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Database: UniProt
Entry: RYK_HUMAN
LinkDB: RYK_HUMAN
Original site: RYK_HUMAN 
ID   RYK_HUMAN               Reviewed;         604 AA.
AC   P34925; Q04696;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   26-NOV-2014, entry version 143.
DE   RecName: Full=Tyrosine-protein kinase RYK;
DE            EC=2.7.10.1;
DE   Flags: Precursor;
GN   Name=RYK; Synonyms=JTK5A;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=8386829;
RA   Stacker S.A., Hovens C.M., Vitali A., Pritchard M.A., Baker E.,
RA   Sutherland G.R., Wilks A.F.;
RT   "Molecular cloning and chromosomal localisation of the human homologue
RT   of a receptor related to tyrosine kinases (RYK).";
RL   Oncogene 8:1347-1356(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX   PubMed=8390040;
RA   Tamagnone L., Partanen J., Armstrong E., Lasota J., Ohgami K.,
RA   Tazunoki T., Laforgia S., Huebner K., Alitalo K.;
RT   "The human ryk cDNA sequence predicts a protein containing two
RT   putative transmembrane segments and a tyrosine kinase catalytic
RT   domain.";
RL   Oncogene 8:2009-2014(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 28-604 (ISOFORM 1).
RC   TISSUE=Ovary;
RX   PubMed=8726462;
RA   Wang X.C., Katso R., Butler R., Hanby A.M., Poulsom R., Jones T.,
RA   Sheer D., Ganesan T.S.;
RT   "H-RYK, an unusual receptor kinase: isolation and analysis of
RT   expression in ovarian cancer.";
RL   Mol. Med. 2:189-203(1996).
RN   [4]
RP   MUTAGENESIS OF LYS-361; ASN-481 AND ALA-482.
RX   PubMed=10454588;
RA   Katso R.M., Russell R.B., Ganesan T.S.;
RT   "Functional analysis of H-Ryk, an atypical member of the receptor
RT   tyrosine kinase family.";
RL   Mol. Cell. Biol. 19:6427-6440(1999).
RN   [5]
RP   FUNCTION, 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   [6]
RP   CLEAVAGE BY PRESENILIN.
RX   PubMed=16116452; DOI=10.1038/nn1520;
RA   Liu Y., Shi J., Lu C.C., Wang Z.B., Lyuksyutova A.I., Song X.J.,
RA   Zou Y.;
RT   "Ryk-mediated Wnt repulsion regulates posterior-directed growth of
RT   corticospinal tract.";
RL   Nat. Neurosci. 8:1151-1159(2005).
RN   [7]
RP   VARIANTS [LARGE SCALE ANALYSIS] SER-96; CYS-224 AND ILE-240.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA   Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA   O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA   Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA   Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA   Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA   Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA   West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA   Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA   DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA   Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA   Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
CC   -!- FUNCTION: May be a coreceptor along with FZD8 of Wnt proteins,
CC       such as WNT1, WNT3, WNT3A and WNT5A. Involved in neuron
CC       differentiation, axon guidance, corpus callosum establishment and
CC       neurite outgrowth. In response to WNT3 stimulation, receptor C-
CC       terminal cleavage occurs in its transmembrane region and allows
CC       the C-terminal intracellular product to translocate from the
CC       cytoplasm to the nucleus where it plays a crucial role in neuronal
CC       development. {ECO:0000269|PubMed:15454084}.
CC   -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
CC       [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE-
CC       ProRule:PRU10028}.
CC   -!- SUBUNIT: Interacts with DVL1 (via PDZ domain).
CC       {ECO:0000269|PubMed:15454084}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC       membrane protein {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm
CC       {ECO:0000250}. Note=In cells that have undergone neuronal
CC       differentiation, the C-terminal cleaved part is translocated from
CC       the cytoplasm to the nucleus. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P34925-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P34925-2; Sequence=VSP_005009;
CC         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Observed in all the tissues examined.
CC   -!- DOMAIN: The extracellular WIF domain is responsible for Wnt
CC       binding. {ECO:0000250}.
CC   -!- PTM: Proteolytically cleaved, in part by presenilin, in response
CC       to WNT3 stimulation. Cleavage occurs during neuronal
CC       differentiation. {ECO:0000269|PubMed:16116452}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC   -!- SIMILARITY: Contains 1 protein kinase domain.
