ID UN13B_RAT Reviewed; 1622 AA.
AC Q62769; Q9WV40;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 27-MAR-2024, entry version 162.
DE RecName: Full=Protein unc-13 homolog B {ECO:0000305};
DE AltName: Full=Munc13-2;
GN Name=Unc13b {ECO:0000312|RGD:619723}; Synonyms=Unc13h2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=7559667; DOI=10.1074/jbc.270.42.25273;
RA Brose N., Hofmann K., Hata Y., Suedhof T.C.;
RT "Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel
RT family of C2-domain proteins.";
RL J. Biol. Chem. 270:25273-25280(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INTERACTION
RP WITH RIMS1.
RC STRAIN=Sprague-Dawley;
RX PubMed=11343654; DOI=10.1016/s0896-6273(01)00272-0;
RA Betz A., Thakur P., Junge H.J., Ashery U., Rhee J.S., Scheuss V.,
RA Rosenmund C., Rettig J., Brose N.;
RT "Functional interaction of the active zone proteins Munc13-1 and RIM1 in
RT synaptic vesicle priming.";
RL Neuron 30:183-196(2001).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=9697857; DOI=10.1016/s0896-6273(00)80520-6;
RA Betz A., Ashery U., Rickmann M., Augustin I., Neher E., Suedhof T.C.,
RA Rettig J., Brose N.;
RT "Munc13-1 is a presynaptic phorbol ester receptor that enhances
RT neurotransmitter release.";
RL Neuron 21:123-136(1998).
RN [4]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9895278; DOI=10.1042/bj3370363;
RA Augustin I., Betz A., Herrmann C., Jo T., Brose N.;
RT "Differential expression of two novel Munc13 proteins in rat brain.";
RL Biochem. J. 337:363-371(1999).
CC -!- FUNCTION: Plays a role in vesicle maturation during exocytosis as a
CC target of the diacylglycerol second messenger pathway. Is involved in
CC neurotransmitter release by acting in synaptic vesicle priming prior to
CC vesicle fusion and participates in the activity-depending refilling of
CC readily releasable vesicle pool (RRP) (By similarity). Essential for
CC synaptic vesicle maturation in a subset of excitatory/glutamatergic but
CC not inhibitory/GABA-mediated synapses (By similarity). In collaboration
CC with UNC13A, facilitates neuronal dense core vesicles fusion as well as
CC controls the location and efficiency of their synaptic release (By
CC similarity). {ECO:0000250|UniProtKB:Q9Z1N9}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with RIMS1. {ECO:0000269|PubMed:11343654}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein.
CC Cell membrane. Synapse. Note=Localized to synapses. Translocated to the
CC plasma membrane in response to phorbol ester binding.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q62769-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q62769-2; Sequence=VSP_011384;
CC -!- TISSUE SPECIFICITY: Isoform 1 is ubiquitously expressed. Isoform 2 is
CC expressed in brain, predominantly in cerebral cortex, hippocampus and
CC striatum. {ECO:0000269|PubMed:11343654, ECO:0000269|PubMed:7559667,
CC ECO:0000269|PubMed:9895278}.
CC -!- DEVELOPMENTAL STAGE: First detected at birth, after which expression
CC level is steadily increasing until it reaches a plateau at P15.
CC {ECO:0000269|PubMed:9895278}.
CC -!- DOMAIN: The C2 domains are not involved in calcium-dependent
CC phospholipid binding.
CC -!- SIMILARITY: Belongs to the unc-13 family. {ECO:0000305}.
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DR EMBL; U24071; AAC52267.1; -; mRNA.
DR EMBL; AF159706; AAD41910.1; -; mRNA.
DR PIR; I61776; I61776.
DR RefSeq; NP_001036044.1; NM_001042579.1.
DR RefSeq; NP_074053.1; NM_022862.1.
DR AlphaFoldDB; Q62769; -.
DR SMR; Q62769; -.
DR CORUM; Q62769; -.
DR STRING; 10116.ENSRNOP00000073250; -.
DR PhosphoSitePlus; Q62769; -.
