SPZ5_DROME
ID SPZ5_DROME Reviewed; 387 AA.
AC Q9VZX1;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Protein spaetzle 5 {ECO:0000305};
DE AltName: Full=Neurotrophic factor 2 {ECO:0000305};
DE AltName: Full=Protein spatzle 5 {ECO:0000312|FlyBase:FBgn0035379};
DE Flags: Precursor;
GN Name=spz5 {ECO:0000312|FlyBase:FBgn0035379};
GN Synonyms=DNT1 {ECO:0000303|PubMed:19018662},
GN NT2 {ECO:0000303|PubMed:19018662};
GN ORFNames=CG9972 {ECO:0000312|FlyBase:FBgn0035379};
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;
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:AAK93159.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAK93159.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAK93159.1};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Farfan D., Frise E., George R., Gonzalez M.,
RA Guarin H., Li P., Liao G., Miranda A., Mungall C.J., Nunoo J., Pacleb J.,
RA Paragas V., Park S., Phouanenavong S., Wan K., Yu C., Lewis S.E.,
RA Rubin G.M., Celniker S.;
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP IDENTIFICATION.
RX PubMed=11536362; DOI=10.1002/prot.1125;
RA Parker J.S., Mizuguchi K., Gay N.J.;
RT "A family of proteins related to Spaetzle, the toll receptor ligand, are
RT encoded in the Drosophila genome.";
RL Proteins 45:71-80(2001).
RN [5] {ECO:0000305}
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=19018662; DOI=10.1371/journal.pbio.0060284;
RA Zhu B., Pennack J.A., McQuilton P., Forero M.G., Mizuguchi K.,
RA Sutcliffe B., Gu C.-J., Fenton J.C., Hidalgo A.;
RT "Drosophila neurotrophins reveal a common mechanism for nervous system
RT formation.";
RL PLoS Biol. 6:E284-E284(2008).
RN [6] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND MASS SPECTROMETRY.
RX PubMed=23892553; DOI=10.1038/nn.3474;
RA McIlroy G., Foldi I., Aurikko J., Wentzell J.S., Lim M.A., Fenton J.C.,
RA Gay N.J., Hidalgo A.;
RT "Toll-6 and Toll-7 function as neurotrophin receptors in the Drosophila
RT melanogaster CNS.";
RL Nat. Neurosci. 16:1248-1256(2013).
RN [7] {ECO:0000305}
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=24124519; DOI=10.1371/journal.pone.0075902;
RA Sutcliffe B., Forero M.G., Zhu B., Robinson I.M., Hidalgo A.;
RT "Neuron-type specific functions of DNT1, DNT2 and Spz at the Drosophila
RT neuromuscular junction.";
RL PLoS ONE 8:E75902-E75902(2013).
CC -!- FUNCTION: Neurotrophin which may function as a ligand for the Toll-
CC related receptors Toll-6 and Toll-7 (PubMed:23892553). Binds to Toll-7
CC and Toll-6, and probably acts as their ligands in the promotion of
CC motor axon targeting and neuronal survival in the central nervous
CC system (CNS) (PubMed:19018662, PubMed:23892553). Involved in synaptic
CC targeting of ISNb/d motorneurons and also some SNa motorneurons
CC (PubMed:19018662). May be involved in the normal development of
CC specific neurons at the neuromuscular junction (PubMed:24124519).
CC {ECO:0000269|PubMed:19018662, ECO:0000269|PubMed:23892553,
CC ECO:0000269|PubMed:24124519}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:P48607}.
CC -!- TISSUE SPECIFICITY: Detected in the fan-shaped body which is a
CC component of the locomotion center in the central nervous system (CNS)
CC (at protein level). {ECO:0000269|PubMed:23892553}.
CC -!- DEVELOPMENTAL STAGE: In larvae, expressed in a punctate pattern along
CC the CNS axons (at protein level) (PubMed:23892553). Expressed in larval
CC body wall muscles and in the synaptic boutons (PubMed:24124519). In
CC embryos, expressed in the CNS midline and muscles (PubMed:19018662).
CC {ECO:0000269|PubMed:19018662, ECO:0000269|PubMed:23892553,
CC ECO:0000269|PubMed:24124519}.
CC -!- MISCELLANEOUS: 'Spaetzle' means 'noodles' in German. {ECO:0000305}.
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DR EMBL; AE014296; AAF47694.1; -; Genomic_DNA.
DR EMBL; AY051735; AAK93159.1; -; mRNA.
