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P34925

- RYK_HUMAN

UniProt

P34925 - RYK_HUMAN

Protein

Tyrosine-protein kinase RYK

Gene

RYK

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 2 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    May be a coreceptor along with FZD8 of Wnt proteins, such as WNT1, WNT3, WNT3A and WNT5A. Involved in neuron differentiation, axon guidance, corpus callosum establishment and neurite outgrowth. In response to WNT3 stimulation, receptor C-terminal cleavage occurs in its transmembrane region and allows the C-terminal intracellular product to translocate from the cytoplasm to the nucleus where it plays a crucial role in neuronal development.1 Publication

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei361 – 3611ATPPROSITE-ProRule annotation
    Active sitei462 – 4621Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi333 – 3419ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. transmembrane receptor protein tyrosine kinase activity Source: ProtInc
    4. transmembrane signaling receptor activity Source: UniProtKB
    5. Wnt-activated receptor activity Source: Ensembl

    GO - Biological processi

    1. axon guidance Source: UniProtKB
    2. commissural neuron axon guidance Source: Ensembl
    3. corpus callosum development Source: UniProtKB
    4. negative chemotaxis Source: Ensembl
    5. negative regulation of axon extension involved in axon guidance Source: Ensembl
    6. neuron differentiation Source: UniProtKB
    7. neuron projection development Source: UniProtKB
    8. peptidyl-tyrosine phosphorylation Source: GOC
    9. positive regulation of MAPK cascade Source: UniProtKB
    10. signal transduction Source: ProtInc
    11. skeletal system morphogenesis Source: Ensembl
    12. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Wnt signaling pathway

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 2681.
    ReactomeiREACT_172581. PCP/CE pathway.
    REACT_200777. TCF dependent signaling in response to WNT.
    SignaLinkiP34925.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase RYK (EC:2.7.10.1)
    Gene namesi
    Name:RYK
    Synonyms:JTK5A
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:10481. RYK.

    Subcellular locationi

    Membrane By similarity; Single-pass type I membrane protein By similarity. Nucleus By similarity. Cytoplasm By similarity
    Note: In cells that have undergone neuronal differentiation, the C-terminal cleaved part is translocated from the cytoplasm to the nucleus.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. integral component of membrane Source: UniProtKB
    3. integral component of plasma membrane Source: ProtInc
    4. membrane Source: UniProtKB
    5. nucleus Source: UniProtKB
    6. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi361 – 3611K → A: No induction of the MAPK pathway. 1 Publication
    Mutagenesisi481 – 4811N → F: Gain of an autophosphorylation activity. Gain of an autophosphorylation activity; when associated with A-359. Gain of an autophosphorylation activity; when associated with G-334 and G-482. 1 Publication
    Mutagenesisi482 – 4821A → G: Gain of an autophosphorylation activity. Gain of an autophosphorylation activity; when associated with G-334 and F-481. 1 Publication

    Organism-specific databases

    PharmGKBiPA34894.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2525Sequence AnalysisAdd
    BLAST
    Chaini26 – 604579Tyrosine-protein kinase RYKPRO_0000024464Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi136 – 1361N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi171 – 1711N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi175 – 1751N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi179 – 1791N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi206 – 2061N-linked (GlcNAc...)Sequence Analysis
    Modified residuei492 – 4921Phosphotyrosine; by autocatalysisBy similarity

    Post-translational modificationi

    Proteolytically cleaved, in part by presenilin, in response to WNT3 stimulation. Cleavage occurs during neuronal differentiation.1 Publication

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiP34925.
    PRIDEiP34925.

    PTM databases

    PhosphoSiteiP34925.

    Expressioni

    Tissue specificityi

    Observed in all the tissues examined.

    Gene expression databases

    ArrayExpressiP34925.
    BgeeiP34925.
    CleanExiHS_RYK.
    GenevestigatoriP34925.

    Organism-specific databases

    HPAiCAB034117.
    HPA045503.

    Interactioni

    Subunit structurei

    Interacts with DVL1 (via PDZ domain).1 Publication

    Protein-protein interaction databases

    BioGridi112171. 70 interactions.
    IntActiP34925. 1 interaction.
    STRINGi9606.ENSP00000296084.

