ID COW_DROME Reviewed; 629 AA.
AC Q9VCR3; B5RJH8;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 27-MAR-2024, entry version 180.
DE RecName: Full=Proteoglycan Cow {ECO:0000305};
DE AltName: Full=Carrier of wingless {ECO:0000303|PubMed:25360738};
DE Short=Carrier of wg {ECO:0000303|PubMed:25360738};
DE Flags: Precursor;
GN Name=Cow {ECO:0000312|FlyBase:FBgn0039054};
GN ORFNames=CG13830 {ECO:0000312|FlyBase:FBgn0039054};
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:ACH92517.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:ACH92517.1};
RC TISSUE=Head {ECO:0000312|EMBL:ACH92517.1};
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH WG, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 287-SER-GLY-288 AND
RP 331-SER-GLY-332.
RX PubMed=25360738; DOI=10.1371/journal.pone.0111573;
RA Chang Y.H., Sun Y.H.;
RT "Carrier of Wingless (Cow), a secreted heparan sulfate proteoglycan,
RT promotes extracellular transport of Wingless.";
RL PLoS ONE 9:E111573-E111573(2014).
CC -!- FUNCTION: Binds to the Wnt signaling protein wg, stabilizes it and
CC promotes its extracellular distribution. This is required for
CC establishment of a wg gradient during development to allow for
CC regulation of target genes at different levels.
CC {ECO:0000269|PubMed:25360738}.
CC -!- SUBUNIT: Interacts (in heparan sulfate-bound form) with wg.
CC {ECO:0000269|PubMed:25360738}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25360738}.
CC -!- TISSUE SPECIFICITY: In the wing disk, detected throughout the disk
CC where it is localized primarily to the apical surface but is also
CC present at the basal surface (at protein level).
CC {ECO:0000269|PubMed:25360738}.
CC -!- PTM: Contains heparan sulfate O-linked oligosaccharides.
CC {ECO:0000269|PubMed:25360738}.
CC -!- DISRUPTION PHENOTYPE: Predominantly embryonic lethal with 50% of
CC embryos dying before cuticle formation and 10% showing a weak denticle
CC belt fusion phenotype. RNAi-mediated knockdown in the developing wing
CC results in development of ectopic chemosensory bristles along or near
CC the wing margin on both the anterior and posterior sides.
CC {ECO:0000269|PubMed:25360738}.
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DR EMBL; AE014297; AAF56093.3; -; Genomic_DNA.
DR EMBL; AE014297; ACZ94990.1; -; Genomic_DNA.
DR EMBL; BT044452; ACH92517.1; -; mRNA.
DR RefSeq; NP_001097883.2; NM_001104413.3.
DR RefSeq; NP_001163695.1; NM_001170224.2.
DR AlphaFoldDB; Q9VCR3; -.
DR SMR; Q9VCR3; -.
DR IntAct; Q9VCR3; 4.
DR STRING; 7227.FBpp0307957; -.
DR GlyCosmos; Q9VCR3; 2 sites, No reported glycans.
DR GlyGen; Q9VCR3; 2 sites.
DR PaxDb; 7227-FBpp0291233; -.
DR DNASU; 42733; -.
DR EnsemblMetazoa; FBtr0302022; FBpp0291232; FBgn0039054.
DR EnsemblMetazoa; FBtr0302023; FBpp0291233; FBgn0039054.
DR GeneID; 42733; -.
DR KEGG; dme:Dmel_CG13830; -.
DR UCSC; CG13830-RB; d. melanogaster.
DR AGR; FB:FBgn0039054; -.
DR CTD; 42733; -.
DR FlyBase; FBgn0039054; Cow.
DR VEuPathDB; VectorBase:FBgn0039054; -.
DR eggNOG; KOG3555; Eukaryota.
DR GeneTree; ENSGT00940000171496; -.
DR InParanoid; Q9VCR3; -.
DR PhylomeDB; Q9VCR3; -.
DR SignaLink; Q9VCR3; -.
DR BioGRID-ORCS; 42733; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Cow; fly.
DR GenomeRNAi; 42733; -.
DR PRO; PR:Q9VCR3; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039054; Expressed in brain and 11 other cell types or tissues.
DR ExpressionAtlas; Q9VCR3; baseline and differential.
DR GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:FlyBase.
DR GO; GO:0035592; P:establishment of protein localization to extracellular region; IMP:FlyBase.
DR GO; GO:0006858; P:extracellular transport; IMP:FlyBase.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:FlyBase.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:FlyBase.
DR GO; GO:0007367; P:segment polarity determination; IGI:FlyBase.
DR GO; GO:0048190; P:wing disc dorsal/ventral pattern formation; IMP:FlyBase.
DR CDD; cd16232; EFh_SPARC_TICN; 1.