DR PaxDb; 10116-ENSRNOP00000058802; -.
DR GeneID; 64830; -.
DR KEGG; rno:64830; -.
DR UCSC; RGD:619723; rat. [Q62769-1]
DR AGR; RGD:619723; -.
DR CTD; 10497; -.
DR RGD; 619723; Unc13b.
DR eggNOG; KOG1011; Eukaryota.
DR InParanoid; Q62769; -.
DR OrthoDB; 5395569at2759; -.
DR Reactome; R-RNO-181429; Serotonin Neurotransmitter Release Cycle.
DR Reactome; R-RNO-181430; Norepinephrine Neurotransmitter Release Cycle.
DR Reactome; R-RNO-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-RNO-212676; Dopamine Neurotransmitter Release Cycle.
DR Reactome; R-RNO-264642; Acetylcholine Neurotransmitter Release Cycle.
DR PRO; PR:Q62769; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0044305; C:calyx of Held; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032009; C:early phagosome; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0031594; C:neuromuscular junction; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IGI:ParkinsonsUK-UCL.
DR GO; GO:0098793; C:presynapse; ISO:RGD.
DR GO; GO:0048786; C:presynaptic active zone; ISO:RGD.
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:0097470; C:ribbon synapse; ISO:RGD.
DR GO; GO:0097060; C:synaptic membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030672; C:synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0043195; C:terminal bouton; IGI:ParkinsonsUK-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005516; F:calmodulin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0019992; F:diacylglycerol binding; IEA:InterPro.
DR GO; GO:0030742; F:GTP-dependent protein binding; ISO:RGD.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0019905; F:syntaxin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0017075; F:syntaxin-1 binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0060478; P:acrosomal vesicle exocytosis; ISO:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IMP:ParkinsonsUK-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; ISS:ParkinsonsUK-UCL.
DR GO; GO:0061789; P:dense core granule priming; IGI:SynGO-UCL.
DR GO; GO:0060384; P:innervation; ISO:RGD.
DR GO; GO:0031914; P:negative regulation of synaptic plasticity; ISO:RGD.
DR GO; GO:0007528; P:neuromuscular junction development; ISO:RGD.
DR GO; GO:0099011; P:neuronal dense core vesicle exocytosis; ISS:UniProtKB.
DR GO; GO:0090382; P:phagosome maturation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:1900426; P:positive regulation of defense response to bacterium; ISO:RGD.
DR GO; GO:0045921; P:positive regulation of exocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0097151; P:positive regulation of inhibitory postsynaptic potential; IGI:ParkinsonsUK-UCL.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010808; P:positive regulation of synaptic vesicle priming; IGI:ParkinsonsUK-UCL.
DR GO; GO:0099525; P:presynaptic dense core vesicle exocytosis; ISO:RGD.
DR GO; GO:0099161; P:regulation of presynaptic dense core granule exocytosis; IDA:SynGO.
DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; ISO:RGD.
DR GO; GO:0061669; P:spontaneous neurotransmitter secretion; IGI:ParkinsonsUK-UCL.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; ISO:RGD.
DR GO; GO:0016081; P:synaptic vesicle docking; ISO:RGD.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0016188; P:synaptic vesicle maturation; IBA:GO_Central.
DR GO; GO:0016082; P:synaptic vesicle priming; IMP:ParkinsonsUK-UCL.
DR CDD; cd20859; C1_Munc13-2-like; 1.
DR CDD; cd08394; C2A_Munc13; 1.
DR CDD; cd04027; C2B_Munc13; 1.
DR CDD; cd08395; C2C_Munc13; 1.
DR Gene3D; 1.10.357.50; -; 1.
DR Gene3D; 1.20.58.1100; -; 1.
DR Gene3D; 3.30.60.20; -; 1.
DR Gene3D; 2.60.40.150; C2 domain; 3.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
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; PROTEIN UNC-13 HOMOLOG; 1.
DR PANTHER; PTHR10480:SF8; PROTEIN UNC-13 HOMOLOG B; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00168; C2; 3.
DR Pfam; PF06292; MUN; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00239; C2; 3.