CC       {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC   -!- SIMILARITY: Contains 1 WIF domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00222}.
CC   -!- CAUTION: According to some authors, has impaired kinase activity.
CC       {ECO:0000305|PubMed:10454588}.
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DR   EMBL; S59184; AAB26341.1; -; mRNA.
DR   EMBL; X69970; CAA49591.1; -; mRNA.
DR   EMBL; X96588; CAA65406.1; -; mRNA.
DR   PIR; I37560; I37560.
DR   RefSeq; NP_001005861.1; NM_001005861.2.
DR   RefSeq; NP_002949.2; NM_002958.3.
DR   UniGene; Hs.654562; -.
DR   ProteinModelPortal; P34925; -.
DR   SMR; P34925; 60-193, 284-595.
DR   BioGrid; 112171; 72.
DR   IntAct; P34925; 1.
DR   STRING; 9606.ENSP00000296084; -.
DR   PhosphoSite; P34925; -.
DR   DMDM; 1710811; -.
DR   PaxDb; P34925; -.
DR   PRIDE; P34925; -.
DR   DNASU; 6259; -.
DR   Ensembl; ENST00000296084; ENSP00000296084; ENSG00000163785.
DR   GeneID; 6259; -.
DR   KEGG; hsa:6259; -.
DR   CTD; 6259; -.
DR   GeneCards; GC03M133794; -.
DR   HGNC; HGNC:10481; RYK.
DR   HPA; CAB034117; -.
DR   HPA; HPA045503; -.
DR   MIM; 600524; gene.
DR   neXtProt; NX_P34925; -.
DR   PharmGKB; PA34894; -.
DR   eggNOG; COG0515; -.
DR   HOGENOM; HOG000236284; -.
DR   HOVERGEN; HBG047417; -.
DR   InParanoid; P34925; -.
DR   KO; K05128; -.
DR   PhylomeDB; P34925; -.
DR   TreeFam; TF317402; -.
DR   BRENDA; 2.7.10.1; 2681.
DR   Reactome; REACT_172581; PCP/CE pathway.
DR   Reactome; REACT_200777; TCF dependent signaling in response to WNT.
DR   SignaLink; P34925; -.
DR   ChiTaRS; RYK; human.
DR   GeneWiki; Related_to_receptor_tyrosine_kinase; -.
DR   GenomeRNAi; 6259; -.
DR   NextBio; 24309; -.
DR   PRO; PR:P34925; -.
DR   Bgee; P34925; -.
DR   CleanEx; HS_RYK; -.
DR   Genevestigator; P34925; -.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR   GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; TAS:ProtInc.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:UniProtKB.
DR   GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR   GO; GO:0022038; P:corpus callosum development; ISS:UniProtKB.
DR   GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR   GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR   GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; TAS:GOC.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR   InterPro; IPR011009; Kinase-like_dom.
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   Pfam; PF07714; Pkinase_Tyr; 1.
DR   Pfam; PF02019; WIF; 1.
DR   PRINTS; PR00109; TYRKINASE.
DR   ProDom; PD013948; WIF; 1.
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   Alternative splicing; ATP-binding; Complete proteome; Cytoplasm;
KW   Glycoprotein; Kinase; Membrane; Nucleotide-binding; Nucleus;
KW   Phosphoprotein; Polymorphism; Receptor; Reference proteome; Signal;
KW   Transferase; Transmembrane; Transmembrane helix;
KW   Tyrosine-protein kinase; Wnt signaling pathway.
FT   SIGNAL        1     25       {ECO:0000255}.
FT   CHAIN        26    604       Tyrosine-protein kinase RYK.
FT                                /FTId=PRO_0000024464.
FT   TOPO_DOM     26    224       Extracellular. {ECO:0000255}.
FT   TRANSMEM    225    252       Helical. {ECO:0000255}.
FT   TOPO_DOM    253    604       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       63    191       WIF. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00222}.
FT   DOMAIN      327    600       Protein kinase. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   NP_BIND     333    341       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   ACT_SITE    462    462       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159, ECO:0000255|PROSITE-
FT                                ProRule:PRU10028}.
FT   BINDING     361    361       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   MOD_RES     492    492       Phosphotyrosine; by autocatalysis.
FT                                {ECO:0000250}.
FT   CARBOHYD    136    136       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    171    171       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    175    175       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    179    179       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    206    206       N-linked (GlcNAc...). {ECO:0000255}.