DR CDD; cd00104; KAZAL_FS; 1.
DR CDD; cd00191; TY; 1.
DR Gene3D; 3.30.60.30; -; 1.
DR Gene3D; 1.10.238.10; EF-hand; 1.
DR Gene3D; 4.10.800.10; Thyroglobulin type-1; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002350; Kazal_dom.
DR InterPro; IPR036058; Kazal_dom_sf.
DR InterPro; IPR019577; SPARC/Testican_Ca-bd-dom.
DR InterPro; IPR000716; Thyroglobulin_1.
DR InterPro; IPR036857; Thyroglobulin_1_sf.
DR PANTHER; PTHR12352; SECRETED MODULAR CALCIUM-BINDING PROTEIN; 1.
DR PANTHER; PTHR12352:SF25; SPARC_OSTEONECTIN, CWCV AND KAZAL-LIKE DOMAINS PROTEOGLYCAN 1; 1.
DR Pfam; PF07648; Kazal_2; 1.
DR Pfam; PF10591; SPARC_Ca_bdg; 1.
DR Pfam; PF00086; Thyroglobulin_1; 1.
DR SMART; SM00280; KAZAL; 1.
DR SMART; SM00211; TY; 1.
DR SUPFAM; SSF47473; EF-hand; 1.
DR SUPFAM; SSF100895; Kazal-type serine protease inhibitors; 1.
DR SUPFAM; SSF57610; Thyroglobulin type-1 domain; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS51465; KAZAL_2; 1.
DR PROSITE; PS00484; THYROGLOBULIN_1_1; 1.
DR PROSITE; PS51162; THYROGLOBULIN_1_2; 1.
PE 1: Evidence at protein level;
KW Calcium; Disulfide bond; Glycoprotein; Heparan sulfate; Metal-binding;
KW Protease inhibitor; Proteoglycan; Reference proteome; Repeat; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..629
FT /note="Proteoglycan Cow"
FT /evidence="ECO:0000255"
FT /id="PRO_5007216230"
FT DOMAIN 222..273
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 468..503
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 508..535
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 533..594
FT /note="Thyroglobulin type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT REGION 118..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 198..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 298..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 602..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 142..165
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 198..215
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..346
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 607..621
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 481
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 483
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 485
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 487
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 492
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT SITE 233..234
FT /note="Reactive bond"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 228..258
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 231..251
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 240..272
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 536..555
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT DISULFID 566..573
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT DISULFID 575..594
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT MUTAGEN 287..288
FT /note="SG->AA: Abolishes interaction with wg and causes
FT significant reduction of 100 kDa form which is likely to be
FT the heparan sulfate-modified form; when associated with A-
FT 331 and A-332."
FT /evidence="ECO:0000269|PubMed:25360738"
FT MUTAGEN 331..332
FT /note="SG->AA: Abolishes interaction with wg and causes
FT significant reduction of 100 kDa form which is likely to be
FT the heparan sulfate-modified form; when associated with A-
FT 287 and A-288."
FT /evidence="ECO:0000269|PubMed:25360738"
SQ SEQUENCE 629 AA; 71474 MW; FB8B3537D41FB17A CRC64;
MKHSPLIASA CLALVLMSSS LIGSTEARNK KKYVGETGGD FEFIDEINKN TQSNKNLGEH
KRWIHDPSSD LCRPLNCKKR EICLLEDEFS AVCVSKKELH KNRDEIITKA KYLEEEAKRR
VNQQDNQDSQ DAEDINNDDE DNSSDGGSSN SSPTGTNNAQ ASVQGNEETD DEDKSLSLGD
DDESKEDDVF YENSIAAGDK QQQQQQLSQP AAGPSVIQQD DDEELDNCKP CPVAKPTFLC
GADNRTYSSL CRLDYHNCIH STSIRIACKG FCPCKEIVDG KRLQRISGYN NKYNKKISLD
QQQQQQQQQQ QQQQQQQAYK DSNNNNIMMN SGNIMGGNNN DFNTIMNDKE DNNRHNNHIN
AQYTFTPEEI KYDNKHYKYL KYTAYKKDSK YQEDKHKMRN YNEVVEKQQQ KFNKNSNLNA
YPSKSAECKP QQLTAIGNRL LDWFSVIMAD SKKRRQHSQK SKAHFPPACK TEAKWMFGHL
DLNNDGQLSL QEMYDLEHDQ NERCIKPFID TCDLDTDSSI NTREWCRCFE KTDRPCAAVR
RRIAGDFAGA YAPDCDIQGF YKPTQCHNSV GVCWCVDKHG VEFANTRTRG KPNCESVVNN
AASLTSDDED EGADDEDSAE GSADQMLVF
//
