RYK_MOUSE
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 03-AUG-2022, entry version 188.
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 GlyGen; Q01887; 5 sites.
DR iPTMnet; Q01887; -.
DR PhosphoSitePlus; Q01887; -.
DR PaxDb; Q01887; -.
DR PRIDE; Q01887; -.
DR ProteomicsDB; 260962; -.
DR Antibodypedia; 33387; 402 antibodies from 33 providers.
DR DNASU; 20187; -.
DR Ensembl; ENSMUST00000175883; ENSMUSP00000135858; ENSMUSG00000032547.
DR GeneID; 20187; -.
DR KEGG; mmu:20187; -.
DR UCSC; uc009rga.1; mouse.
DR CTD; 6259; -.
DR MGI; MGI:101766; Ryk.
DR VEuPathDB; HostDB:ENSMUSG00000032547; -.
DR eggNOG; KOG1024; Eukaryota.
DR GeneTree; ENSGT00940000155119; -.
DR InParanoid; Q01887; -.
DR OMA; NTRNLKQ; -.
DR OrthoDB; 833475at2759; -.
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; 1 hit in 75 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 275 other tissues.
DR ExpressionAtlas; Q01887; baseline and differential.
DR Genevisible; Q01887; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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:0033278; P:cell proliferation in midbrain; IEA:Ensembl.
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:1904938; P:planar cell polarity pathway involved in axon guidance; IGI:ParkinsonsUK-UCL.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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:1904953; P:Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation; ISS:ParkinsonsUK-UCL.
DR Gene3D; 2.60.40.2170; -; 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 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; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50814; WIF; 1.
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
