UN13B_DROME
ID UN13B_DROME Reviewed; 1153 AA.
AC Q9VBY8; A0A0B4KHI5; A8JRA6; B3DN10; C6SV37;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 5.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Protein unc-13 homolog 4B {ECO:0000305|PubMed:27323327};
DE AltName: Full=Protein Staccato {ECO:0000303|PubMed:27323327};
GN Name=stac {ECO:0000303|PubMed:27323327, ECO:0000312|FlyBase:FBgn0266719};
GN Synonyms=Unc-13-4B {ECO:0000303|PubMed:27323327};
GN ORFNames=CG34349 {ECO:0000312|FlyBase:FBgn0266719};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:ACD81812.1, ECO:0000312|EMBL:ACU00262.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-239 AND 783-1153.
RC STRAIN=Berkeley {ECO:0000312|EMBL:ACU00262.1};
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (AUG-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP INTERACTION WITH CAM, AND DEVELOPMENTAL STAGE.
RX PubMed=9813038; DOI=10.1074/jbc.273.47.31297;
RA Xu X.-Z.S., Wes P.D., Chen H., Li H.-S., Yu M., Morgan S., Liu Y.,
RA Montell C.;
RT "Retinal targets for calmodulin include proteins implicated in synaptic
RT transmission.";
RL J. Biol. Chem. 273:31297-31307(1998).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP 1124-ASP--SER-1153.
RX PubMed=27323327; DOI=10.1038/ncb3374;
RA Caviglia S., Brankatschk M., Fischer E.J., Eaton S., Luschnig S.;
RT "Staccato/Unc-13-4 controls secretory lysosome-mediated lumen fusion during
RT epithelial tube anastomosis.";
RL Nat. Cell Biol. 18:727-739(2016).
CC -!- FUNCTION: Essential for tracheal development in embryos. Functions with
CC the GTPase Rab39 and downstream of dnd, to regulate lumen fusion
CC between previously separate tracheal branches (anastomosis). Essential
CC component of secretory lysosome-related organelles (SLs) that are
CC present in the tracheal fusion tip cells (FCs). Mediates intracellular
CC fusion of the extending tracheal stalk cell lumen in the FCs by
CC recruiting the SNARE complex component Syx1A to the SLs, this may then
CC enable the SLs to interact with complementary SNAREs (such as Syb)
CC present in the apical membrane of the FC-FC interface and the membranes
CC of the separate tracheal stalk cells. May also function in the
CC maturation and exocytosis of the SLs. {ECO:0000269|PubMed:27323327}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with Cam. {ECO:0000269|PubMed:9813038}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27323327}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:27323327}. Cell projection,
CC filopodium {ECO:0000269|PubMed:27323327}. Late endosome
CC {ECO:0000269|PubMed:27323327}. Lysosome {ECO:0000269|PubMed:27323327}.
CC Note=Expressed throughout the cytoplasm of embryonic tracheal cells,
CC except in the tracheal fusion cells (FCs) where it localizes to
CC discrete intracellular vesicles. These vesicles also accumulate Rab39
CC and display late-endosomal, lysosomal, and SNARE components (Syx1A),
CC characteristics of lysosome-related organelles. Prior to contact
CC between FCs the vesicles localize to the presumed fusion point and
CC sometimes to the filopodia. On contact between FCs, the lysosomes
CC accumulate and move along the cytoskeleton track in a dynein-dependent
CC manner between the two apical domains, becoming densely packed around
CC the interface between the fusion cells. Some of the puncta remain
CC associated with the primary apical FC membrane.
CC {ECO:0000269|PubMed:27323327}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=C {ECO:0000312|FlyBase:FBgn0266719};
CC IsoId=Q9VBY8-1; Sequence=Displayed;
CC Name=D {ECO:0000312|FlyBase:FBgn0266719};
CC IsoId=Q9VBY8-2; Sequence=VSP_058549;
CC Name=E {ECO:0000312|FlyBase:FBgn0266719};
CC IsoId=Q9VBY8-3; Sequence=VSP_058550;
CC -!- DEVELOPMENTAL STAGE: In stage 16-17 embryos, expressed in the
CC epidermis, tracheal system, Malpighian tubules, boundary cells of the
CC hindgut, muscles and dorsal vessel. Expressed in large puncta in the
CC hemocytes. Expressed in the fusion cells of the tracheal branch tips
CC (PubMed:27323327). Detected first in early pupae and has very high
CC levels of expression in the adult head (PubMed:9813038).