DR SMART; SM01145; DUF1041; 1.
DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 3.
DR SUPFAM; SSF57889; Cysteine-rich domain; 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; Cell membrane; Coiled coil; Cytoplasm;
KW Exocytosis; Membrane; Metal-binding; Phosphoprotein; Reference proteome;
KW Repeat; Synapse; Zinc; Zinc-finger.
FT CHAIN 1..1622
FT /note="Protein unc-13 homolog B"
FT /id="PRO_0000188577"
FT DOMAIN 1..97
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 596..720
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1025..1168
FT /note="MHD1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00587"
FT DOMAIN 1275..1417
FT /note="MHD2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00588"
FT DOMAIN 1450..1577
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT ZN_FING 490..540
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 189..280
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 292..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1210..1231
FT /evidence="ECO:0000255"
FT COMPBIAS 190..205
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..226
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 237..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 264..280
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 292..307
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..351
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 629
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 629
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 635
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 681
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 681
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 683
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 683
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 700
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14795"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14795"
FT MOD_RES 378
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14795"
FT VAR_SEQ 1..400
FT /note="MSLLCVRVKRAKFQGSPDKFNTYVTLKVQNVKSTTVAVRGDQPSWEQDFMFE
FT ISRLDLGLSVEVWNKGLIWDTMVGTVWIALKTIRQSDEEGPGEWSTLEAETLMKNDEIC
FT GTKNPTPHKILLGTRFELPFDIPEEEARYWTYKLEQINALADDNEYSSQEESQRKLLPT
FT AAAQCRHWTYLGWGEHQTFEDPDSAVDDRDSDYRSETSNSAPPPYHTTTQPNASAHQFP
FT MPVPLPQQLFLQGSSRDSCNDSMQSYDLDYPERRALSPTSSSRYGSSCNVSRGSSLLSE
FT LDQYHEQDDDGRERDSIHSSHSYGSLSRDGQAGLGEQEKALEVACESQKEKTGESKERD
FT DATVCPPSDLMLHKDLTLGPQESFPEEKASSPFTQARAHWFRAVTKVRLQLQE -> MK
FT RLLRESEEEIMLTLGPSSSLSPDQVRTETVCIVKGKSTGPTGSLPEDNFPPPCCESADS
FT TTSGERDRNLAQLGSFEQQASSQPSLACTACASGSDSRELSPASITSCSEPSERNKARP
