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Q01887

- RYK_MOUSE

UniProt

Q01887 - RYK_MOUSE

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Protein

Tyrosine-protein kinase RYK

Gene
Ryk, Mrk
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.4 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei351 – 3511ATP By similarity
Active sitei452 – 4521Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi323 – 3319ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. frizzled binding Source: UniProtKB
  3. protein binding Source: MGI
  4. protein kinase activity Source: InterPro
  5. Wnt-activated receptor activity Source: MGI
  6. Wnt-protein binding Source: UniProtKB

GO - Biological processi

  1. axon guidance Source: UniProtKB
  2. axonogenesis Source: MGI
  3. commissural neuron axon guidance Source: MGI
  4. corpus callosum development Source: UniProtKB
  5. negative chemotaxis Source: MGI
  6. negative regulation of axon extension involved in axon guidance Source: MGI
  7. neuron differentiation Source: UniProtKB
  8. neuron projection development Source: UniProtKB
  9. positive regulation of MAPK cascade Source: UniProtKB
  10. skeletal system morphogenesis Source: MGI
  11. Wnt signaling pathway Source: UniProtKB
Complete GO annotation...

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. 3474.
ReactomeiREACT_207044. TCF dependent signaling in response to WNT.
REACT_214043. PCP/CE pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase RYK (EC:2.7.10.1)
Alternative name(s):
Kinase VIK
Met-related kinase
NYK-R
Gene namesi
Name:Ryk
Synonyms:Mrk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:101766. Ryk.

Subcellular locationi

Membrane; Single-pass type I membrane protein. Nucleus. Cytoplasm
Note: In cells that have undergone neuronal differentiation, the C-terminal cleaved part is translocated from the cytoplasm to the nucleus.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini35 – 211177Extracellular Reviewed predictionAdd
BLAST
Transmembranei212 – 23928Helical; Reviewed predictionAdd
BLAST
Topological domaini240 – 594355Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. integral component of membrane Source: UniProtKB-KW
  3. membrane Source: UniProtKB
  4. nucleus Source: UniProtKB
  5. plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3434 Reviewed predictionAdd
BLAST
Chaini35 – 594560Tyrosine-protein kinase RYKPRO_0000024465Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi123 – 1231N-linked (GlcNAc...) Reviewed prediction
Glycosylationi158 – 1581N-linked (GlcNAc...) Reviewed prediction
Glycosylationi162 – 1621N-linked (GlcNAc...) Reviewed prediction
Glycosylationi166 – 1661N-linked (GlcNAc...) Reviewed prediction
Glycosylationi193 – 1931N-linked (GlcNAc...) Reviewed prediction
Modified residuei482 – 4821Phosphotyrosine; by autocatalysis By similarity

Post-translational modificationi

Proteolytically cleaved, in part by presenilin, in response to WNT3 stimulation.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiQ01887.

PTM databases

PhosphoSiteiQ01887.

Expressioni

Tissue specificityi

Is detected in all the tissues. Highest levels are seen in the ovary, lung and placenta.

Developmental stagei

Highest expression at E16 when callosal axons are beginning to cross the midline. At E17-E18, when the majority of axons are projecting away from the midline, expression is observed but at a lower level. Present on the cell bodies of neurons in cortical layers at E18.2 Publications

Gene expression databases

ArrayExpressiQ01887.
BgeeiQ01887.
CleanExiMM_RYK.
GenevestigatoriQ01887.

Interactioni

Subunit structurei

Interacts with DVL1 (via PDZ domain).1 Publication

Protein-protein interaction databases

BioGridi203044. 11 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ01887.
SMRiQ01887. Positions 47-186, 289-585.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini50 – 178129WIFAdd
BLAST
Domaini317 – 590274Protein kinaseAdd
BLAST

Domaini

The extracellular WIF domain is responsible for Wnt binding.1 Publication

Sequence similaritiesi

Contains 1 WIF domain.

