COS_DROME
ID COS_DROME Reviewed; 1201 AA.
AC O16844; A1Z6X4; B5RIP3; Q6AWI9; Q8IH04;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Kinesin-like protein costa;
DE AltName: Full=Kinesin-like protein costal2;
GN Name=cos; Synonyms=cos2, costal-2; ORFNames=CG1708;
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], FUNCTION, SUBCELLULAR LOCATION, SUBUNIT,
RP DEVELOPMENTAL STAGE, AND INTERACTION WITH CI.
RX PubMed=9244298; DOI=10.1016/s0092-8674(00)80332-3;
RA Sisson J.C., Ho K.S., Suyama K., Scott M.P.;
RT "Costal2, a novel kinesin-related protein in the Hedgehog signaling
RT pathway.";
RL Cell 90:235-245(1997).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Stapleton M., Carlson J.W., Booth B., Chavez C., Frise E., George R.A.,
RA Pacleb J.M., Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E.;
RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, AND INTERACTION WITH SMO; SGG; CKI ALPHA AND PROTEIN KINASE A
RP CATALYTIC SUBUNIT.
RX PubMed=15691767; DOI=10.1016/j.devcel.2005.01.001;
RA Zhang W., Zhao Y., Tong C., Wang G., Wang B., Jia J., Jiang J.;
RT "Hedgehog-regulated Costal2-kinase complexes control phosphorylation and
RT proteolytic processing of Cubitus interruptus.";
RL Dev. Cell 8:267-278(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-599 AND SER-605, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25639794; DOI=10.1016/j.chom.2014.12.012;
RA Lee K.A., Kim B., Bhin J., Kim D.H., You H., Kim E.K., Kim S.H., Ryu J.H.,
RA Hwang D., Lee W.J.;
RT "Bacterial uracil modulates Drosophila DUOX-dependent gut immunity via
RT Hedgehog-induced signaling endosomes.";
RL Cell Host Microbe 17:191-204(2015).
RN [9]
RP FUNCTION, INTERACTION WITH UBR3, AND UBIQUITINATION.
RX PubMed=27195754; DOI=10.1371/journal.pgen.1006054;
RA Li T., Fan J., Blanco-Sanchez B., Giagtzoglou N., Lin G., Yamamoto S.,
RA Jaiswal M., Chen K., Zhang J., Wei W., Lewis M.T., Groves A.K.,
RA Westerfield M., Jia J., Bellen H.J.;
RT "Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-
RT 2 and Kif7 through Poly-ubiquitination.";
RL PLoS Genet. 12:E1006054-E1006054(2016).
CC -!- FUNCTION: Regulates cubitus interruptus (ci) processing by recruiting
CC multiple kinases to promote its efficient phosphorylation. Scaffolds
CC multiple kinases and ci into proximity to promote its
CC hyperphosphorylation, which then targets it for SCFSlimb/proteasome-
CC mediated processing to generate its repressor form. Hh signaling
CC inhibits ci phosphorylation by interfering with the cos-ci-kinases
CC complex formation. Negatively regulates hh-signaling pathways during
CC various processes, including photoreceptor differentiation
CC (PubMed:25639794, PubMed:27195754). May negatively regulate a hh-
CC signaling pathway which functions in the intestinal immune response to
CC bacterial uracil by activating the Duox-dependent production of
CC reactive oxygen species (ROS) (PubMed:25639794).
CC {ECO:0000269|PubMed:15691767, ECO:0000269|PubMed:25639794,
CC ECO:0000269|PubMed:9244298}.
CC -!- SUBUNIT: Homodimer (Potential). Binds microtubules. Interacts with ci,
CC smo, sgg, CkIalpha and protein kinase A catalytic subunit
CC (PubMed:15691767, PubMed:9244298). Interacts (via kinesin motor domain)
CC with Ubr3 (PubMed:27195754). {ECO:0000269|PubMed:15691767,
CC ECO:0000269|PubMed:9244298, ECO:0000305}.
CC -!- INTERACTION:
CC O16844; P19538: ci; NbExp=12; IntAct=EBI-102069, EBI-94976;
CC O16844; P23647: fu; NbExp=6; IntAct=EBI-102069, EBI-165536;
CC O16844; P91682: smo; NbExp=6; IntAct=EBI-102069, EBI-142245;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:9244298}.
CC -!- DEVELOPMENTAL STAGE: Present at high levels during the first 4 hours of
CC embryogenesis and at moderate levels between 4-12 hours.
CC {ECO:0000269|PubMed:9244298}.
CC -!- PTM: Polyubiquitinated by Ubr3, which leads to proteasomal degradation.
CC {ECO:0000269|PubMed:27195754}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in the increased
CC expression of reactive oxygen species (ROS) in the gut of 7 day old
CC conventionally reared adult flies. No increased ROS expression in germ-
CC free adults and in response to bacteria-derived uracil.
CC {ECO:0000269|PubMed:25639794}.
CC -!- SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase
CC superfamily. Kinesin family. KIF27 subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00283}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAN71259.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF019250; AAB66813.1; -; mRNA.
DR EMBL; AE013599; AAF59270.1; -; Genomic_DNA.
DR EMBL; BT001504; AAN71259.1; ALT_FRAME; mRNA.
DR EMBL; BT015259; AAT94488.1; -; mRNA.
DR EMBL; BT044167; ACH92232.1; -; mRNA.
DR PIR; T08603; T08603.
DR RefSeq; NP_001260765.1; NM_001273836.1.
DR RefSeq; NP_477092.1; NM_057744.3.
DR AlphaFoldDB; O16844; -.
DR SMR; O16844; -.
DR BioGRID; 61534; 30.
DR DIP; DIP-22550N; -.
DR IntAct; O16844; 8.
DR STRING; 7227.FBpp0088087; -.
DR iPTMnet; O16844; -.
DR PaxDb; O16844; -.
DR DNASU; 35653; -.
DR EnsemblMetazoa; FBtr0089015; FBpp0088087; FBgn0000352.
DR EnsemblMetazoa; FBtr0336916; FBpp0307854; FBgn0000352.
DR GeneID; 35653; -.
DR KEGG; dme:Dmel_CG1708; -.
DR CTD; 35653; -.
DR FlyBase; FBgn0000352; cos.
DR VEuPathDB; VectorBase:FBgn0000352; -.
DR eggNOG; ENOG502QUYG; Eukaryota.
DR GeneTree; ENSGT00940000169432; -.
DR HOGENOM; CLU_010897_0_0_1; -.
DR InParanoid; O16844; -.
DR OMA; SDLCGTE; -.
DR OrthoDB; 216446at2759; -.
DR PhylomeDB; O16844; -.
DR Reactome; R-DME-209159; Assembly of the CI containing complexes.
DR Reactome; R-DME-209190; Phosphorylation of CI.
DR Reactome; R-DME-209214; Phosphorylation of SMO.
DR Reactome; R-DME-209338; Assembly of the 'signalling complexes'.
DR Reactome; R-DME-209360; Ubiquitination and proteolysis of phosphorylated CI.
DR Reactome; R-DME-216119; Activation of CI.
DR Reactome; R-DME-216217; Activation of SMO.
DR Reactome; R-DME-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
DR Reactome; R-DME-983189; Kinesins.
DR SignaLink; O16844; -.
DR BioGRID-ORCS; 35653; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 35653; -.
DR PRO; PR:O16844; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0000352; Expressed in eye disc (Drosophila) and 22 other tissues.
DR ExpressionAtlas; O16844; baseline and differential.
DR Genevisible; O16844; DM.
DR GO; GO:0005929; C:cilium; IEA:GOC.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:FlyBase.
DR GO; GO:0035301; C:Hedgehog signaling complex; IPI:FlyBase.
DR GO; GO:0005871; C:kinesin complex; ISS:FlyBase.
DR GO; GO:0005874; C:microtubule; IBA:GO_Central.
DR GO; GO:0005875; C:microtubule associated complex; IPI:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0012506; C:vesicle membrane; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0003774; F:cytoskeletal motor activity; ISS:FlyBase.
DR GO; GO:0008017; F:microtubule binding; IDA:FlyBase.
DR GO; GO:0003777; F:microtubule motor activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:FlyBase.
DR GO; GO:0140311; F:protein sequestering activity; IMP:FlyBase.
DR GO; GO:0035591; F:signaling adaptor activity; IDA:FlyBase.
DR GO; GO:0005119; F:smoothened binding; IPI:FlyBase.
DR GO; GO:0008134; F:transcription factor binding; IPI:FlyBase.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:FlyBase.
DR GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; IGI:FlyBase.
DR GO; GO:0007476; P:imaginal disc-derived wing morphogenesis; IMP:FlyBase.
DR GO; GO:0042073; P:intraciliary transport; IMP:FlyBase.
DR GO; GO:0007018; P:microtubule-based movement; IBA:GO_Central.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IDA:FlyBase.
DR GO; GO:0030707; P:ovarian follicle cell development; IMP:FlyBase.
DR GO; GO:0042981; P:regulation of apoptotic process; IGI:FlyBase.
DR GO; GO:0007224; P:smoothened signaling pathway; IDA:FlyBase.
DR Gene3D; 3.40.850.10; -; 2.
