ID   RYK_MOUSE               Reviewed;         594 AA.
AC   Q01887; Q61890;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 2.
DT   27-MAR-2024, entry version 197.
DE   RecName: Full=Tyrosine-protein kinase RYK;
DE            EC=2.7.10.1;
DE   AltName: Full=Kinase VIK;
DE   AltName: Full=Met-related kinase;
DE   AltName: Full=NYK-R;
DE   Flags: Precursor;
GN   Name=Ryk; Synonyms=Mrk;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1333503; DOI=10.1002/stem.5530100509;
RA   Paul S.R., Merberg D., Finnerty H., Morris G.E., Morris J.C., Jones S.S.,
RA   Kriz R., Turner K.J., Wood C.R.;
RT   "Molecular cloning of the cDNA encoding a receptor tyrosine kinase-related
RT   molecule with a catalytic region homologous to c-met.";
RL   Int. J. Cell Cloning 10:309-314(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8380921;
RA   Kelman Z., Simon-Chazottes D., Guenet J.-L., Yarden Y.;
RT   "The murine vik gene (chromosome 9) encodes a putative receptor with unique
RT   protein kinase motifs.";
RL   Oncogene 8:37-44(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ; TISSUE=Peritoneal macrophage;
RX   PubMed=1334548; DOI=10.1073/pnas.89.24.11818;
RA   Hovens C.M., Stacker S.A., Andres A.-C., Harpur A.G., Ziemiecki A.,
RA   Wilks A.F.;
RT   "RYK, a receptor tyrosine kinase-related molecule with unusual kinase
RT   domain motifs.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:11818-11822(1992).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7822791;
RA   Simoneaux D.K., Fletcher F.A., Jurecic R., Shilling H.G., Van N.T.,
RA   Patel P., Belmont J.W.;
RT   "The receptor tyrosine kinase-related gene (ryk) demonstrates lineage and
RT   stage-specific expression in hematopoietic cells.";
RL   J. Immunol. 154:1157-1166(1995).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-318.
RX   PubMed=8394755;
RA   Yee K., Bishop T.R., Mather C., Zon L.I.;
RT   "Isolation of a novel receptor tyrosine kinase cDNA expressed by developing
RT   erythroid progenitors.";
RL   Blood 82:1335-1343(1993).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 190-594.
RC   TISSUE=Mammary tumor;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   FUNCTION, DOMAIN, AND INTERACTION WITH DVL1.
RX   PubMed=15454084; DOI=10.1016/j.cell.2004.09.019;
RA   Lu W., Yamamoto V., Ortega B., Baltimore D.;
RT   "Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite
RT   outgrowth.";
RL   Cell 119:97-108(2004).
RN   [8]
RP   FUNCTION.
RX   PubMed=16116452; DOI=10.1038/nn1520;
RA   Liu Y., Shi J., Lu C.C., Wang Z.B., Lyuksyutova A.I., Song X.J., Zou Y.;
RT   "Ryk-mediated Wnt repulsion regulates posterior-directed growth of
RT   corticospinal tract.";
RL   Nat. Neurosci. 8:1151-1159(2005).
RN   [9]
RP   FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=16723543; DOI=10.1523/jneurosci.1175-06.2006;
RA   Keeble T.R., Halford M.M., Seaman C., Kee N., Macheda M., Anderson R.B.,
RA   Stacker S.A., Cooper H.M.;
RT   "The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the
RT   contralateral side of the corpus callosum.";
RL   J. Neurosci. 26:5840-5848(2006).
RN   [10]
RP   FUNCTION, CLEAVAGE BY PRESENILIN, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP   STAGE.
RX   PubMed=19000841; DOI=10.1016/j.devcel.2008.10.004;
RA   Lyu J., Yamamoto V., Lu W.;
RT   "Cleavage of the Wnt receptor Ryk regulates neuronal differentiation during
RT   cortical neurogenesis.";
RL   Dev. Cell 15:773-780(2008).
CC   -!- FUNCTION: May be a coreceptor along with FZD8 of Wnt proteins, such as
CC       WNT1, WNT3, WNT3A and WNT5A. Involved in neuron differentiation, axon
CC       guidance, corpus callosum establishment and neurite outgrowth. In
CC       response to WNT3 stimulation, receptor C-terminal cleavage occurs in
CC       its transmembrane region and allows the C-terminal intracellular
CC       product to translocate from the cytoplasm to the nucleus where it plays
CC       a crucial role in neuronal development. {ECO:0000269|PubMed:15454084,
CC       ECO:0000269|PubMed:16116452, ECO:0000269|PubMed:16723543,
CC       ECO:0000269|PubMed:19000841}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC         [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC   -!- SUBUNIT: Interacts with DVL1 (via PDZ domain).
CC       {ECO:0000269|PubMed:15454084}.