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00720000108377.
HOGENOMiHOG000236284.
HOVERGENiHBG047417.
InParanoidiQ01887.
KOiK05128.
OMAiDHASEVQ.
OrthoDBiEOG7M98KK.
PhylomeDBiQ01887.
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]

Sequencei

Sequence statusi: Complete.

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

Q01887-1 [UniParc]FASTAAdd to Basket

« Hide

MRAGRGGVPG SGGLRAPPPP LLLLLLAMLP AAAPRSPALA AAPAGPSVSL    50
YLSEDEVRRL LGLDAELYYV RNDLISHYAL SFNLLVPSET NFLHFTWHAK 100
SKVEYKLGFQ VDNFVAMGMP QVNISAQGEV PRTLSVFRVE LSCTGKVDSE 150
VMILMQLNLT VNSSKNFTVL NFKRRKMCYK KLEEVKTSAL DKNTSRTIYD 200
PVHAAPTTST RVFYISVGVC CAVIFLVAII LAVLHLHSMK RIELDDSISA 250
SSSSQGLSQP STQTTQYLRA DTPNNATPIT SSSGYPTLRI EKNDLRSVTL 300
LEAKAKVKDI AISRERITLK DVLQEGTFGR IFHGILVDEK DPNKEKQTFV 350
KTVKDQASEV QVTMMLTESC KLRGLHHRNL LPITHVCIEE GEKPMVVLPY 400
MNWGNLKLFL RQCKLVEANN PQAISQQDLV HMAIQIACGM SYLARREVIH 450
RDLAARNCVI DDTLQVKITD NALSRDLFPM DYHCLGDNEN RPVRWMALES 500
LVNNEFSSAS DVWAFGVTLW ELMTLGQTPY VDIDPFEMAA YLKDGYRIAQ 550
PINCPDELFA VMACCWALDP EERPKFQQLV QCLTEFHAAL GAYV 594
Length:594
Mass (Da):66,285
Last modified:June 1, 1994 - v2
Checksum:i5C7261A3F7824520
GO

Sequence cautioni

The sequence AAA40079.1 differs from that shown. Reason: Frameshift at positions 17 and 28.
The sequence AAA40079.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti17 – 171Missing in AAA02913. 1 Publication
Sequence conflicti20 – 201P → A in AAA40079. 1 Publication
Sequence conflicti31 – 311A → P in AAA40079. 1 Publication
Sequence conflicti35 – 362RS → V in AAA40079. 1 Publication
Sequence conflicti38 – 414ALAA → GPGR in AAA40079. 1 Publication
Sequence conflicti112 – 1121D → N in AAA40079. 1 Publication
Sequence conflicti130 – 1301V → G in AAA40079. 1 Publication
Sequence conflicti311 – 3111A → G in AAA40079. 1 Publication
Sequence conflicti316 – 3183RIT → GSH in AAA02913. 1 Publication
Sequence conflicti327 – 3271T → S in AAA40079. 1 Publication
Sequence conflicti341 – 3411D → R in AAA40079. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L02210 mRNA. Translation: AAA40579.1.
S53216 mRNA. Translation: AAB25044.1.
M98547 mRNA. Translation: AAA40079.1. Sequence problems.
L38394 mRNA. Translation: AAA67060.1.
L21707 mRNA. Translation: AAA02913.1.
BC006963 mRNA. Translation: AAH06963.1.
CCDSiCCDS40747.1.
PIRiA47186.
I56248.
I58386.
RefSeqiNP_001036072.1. NM_001042607.1.
NP_038677.3. NM_013649.3.
UniGeneiMm.335391.

