).
calmodulin binding Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states.
diacylglycerol binding Binding to a diacylglycerol, a diester of glycerol and two fatty acids.
phospholipid binding Binding to a phospholipid, a class of lipids containing phosphoric acid as a mono- or diester.
syntaxin-1 binding Binding to a syntaxin-1 SNAP receptor.

12 GO annotations of biological process

Name Definition
dense core granule priming A process that converts unprimed dense core granules (DCVs) to a pool of primed vesicles that are capable of fusing with the plasma membrane (fusion-competent) and thereby releasing their contents. Priming typically occurs after docking.
neuromuscular junction development A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a neuromuscular junction.
positive regulation of oocyte development Any process that increases the rate or extent of the process whose specific outcome is the progression of an oocyte over time, from initial commitment of the cell to its specific fate, to the fully functional differentiated cell.
presynaptic dense core vesicle exocytosis The secretion of molecules (e.g. neuropeptides and neuromodulators such as serotonin and dopamine) contained within a membrane-bounced dense in response to increased presynaptic cytosolic calcium levels.
regulation of egg-laying behavior Any process that modulates the frequency, rate or extent of the deposition of eggs, either fertilized or not, upon a surface or into a medium.
regulation of pharyngeal pumping Any process that modulates the contraction and relaxation movements of the pharyngeal muscle that mediates feeding in nematodes.
spermatogenesis The developmental process by which male germ line stem cells self renew or give rise to successive cell types resulting in the development of a spermatozoa.
synaptic transmission, glutamatergic The vesicular release of glutamate from a presynapse, across a chemical synapse, the subsequent activation of glutamate receptors at the postsynapse of a target cell (neuron, muscle, or secretory cell) and the effects of this activation on the postsynaptic membrane potential and ionic composition of the postsynaptic cytosol. This process encompasses both spontaneous and evoked release of neurotransmitter and all parts of synaptic vesicle exocytosis. Evoked transmission starts with the arrival of an action potential at the presynapse.
synaptic vesicle docking The initial (indirect) attachment of a synaptic vesicle membrane to the presynaptic active zone membrane, mediated by proteins protruding from the membrane and proteins of the presynaptic active zone cytoplasmic component. Synaptic vesicle tethering is the first step in this process.
synaptic vesicle exocytosis Fusion of intracellular membrane-bounded vesicles with the pre-synaptic membrane of the neuronal cell resulting in release of neurotransmitter into the synaptic cleft.
synaptic vesicle maturation Steps required to form an initiated synaptic vesicle into a fully formed and transmissible synaptic vesicle.
synaptic vesicle priming A process that converts synaptic vesicles to a state of competence for calcium triggered fusion with the active zone membrane by bringing the two membranes into very close proximity. Priming typically (but not always) occurs after docking (Jahn and Fasshauer, 2012). Primed vesicles are also capable of spontaneously fusing with the active zone membrane.