CC   -!- INTERACTION:
CC       Q01887; P35222: CTNNB1; Xeno; NbExp=2; IntAct=EBI-16110594, EBI-491549;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:19000841}; Single-
CC       pass type I membrane protein {ECO:0000269|PubMed:19000841}. Nucleus
CC       {ECO:0000269|PubMed:19000841}. Cytoplasm {ECO:0000269|PubMed:19000841}.
CC       Note=In cells that have undergone neuronal differentiation, the C-
CC       terminal cleaved part is translocated from the cytoplasm to the
CC       nucleus.
CC   -!- TISSUE SPECIFICITY: Is detected in all the tissues. Highest levels are
CC       seen in the ovary, lung and placenta.
CC   -!- DEVELOPMENTAL STAGE: Highest expression at 16 dpc when callosal axons
CC       are beginning to cross the midline. At 17 dpc-18 dpc, when the majority
CC       of axons are projecting away from the midline, expression is observed
CC       but at a lower level. Present on the cell bodies of neurons in cortical
CC       layers at 18 dpc. {ECO:0000269|PubMed:16723543,
CC       ECO:0000269|PubMed:19000841}.
CC   -!- DOMAIN: The extracellular WIF domain is responsible for Wnt binding.
CC       {ECO:0000269|PubMed:15454084}.
CC   -!- PTM: Proteolytically cleaved, in part by presenilin, in response to
CC       WNT3 stimulation. {ECO:0000269|PubMed:19000841}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA40079.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAA40079.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; L02210; AAA40579.1; -; mRNA.
DR   EMBL; S53216; AAB25044.1; -; mRNA.
DR   EMBL; M98547; AAA40079.1; ALT_SEQ; mRNA.
DR   EMBL; L38394; AAA67060.1; -; mRNA.
DR   EMBL; L21707; AAA02913.1; -; mRNA.
DR   EMBL; BC006963; AAH06963.1; -; mRNA.
DR   CCDS; CCDS40747.1; -.
DR   PIR; A47186; A47186.
DR   PIR; I56248; I56248.
DR   PIR; I58386; I58386.
DR   RefSeq; NP_001036072.1; NM_001042607.1.
DR   RefSeq; NP_038677.3; NM_013649.3.
DR   AlphaFoldDB; Q01887; -.
DR   SMR; Q01887; -.
DR   BioGRID; 203044; 10.
DR   CORUM; Q01887; -.
DR   DIP; DIP-61011N; -.
DR   IntAct; Q01887; 1.
DR   STRING; 10090.ENSMUSP00000135858; -.
DR   GlyCosmos; Q01887; 5 sites, No reported glycans.
DR   GlyGen; Q01887; 5 sites.
DR   iPTMnet; Q01887; -.
DR   PhosphoSitePlus; Q01887; -.
DR   PaxDb; 10090-ENSMUSP00000135858; -.
DR   ProteomicsDB; 260962; -.
DR   Antibodypedia; 33387; 450 antibodies from 33 providers.
DR   DNASU; 20187; -.
DR   Ensembl; ENSMUST00000175883.8; ENSMUSP00000135858.2; ENSMUSG00000032547.13.
DR   GeneID; 20187; -.
DR   KEGG; mmu:20187; -.
DR   UCSC; uc009rga.1; mouse.
DR   AGR; MGI:101766; -.
DR   CTD; 6259; -.
DR   MGI; MGI:101766; Ryk.
DR   VEuPathDB; HostDB:ENSMUSG00000032547; -.
DR   eggNOG; KOG1024; Eukaryota.
DR   GeneTree; ENSGT00940000155119; -.
DR   InParanoid; Q01887; -.
DR   OMA; CWAMSPD; -.
DR   OrthoDB; 1614410at2759; -.
DR   PhylomeDB; Q01887; -.
DR   TreeFam; TF317402; -.
DR   BRENDA; 2.7.10.1; 3474.
DR   Reactome; R-MMU-201681; TCF dependent signaling in response to WNT.
DR   BioGRID-ORCS; 20187; 2 hits in 80 CRISPR screens.
DR   ChiTaRS; Ryk; mouse.
DR   PRO; PR:Q01887; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; Q01887; Protein.
DR   Bgee; ENSMUSG00000032547; Expressed in metanephric loop of Henle and 279 other cell types or tissues.
DR   ExpressionAtlas; Q01887; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005109; F:frizzled binding; IPI:UniProtKB.
DR   GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; ISO:MGI.
DR   GO; GO:0042813; F:Wnt receptor activity; IPI:MGI.
DR   GO; GO:0017147; F:Wnt-protein binding; IPI:UniProtKB.
DR   GO; GO:0048846; P:axon extension involved in axon guidance; IGI:MGI.
DR   GO; GO:0007411; P:axon guidance; IDA:UniProtKB.
DR   GO; GO:0007409; P:axonogenesis; IGI:MGI.
