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SCA_DROME
ID   SCA_DROME               Reviewed;         799 AA.
AC   P21520; Q0E998; Q8MQI8; Q9V6G9;
DT   01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT   24-OCT-2003, sequence version 3.
DT   03-AUG-2022, entry version 175.
DE   RecName: Full=Protein scabrous;
DE   Flags: Precursor;
GN   Name=sca; ORFNames=CG17579;
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 [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=2175046; DOI=10.1126/science.2175046;
RA   Baker N.E., Mlodzik M., Rubin G.M.;
RT   "Spacing differentiation in the developing Drosophila eye: a fibrinogen-
RT   related lateral inhibitor encoded by scabrous.";
RL   Science 250:1370-1377(1990).
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=Embryo;
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, AND SUBCELLULAR LOCATION.
RX   PubMed=12756167; DOI=10.1242/dev.00495;
RA   Li Y., Fetchko M., Lai Z.C., Baker N.E.;
RT   "Scabrous and Gp150 are endosomal proteins that regulate Notch activity.";
RL   Development 130:2819-2827(2003).
CC   -!- FUNCTION: Involved in regulation of neurogenesis. May encode a lateral
CC       inhibitor of R8 differentiation. In conjunction with Gp150, promotes
CC       Notch activation in response to Delta by regulating acquisition of
CC       insensitivity to Delta in a subset of cells.
CC       {ECO:0000269|PubMed:12756167, ECO:0000269|PubMed:2175046}.
CC   -!- SUBCELLULAR LOCATION: Late endosome {ECO:0000269|PubMed:12756167,
CC       ECO:0000269|PubMed:2175046}. Note=Colocalizes in late endosomes with
CC       Gp150.
CC   -!- PTM: Possesses five pairs of dibasic residues that may be the target of
CC       proteolytic processing.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA28880.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; M60065; AAA28880.1; ALT_INIT; Genomic_DNA.
DR   EMBL; AE013599; AAF58455.2; -; Genomic_DNA.
DR   EMBL; AY129456; AAM76198.1; -; mRNA.
DR   PIR; A39832; A39832.
DR   RefSeq; NP_476710.2; NM_057362.3.
DR   RefSeq; NP_725230.2; NM_165951.2.
DR   AlphaFoldDB; P21520; -.
DR   SMR; P21520; -.
DR   BioGRID; 62183; 14.
DR   IntAct; P21520; 2.
DR   MINT; P21520; -.
DR   STRING; 7227.FBpp0086969; -.
DR   GlyGen; P21520; 6 sites.
DR   PaxDb; P21520; -.
DR   DNASU; 36411; -.
DR   EnsemblMetazoa; FBtr0087855; FBpp0086968; FBgn0003326.
DR   EnsemblMetazoa; FBtr0087856; FBpp0086969; FBgn0003326.
DR   GeneID; 36411; -.
DR   KEGG; dme:Dmel_CG17579; -.
DR   CTD; 36411; -.
DR   FlyBase; FBgn0003326; sca.
DR   VEuPathDB; VectorBase:FBgn0003326; -.
DR   eggNOG; KOG2579; Eukaryota.
DR   HOGENOM; CLU_021665_0_0_1; -.
DR   InParanoid; P21520; -.
DR   OMA; DADMRTE; -.
DR   OrthoDB; 497548at2759; -.
DR   PhylomeDB; P21520; -.
DR   Reactome; R-DME-114608; Platelet degranulation.
DR   Reactome; R-DME-1474228; Degradation of the extracellular matrix.
DR   Reactome; R-DME-1474244; Extracellular matrix organization.
DR   Reactome; R-DME-1566977; Fibronectin matrix formation.
DR   Reactome; R-DME-202733; Cell surface interactions at the vascular wall.
DR   Reactome; R-DME-210993; Tie2 Signaling.
DR   Reactome; R-DME-216083; Integrin cell surface interactions.
DR   Reactome; R-DME-3000170; Syndecan interactions.
DR   Reactome; R-DME-3000178; ECM proteoglycans.
DR   Reactome; R-DME-354192; Integrin signaling.
DR   Reactome; R-DME-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-DME-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-DME-5674135; MAP2K and MAPK activation.
DR   Reactome; R-DME-8957275; Post-translational protein phosphorylation.
DR   Reactome; R-DME-9634597; GPER1 signaling.
DR   SignaLink; P21520; -.
DR   BioGRID-ORCS; 36411; 0 hits in 3 CRISPR screens.
DR   GenomeRNAi; 36411; -.
DR   PRO; PR:P21520; -.
DR   Proteomes; UP000000803; Chromosome 2R.
DR   Bgee; FBgn0003326; Expressed in eye disc (Drosophila) and 24 other tissues.
DR   Genevisible; P21520; DM.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0008407; P:chaeta morphogenesis; IMP:FlyBase.
DR   GO; GO:0048749; P:compound eye development; IMP:FlyBase.
DR   GO; GO:0008587; P:imaginal disc-derived wing margin morphogenesis; IMP:FlyBase.
DR   GO; GO:0007399; P:nervous system development; IGI:FlyBase.
DR   GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0016318; P:ommatidial rotation; IMP:FlyBase.
DR   GO; GO:0097305; P:response to alcohol; IMP:FlyBase.
DR   CDD; cd00087; FReD; 1.
DR   Gene3D; 3.90.215.10; -; 1.
DR   InterPro; IPR036056; Fibrinogen-like_C.
DR   InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR   InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR   InterPro; IPR020837; Fibrinogen_CS.
DR   Pfam; PF00147; Fibrinogen_C; 1.
DR   SMART; SM00186; FBG; 1.
DR   SUPFAM; SSF56496; SSF56496; 1.
DR   PROSITE; PS00514; FIBRINOGEN_C_1; 1.
DR   PROSITE; PS51406; FIBRINOGEN_C_2; 1.
PE   2: Evidence at transcript level;
KW   Developmental protein; Differentiation; Disulfide bond; Endosome;
KW   Glycoprotein; Neurogenesis; Notch signaling pathway; Reference proteome;
KW   Signal.
FT   SIGNAL          1..51
FT                   /evidence="ECO:0000255"
FT   CHAIN           52..799
FT                   /note="Protein scabrous"
FT                   /id="PRO_0000009108"
FT   DOMAIN          533..737
FT                   /note="Fibrinogen C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT   REGION          287..316
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          489..509
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        287..312
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        372
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        587
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        618
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        660
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        744
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        787
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        542..568
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT   DISULFID        687..700
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT   CONFLICT        301
FT                   /note="G -> C (in Ref. 1; AAA28880)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   799 AA;  90119 MW;  87E1B4D60D4F5C29 CRC64;
     MRDWQTFPDL QKKKVSRDHL NCPATMAGSN VLWPILLAVV LLQISVAFVS GAASGGVVLS
     DVNNMLRDAK VVTSEKPVVH SKQETEAPES SVELLRFVDD DEDSEDISSI ERQDGRTMES
     KKMADQVRLL TKQLNALMLR RREDYEMLEH NLRKSLRLTT NANSVDADMR SELNQLREEL
     AALRSSQSGN KERLTVEWLQ QTISEIRKQL VDLQRTASNV AQDVQQRSST FEDLATIRSD
     YQQLKLDLAA QRERQQQTEV YVQELREEML QQEQDFQHAL VKLQQRTRKD GSSASVEEES
     GSQEANQEQT GLETTADHKR RHCRFQSEQI HQLQLAQRNL RRQVNGLRFH HIDERVRSIE
     VEQHRIANAN FNLSSQIASL DKLHTSMLEL LEDVEGLQTK MDKSIPELRH EISKLEFANA
     QITSEQSLIR EEGTNAARSL QAMAVSVSVL QEEREGMRKL SANVDQLRTN VDRLQSLVND
     EMKNKLTHLN KPHKRPHHQN VQAQMPQDDS PIDSVLAETL VSELENVETQ YEAIINKLPH
     DCSEVHTQTD GLHLIAPAGQ RHPLMTHCTA DGWTTVQRRF DGSADFNRSW ADYAQGFGAP
     GGEFWIGNEQ LHHLTLDNCS RLQVQMQDIY DNVWVAEYKR FYISSRADGY RLHIAEYSGN
     ASDALNYQQG MQFSAIDDDR DISQTHCAAN YEGGWWFSHC QHANLNGRYN LGLTWFDAAR
     NEWIAVKSSR MLVKRLPAVE CQANASASGA FVSVSGSAAD AAPSSGATTT TTTATAAPAT
     VTTPKTNNSV VQFVAAGQA
 
 
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