    Structurei

    3D structure databases

    ProteinModelPortaliP34925.
    SMRiP34925. Positions 60-193, 327-595.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini26 – 224199ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini253 – 604352CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei225 – 25228HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini63 – 191129WIFPROSITE-ProRule annotationAdd
    BLAST
    Domaini327 – 600274Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The extracellular WIF domain is responsible for Wnt binding.By similarity

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 WIF domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000236284.
    HOVERGENiHBG047417.
    InParanoidiP34925.
    KOiK05128.
    PhylomeDBiP34925.
    TreeFamiTF317402.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR003306. WIF.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    PF02019. WIF. 1 hit.
    [Graphical view]
    PRINTSiPR00109. TYRKINASE.
    ProDomiPD013948. WIF. 1 hit.
    [Graphical view] [Entries sharing at least one domain]
    SMARTiSM00219. TyrKc. 1 hit.
    SM00469. WIF. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50814. WIF. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P34925-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MRGAARLGRP GRSCLPGPAL RAAAAPALLL ARCAVAAAAG LRAAARPRPP    50
    ELQSASAGPS VSLYLSEDEV RRLIGLDAEL YYVRNDLISH YALSFNLLVP 100
    SETNFLHFTW HAKSKVEYKL GFQVDNVLAM DMPQVNISVQ GEVPRTLSVF 150
    RVELSCTGKV DSEVMILMQL NLTVNSSKNF TVLNFKRRKM CYKKLEEVKT 200
    SALDKNTSRT IYDPVHAAPT TSTRVFYISV GVCCAVIFLV AIILAVLHLH 250
    NMKRIELDDS ISASSSSQGL SQPSTQTTQY LRADTPNNAT PITSYPTLRI 300
    EKNDLRSVTL LEAKGKVKDI AISRERITLK DVLQEGTFGR IFHGILIDEK 350
    DPNKEKQAFV KTVKDQASEI QVTMMLTESC KLRGLHHRNL LPITHVCIEE 400
    GEKPMVILPY MNWGNLKLFL RQCKLVEANN PQAISQQDLV HMAIQIACGM 450
    SYLARREVIH KDLAARNCVI DDTLQVKITD NALSRDLFPM DYHCLGDNEN 500
    RPVRWMALES LVNNEFSSAS DVWAFGVTLW ELMTLGQTPY VDIDPFEMAA 550
    YLKDGYRIAQ PINCPDELFA VMACCWALDP EERPKFQQLV QCLTEFHAAL 600
    GAYV 604
    Length:604
    Mass (Da):67,507
    Last modified:October 1, 1996 - v2
    Checksum:i06D59C0FEAB63397
    GO
    Isoform 2 (identifier: P34925-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         294-294: S → SSLG

    Note: No experimental confirmation available.

    Show »
    Length:607
    Mass (Da):67,764
    Checksum:i9FA455AE7922F597
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti18 – 4629PALRA…RAAAR → RGLRAPPPPPLLLLLALLPL LPAPGAAAAPA(PubMed:8390040)CuratedAdd
    BLAST
    Sequence conflicti251 – 2511N → S in CAA49591. (PubMed:8390040)Curated
    Sequence conflicti316 – 3161K → E in CAA49591. (PubMed:8390040)Curated
    Sequence conflicti355 – 3551E → K(PubMed:8726462)Curated
    Sequence conflicti437 – 4371Q → H in CAA49591. (PubMed:8390040)Curated
    Sequence conflicti443 – 4431A → P in CAA49591. (PubMed:8390040)Curated
    Sequence conflicti528 – 5281T → NS in AAB26341. (PubMed:8386829)Curated
    Sequence conflicti541 – 5411V → TL in AAB26341. (PubMed:8386829)Curated
    Sequence conflicti563 – 5631N → T in AAB26341. (PubMed:8386829)Curated
    Sequence conflicti585 – 5851K → R in AAB26341. (PubMed:8386829)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti96 – 961N → S.1 Publication
    VAR_041800
    Natural varianti224 – 2241R → C.1 Publication
    VAR_041801
    Natural varianti240 – 2401V → I in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication
    VAR_041802

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei294 – 2941S → SSLG in isoform 2. 1 PublicationVSP_005009

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    S59184 mRNA. Translation: AAB26341.1.
    X69970 mRNA. Translation: CAA49591.1.
    X96588 mRNA. Translation: CAA65406.1.
    PIRiI37560.
    RefSeqiNP_001005861.1. NM_001005861.2.
    NP_002949.2. NM_002958.3.
    UniGeneiHs.654562.

