SPZ2_DROME
ID SPZ2_DROME Reviewed; 886 AA.
AC B7TB45; Q8IRB0;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Neurotrophin 1 {ECO:0000312|FlyBase:FBgn0261526};
DE AltName: Full=Neurotrophic factor 1 {ECO:0000305};
DE AltName: Full=Protein spaetzle 2 {ECO:0000303|PubMed:19018662};
DE AltName: Full=Protein spatzle 2 {ECO:0000305};
DE Flags: Precursor;
GN Name=NT1 {ECO:0000312|FlyBase:FBgn0261526};
GN Synonyms=DNT1 {ECO:0000303|PubMed:19018662},
GN spz2 {ECO:0000303|PubMed:19018662};
GN ORFNames=CG42576 {ECO:0000312|FlyBase:FBgn0261526};
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|EMBL:ACH98104.1, ECO:0000312|EMBL:DAA06447.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND D), FUNCTION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND POSSIBLE CLEAVAGE.
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 [2] {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 [3] {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 [4] {ECO:0000312|EMBL:ADB91456.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (JAN-2010) to the EMBL/GenBank/DDBJ databases.
RN [5] {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 [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=22022271; DOI=10.1371/journal.ppat.1002319;
RA Akhouayri I., Turc C., Royet J., Charroux B.;
RT "Toll-8/Tollo negatively regulates antimicrobial response in the Drosophila
RT respiratory epithelium.";
RL PLoS Pathog. 7:E1002319-E1002319(2011).
RN [7] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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 [8] {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-7 and Tollo (PubMed:22022271, PubMed:23892553).
CC Binds to Toll-7 and probably acts as its ligand in promoting motor axon
CC targeting and neuronal survival in the central nervous system (CNS)
CC (PubMed:23892553). Involved in synaptic targeting of ISNb/d
CC motorneurons and also some SNa motorneurons (PubMed:19018662). In
CC larvae, involved in the negative regulation of the tracheal immune
CC response to bacterial infection perhaps by acting as a ligand for the
CC Toll-related receptor Tollo (PubMed:22022271). May be involved in the
CC normal development of specific neurons at the neuromuscular junction
CC (PubMed:24124519). {ECO:0000269|PubMed:19018662,
CC ECO:0000269|PubMed:22022271, ECO:0000269|PubMed:23892553,
CC ECO:0000269|PubMed:24124519}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:P48607}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=D {ECO:0000312|FlyBase:FBgn0261526}; Synonyms=long
CC {ECO:0000303|PubMed:19018662};
CC IsoId=B7TB45-1; Sequence=Displayed;
CC Name=B {ECO:0000312|FlyBase:FBgn0261526}; Synonyms=C
CC {ECO:0000312|FlyBase:FBgn0261526}, E {ECO:0000312|FlyBase:FBgn0261526},
CC short {ECO:0000303|PubMed:19018662};
CC IsoId=B7TB45-2; Sequence=VSP_058559;
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) (PubMed:23892553). Expressed in the optic lobes and
CC brain (PubMed:19018662). {ECO:0000269|PubMed:19018662,
CC ECO:0000269|PubMed:23892553}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development
CC (PubMed:19018662). Expressed in the embryonic CNS midline (at protein
CC level) (PubMed:23892553). Also expressed in various longitudinal
CC muscles (at protein level) (PubMed:23892553). In embryos, expressed in
CC the CNS midline and in the muscles (PubMed:19018662). In larvae,
CC expressed in the lamina of the optic lobe (PubMed:19018662). Expressed
CC in larval body wall muscles (PubMed:24124519).
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; FJ172423; ACH98104.1; -; mRNA.
DR EMBL; BT120209; ADB91457.1; -; mRNA.
DR EMBL; FJ172424; ACH98105.1; -; mRNA.
DR EMBL; BK006739; DAA06447.1; -; mRNA.
DR EMBL; BK006740; DAA06448.1; -; mRNA.
DR EMBL; AE014296; ACZ94620.1; -; Genomic_DNA.
DR EMBL; AE014296; ACZ94621.1; -; Genomic_DNA.
DR EMBL; AE014296; AAN11606.1; -; Genomic_DNA.
DR EMBL; AE014296; AAN11607.1; -; Genomic_DNA.
DR EMBL; BT120208; ADB91456.1; -; mRNA.
DR RefSeq; NP_001163348.1; NM_001169877.2. [B7TB45-1]
DR RefSeq; NP_001163349.1; NM_001169878.2. [B7TB45-2]
DR RefSeq; NP_729010.1; NM_168091.3. [B7TB45-2]
DR RefSeq; NP_729011.1; NM_168092.3. [B7TB45-2]
DR AlphaFoldDB; B7TB45; -.
DR SMR; B7TB45; -.
DR IntAct; B7TB45; 1.
DR STRING; 7227.FBpp0290823; -.
DR GlyGen; B7TB45; 4 sites.