Genome annotation databases

EnsembliENSMUST00000175883; ENSMUSP00000135858; ENSMUSG00000032547.
GeneIDi20187.
KEGGimmu:20187.
UCSCiuc009rga.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L02210 mRNA. Translation: AAA40579.1 .
S53216 mRNA. Translation: AAB25044.1 .
M98547 mRNA. Translation: AAA40079.1 . Sequence problems.
L38394 mRNA. Translation: AAA67060.1 .
L21707 mRNA. Translation: AAA02913.1 .
BC006963 mRNA. Translation: AAH06963.1 .
CCDSi CCDS40747.1.
PIRi A47186.
I56248.
I58386.
RefSeqi NP_001036072.1. NM_001042607.1.
NP_038677.3. NM_013649.3.
UniGenei Mm.335391.

3D structure databases

ProteinModelPortali Q01887.
SMRi Q01887. Positions 47-186, 289-585.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 203044. 11 interactions.

PTM databases

PhosphoSitei Q01887.

Proteomic databases

PRIDEi Q01887.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000175883 ; ENSMUSP00000135858 ; ENSMUSG00000032547 .
GeneIDi 20187.
KEGGi mmu:20187.
UCSCi uc009rga.1. mouse.

Organism-specific databases

CTDi 6259.
MGIi MGI:101766. Ryk.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00720000108377.
HOGENOMi HOG000236284.
HOVERGENi HBG047417.
InParanoidi Q01887.
KOi K05128.
OMAi DHASEVQ.
OrthoDBi EOG7M98KK.
PhylomeDBi Q01887.
TreeFami TF317402.

Enzyme and pathway databases

BRENDAi 2.7.10.1. 3474.
Reactomei REACT_207044. TCF dependent signaling in response to WNT.
REACT_214043. PCP/CE pathway.

Miscellaneous databases

ChiTaRSi RYK. mouse.
NextBioi 297729.
PROi Q01887.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q01887.
Bgeei Q01887.
CleanExi MM_RYK.
Genevestigatori Q01887.

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

« Hide 'large scale' publications
  1. "Molecular cloning of the cDNA encoding a receptor tyrosine kinase-related molecule with a catalytic region homologous to c-met."
    Paul S.R., Merberg D., Finnerty H., Morris G.E., Morris J.C., Jones S.S., Kriz R., Turner K.J., Wood C.R.
    Int. J. Cell Cloning 10:309-314(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The murine vik gene (chromosome 9) encodes a putative receptor with unique protein kinase motifs."
    Kelman Z., Simon-Chazottes D., Guenet J.-L., Yarden Y.
    Oncogene 8:37-44(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "RYK, a receptor tyrosine kinase-related molecule with unusual kinase domain motifs."
    Hovens C.M., Stacker S.A., Andres A.-C., Harpur A.G., Ziemiecki A., Wilks A.F.
    Proc. Natl. Acad. Sci. U.S.A. 89:11818-11822(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
    Tissue: Peritoneal macrophage.
  4. "The receptor tyrosine kinase-related gene (ryk) demonstrates lineage and stage-specific expression in hematopoietic cells."
    Simoneaux D.K., Fletcher F.A., Jurecic R., Shilling H.G., Van N.T., Patel P., Belmont J.W.
    J. Immunol. 154:1157-1166(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. "Isolation of a novel receptor tyrosine kinase cDNA expressed by developing erythroid progenitors."
    Yee K., Bishop T.R., Mather C., Zon L.I.
    Blood 82:1335-1343(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-318.
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 190-594.
    Tissue: Mammary tumor.
  7. "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, DOMAIN, INTERACTION WITH DVL1.
  8. "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: FUNCTION.
  9. "The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum."
    Keeble T.R., Halford M.M., Seaman C., Kee N., Macheda M., Anderson R.B., Stacker S.A., Cooper H.M.
    J. Neurosci. 26:5840-5848(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE.
  10. "Cleavage of the Wnt receptor Ryk regulates neuronal differentiation during cortical neurogenesis."
    Lyu J., Yamamoto V., Lu W.
    Dev. Cell 15:773-780(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CLEAVAGE BY PRESENILIN, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiRYK_MOUSE
AccessioniPrimary (citable) accession number: Q01887
Secondary accession number(s): Q61890
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: June 1, 1994
Last modified: September 3, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi