SPITZ_DROME
ID SPITZ_DROME Reviewed; 234 AA.
AC Q01083; Q8SXE0; Q9VIT4;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Protein spitz;
DE Flags: Precursor;
GN Name=spi; ORFNames=CG10334;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1644292; DOI=10.1101/gad.6.8.1503;
RA Rutledge B.J., Zhang K., Bier E., Jan Y.N., Perrimon N.;
RT "The Drosophila spitz gene encodes a putative EGF-like growth factor
RT involved in dorsal-ventral axis formation and neurogenesis.";
RL Genes Dev. 6:1503-1517(1992).
RN [2]
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]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP FUNCTION.
RX PubMed=7833286; DOI=10.1016/0925-4773(94)90003-5;
RA Freeman M.;
RT "The spitz gene is required for photoreceptor determination in the
RT Drosophila eye where it interacts with the EGF receptor.";
RL Mech. Dev. 48:25-33(1994).
RN [6]
RP SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING.
RX PubMed=11672524; DOI=10.1016/s0092-8674(01)00526-8;
RA Lee J.R., Urban S., Garvey C.F., Freeman M.;
RT "Regulated intracellular ligand transport and proteolysis control EGF
RT signal activation in Drosophila.";
RL Cell 107:161-171(2001).
RN [7]
RP REVIEW.
RX PubMed=11790319; DOI=10.1016/s0960-9822(01)00642-x;
RA Klaembt C.;
RT "EGF receptor signalling: roles of Star and Rhomboid revealed.";
RL Curr. Biol. 12:R21-R23(2002).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 76-127 IN COMPLEX WITH ARGOS, AND
RP DISULFIDE BONDS.
RX PubMed=18500331; DOI=10.1038/nature06978;
RA Klein D.E., Stayrook S.E., Shi F., Narayan K., Lemmon M.A.;
RT "Structural basis for EGFR ligand sequestration by Argos.";
RL Nature 453:1271-1275(2008).
CC -!- FUNCTION: Ligand for the EGF receptor (Gurken). Involved in a number of
CC unrelated developmental choices, for example, dorsal-ventral axis
CC formation, glial migration, sensory organ determination, and muscle
CC development. It is required for photoreceptor determination.
CC {ECO:0000269|PubMed:7833286}.
CC -!- SUBUNIT: Interacts with Star via the lumenal domain.
CC {ECO:0000269|PubMed:18500331}.
CC -!- INTERACTION:
CC Q01083; Q00805: aos; NbExp=2; IntAct=EBI-91342, EBI-596393;
CC Q01083; P04412: Egfr; NbExp=4; IntAct=EBI-91342, EBI-197863;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11672524};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:11672524}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:11672524}; Single-
CC pass type I membrane protein {ECO:0000269|PubMed:11672524}. Golgi
CC apparatus membrane {ECO:0000269|PubMed:11672524}; Single-pass type I
CC membrane protein {ECO:0000269|PubMed:11672524}. Note=Relocalization to
CC the Golgi apparatus and the plasma membrane is mediated by Star. In the
CC presence of Rhomboid, Spitz is found only in the Golgi, not at the cell
CC surface.
CC -!- TISSUE SPECIFICITY: Expressed throughout the embryo.
CC -!- PTM: Proteolytic processing by Rhomboid occurs in the Golgi. Cleavage
CC takes place within the transmembrane domain close to residue 144 and
CC the active growth factor is released. {ECO:0000269|PubMed:11672524}.
CC -!- PTM: N-glycosylated and O-glycosylated.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA28894.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M95199; AAA28894.1; ALT_INIT; mRNA.
DR EMBL; AE014134; AAF53831.2; -; Genomic_DNA.
DR EMBL; AY089693; AAL90431.1; -; mRNA.
DR PIR; A44074; A44074.
DR RefSeq; NP_001027281.1; NM_001032110.2.
DR RefSeq; NP_476909.2; NM_057561.6.
DR RefSeq; NP_599118.2; NM_134291.5.
DR RefSeq; NP_599119.2; NM_134292.3.
DR RefSeq; NP_599120.2; NM_134293.3.
DR PDB; 3C9A; X-ray; 1.60 A; C/D=76-127.
DR PDB; 3CA7; X-ray; 1.50 A; A=76-127.
DR PDB; 3LTF; X-ray; 3.20 A; B/D=76-133.
DR PDB; 3LTG; X-ray; 3.40 A; D=76-126.
DR PDBsum; 3C9A; -.
DR PDBsum; 3CA7; -.
DR PDBsum; 3LTF; -.
DR PDBsum; 3LTG; -.
DR AlphaFoldDB; Q01083; -.
DR SMR; Q01083; -.
DR BioGRID; 61229; 74.
DR DIP; DIP-18037N; -.
DR IntAct; Q01083; 6.
DR STRING; 7227.FBpp0080808; -.
DR GlyGen; Q01083; 1 site.
DR SwissPalm; Q01083; -.
DR PaxDb; Q01083; -.
DR PRIDE; Q01083; -.
DR EnsemblMetazoa; FBtr0081267; FBpp0080808; FBgn0005672.
DR EnsemblMetazoa; FBtr0081268; FBpp0080809; FBgn0005672.
DR EnsemblMetazoa; FBtr0081269; FBpp0080810; FBgn0005672.
DR EnsemblMetazoa; FBtr0081270; FBpp0080811; FBgn0005672.
DR EnsemblMetazoa; FBtr0100597; FBpp0100054; FBgn0005672.
DR GeneID; 35253; -.
DR KEGG; dme:Dmel_CG10334; -.
DR UCSC; CG10334-RA; d. melanogaster.
DR CTD; 35253; -.
DR FlyBase; FBgn0005672; spi.
DR VEuPathDB; VectorBase:FBgn0005672; -.
DR eggNOG; ENOG502S08N; Eukaryota.
DR GeneTree; ENSGT00520000062215; -.
DR HOGENOM; CLU_096616_0_0_1; -.
DR InParanoid; Q01083; -.
DR OMA; DGQCECC; -.
DR OrthoDB; 1421708at2759; -.
DR PhylomeDB; Q01083; -.
DR SignaLink; Q01083; -.
DR BioGRID-ORCS; 35253; 0 hits in 1 CRISPR screen.
DR ChiTaRS; spi; fly.
DR EvolutionaryTrace; Q01083; -.
DR GenomeRNAi; 35253; -.
DR PRO; PR:Q01083; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0005672; Expressed in eye disc (Drosophila) and 42 other tissues.
DR ExpressionAtlas; Q01083; baseline and differential.
DR Genevisible; Q01083; DM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:FlyBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:FlyBase.
DR GO; GO:0048018; F:receptor ligand activity; IDA:FlyBase.
DR GO; GO:0048149; P:behavioral response to ethanol; IMP:FlyBase.
DR GO; GO:0007298; P:border follicle cell migration; IMP:FlyBase.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0035225; P:determination of genital disc primordium; IMP:FlyBase.
DR GO; GO:0007391; P:dorsal closure; IMP:UniProtKB.
DR GO; GO:0001713; P:ectodermal cell fate determination; IMP:FlyBase.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:FlyBase.
DR GO; GO:0061331; P:epithelial cell proliferation involved in Malpighian tubule morphogenesis; IMP:FlyBase.
DR GO; GO:0003015; P:heart process; IMP:FlyBase.
DR GO; GO:0007476; P:imaginal disc-derived wing morphogenesis; IMP:FlyBase.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:FlyBase.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007438; P:oenocyte development; IMP:FlyBase.
DR GO; GO:0008355; P:olfactory learning; IMP:FlyBase.
DR GO; GO:0016318; P:ommatidial rotation; IMP:FlyBase.
DR GO; GO:0007422; P:peripheral nervous system development; IMP:FlyBase.
DR GO; GO:0046530; P:photoreceptor cell differentiation; IMP:FlyBase.
DR GO; GO:0043703; P:photoreceptor cell fate determination; IGI:FlyBase.
DR GO; GO:1903688; P:positive regulation of border follicle cell migration; IMP:FlyBase.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:FlyBase.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:FlyBase.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:FlyBase.
DR GO; GO:0035277; P:spiracle morphogenesis, open tracheal system; IMP:FlyBase.
DR GO; GO:0048865; P:stem cell fate commitment; IMP:FlyBase.
DR GO; GO:0007421; P:stomatogastric nervous system development; IMP:FlyBase.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR043403; Gurken/Spitz.
DR PANTHER; PTHR12332; PTHR12332; 1.
DR SMART; SM00181; EGF; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Developmental protein; Differentiation;
KW Disulfide bond; EGF-like domain; Endoplasmic reticulum; Glycoprotein;
KW Golgi apparatus; Membrane; Neurogenesis; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..234
FT /note="Protein spitz"
FT /id="PRO_0000007737"
FT TOPO_DOM 29..143
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..234
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 78..122
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 33..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 82..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:18500331"
FT DISULFID 91..110
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:18500331"
FT DISULFID 112..121
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:18500331"
FT CONFLICT 119
FT /note="Q -> R (in Ref. 4; AAL90431)"
FT /evidence="ECO:0000305"
FT HELIX 84..89
FT /evidence="ECO:0007829|PDB:3CA7"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:3CA7"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:3CA7"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:3CA7"
SQ SEQUENCE 234 AA; 26424 MW; 237F7A3B03DBD685 CRC64;
MHSTMSVQHG LVALVLIGCL AHPWHVEACS SRTVPKPRSS ISSSMSGTAL PPTQAPVTSS
TTMRTTTTTT PRPNITFPTY KCPETFDAWY CLNDAHCFAV KIADLPVYSC ECAIGFMGQR
CEYKEIDNTY LPKRPRPMLE KASIASGAMC ALVFMLFVCL AFYLRFEQRA AKKAYELEQE
LQQEYDDDDG QCECCRNRCC PDGQEPVILE RKLPYHMRLE HALMSFAIRR SNKL
