Q62769
SS
Gene name |
Unc13b (Unc13h2) |
Protein name |
Protein unc-13 homolog B |
Names |
Munc13-2 |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:64830 |
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)
Target domain |
930-1417 (MUN domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Target domain |
930-1417 (MUN domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Target domain |
930-1417 (MUN domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for Q62769
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q62769-F1 | Predicted | AlphaFoldDB |
No variants for Q62769
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q62769 | |||||
No associated diseases with Q62769
8 regional properties for Q62769
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | C2 domain | 1 - 97 | IPR000008-1 |
| domain | C2 domain | 596 - 722 | IPR000008-2 |
| domain | C2 domain | 1450 - 1579 | IPR000008-3 |
| domain | Protein kinase C-like, phorbol ester/diacylglycerol-binding domain | 490 - 540 | IPR002219 |
| domain | MUN domain | 930 - 1417 | IPR010439 |
| domain | Munc13 homology 1 | 1025 - 1168 | IPR014770 |
| domain | Mammalian uncoordinated homology 13, domain 2 | 1275 - 1417 | IPR014772 |
| domain | Protein Unc-13, C2B domain | 613 - 739 | IPR037302 |
Functions
18 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. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| early phagosome | A membrane-bounded intracellular vesicle as initially formed upon the ingestion of particulate material by phagocytosis. |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| Golgi apparatus | A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways. |
| hippocampal mossy fiber to CA3 synapse | One of the giant synapses that form between the mossy fiber axons of dentate gyrus granule cells and the large complex spines of CA3 pyramidal cells. It consists of a giant bouton known as the mossy fiber expansion, synapsed to the complex, multiheaded spine (thorny excresence) of a CA3 pyramidal cell. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. |
| 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. |
| presynapse | The part of a synapse that is part of the presynaptic cell. |
| 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. |
| ribbon synapse | Type of synapse characterized by an electron-dense ribbon, lamella (bar) or spherical body in the presynaptic process cytoplasm. |
| 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 membrane | A specialized area of membrane on either the presynaptic or the postsynaptic side of a synapse, the junction between a nerve fiber of one neuron and another neuron or muscle fiber or glial cell. |
| 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. |
7 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. |
| GTP-dependent protein binding | Binding to a protein or protein complex when at least one of the interacting partners is in the GTP-bound state. |
| 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. |
24 GO annotations of biological process
| Name | Definition |
|---|---|
| acrosomal vesicle exocytosis | The calcium ion regulated exocytosis which results in fusion of the acrosomal vesicle with the plasma membrane of the sperm as part of the acrosome reaction. |
| cellular response to glucose stimulus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucose stimulus. |
| 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. |
| innervation | The process in which a nerve invades a tissue and makes functional synaptic connection within the tissue. |
| 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. |
| neuronal dense core vesicle exocytosis | The secretion of molecules (e.g. neuropeptides, insulin-related peptides or neuromodulators such as serotonin and dopamine) contained within a neuronal dense core vesicle by fusion of the granule with the plasma membrane of a neuron in response to increased cytosolic calcium levels. |
| phagosome maturation | A process that is carried out at the cellular level which results in the arrangement of constituent parts of a phagosome within a cell. Phagosome maturation begins with endocytosis and formation of the early phagosome and ends with the formation of the hybrid organelle, the phagolysosome. |
| positive regulation of apoptotic process | Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process. |
| positive regulation of defense response to bacterium | Any process that activates or increases the frequency, rate or extent of defense response to bacterium. |
| positive regulation of exocytosis | Any process that activates or increases the frequency, rate or extent of exocytosis. |
| positive regulation of inhibitory postsynaptic potential | Any process that activates or increases the frequency, rate or extent of inhibitory postsynaptic potential (IPSP). IPSP is a temporary decrease in postsynaptic membrane potential due to the flow of negatively charged ions into the postsynaptic cell. The flow of ions that causes an IPSP is an inhibitory postsynaptic current (IPSC) and makes it more difficult for the neuron to fire an action potential. |