FT IFPRGPGQRCRHEHQEPLGDVVEYIIRELQGISRLQSEIAELQQHLNQVRGSVDEVSSC
FT VDSVLSEIEGLHVGSSSLGKVRHGEKAQELHVERSREEAILYLYGLPEHDGESTVELVD
FT NFLAKHLCVNGMQCNRYVREAYRAGTAPAPRPTVVKLVHPEHRDLILQKSILLQSVGVR
FT VATREEPVWPEGCKNPPKESLSCLQQFQDHSRNHQGKPALQLETGNRRQMSGPHQMRTQ
FT NQHRELQASEHQGLSFLPKDGSAKQSDVSKLQDEVKGTSGAPQVISDPCGELSLLHQLE
FT GSSPVLIPKEEDCGKLQIFKQDSQEHKACNVTKLQSDCNNAIKASSCLSLSGPLKAEKV
FT NAEDRMLGGEDGLDILSPKQLEDLLADKSRRFATLNPDSAVEEVIIGPETFSNMVHIDL
FT NEEETCTAQVLKNVFDKSSCVLGGSQEDEDVEIKFHTTKLSRAIHHFRLALQGVFQKLE
FT NNGSISPEDLESNESGSQSENSDRLLWTVSSGGAHDCSVESPASQGSESLLSVVSGGVG
FT ISVQGDQTPQAPSNFSLASNNSPLTNSLLSFPLAPGLGNETCSRPDSPNQGKLSLEQVC
FT AETIYLNKCINNFKNVLREKRLRQKKLLQELVQTASHLSVEDIPSEGKREALQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:7559667"
FT /id="VSP_011384"
SQ SEQUENCE 1622 AA; 184063 MW; 885C210A13086ACD CRC64;
MSLLCVRVKR AKFQGSPDKF NTYVTLKVQN VKSTTVAVRG DQPSWEQDFM FEISRLDLGL
SVEVWNKGLI WDTMVGTVWI ALKTIRQSDE EGPGEWSTLE AETLMKNDEI CGTKNPTPHK
ILLGTRFELP FDIPEEEARY WTYKLEQINA LADDNEYSSQ EESQRKLLPT AAAQCRHWTY
LGWGEHQTFE DPDSAVDDRD SDYRSETSNS APPPYHTTTQ PNASAHQFPM PVPLPQQLFL
QGSSRDSCND SMQSYDLDYP ERRALSPTSS SRYGSSCNVS RGSSLLSELD QYHEQDDDGR
ERDSIHSSHS YGSLSRDGQA GLGEQEKALE VACESQKEKT GESKERDDAT VCPPSDLMLH
KDLTLGPQES FPEEKASSPF TQARAHWFRA VTKVRLQLQE ISDDGDPSLP QWLPEGPAGG
LYGIDSMPDL RRKKPLPLVS DLAMSLVQSR KAGITSAMAT RTSLKDEDLK SHVYKKTLQA
LIYPISCTTP HNFEVWSATT PTYCYECEGL LWGLARQGMR CSECGVKCHE KCQDLLNADC
LQRAAEKSSK HGAEDRTQNI IMAMKDRMKI RERNKPEIFE VIRDVFTVSK VAHVQQMKTV
KQSVLDGTSK WSAKITITVV CAQGLQAKDK TGSSDPYVTV QVGKTKKRTK TIFGNLNPVW
EEKFHFECHN SSDRIKVRVW DEDDDIKSRV KQRLKRESDD FLGQTIIEVR TLSGEMDVWY
NLEKRTDKSA VSGAIRLQIN VEIKGEEKVA PYHVQYTCLH ENLFHYLTDI QGSGGVWIPD
ARGDDAWKVY FDETAQEIVD EFAMRYGIES IYQAMTHFAC LSSKYMCPGV PAVMSTLLAN
INAYYAHTTA STNVSASDRF AASNFGKERF VKLLDQLHNS LRIDLSTYRN NFPAGSPERL
QDLKSTVDLL TSITFFRMKV QELQSPPRAS QVVKDCVKAC LNSTYEYIFN NCHDLYSHQY
QLQEQPLEEP GPSIRNLDFW PKLITLIVSI IEEDKNSYTP VLNQFPQELN VGKVSAEVMW
HLFAQDMKYA LEEHEKDRLC KSADYMNLHF KVKWLHNEYV RELPALQGQV PEYPAWFEQF
VLQWLDENED VSLEFLRGGL ERDKRDGFQQ TSEHALFSCS VVDVFTQLNQ SFEIIRKLEC
PDPSILAHYM RRFAKTIGKV LIQYADILSK NFPAYCTKER LPCILMNNMQ QLRVQLEKMF
EAMGGKELDS EAADSLKELQ VKLNTVLDEL SMVFGNSFQV RIDECVRQMA DILGQVRGTG
NASPNARASV AQDADSVLRP LMDFLDGNLT LFATVCEKTV LKRVLKELWR VVMNTMERVI
VLPPLIDQTG TQLILTAAKE LSQLSKLKDH MVREETRNLT PKQCAVLDLA LDTVKQYFHA
GGNGLKKTFL EKSPDLQSLR YALSLYTQTT DTLIKTFVRS QTAQVHDGKG IRFTANEDIR
PEKGAGVDDP VGEVSIQVDL FTHPGTGEHK VTVKVVAAND LKWQTAGMFR PFVEVTMVGP
HQSDKKRKFT TKSKSNSWTP KYNETFHFLL GNEEGPEAYE LQICVKDYCF AREDRVIGLA
VMPLRDVAAK GSCACWCPLG RKIHMDETGM TILRILSQRS NDEVAREFVK LKSESRSIEE
GS
//
