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Q01887 (RYK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase RYK
EC=2.7.10.1
Alternative name(s):
Kinase VIK
Met-related kinase
NYK-R
Gene names
Name:Ryk
Synonyms:Mrk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length594 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.8 Ref.9 Ref.10

Catalytic activity

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

Subunit structure

Interacts with DVL1 (via PDZ domain). Ref.7

Subcellular location

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. Ref.10

Tissue specificity

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

Developmental stage

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. Ref.9 Ref.10

Domain

The extracellular WIF domain is responsible for Wnt binding. Ref.7

Post-translational modification

Proteolytically cleaved, in part by presenilin, in response to WNT3 stimulation. Ref.10

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family.

Contains 1 protein kinase domain.

Contains 1 WIF domain.

Sequence caution

The sequence AAA40079.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAA40079.1 differs from that shown. Reason: Frameshift at positions 17 and 28.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCytoplasm
Membrane
Nucleus
   DomainSignal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt receptor signaling pathway

Inferred from direct assay Ref.7. