FOJO_DROME
ID FOJO_DROME Reviewed; 583 AA.
AC P54360; Q24176; Q8SZ37; Q9V8E3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Extracellular serine/threonine protein kinase four-jointed {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000305};
DE Contains:
DE RecName: Full=Protein four-jointed, secreted isoform;
GN Name=fj {ECO:0000312|FlyBase:FBgn0000658}; ORFNames=CG10917;
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, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RC TISSUE=Eye imaginal disk;
RX PubMed=7555705; DOI=10.1242/dev.121.9.2767;
RA Villano J.L., Katz F.N.;
RT "four-jointed is required for intermediate growth in the proximal-distal
RT axis in Drosophila.";
RL Development 121:2767-2777(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Canton-S;
RX PubMed=8606003; DOI=10.1006/dbio.1996.0038;
RA Brodsky M.H., Steller H.;
RT "Positional information along the dorsal-ventral axis of the Drosophila
RT eye: graded expression of the four-jointed gene.";
RL Dev. Biol. 173:428-446(1996).
RN [3]
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 [4]
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 [5]
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 [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10607560; DOI=10.1016/s0960-9822(00)80081-0;
RA Zeidler M.P., Perrimon N., Strutt D.I.;
RT "The four-jointed gene is required in the Drosophila eye for ommatidial
RT polarity specification.";
RL Curr. Biol. 9:1363-1372(1999).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11566858; DOI=10.1242/dev.128.18.3533;
RA Buckles G.R., Rauskolb C., Villano J.L., Katz F.N.;
RT "Four-jointed interacts with dachs, abelson and enabled and feeds back onto
RT the Notch pathway to affect growth and segmentation in the Drosophila
RT leg.";
RL Development 128:3533-3542(2001).
RN [8]
RP FUNCTION, PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=14757640; DOI=10.1242/dev.00996;
RA Strutt H., Mundy J., Hofstra K., Strutt D.;
RT "Cleavage and secretion is not required for four-jointed function in
RT Drosophila patterning.";
RL Development 131:881-890(2004).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF 490-ASP--GLU-492.
RX PubMed=18635802; DOI=10.1126/science.1158159;
RA Ishikawa H.O., Takeuchi H., Haltiwanger R.S., Irvine K.D.;
RT "Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin
RT domains.";
RL Science 321:401-404(2008).
CC -!- FUNCTION: Golgi serine/threonine protein kinase required for
CC intermediate growth in the proximal-distal axis. Phosphorylates
CC specific residues within extracellular cadherin domains of Fat (ft) and
CC Dachsous (ds) as they transit through the Golgi (PubMed:18635802). Acts
CC in ommatidial polarity determination as a secondary signal downstream
CC of Notch, JAK/STAT and wingless. Also necessary for the initiation, up-
CC regulation or maintenance of Notch ligand, Serrate (Ser) expression in
CC legs, thereby participating in a feedback loop with N signaling.
CC Sufficient for joint formation and growth in the leg (PubMed:10607560,
CC PubMed:11566858, PubMed:14757640, PubMed:7555705, PubMed:8606003).
CC {ECO:0000269|PubMed:10607560, ECO:0000269|PubMed:11566858,
CC ECO:0000269|PubMed:14757640, ECO:0000269|PubMed:18635802,
CC ECO:0000269|PubMed:7555705, ECO:0000269|PubMed:8606003}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000305};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:11566858, ECO:0000269|PubMed:14757640}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:11566858,
CC ECO:0000269|PubMed:14757640}. Note=Golgi apparatus, in the wing pouch.
CC -!- SUBCELLULAR LOCATION: [Protein four-jointed, secreted isoform]:
CC Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: In the eye disk, expressed in a gradient ahead of
CC the morphogenetic furrow, high at the equator and low at the poles of
CC the eye. In the leg disk, expressed in concentric rings, possibly
CC corresponding to segmental boundaries. In the wing disk, expression is
CC localized in the wing pouch; low in peripheral regions and high towards
CC the center. {ECO:0000269|PubMed:10607560, ECO:0000269|PubMed:11566858,
CC ECO:0000269|PubMed:14757640, ECO:0000269|PubMed:7555705,
CC ECO:0000269|PubMed:8606003}.
CC -!- PTM: Proteolytically cleaved to yield a secreted protein.
CC {ECO:0000269|PubMed:14757640}.
CC -!- DISRUPTION PHENOTYPE: Mutants show reduced growth and altered
CC differentiation only within restricted sectors of the proximal-distal
CC (PD) axis in the leg and wing. {ECO:0000269|PubMed:7555705}.
CC -!- SIMILARITY: Belongs to the FJX1/FJ family. {ECO:0000305}.
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DR EMBL; U28837; AAA69524.1; -; mRNA.
DR EMBL; U44904; AAB01809.1; -; mRNA.
DR EMBL; AE013599; AAF57724.2; -; Genomic_DNA.
DR EMBL; AY071147; AAL48769.1; -; mRNA.
DR RefSeq; NP_477483.1; NM_058135.4.
DR AlphaFoldDB; P54360; -.
DR BioGRID; 62770; 23.
DR STRING; 7227.FBpp0085933; -.