DR InterPro; IPR027640; Kinesin-like_fam.
DR InterPro; IPR001752; Kinesin_motor_dom.
DR InterPro; IPR036961; Kinesin_motor_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR24115; PTHR24115; 1.
DR Pfam; PF00225; Kinesin; 2.
DR PRINTS; PR00380; KINESINHEAVY.
DR SMART; SM00129; KISc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50067; KINESIN_MOTOR_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Coiled coil; Cytoplasm; Cytoskeleton; Microtubule;
KW Motor protein; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Repressor; Ubl conjugation.
FT CHAIN 1..1201
FT /note="Kinesin-like protein costa"
FT /id="PRO_0000307148"
FT DOMAIN 4..391
FT /note="Kinesin motor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00283"
FT REGION 23..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 502..536
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 565..606
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 618..639
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 652..821
FT /evidence="ECO:0000255"
FT COILED 968..1001
FT /evidence="ECO:0000255"
FT COMPBIAS 23..50
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..90
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 565..595
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 175..182
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00283"
FT MOD_RES 599
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 605
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 7
FT /note="V -> L (in Ref. 1; AAB66813)"
FT /evidence="ECO:0000305"
FT CONFLICT 471
FT /note="E -> D (in Ref. 1; AAB66813)"
FT /evidence="ECO:0000305"
FT CONFLICT 568
FT /note="A -> E (in Ref. 5; AAT94488)"
FT /evidence="ECO:0000305"
FT CONFLICT 736
FT /note="D -> G (in Ref. 1; AAB66813)"
FT /evidence="ECO:0000305"
FT CONFLICT 807
FT /note="A -> V (in Ref. 1; AAB66813)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1201 AA; 133148 MW; 6DC898F8B4C8F20F CRC64;
MEIPIQVAVR IFPHRELKDL LRSFGPTEPK KDAQAVDEGA DSKDSEAQVP AAEKDNPSIS
ETDPNGNAEQ DSAADSKTIP DANGNDSGQK DYPDSAYCVQ AIPISASALG LPSALPGGDP
MDSIAAGLIQ VGPHTVPVTH ALPSSSSQEQ VYHQTVFPLI TLFLEGFDAS VVTYGQRGQG
KSYTLYGNVQ DPTLTDSTEG VVQLCVRDIF SHISLHPERT YAINVGFVEI CGGDVCDLLG
MGNIHCTNVD AVFHWLQVGL SARQSLPAHT LFTLTLEQQW VSKEGLLQHR LSTASFSDLC
GTERCGDQPP GRPLDAGLCM LEQVISTLTD PGLMYGVNGN IPYGQTTLTT LLKDSFGGRA
QTLVILCVSP LEEHLPETLG NLQFAFKVQC VRNFVIMNTY SDDNTMIVQP AEPVPESNSS
AGPLSQAGPG DNFGLQFAAS QWSKLVTNAE GLFSKLIDSK LITEVEKEQI EEWLFLKQEC
EECLSSTEAM RQQKQLVPIL EAEEPEDVNS EAANSESPNS DNENDTDNES HRPDLDDKIE
SLMEEFRDKT DALILEKHAE YLSKHPKAVM QSQDREIEAQ PPEENGDDRK VSIGSRRRSV
QPGASLSTAE LAMLNRVASQ QPPPPIDPES VVDPLESSSG EGIRQAALAA AAATAPIEQL
QKKLRKLVAE IEGKQRQLRE IEETIQVKQN IIAELVKNSD TRSHAKQRFH KKRAKLEAEC
DKAKKQLGKA LVQGRDQSEI ERWTTIIGHL ERRLEDLSSM KHIAGESGQK VKKLQQSVGE
SRKQADDLQK KLRKECKLRC QMEAELAKLR ESRETGKELV KAQGSPEQQG RQLKAVQARI
THLNHILREK SDNLEEQPGP EQQETLRHEI RNLRGTRDLL LEERCHLDRK LKRDKVLTQK
EERKLLECDE AIEAIDAAIE FKNEMITGHR SIDTSDRIQR EKGEQMLMAR LNRLSTEEMR
TLLYKYFTKV IDLRDSSRKL ELQLVQLERE RDAWEWKERV LSNAVRQARL EGERNAVLLQ
RQHEMKLTLM LRHMAEETSA SSASYGERAL APACVAPPVQ ASSDFDYDHF YKGGGNPSKA
LIKAPKPMPT GSALDKYKDK EQRSGRNIFA KFHVLTRYAS AAAAGSSGST AEESTALIES
TTTATATTTS TTTTGAVGKV KDKALVSFRP EQLKRLMPAP TATKVTRQKN KIIIQDASRR
N