CC {ECO:0000269|PubMed:27323327, ECO:0000269|PubMed:9813038}.
CC -!- MISCELLANEOUS: 'Staccato' means detached in Italian, referring to the
CC unclosed gaps in the tracheal lumen of mutants.
CC {ECO:0000303|PubMed:27323327}.
CC -!- SIMILARITY: Belongs to the unc-13 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ACU00262.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE014297; AAF56388.5; -; Genomic_DNA.
DR EMBL; AE014297; ABW08753.2; -; Genomic_DNA.
DR EMBL; AE014297; AGB96327.1; -; Genomic_DNA.
DR EMBL; BT032798; ACD81812.1; -; mRNA.
DR EMBL; BT089029; ACU00262.1; ALT_INIT; mRNA.
DR RefSeq; NP_001097909.2; NM_001104439.3. [Q9VBY8-2]
DR RefSeq; NP_001262947.1; NM_001276018.1. [Q9VBY8-3]
DR RefSeq; NP_651329.4; NM_143072.4. [Q9VBY8-1]
DR AlphaFoldDB; Q9VBY8; -.
DR SMR; Q9VBY8; -.
DR STRING; 7227.FBpp0292144; -.
DR PaxDb; Q9VBY8; -.
DR PRIDE; Q9VBY8; -.
DR EnsemblMetazoa; FBtr0303025; FBpp0292144; FBgn0266719. [Q9VBY8-1]
DR EnsemblMetazoa; FBtr0303026; FBpp0292145; FBgn0266719. [Q9VBY8-2]
DR EnsemblMetazoa; FBtr0334505; FBpp0306572; FBgn0266719. [Q9VBY8-3]
DR GeneID; 43002; -.
DR KEGG; dme:Dmel_CG34349; -.
DR UCSC; CG34349-RA; d. melanogaster. [Q9VBY8-1]
DR UCSC; CG34349-RB; d. melanogaster.
DR CTD; 6769; -.
DR FlyBase; FBgn0266719; stac.
DR VEuPathDB; VectorBase:FBgn0266719; -.
DR eggNOG; KOG1328; Eukaryota.
DR GeneTree; ENSGT00730000110939; -.
DR HOGENOM; CLU_003295_0_0_1; -.
DR InParanoid; Q9VBY8; -.
DR OMA; FYQIKVF; -.
DR PhylomeDB; Q9VBY8; -.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 43002; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 43002; -.
DR PRO; PR:Q9VBY8; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0266719; Expressed in crop (Drosophila) and 24 other tissues.
DR ExpressionAtlas; Q9VBY8; baseline and differential.
DR Genevisible; Q9VBY8; DM.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0099503; C:secretory vesicle; IDA:FlyBase.
DR GO; GO:0008021; C:synaptic vesicle; NAS:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035147; P:branch fusion, open tracheal system; IMP:FlyBase.
DR GO; GO:0007269; P:neurotransmitter secretion; NAS:FlyBase.
DR GO; GO:0016082; P:synaptic vesicle priming; NAS:FlyBase.
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 PRINTS; PR00360; C2DOMAIN.
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 Alternative splicing; Calcium; Cell projection; Cytoplasm; Cytoskeleton;
KW Developmental protein; Endosome; Exocytosis; Lysosome; Metal-binding;
KW Reference proteome; Repeat.
