Q62770

SS
Gene name
Unc13c (Unc13h3)
Protein name
Protein unc-13 homolog C
Names
Munc13-3
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:286931
EC number
Protein Class

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)

1088-1137 (C1 domain) SS

Target domain

1529-2018 (MUN domain)

Relief mechanism

Ligand binding

Assay

1193-1321 (C2B domain) SS

Target domain

1529-2018 (MUN domain)

Relief mechanism

Ligand binding

Assay

1322-1528 (C2B-MUN linker region) SS

Target domain

1529-2018 (MUN domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q62770

Entry ID Method Resolution Chain Position Source
AF-Q62770-F1 Predicted AlphaFoldDB

No variants for Q62770

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q62770

No associated diseases with Q62770

7 regional properties for Q62770

Type Name Position InterPro Accession
domain C2 domain 1193 - 1319 IPR000008-1
domain C2 domain 2032 - 2161 IPR000008-2
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 1087 - 1137 IPR002219
domain MUN domain 1529 - 2018 IPR010439
domain Munc13 homology 1 1627 - 1770 IPR014770
domain Mammalian uncoordinated homology 13, domain 2 1876 - 2018 IPR014772
domain Protein Unc-13, C2B domain 1210 - 1336 IPR037302

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Membrane ; Peripheral membrane protein
  • Presynaptic cell membrane ; Peripheral membrane protein
  • Localized to presynaptic structures
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 GO annotations of cellular component

Name Definition
calyx of Held The terminal specialization of a calyciferous axon which forms large synapses in the mammalian auditory central nervous system.
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.
parallel fiber to Purkinje cell synapse An excitatory synapse formed by the parallel fibers of granule cells synapsing onto the dendrites of Purkinje cells.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
presynapse The part of a synapse that is part of the presynaptic cell.
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.
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.

6 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 binding Binding to a syntaxin, a SNAP receptor involved in the docking of synaptic vesicles at the presynaptic zone of a synapse.
syntaxin-1 binding Binding to a syntaxin-1 SNAP receptor.