    Genome annotation databases

    EnsembliENST00000296084; ENSP00000296084; ENSG00000163785.
    GeneIDi6259.
    KEGGihsa:6259.

    Polymorphism databases

    DMDMi1710811.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    S59184 mRNA. Translation: AAB26341.1 .
    X69970 mRNA. Translation: CAA49591.1 .
    X96588 mRNA. Translation: CAA65406.1 .
    PIRi I37560.
    RefSeqi NP_001005861.1. NM_001005861.2.
    NP_002949.2. NM_002958.3.
    UniGenei Hs.654562.

    3D structure databases

    ProteinModelPortali P34925.
    SMRi P34925. Positions 60-193, 327-595.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112171. 70 interactions.
    IntActi P34925. 1 interaction.
    STRINGi 9606.ENSP00000296084.

    PTM databases

    PhosphoSitei P34925.

    Polymorphism databases

    DMDMi 1710811.

    Proteomic databases

    PaxDbi P34925.
    PRIDEi P34925.

    Protocols and materials databases

    DNASUi 6259.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000296084 ; ENSP00000296084 ; ENSG00000163785 .
    GeneIDi 6259.
    KEGGi hsa:6259.

    Organism-specific databases

    CTDi 6259.
    GeneCardsi GC03M133794.
    HGNCi HGNC:10481. RYK.
    HPAi CAB034117.
    HPA045503.
    MIMi 600524. gene.
    neXtProti NX_P34925.
    PharmGKBi PA34894.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000236284.
    HOVERGENi HBG047417.
    InParanoidi P34925.
    KOi K05128.
    PhylomeDBi P34925.
    TreeFami TF317402.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 2681.
    Reactomei REACT_172581. PCP/CE pathway.
    REACT_200777. TCF dependent signaling in response to WNT.
    SignaLinki P34925.

    Miscellaneous databases

    GeneWikii Related_to_receptor_tyrosine_kinase.
    GenomeRNAii 6259.
    NextBioi 24309.
    PROi P34925.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P34925.
    Bgeei P34925.
    CleanExi HS_RYK.
    Genevestigatori P34925.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR003306. WIF.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    PF02019. WIF. 1 hit.
    [Graphical view ]
    PRINTSi PR00109. TYRKINASE.
    ProDomi PD013948. WIF. 1 hit.
    [Graphical view ] [Entries sharing at least one domain ]
    SMARTi SM00219. TyrKc. 1 hit.
    SM00469. WIF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50814. WIF. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning and chromosomal localisation of the human homologue of a receptor related to tyrosine kinases (RYK)."
      Stacker S.A., Hovens C.M., Vitali A., Pritchard M.A., Baker E., Sutherland G.R., Wilks A.F.
      Oncogene 8:1347-1356(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "The human ryk cDNA sequence predicts a protein containing two putative transmembrane segments and a tyrosine kinase catalytic domain."
      Tamagnone L., Partanen J., Armstrong E., Lasota J., Ohgami K., Tazunoki T., Laforgia S., Huebner K., Alitalo K.
      Oncogene 8:2009-2014(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    3. "H-RYK, an unusual receptor kinase: isolation and analysis of expression in ovarian cancer."
      Wang X.C., Katso R., Butler R., Hanby A.M., Poulsom R., Jones T., Sheer D., Ganesan T.S.
      Mol. Med. 2:189-203(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 28-604 (ISOFORM 1).
      Tissue: Ovary.
    4. "Functional analysis of H-Ryk, an atypical member of the receptor tyrosine kinase family."
      Katso R.M., Russell R.B., Ganesan T.S.
      Mol. Cell. Biol. 19:6427-6440(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF LYS-361; ASN-481 AND ALA-482.
    5. "Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth."
      Lu W., Yamamoto V., Ortega B., Baltimore D.
      Cell 119:97-108(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH DVL1.
    6. "Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract."
      Liu Y., Shi J., Lu C.C., Wang Z.B., Lyuksyutova A.I., Song X.J., Zou Y.
      Nat. Neurosci. 8:1151-1159(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: CLEAVAGE BY PRESENILIN.
    7. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-96; CYS-224 AND ILE-240.

    Entry informationi

    Entry nameiRYK_HUMAN
    AccessioniPrimary (citable) accession number: P34925
    Secondary accession number(s): Q04696
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 141 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3