DR RefSeq; NP_647753.1; NM_139496.3.
DR AlphaFoldDB; Q9VZX1; -.
DR IntAct; Q9VZX1; 1.
DR STRING; 7227.FBpp0072881; -.
DR GlyGen; Q9VZX1; 2 sites.
DR PaxDb; Q9VZX1; -.
DR DNASU; 38350; -.
DR EnsemblMetazoa; FBtr0073011; FBpp0072881; FBgn0035379.
DR GeneID; 38350; -.
DR KEGG; dme:Dmel_CG9972; -.
DR UCSC; CG9972-RA; d. melanogaster.
DR CTD; 38350; -.
DR FlyBase; FBgn0035379; spz5.
DR VEuPathDB; VectorBase:FBgn0035379; -.
DR eggNOG; ENOG502S37H; Eukaryota.
DR GeneTree; ENSGT00700000106225; -.
DR HOGENOM; CLU_043206_0_0_1; -.
DR InParanoid; Q9VZX1; -.
DR OMA; DTPVFYD; -.
DR OrthoDB; 1422410at2759; -.
DR PhylomeDB; Q9VZX1; -.
DR BioGRID-ORCS; 38350; 0 hits in 1 CRISPR screen.
DR ChiTaRS; NT1; fly.
DR GenomeRNAi; 38350; -.
DR PRO; PR:Q9VZX1; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0035379; Expressed in insect abdominal segment and 27 other tissues.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR GO; GO:0008083; F:growth factor activity; IMP:FlyBase.
DR GO; GO:0048018; F:receptor ligand activity; IDA:FlyBase.
DR GO; GO:0005121; F:Toll binding; IDA:FlyBase.
DR GO; GO:0007411; P:axon guidance; IMP:FlyBase.
DR GO; GO:0021556; P:central nervous system formation; IMP:FlyBase.
DR GO; GO:0045087; P:innate immune response; IMP:FlyBase.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:FlyBase.
DR GO; GO:0007399; P:nervous system development; IMP:FlyBase.
DR GO; GO:0002225; P:positive regulation of antimicrobial peptide production; IMP:FlyBase.
DR GO; GO:0010941; P:regulation of cell death; IDA:FlyBase.
DR GO; GO:0031637; P:regulation of neuronal synaptic plasticity in response to neurotrophin; IMP:FlyBase.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IGI:FlyBase.
DR GO; GO:0008592; P:regulation of Toll signaling pathway; IBA:GO_Central.
DR GO; GO:0008063; P:Toll signaling pathway; IDA:FlyBase.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR032104; Spaetzle.
DR Pfam; PF16077; Spaetzle; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Reference proteome; Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000303|PubMed:23892553"
FT PROPEP 30..284
FT /evidence="ECO:0000303|PubMed:23892553"
FT /id="PRO_0000437523"
FT CHAIN 285..387
FT /note="Protein spaetzle 5"
FT /evidence="ECO:0000305"
FT /id="PRO_5007325435"
FT DOMAIN 291..384
FT /note="Spaetzle"
FT /evidence="ECO:0000255"
FT REGION 133..197
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 219..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 293..350
FT /evidence="ECO:0000250|UniProtKB:P48607"
FT DISULFID 331..380
FT /evidence="ECO:0000250|UniProtKB:P48607"
FT DISULFID 340..382
FT /evidence="ECO:0000250|UniProtKB:P48607"
FT DISULFID 379
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P48607"
SQ SEQUENCE 387 AA; 42827 MW; E18406C0D9590558 CRC64;
MTKSIKRPPP FSCKQVLLTY VILAYTVAAH SSPPPCGLYG APPCQFLPAP PGQTPTCARP
GKTYCEHADN YPTYLIKSLV RKWGYEAATL LVDETWEDFA AVAWHDTPVF YDPKSIFPPR
DPAAQDFNGY SYQTPFGGNP QRPSGGGNPL FVSNPSTEAP TYLLYTSSGG GHRSGHRYNS
QGGGTSSSGG HLYINQSDKS TPYNATLWLK RLVRDLSRKQ RQPDEVQAEV VEPVNEQTEE
AEEQDNPAED HPQSKRDVSL NMDLLDIVGV EAPNPLKKRS RTKRQSPGRS TLCQTTSQFI
TPQAALNSRG NWMFVVNEQN TARQMVKAEL CASNTCSNLC ELPNGYNSRC EQKFVQKRLI
ALQGNGQNLY TDTFWFPSCC VCTIAAN