11 GO annotations of biological process

Name Definition
chemical synaptic transmission The vesicular release of classical neurotransmitter molecules from a presynapse, across a chemical synapse, the subsequent activation of neurotransmitter 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.
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.
negative regulation of synaptic plasticity A process that decreases synaptic plasticity, the ability of synapses to change as circumstances require. They may alter function, such as increasing or decreasing their sensitivity, or they may increase or decrease in actual numbers.
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.
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 neurotransmitter secretion Any process that modulates the frequency, rate or extent of the regulated release of a neurotransmitter from a cell.
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
O14795 UNC13B Protein unc-13 homolog B Homo sapiens (Human) SS
Q9UPW8 UNC13A Protein unc-13 homolog A Homo sapiens (Human) SS
Q8NB66 UNC13C Protein unc-13 homolog C Homo sapiens (Human) SS
Q4KUS2 Unc13a Protein unc-13 homolog A Mus musculus (Mouse) SS
Q9Z1N9 Unc13b Protein unc-13 homolog B Mus musculus (Mouse) SS
Q8K0T7 Unc13c Protein unc-13 homolog C Mus musculus (Mouse) SS
Q62768 Unc13a Protein unc-13 homolog A Rattus norvegicus (Rat) SS
Q62769 Unc13b Protein unc-13 homolog B Rattus norvegicus (Rat) SS
P27715 unc-13 Phorbol ester/diacylglycerol-binding protein unc-13 Caenorhabditis elegans EV
10 20 30 40 50 60
MVASLFKSLI LAYIHKLCKG MFTKKLGNTT KKKENRQQNK DQDFPTAGHT KPPKLSNALK
70 80 90 100 110 120
STVKKIAKCS STRNFSVEDE EGHKDFSLSP TFSYRVAIAN GLQTAVTNSD EDLLQELSSI
130 140 150 160 170 180
ESSYSESFNE LRSSTENQVQ STHTMPVRRN RKSSSSLAPS EGSSDGERTL HTLKLGALRK
190 200 210 220 230 240
LRKWKKSQEC VSSDSELSTV KKTWGIRSKS LDRTARNPKT NVLEPGFSSS GCISQTHDVM
250 260 270 280 290 300
EMIFKELQGI SQIETELSEL RGHVNALKYS IDEISSSVEV VQSEIEQLRT GFVQARRETR
310 320 330 340 350 360
DIHDYIKHLG HMGSKVSLRF LNVPEERHEY VESVVYQILV DKMGFSDVPN AIKIEFAQRI
370 380 390 400 410 420
GQQRDCPNAK PRPILVYFET PQQRDSVLKK SYKLKGTGIA ISTDILTYDI RERKEKGVLP
430 440 450 460 470 480
SSQTYESMDM KLSTPEPKAK KNAWLSPNDS DRELESDLSR SSYADSPAKG SSSKSSSKSH
490 500 510 520 530 540
SARSKNKAAN SRTSQKSDYN KRPSKPPASE KPTPHYVEAT PLWHSQSDFF TPKLSRSESD
550 560 570 580 590 600
FSKLCQSYSE DFSESQFFCR TNGSSLLSSS DRELWQRKQE GMTALYHSPQ DQGLDGNIPT
610 620 630 640 650 660
VPGQGEIENT ETVDSGMSNS VVCASGDRSN YSGSQLSLHE DLSPWKEWNQ AGHGTDGLDS
670 680 690 700 710 720
STQEPFDYDT NSLSDQQLDM SSKDLDDLGK CHSDLQDDSE SYDLTQDDNS SPCPGLDNEP
730 740 750 760 770 780
QGQWVGQYDS YQKTNSNDLY PNQSHPSMMY RSQSELQSDD SEAAQPKSWH SRLSIDLSDK
790 800 810 820 830 840
TFKFPKFGST LQRAKSALEV VWNKSTQSLS GCEDSGSSLM GRFRTLSQST ANESSTTLDS
850 860 870 880 890 900
DIYTEPYYYK AEEEEDYCEP VADSETDYVE VMEQVLAKLE NRTSVTEVDE HIKEYDHPSY
910 920 930 940 950 960
ETPYETPQDE GYDGQADDII SEGELETLNE PAVEMELVED ESQNLPVEPP EVMKPKRIRP
970 980 990 1000 1010 1020
SFKEAALRAY KKQMAELEEK ILAGDSSSVD EKARIVSGND LDASKFSALQ VFGGAGRGLY
1030 1040 1050 1060 1070 1080
GIDSMPDLRR KKTLPIVRDV AMTLAARKSG LSLAMVIRTS LNNEELKMHV FRKTLQALIY
1090 1100 1110 1120 1130 1140
PISSTTPHNF EVWTATTPTY CYECEGLLWG IARQGMKCLE CGVKCHEKCQ DLLNADCLQR
1150 1160 1170 1180 1190 1200
AAEKSSKHGA EDKTQTIITA MKERMKIRER NRPEVFEVIQ EMFQISKEDF VQYTKAAKQS
1210 1220 1230 1240 1250 1260
VLDGTSKWSA KITITVVSAQ GLQAKDKTGS SDPYVTVQVG KNKRRTKTIF GNLNPVWDEK
1270 1280 1290 1300 1310 1320
FYFECHNSTD RIKVRVWDED DDIKSRVKQH FKKESDDFLG QTIVEVRTLS GEMDVWYNLE
1330 1340 1350 1360 1370 1380
KRTDKSAVSG AIRLKINVEI KGEEKVAPYH IQYTCLHENL FHYLTEVKSN GSVKIPEVKG
1390 1400 1410 1420 1430 1440
DEAWKVFFDD ASQEIVDEFA MRYGVESIYQ AMTHFSCLSS KYMCPGVPAV MSALLANINA
1450 1460 1470 1480 1490 1500
FYAHTTVSTN VQVSASDRFA ATNFGREKFI KLLDQLHNSL RIDLSKYREN FPASNSERLQ
1510 1520 1530 1540 1550 1560
DLKSTVDLLT SITFFRMKVL ELQSPPKASA VVKDCVRACL DSTYKYIFDN CHELYSQLID
1570 1580 1590 1600 1610 1620
PSKKQDVPRE EQGPTTKNLD FWPQLITLMV TIIDEDKTAY TPVLNQFPQE LNMGKISAEI
1630 1640 1650 1660 1670 1680
MWSLFALDMK YALEEHEKQR LCKSTDYMNL HFKVKWFYNE YVRELPAFKD AVPEYSLWFE
1690 1700 1710 1720 1730 1740
PFVMQWLDEN EDVSMEFLHG ALGRDKKDGF QQTSDHALFS CSVVDVFAQL NQSFEIIKKL
1750 1760 1770 1780 1790 1800
ECPNPEALSH LMRRFAKTIN KVLVQYAAIV SSDFSSYCDK ETVPCILMNN IQQLRVQLEK
1810 1820 1830 1840 1850 1860
MFESMGGKEL DPEASTILKE LQIKLNGVLD ALSVTYGESF QLVIEECIKQ MGAELNQMRA
1870 1880 1890 1900 1910 1920
NGNSAANKNN AAMDAEIVLR PLMDFLDKIL SLSAKICEKT VLKRVLKELW KLVLNKIEKQ
1930 1940 1950 1960 1970 1980
IVLPPLTDQT GPQMIFIAAK ELGQLSKLKE HMIRDDAKGL TPRQCAIMEV VLATIKQYFH
1990 2000 2010 2020 2030 2040
AGGNGLKKNF LEKSPDLHSL RYALSLYTQT TDALIKKFIE TQGSQSRSSK DAVGQISVHV
2050 2060 2070 2080 2090 2100
DVTTTPGTGE HKVTVKVIAI NDLNWQTTTM FRPFVEVCML GPSLGDKKRK QGTKTKSNTW
2110 2120 2130 2140 2150 2160
SPKYNETFQF ILGNENRPGA YELHLSVKDY CFAREDRIIG MTVIQLQNIA EKGSYGAWYP
2170 2180 2190 2200
LLKNLSMDET GLTILRILSQ RTSDDVAKEF VRLKSETRSI DESA