UN13D_RAT
ID UN13D_RAT Reviewed; 1088 AA.
AC Q9R189;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Protein unc-13 homolog D;
DE AltName: Full=Munc13-4;
GN Name=Unc13d; Synonyms=Unc13h4;
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], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Lung;
RX PubMed=10861235; DOI=10.1042/0264-6021:3490247;
RA Koch H., Hofmann K., Brose N.;
RT "Definition of Munc13-homology-domains and characterization of a novel
RT ubiquitously expressed Munc13-isoform.";
RL Biochem. J. 349:247-253(2000).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-150, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Plays a role in cytotoxic granule exocytosis in lymphocytes.
CC Required for both granule maturation and granule docking and priming at
CC the immunologic synapse. Regulates assembly of recycling and late
CC endosomal structures, leading to the formation of an endosomal exocytic
CC compartment that fuses with perforin-containing granules at the
CC immunologic synapse and licences them for exocytosis. Regulates Ca(2+)-
CC dependent secretory lysosome exocytosis in mast cells (By similarity).
CC {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with RAB27A and DOC2A. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Late endosome {ECO:0000250}.
CC Recycling endosome {ECO:0000250}. Lysosome {ECO:0000250}.
CC Note=Colocalizes with cytotoxic granules at the plasma membrane.
CC Localizes to endosomal exocytic vesicles. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in lung bronchial epithelium
CC goblet/mucous cells. Also expressed in spleen and testis. Expressed at
CC very low levels in heart muscle, kidney, liver, brain and skeletal
CC muscle. {ECO:0000269|PubMed:10861235}.
CC -!- DOMAIN: The MHD1 and MHD2 domains mediate localization on recycling
CC endosomes and lysosome. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the unc-13 family. {ECO:0000305}.
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DR EMBL; AF159356; AAD44333.1; -; mRNA.
DR RefSeq; NP_620199.1; NM_138844.1.
DR AlphaFoldDB; Q9R189; -.
DR SMR; Q9R189; -.
DR STRING; 10116.ENSRNOP00000010466; -.
DR iPTMnet; Q9R189; -.
DR PhosphoSitePlus; Q9R189; -.
DR PaxDb; Q9R189; -.
DR PRIDE; Q9R189; -.
DR GeneID; 192177; -.
DR KEGG; rno:192177; -.
DR CTD; 201294; -.
DR RGD; 628593; Unc13d.
DR eggNOG; KOG1328; Eukaryota.
DR InParanoid; Q9R189; -.
DR OrthoDB; 72416at2759; -.
DR PhylomeDB; Q9R189; -.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:Q9R189; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070382; C:exocytic vesicle; ISO:RGD.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISO:RGD.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0099503; C:secretory vesicle; IBA:GO_Central.
DR GO; GO:0033093; C:Weibel-Palade body; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; ISO:RGD.
DR GO; GO:0051607; P:defense response to virus; ISO:RGD.
DR GO; GO:0061789; P:dense core granule priming; IGI:SynGO-UCL.
DR GO; GO:0002467; P:germinal center formation; ISO:RGD.
DR GO; GO:0002432; P:granuloma formation; ISO:RGD.
DR GO; GO:0043320; P:natural killer cell degranulation; ISO:RGD.
DR GO; GO:0006909; P:phagocytosis; ISO:RGD.
DR GO; GO:0045921; P:positive regulation of exocytosis; ISO:RGD.
DR GO; GO:1903307; P:positive regulation of regulated secretory pathway; ISO:RGD.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISO:RGD.
DR GO; GO:0043304; P:regulation of mast cell degranulation; ISO:RGD.
DR GO; GO:0046903; P:secretion; IEP:RGD.
DR Gene3D; 2.60.40.150; -; 2.
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 Pfam; PF00168; C2; 2.
DR Pfam; PF06292; MUN; 1.
DR SMART; SM00239; C2; 2.
DR SUPFAM; SSF49562; SSF49562; 2.
DR PROSITE; PS50004; C2; 2.
DR PROSITE; PS51258; MHD1; 1.
DR PROSITE; PS51259; MHD2; 1.
PE 1: Evidence at protein level;
KW Calcium; Cytoplasm; Endosome; Exocytosis; Lysosome; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..1088
FT /note="Protein unc-13 homolog D"
FT /id="PRO_0000188582"
FT DOMAIN 92..239
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 557..675
FT /note="MHD1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00587"
FT DOMAIN 786..893
FT /note="MHD2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00588"
FT DOMAIN 908..1033
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 26..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..543
FT /note="Interaction with RAB27A"
FT /evidence="ECO:0000250"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 133
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 938
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 939
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 939
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 945
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1003
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1003
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1005
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1005
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1011
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 1088 AA; 123454 MW; 1646C55EEC22541C CRC64;
MATHLSHPQR RPPLLRQAVK IRRRRVRDLQ DPPPQATPEV QVQSHHFSPE ERDLLYEEAL
YTVLHRLGQP EPNHVKEASE LLCYLQEAFQ VQPEEHQQML QRVRELEKPI FCLKATVKQA
KGILGKDVSG FSDPYCLLGI EQKVGVPEGS PVSRRRQKAV VRHTIPEEET HRTQVKTQTL
NPVWDETFIL EFEDITNASF HLDMWDLDTV ESVRHKLGEL TDLHGLRRIF KEARKDKGQD
DFLGNVMLRL QDLRCREDQW FPLEPCTETY PDRGQCHLQF QFIHKRRATV ASRSQPSYTV
HFHLLQQLVS HEVTQHQAGG TSWGRIAESQ AVTILFLHAT QKDLSDFHQS MAQWLAYSRL
YQSLEFPSSC LLHPITSIEY QWIQGRLKAE QREELATSFT SLLAYGLSLI RKFRSVFPLS
VSDSPSRLQS LLRVLVQMCK MKAFGELCPD SAPLPQLVSE ALRMGTVEWF HLMQQHHQPM
VQGILEAGKA LLSLVQDVMG DLYQCRRTWN KIFHNVLKID LFTMAFLELQ WLVAKRVQDH
TAAVGDLVSP DVGESLFQLY VSLREFCQLG PSDSHEVLAL DGFHRWFQSA IPSWLQRTYS
VALERVQRAV QMDSLVPLGE LTKHSTSAVD LSTCFAQISH TARQLDWPDP EEAFMITVKF
VEDTCRLALV YCSLIKARAR ELSAVQKDQS QAADMLCVVV NNVERLRLII DKLPTQLAWE
ALEQRVGAVL EQGQLQNTLH TQLQGALAGL GHEIRTGVRT LAEQLEVGIA THIQKLIDAK
GSILPEDAIL PLMKFLEVKL CYMNTNLVQE NFSSLLTLLW THTLTVLVEA AASHRNSSLA
SSRLKVALQN LEICFHAEGC GLPPEALHTD TFLALQSDLE LQAASSRELI QKYFRSRIQQ
QAETTSERLG AVTVKASYRA SEQKLHVELL SASSLLPLDS NGSSDPFVQL TLEPRHEFPE
LAPRETQKHK KELHPLFDET FEFLVPAEPC QKDGACLLLT VLDHDRLGAD DLEGEAFLPL
CRVPGLTGCV EPGEAPQMRL PLTYPAPNGD PILRLLESRK GDREAQAFVK LRRQRAKQAS
QHAPATEP