| positive regulation of protein secretion | Any process that activates or increases the frequency, rate or extent of the controlled release of a protein from a cell. |
| positive regulation of synaptic vesicle priming | Any process that increases the frequency, rate or extent of synaptic vesicle priming. Synaptic vesicle priming is the formation of SNARE-containing complexes, bringing synaptic vesicle membrane and plasma membranes into close proximity and thereby facilitating membrane fusion. |
| 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 presynaptic dense core granule exocytosis | Any process that modulates the frequency, rate or extent of presynaptic dense core granule exocytosis. |
| regulation of short-term neuronal synaptic plasticity | A process that modulates short-term neuronal synaptic plasticity, the ability of neuronal synapses to change in the short-term as circumstances require. Short-term neuronal synaptic plasticity generally involves increasing or decreasing synaptic sensitivity. |
| spontaneous neurotransmitter secretion | Neurotransmitter secretion that occurs in the absence of the action of a secretagogue or a presynaptic action potential. |
| 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 |
|---|---|---|---|---|
| Q8NB66 | UNC13C | Protein unc-13 homolog C | Homo sapiens (Human) | SS |
| Q9UPW8 | UNC13A | Protein unc-13 homolog A | Homo sapiens (Human) | SS |
| O14795 | UNC13B | Protein unc-13 homolog B | Homo sapiens (Human) | SS |
| Q4KUS2 | Unc13a | Protein unc-13 homolog A | Mus musculus (Mouse) | SS |
| Q8K0T7 | Unc13c | Protein unc-13 homolog C | Mus musculus (Mouse) | SS |
| Q9Z1N9 | Unc13b | Protein unc-13 homolog B | 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 |
| P27715 | unc-13 | Phorbol ester/diacylglycerol-binding protein unc-13 | Caenorhabditis elegans | EV |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSLLCVRVKR | AKFQGSPDKF | NTYVTLKVQN | VKSTTVAVRG | DQPSWEQDFM | FEISRLDLGL |
| 70 | 80 | 90 | 100 | 110 | 120 |
| SVEVWNKGLI | WDTMVGTVWI | ALKTIRQSDE | EGPGEWSTLE | AETLMKNDEI | CGTKNPTPHK |
| 130 | 140 | 150 | 160 | 170 | 180 |
| ILLGTRFELP | FDIPEEEARY | WTYKLEQINA | LADDNEYSSQ | EESQRKLLPT | AAAQCRHWTY |
| 190 | 200 | 210 | 220 | 230 | 240 |
| LGWGEHQTFE | DPDSAVDDRD | SDYRSETSNS | APPPYHTTTQ | PNASAHQFPM | PVPLPQQLFL |
| 250 | 260 | 270 | 280 | 290 | 300 |
| QGSSRDSCND | SMQSYDLDYP | ERRALSPTSS | SRYGSSCNVS | RGSSLLSELD | QYHEQDDDGR |
| 310 | 320 | 330 | 340 | 350 | 360 |
| ERDSIHSSHS | YGSLSRDGQA | GLGEQEKALE | VACESQKEKT | GESKERDDAT | VCPPSDLMLH |
| 370 | 380 | 390 | 400 | 410 | 420 |
| KDLTLGPQES | FPEEKASSPF | TQARAHWFRA | VTKVRLQLQE | ISDDGDPSLP | QWLPEGPAGG |
| 430 | 440 | 450 | 460 | 470 | 480 |
| LYGIDSMPDL | RRKKPLPLVS | DLAMSLVQSR | KAGITSAMAT | RTSLKDEDLK | SHVYKKTLQA |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LIYPISCTTP | HNFEVWSATT | PTYCYECEGL | LWGLARQGMR | CSECGVKCHE | KCQDLLNADC |
| 550 | 560 | 570 | 580 | 590 | 600 |
| LQRAAEKSSK | HGAEDRTQNI | IMAMKDRMKI | RERNKPEIFE | VIRDVFTVSK | VAHVQQMKTV |
| 610 | 620 | 630 | 640 | 650 | 660 |
| KQSVLDGTSK | WSAKITITVV | CAQGLQAKDK | TGSSDPYVTV | QVGKTKKRTK | TIFGNLNPVW |
| 670 | 680 | 690 | 700 | 710 | 720 |
| EEKFHFECHN | SSDRIKVRVW | DEDDDIKSRV | KQRLKRESDD | FLGQTIIEVR | TLSGEMDVWY |
| 730 | 740 | 750 | 760 | 770 | 780 |
| NLEKRTDKSA | VSGAIRLQIN | VEIKGEEKVA | PYHVQYTCLH | ENLFHYLTDI | QGSGGVWIPD |
| 790 | 800 | 810 | 820 | 830 | 840 |
| ARGDDAWKVY | FDETAQEIVD | EFAMRYGIES | IYQAMTHFAC | LSSKYMCPGV | PAVMSTLLAN |
| 850 | 860 | 870 | 880 | 890 | 900 |
| INAYYAHTTA | STNVSASDRF | AASNFGKERF | VKLLDQLHNS | LRIDLSTYRN | NFPAGSPERL |
| 910 | 920 | 930 | 940 | 950 | 960 |
| QDLKSTVDLL | TSITFFRMKV | QELQSPPRAS | QVVKDCVKAC | LNSTYEYIFN | NCHDLYSHQY |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| QLQEQPLEEP | GPSIRNLDFW | PKLITLIVSI | IEEDKNSYTP | VLNQFPQELN | VGKVSAEVMW |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| HLFAQDMKYA | LEEHEKDRLC | KSADYMNLHF | KVKWLHNEYV | RELPALQGQV | PEYPAWFEQF |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| VLQWLDENED | VSLEFLRGGL | ERDKRDGFQQ | TSEHALFSCS | VVDVFTQLNQ | SFEIIRKLEC |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| PDPSILAHYM | RRFAKTIGKV | LIQYADILSK | NFPAYCTKER | LPCILMNNMQ | QLRVQLEKMF |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| EAMGGKELDS | EAADSLKELQ | VKLNTVLDEL | SMVFGNSFQV | RIDECVRQMA | DILGQVRGTG |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| NASPNARASV | AQDADSVLRP | LMDFLDGNLT | LFATVCEKTV | LKRVLKELWR | VVMNTMERVI |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| VLPPLIDQTG | TQLILTAAKE | LSQLSKLKDH | MVREETRNLT | PKQCAVLDLA | LDTVKQYFHA |
| 1390 | 1400 | 1410 | 1420 | 1430 | 1440 |
| GGNGLKKTFL | EKSPDLQSLR | YALSLYTQTT | DTLIKTFVRS | QTAQVHDGKG | IRFTANEDIR |
| 1450 | 1460 | 1470 | 1480 | 1490 | 1500 |
| PEKGAGVDDP | VGEVSIQVDL | FTHPGTGEHK | VTVKVVAAND | LKWQTAGMFR | PFVEVTMVGP |
| 1510 | 1520 | 1530 | 1540 | 1550 | 1560 |
| HQSDKKRKFT | TKSKSNSWTP | KYNETFHFLL | GNEEGPEAYE | LQICVKDYCF | AREDRVIGLA |
| 1570 | 1580 | 1590 | 1600 | 1610 | 1620 |
| VMPLRDVAAK | GSCACWCPLG | RKIHMDETGM | TILRILSQRS | NDEVAREFVK | LKSESRSIEE |
| GS |