DR   GO; GO:0061643; P:chemorepulsion of axon; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0036518; P:chemorepulsion of dopaminergic neuron axon; IGI:ParkinsonsUK-UCL.
DR   GO; GO:0071679; P:commissural neuron axon guidance; IMP:MGI.
DR   GO; GO:0022038; P:corpus callosum development; IMP:UniProtKB.
DR   GO; GO:1904948; P:midbrain dopaminergic neuron differentiation; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0050919; P:negative chemotaxis; IGI:MGI.
DR   GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IGI:MGI.
DR   GO; GO:0030182; P:neuron differentiation; IDA:UniProtKB.
DR   GO; GO:0031175; P:neuron projection development; IMP:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:1904935; P:positive regulation of cell proliferation in midbrain; ISO:MGI.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR   GO; GO:0048705; P:skeletal system morphogenesis; IMP:MGI.
DR   GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR   GO; GO:0016055; P:Wnt signaling pathway; IDA:UniProtKB.
DR   GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; TAS:ARUK-UCL.
DR   CDD; cd05043; PTK_Ryk; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   Gene3D; 2.60.40.2170; Wnt, WIF domain; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR020635; Tyr_kinase_cat_dom.
DR   InterPro; IPR003306; WIF.
DR   InterPro; IPR038677; WIF_sf.
DR   PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR   PANTHER; PTHR24416:SF349; TYROSINE-PROTEIN KINASE RYK; 1.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   Pfam; PF02019; WIF; 1.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00219; TyrKc; 1.
DR   SMART; SM00469; WIF; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR   PROSITE; PS50814; WIF; 1.
DR   Genevisible; Q01887; MM.
PE   1: Evidence at protein level;
KW   ATP-binding; Cytoplasm; Glycoprotein; Kinase; Membrane; Nucleotide-binding;
KW   Nucleus; Phosphoprotein; Receptor; Reference proteome; Signal; Transferase;
KW   Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW   Wnt signaling pathway.
FT   SIGNAL          1..34
FT                   /evidence="ECO:0000255"
FT   CHAIN           35..594
FT                   /note="Tyrosine-protein kinase RYK"
FT                   /id="PRO_0000024465"
FT   TOPO_DOM        35..211
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        212..239
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        240..594
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          50..178
FT                   /note="WIF"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00222"
FT   DOMAIN          317..590
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          250..283
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        452
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10028"
FT   BINDING         323..331
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         351
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         482
FT                   /note="Phosphotyrosine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        123
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        158
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        162
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        166
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        193
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        17
FT                   /note="Missing (in Ref. 5; AAA02913)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        20
FT                   /note="P -> A (in Ref. 3; AAA40079)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        31
FT                   /note="A -> P (in Ref. 3; AAA40079)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        35..36
FT                   /note="RS -> V (in Ref. 3; AAA40079)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        38..41
FT                   /note="ALAA -> GPGR (in Ref. 3; AAA40079)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        112
FT                   /note="D -> N (in Ref. 3; AAA40079)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        130
FT                   /note="V -> G (in Ref. 3; AAA40079)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        311
FT                   /note="A -> G (in Ref. 3; AAA40079)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        316..318
FT                   /note="RIT -> GSH (in Ref. 5; AAA02913)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        327
FT                   /note="T -> S (in Ref. 3; AAA40079)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        341
FT                   /note="D -> R (in Ref. 3; AAA40079)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   594 AA;  66285 MW;  5C7261A3F7824520 CRC64;
     MRAGRGGVPG SGGLRAPPPP LLLLLLAMLP AAAPRSPALA AAPAGPSVSL YLSEDEVRRL
     LGLDAELYYV RNDLISHYAL SFNLLVPSET NFLHFTWHAK SKVEYKLGFQ VDNFVAMGMP
     QVNISAQGEV PRTLSVFRVE LSCTGKVDSE VMILMQLNLT VNSSKNFTVL NFKRRKMCYK
     KLEEVKTSAL DKNTSRTIYD PVHAAPTTST RVFYISVGVC CAVIFLVAII LAVLHLHSMK
     RIELDDSISA SSSSQGLSQP STQTTQYLRA DTPNNATPIT SSSGYPTLRI EKNDLRSVTL
     LEAKAKVKDI AISRERITLK DVLQEGTFGR IFHGILVDEK DPNKEKQTFV KTVKDQASEV
     QVTMMLTESC KLRGLHHRNL LPITHVCIEE GEKPMVVLPY MNWGNLKLFL RQCKLVEANN
     PQAISQQDLV HMAIQIACGM SYLARREVIH RDLAARNCVI DDTLQVKITD NALSRDLFPM
     DYHCLGDNEN RPVRWMALES LVNNEFSSAS DVWAFGVTLW ELMTLGQTPY VDIDPFEMAA
     YLKDGYRIAQ PINCPDELFA VMACCWALDP EERPKFQQLV QCLTEFHAAL GAYV
//