FT CHAIN 1..1153
FT /note="Protein unc-13 homolog 4B"
FT /id="PRO_0000437524"
FT DOMAIN 162..288
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 637..755
FT /note="MHD1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00587"
FT DOMAIN 869..975
FT /note="MHD2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00588"
FT DOMAIN 990..1114
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 54..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 195
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 253
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1019
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1025
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1083
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1085
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT VAR_SEQ 1..121
FT /note="MDEEQMWKGFFFKLQELKMNPPTEHEHQLQDGDDGFFEKFGSLLRQKSQIDE
FT GVLKSSLAPLEENGSGGEEDSDESPDGTLQLSQDSECTSIDTFATESTLASSSDKDIST
FT SVLDSAPVMN -> MSYLSLPRVLSKFGSQNHSSSNQSSKTNSLTRSSTRTGCDEIRLP
FT RKASSTQSLNKPFERRMSILNRNGSISSRHFRGVHKHLLDSHAKAVCHSMT (in
FT isoform D)"
FT /id="VSP_058549"
FT VAR_SEQ 1..28
FT /note="MDEEQMWKGFFFKLQELKMNPPTEHEHQ -> MLKSYFRRSELRIFEKIR
FT (in isoform E)"
FT /id="VSP_058550"
FT MUTAGEN 1124..1153
FT /note="Missing: In 3B20; probable loss of function. The
FT lumen of separate tracheal branches fails to fuse during
FT anastomosis and Syx1A does not localize to the fusion
FT point."
FT /evidence="ECO:0000269|PubMed:27323327"
SQ SEQUENCE 1153 AA; 131921 MW; 37584AFC473FB456 CRC64;
MDEEQMWKGF FFKLQELKMN PPTEHEHQLQ DGDDGFFEKF GSLLRQKSQI DEGVLKSSLA
PLEENGSGGE EDSDESPDGT LQLSQDSECT SIDTFATEST LASSSDKDIS TSVLDSAPVM
NVTDLYEEIL FEIFNNIGCE NNEECTNSLV EFVQDAFKIP NATHEEIYEA ARLKEPPNVR
LNVEIIKAEN LMSKDSNGLS DPFVTLYLES NGSHRYNSSV KPATLNPIWE EHFSLPITEN
ARDEVLIVEV WDFDAAETVK EKVNKILDVK GVKGLSKLMK EIAVTASSGK HDNELIGRAA
ITLKSIPVSG LTVWYNLEKG SKGRSRGSLL VNLALSAEKN KSVAVQEHKN LLKLLLMYEL
ETSQVANYWW SGKFSPNAEL IRSQHAAQSG LTPFDCALSQ WHAYSTIHET HKLNFTLFNS
ILDVVVPVIT YMQNDSEDVK TFWDGVKRLL PSCFAVLRKL RSKNTSDKNI IRALNEVLDI
LKKIKELEVP ESVDIFPKSV YGWLHTNDTD ETCNIDTAIE DAINTGTREW LEHIVEGSRQ
SKNTETDDEK LQYVIKLIQM VRSDLQRAME YFDKIFYHKI QLNYSAVLYL FYDSKLAEIC
KSIIIEVCNN IKRLDVPDDQ FEYLPNLENV NMGTTLFEVY LILKRYVQLG ESLCSEPLEL
SNFYPWFERG VTHWLDISII KALSRIQKAI DLDQLKAVDE TVKYSSSAVD TLSIFYQIKI
FWQQLDWPEV EGSYIFVAKI VNDLCRCCIF YAQQMSRRVE NIFIADDNNK NFILSEEWCI
AINNMDYIRQ SLPSFIKELS IDDIIKRLGE YRTNLEAERC ASTIKTVIEN ALDTERNQIV
ELIEIVARKM APPIRRYLAE GAEVLAKDSN SMDQLMMYLE SSLATLYDTL NEINFQRILD
GIWSELSIIM YDLIQSNLDK RRPPAFFQNL NNTLQTMMDC FKMGNLQTSD IKILSSIQSR
LRLYSLETSD LIHQYYLERL ENQKSQESSP YGQLTITAQL TDTGLLLNIL NARNLLPMDS
NGSVDSFVKA SFMPTSRFND VPTVKTNVHN KSCFPLYDQE FRINLSDHQR SEKNSLIVFS
IKDKDLFGMS SQYIAESYIS FADLEATPPG EQIMMNLSRP EYTDSESLRA LEYRLGDKQA
KDFLKKLKNR SFS