DR GlyGen; P54360; 3 sites.
DR PaxDb; P54360; -.
DR DNASU; 37089; -.
DR EnsemblMetazoa; FBtr0086754; FBpp0085933; FBgn0000658.
DR GeneID; 37089; -.
DR KEGG; dme:Dmel_CG10917; -.
DR UCSC; CG10917-RA; d. melanogaster.
DR CTD; 37089; -.
DR FlyBase; FBgn0000658; fj.
DR VEuPathDB; VectorBase:FBgn0000658; -.
DR eggNOG; ENOG502QUJ4; Eukaryota.
DR GeneTree; ENSGT00390000016768; -.
DR HOGENOM; CLU_033850_1_0_1; -.
DR InParanoid; P54360; -.
DR OMA; NAFHLEQ; -.
DR OrthoDB; 1414662at2759; -.
DR PhylomeDB; P54360; -.
DR BioGRID-ORCS; 37089; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 37089; -.
DR PRO; PR:P54360; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0000658; Expressed in wing disc and 72 other tissues.
DR Genevisible; P54360; DM.
DR GO; GO:0005737; C:cytoplasm; HDA:FlyBase.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:FlyBase.
DR GO; GO:0004672; F:protein kinase activity; IDA:FlyBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:FlyBase.
DR GO; GO:0007267; P:cell-cell signaling; IDA:FlyBase.
DR GO; GO:0001737; P:establishment of imaginal disc-derived wing hair orientation; IMP:FlyBase.
DR GO; GO:0042067; P:establishment of ommatidial planar polarity; IMP:UniProtKB.
DR GO; GO:0001736; P:establishment of planar polarity; IMP:FlyBase.
DR GO; GO:0007446; P:imaginal disc growth; IMP:FlyBase.
DR GO; GO:0016348; P:imaginal disc-derived leg joint morphogenesis; IMP:FlyBase.
DR GO; GO:0007474; P:imaginal disc-derived wing vein specification; IMP:FlyBase.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0090175; P:regulation of establishment of planar polarity; IMP:FlyBase.
DR GO; GO:0043393; P:regulation of protein binding; IDA:UniProtKB.
DR GO; GO:0035159; P:regulation of tube length, open tracheal system; IMP:FlyBase.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR024868; FJX1/FJ.
DR PANTHER; PTHR13147; PTHR13147; 1.
DR PRINTS; PR02072; 4JOINTEDBOX1.
PE 1: Evidence at protein level;
KW Glycoprotein; Golgi apparatus; Kinase; Membrane; Notch signaling pathway;
KW Reference proteome; Secreted; Serine/threonine-protein kinase;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix;
KW Wnt signaling pathway.
FT CHAIN 1..583
FT /note="Extracellular serine/threonine protein kinase four-
FT jointed"
FT /id="PRO_0000087324"
FT CHAIN ?..583
FT /note="Protein four-jointed, secreted isoform"
FT /id="PRO_0000292347"
FT TOPO_DOM 1..78
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 79..99
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 100..583
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 179..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 384..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 179..202
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 203..222
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 406..421
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 491
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 490..492
FT /note="DNE->GGG: Abolishes the protein kinase activity."
FT /evidence="ECO:0000269|PubMed:18635802"
FT CONFLICT 48
FT /note="P -> S (in Ref. 1; AAA69524 and 2; AAB01809)"
FT /evidence="ECO:0000305"
FT CONFLICT 126
FT /note="S -> T (in Ref. 1; AAA69524)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="L -> M (in Ref. 1; AAA69524)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="F -> L (in Ref. 1; AAA69524 and 2; AAB01809)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="R -> P (in Ref. 1; AAA69524)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="A -> R (in Ref. 1; AAA69524)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 583 AA; 65490 MW; 8AADC85FC85D09A4 CRC64;
MYDIKRLEAG QQKLQQAQQP LGLDLSGQQQ QLTCSVITAP EHRANPNPSS ISQSNPSEAT
HMTLLTLRRR RSLQRRACLL SILAAFVFGM ALGVVVPMFG LPRHQDSPPD LPEEQIQMVA
VEPLSSYRVE FIKETDELSA EQVFRNAFHL EQDKDAPDSM VVKKLDTNDG SIKEFHVQRT
ASGRYRKGPE RRLSKKMPER VQPQETSRSP TTSPTNPTSE HQAGFIEEDV YWGPTVEQAL
PKGFAAKDQV SWERFVGEQG RVVRLEQGCG RMQNRMVVFA DGTRACARYR QNTDQIQGEI
FSYYLGQLLN ISNLAPSAAT VVDTSTPNWA AALGDITQAQ WKERRPVVLT RWLSDLEPAG
IPQPFQPLER HLNKHDVWNL TRHMQSERQA QSQPHGLLKR LGAASSPGSA HQSNAIEETG
TGTETANGAL VQRLIELAQW SDLIVFDYLI ANLDRVVNNL YNFQWNADIM AAPAHNLARQ
SASQLLVFLD NESGLLHGYR LLKKYEAYHS LLLDNLCVFR RPTIDALRRL RAAGAGRRLR
DLFERTTSAG VRDVLPSLPD KSVKILVERI DRVLGQVQKC QGS