DR PRIDE; B7TB45; -.
DR DNASU; 38558; -.
DR EnsemblMetazoa; FBtr0301517; FBpp0290732; FBgn0261526. [B7TB45-2]
DR EnsemblMetazoa; FBtr0301518; FBpp0290733; FBgn0261526. [B7TB45-2]
DR EnsemblMetazoa; FBtr0301519; FBpp0290734; FBgn0261526. [B7TB45-1]
DR EnsemblMetazoa; FBtr0301520; FBpp0290735; FBgn0261526. [B7TB45-2]
DR GeneID; 38558; -.
DR KEGG; dme:Dmel_CG42576; -.
DR UCSC; CG32244-RB; d. melanogaster.
DR CTD; 38558; -.
DR FlyBase; FBgn0261526; NT1.
DR VEuPathDB; VectorBase:FBgn0261526; -.
DR eggNOG; ENOG502RZ0W; Eukaryota.
DR HOGENOM; CLU_325493_0_0_1; -.
DR OMA; AHAHQTG; -.
DR BioGRID-ORCS; 38558; 0 hits in 1 CRISPR screen.
DR ChiTaRS; NT1; fly.
DR GenomeRNAi; 38558; -.
DR PRO; PR:B7TB45; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0261526; Expressed in ventral longitudinal muscle (Drosophila) and 26 other tissues.
DR ExpressionAtlas; B7TB45; baseline and differential.
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; IBA:GO_Central.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:FlyBase.
DR GO; GO:0007399; P:nervous system development; 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: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 Alternative splicing; Disulfide bond; Glycoprotein; Reference proteome;
KW Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT PROPEP 30..498
FT /evidence="ECO:0000303|PubMed:24124519"
FT /id="PRO_0000437664"
FT CHAIN 499..886
FT /note="Neurotrophin 1"
FT /evidence="ECO:0000303|PubMed:24124519"
FT /id="PRO_5007308668"
FT DOMAIN 508..597
FT /note="Spaetzle"
FT /evidence="ECO:0000255"
FT REGION 321..340
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..436
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 675..754
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 789..886
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 714..754
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 793..809
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 498..499
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:19018662"
FT CARBOHYD 267
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 623
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 509..564
FT /evidence="ECO:0000250|UniProtKB:P48607"
FT DISULFID 546..593
FT /evidence="ECO:0000250|UniProtKB:P48607"
FT DISULFID 553..595
FT /evidence="ECO:0000250|UniProtKB:P48607"
FT DISULFID 592
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P48607"
FT VAR_SEQ 455..886
FT /note="Missing (in isoform B)"
FT /id="VSP_058559"
SQ SEQUENCE 886 AA; 100315 MW; 041F14FAD5547958 CRC64;
MKAGRAFGCL FWALLYCVLY LDLVSGNSAD DELMDFDFAD SNDAAMEDWQ LDDLEEAKKA
EQAEKKLESN MLDFSVDLDE PEPEKQLPPF DWRERVLRNA LAKALADEGL RQKFAEVLPI
LRMLSSQQRL ALSALISAQM NAKKGHELKF EQVRMMFGNE KKLLLPIVFD IANLIKSSTR
KYINLGSDLA SSALYHTPIN RREDDLTPEE SQQDDQLGTI AVEVEPKKVS TEEVQLESLE
DFFDEMGSEV LDPQMINEAL TGDLHDNKTK TFKPENHGQR VRRSANEFVH KLTRSVPASV
TEQQLLGGIA GRTIKLNTTA FQQPSSQEEE KMASSNGGQS YSEVEDLAFA GLNGTEIPLS
ADERLDLQRN SAEETEEPLP SPEELIAGPR YRLGKRPLPG QKSGSPIKRK RVTSSLRGRP
KTAASSHKPV VTPPNKKCER FTSNMCIRTD DYPLEQIMGS IRRHKNAMSA LLAEFYDKPN
NNLEFSDDFD DFSLSKKRRE DEGSAGGMCQ SVVRYARPQK AKSASGEWKY IVNTGQHTQT
LRLEKCSNPV ESCSYLAQTY RSHCSQVYNY HRLLSWDKVR GLHVDIFKVP TCCSCQVDGY
RQQFPPLSSI QAKDYSPQSP VINHSHNGYS TINEEDLDYA EESEEDELGL RYPSFNNRET
NELYSSSNKV RVKLPGISSS VGPYLSPPDD DEDRYGGYKS SSSSSKKYYS QVSRRRPQHS
EARLDLDLAP SETHSDQEPP PPQHHQHHHL QYHRPQEELP SAYDFHRPQV YQPEREQLPL
VRDPALSPVS APVLASPAPP LPMPPMPIKQ VPSHHQAHHQ QPHHHLHQST GKVAANRDPA
SMHHQPPRRP TQQWLPGQRR PFRPSAPLSG SGISRRHYHN RRQSIQ