FT   VAR_SEQ     294    294       S -> SSLG (in isoform 2).
FT                                {ECO:0000303|PubMed:8390040}.
FT                                /FTId=VSP_005009.
FT   VARIANT      96     96       N -> S. {ECO:0000269|PubMed:17344846}.
FT                                /FTId=VAR_041800.
FT   VARIANT     224    224       R -> C. {ECO:0000269|PubMed:17344846}.
FT                                /FTId=VAR_041801.
FT   VARIANT     240    240       V -> I (in an ovarian mucinous carcinoma
FT                                sample; somatic mutation).
FT                                {ECO:0000269|PubMed:17344846}.
FT                                /FTId=VAR_041802.
FT   MUTAGEN     361    361       K->A: No induction of the MAPK pathway.
FT                                {ECO:0000269|PubMed:10454588}.
FT   MUTAGEN     481    481       N->F: Gain of an autophosphorylation
FT                                activity. Gain of an autophosphorylation
FT                                activity; when associated with A-359.
FT                                Gain of an autophosphorylation activity;
FT                                when associated with G-334 and G-482.
FT                                {ECO:0000269|PubMed:10454588}.
FT   MUTAGEN     482    482       A->G: Gain of an autophosphorylation
FT                                activity. Gain of an autophosphorylation
FT                                activity; when associated with G-334 and
FT                                F-481. {ECO:0000269|PubMed:10454588}.
FT   CONFLICT     18     46       PALRAAAAPALLLARCAVAAAAGLRAAAR -> RGLRAPPP
FT                                PPLLLLLALLPLLPAPGAAAAPA (in Ref. 2).
FT                                {ECO:0000305}.
FT   CONFLICT    251    251       N -> S (in Ref. 2; CAA49591).
FT                                {ECO:0000305}.
FT   CONFLICT    316    316       K -> E (in Ref. 2; CAA49591).
FT                                {ECO:0000305}.
FT   CONFLICT    355    355       E -> K (in Ref. 3). {ECO:0000305}.
FT   CONFLICT    437    437       Q -> H (in Ref. 2; CAA49591).
FT                                {ECO:0000305}.
FT   CONFLICT    443    443       A -> P (in Ref. 2; CAA49591).
FT                                {ECO:0000305}.
FT   CONFLICT    528    528       T -> NS (in Ref. 1; AAB26341).
FT                                {ECO:0000305}.
FT   CONFLICT    541    541       V -> TL (in Ref. 1; AAB26341).
FT                                {ECO:0000305}.
FT   CONFLICT    563    563       N -> T (in Ref. 1; AAB26341).
FT                                {ECO:0000305}.
FT   CONFLICT    585    585       K -> R (in Ref. 1; AAB26341).
FT                                {ECO:0000305}.
SQ   SEQUENCE   604 AA;  67507 MW;  06D59C0FEAB63397 CRC64;
     MRGAARLGRP GRSCLPGPAL RAAAAPALLL ARCAVAAAAG LRAAARPRPP ELQSASAGPS
     VSLYLSEDEV RRLIGLDAEL YYVRNDLISH YALSFNLLVP SETNFLHFTW HAKSKVEYKL
     GFQVDNVLAM DMPQVNISVQ GEVPRTLSVF RVELSCTGKV DSEVMILMQL NLTVNSSKNF
     TVLNFKRRKM CYKKLEEVKT SALDKNTSRT IYDPVHAAPT TSTRVFYISV GVCCAVIFLV
     AIILAVLHLH NMKRIELDDS ISASSSSQGL SQPSTQTTQY LRADTPNNAT PITSYPTLRI
     EKNDLRSVTL LEAKGKVKDI AISRERITLK DVLQEGTFGR IFHGILIDEK DPNKEKQAFV
     KTVKDQASEI QVTMMLTESC KLRGLHHRNL LPITHVCIEE GEKPMVILPY MNWGNLKLFL
     RQCKLVEANN PQAISQQDLV HMAIQIACGM SYLARREVIH KDLAARNCVI DDTLQVKITD
     NALSRDLFPM DYHCLGDNEN RPVRWMALES LVNNEFSSAS DVWAFGVTLW ELMTLGQTPY
     VDIDPFEMAA YLKDGYRIAQ PINCPDELFA VMACCWALDP EERPKFQQLV QCLTEFHAAL
     GAYV
//
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