9 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q9UPW8 UNC13A Protein unc-13 homolog A Homo sapiens (Human) SS
Q8NB66 UNC13C Protein unc-13 homolog C Homo sapiens (Human) SS
O14795 UNC13B Protein unc-13 homolog B Homo sapiens (Human) SS
Q9Z1N9 Unc13b Protein unc-13 homolog B Mus musculus (Mouse) SS
Q8K0T7 Unc13c Protein unc-13 homolog C Mus musculus (Mouse) SS
Q4KUS2 Unc13a Protein unc-13 homolog A Mus musculus (Mouse) SS
Q62768 Unc13a Protein unc-13 homolog A Rattus norvegicus (Rat) SS
Q62770 Unc13c Protein unc-13 homolog C Rattus norvegicus (Rat) SS
Q62769 Unc13b Protein unc-13 homolog B Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MDDVGDYNDD QLSDGMSMRL LCITIKKARL QGAVDEFNSY VTVKLQTVKS TTVAVRGNLP
70 80 90 100 110 120
CWEQEFIFET NRPDDGMVLE LWAKGVLWDK LIGVHYMPLS EIRYSNAAGS GQWLQMDHEL
130 140 150 160 170 180
ETRNGQTVGT RGPTGHNLLT DVRFELPFDV QGHDEDIQSR LLALNGLIEH DQLGPNNHHR
190 200 210 220 230 240
APFNHSGLSE DSDYTSDVSV PVNHHQLHPN SSAHQYESHL HPHRTRQLLH TREGAASYED
250 260 270 280 290 300
EEDAYHARHQ PESDDYNHQD TYDQHSSYYN DEYAPSGSSS QYQRQGYQDQ DQQHQNIYED
310 320 330 340 350 360
TVTPVREFGE SAVPPAASSS RRQFDQVYGY ASSSEERYDT PMSSGRLPRD EPILEHSEPE
370 380 390 400 410 420
YVYDQNGYPE EDNYGINPTY SEDHFEGQTN DYSTTHQEPN DFRNDYNSSY QREYWNESEP
430 440 450 460 470 480
LSYNSRPPNG HIRTGANTWR EPSTSSRPTS SQAWNYQDDT HQYDEVDRGS RVSFTRTPSV
490 500 510 520 530 540
DRTDRPSESG GGFYDEMSES GRPGRPDSHH NWRYDSIQEE DNEKDNWKQH VEGYEEGQEE
550 560 570 580 590 600
KQKDNQKPND HSAASPQDHY HRSDSTAQQD FGNNIVRQTI QEEEEKRNYQ ELWHNAYKRV
610 620 630 640 650 660
CADLGIKSSQ ASLVATTGGT LLQNLFLYRP KLAPAGHGAT ASQFQSPAGA TRFYANHNNN
670 680 690 700 710 720
NNNVSKNELD STTETPPDPS RTPSTSSMNP VPSLAVPMSP GPYLNSDPPS PVSPNPQIKR
730 740 750 760 770 780
SIYRIKESYE DRNGGRERIY TTNLVSVYLE KMKPPDELEE GSSGSMRETQ NEIKNGTQLH
790 800 810 820 830 840
NAESNIFFPQ DSVPKSISYN AGNLKNTSIT TSKTSSAITN HSSLPPQPPS KPASRDSDPM
850 860 870 880 890 900
KQLLTFSKSF KKVRRVRSAM PRRRKRKRVK IKKSRSCPIL WKTEKTPHPM KSKSMTCIRI
910 920 930 940 950 960
PKKTVIAPLR KEIKIVRMKP PAARCESDSK AHKKKNLLDV YKDMGKSTVL DGNGSSAANA
970 980 990 1000 1010 1020
FYKSIDAAPN MNVARTKTSI PLVSELVLKT MATKRAQAGL ANAARTTFSD TELKTHVYKK
1030 1040 1050 1060 1070 1080
TLQALIYPIS ATTPHNFATT TFQTPTFCYE CEGLLWGLAR QGLRCTQCQV KVHDKCRELL
1090 1100 1110 1120 1130 1140
SADCLQRAAE KSTKHGEADR TQSLVNVIRD RMKIQEQNKP EVFQMIRTVF DVDENIQKET
1150 1160 1170 1180 1190 1200
LKTVKASILE GSSKWSAKIT LTVLCAQGLI AKDKTGKSDP YVTAQVGKTK RRTRTIHQEL
1210 1220 1230 1240 1250 1260
NPVWNEKFHF ECHNSTDRIK VRVWDEDNDL KSKLRQKLTR ESDDFLGQTV IEVRTLSGEM
1270 1280 1290 1300 1310 1320
DVWYNLEKRT DKSAVSGAIR LHINVEIKGE EKLAPYHVQY TCLHEHLFAA HCVDEEVKLP
1330 1340 1350 1360 1370 1380
KVRGEDSWKV CFQETGQEIA EEFAMRYGIE SIYQAMTHFA CLCTRYMCAG VPAVLSTLLA
1390 1400 1410 1420 1430 1440
NINAYYAHTT ATSAVSAPDR FAASNFGKER FVKLLDQLHN SLRIDLSAYR NHFPSSSPAK
1450 1460 1470 1480 1490 1500
LQDLKSTVDL LTSITFFRMK VLELASPPRA STVVRECAKA CMQQTYQLMF ESCAEQFPIL
1510 1520 1530 1540 1550 1560
DTSVQFWYEF IDYIMRVIEE DQKNYTPALN QFPQELNVGN LSAETLWSMY KNDLKMALEE
1570 1580 1590 1600 1610 1620
HAQKKRCKTP EYMNLYFKVK GFYFKYVADL STYKSSIPEF PAWFIPFVMD WLNENDEHSM
1630 1640 1650 1660 1670 1680
DILRNAYNVD KADNFPQTSE HTKFSNSVVD VFTQLNAALK LLKQMDCPNP EVAADMMKRF
1690 1700 1710 1720 1730 1740
SKTLNKVLLA YADMVQKDFP KFAHDEKLAC ILMNNVQQLR VQLEKIYETM GGAELDEHIG
1750 1760 1770 1780 1790 1800
QVLTVLQKKL NSVLDRLSAE FVTTLEPHIH EQTIKLGMLL VKIKGPQLQK TQVQPEADAV
1810 1820 1830 1840 1850 1860
LEPLMDLLEG SLRRYADQCE KTVLKYILKE LWKITIVNME KRVVLPPLSD KALLKQLPNA
1870 1880 1890 1900 1910 1920
KIGDVTKLMS TNIQSIKGMN SVKDMMDMAR ESEKSLTPRQ CTVLDCALDA IKDSFHASGK
1930 1940 1950 1960 1970 1980
GLKKSFFEKS PELQSLKYAL SLYTQTTEQL IKTFITSQRQ QDLPSQEQPV GEVSVQVDLF
1990 2000 2010 2020 2030 2040
SHPGTGEQKV TVKILAANDL RWQTSSAFKP FVEVHLVGPH LSDKKRKWST KTKAGNWAPK
2050 2060 2070 2080 2090 2100
FNETFHFFLG NEGEPEHYEL MFQVKDYCFA RDDRVVGVGV LQLSSVVDQA GSCAMWVQLG
2110 2120 2130 2140 2150
TRLHIDETGL ILLRILSQRQ TDEVAKDFVR LKTECRYETE TVMAASASSQ NINRT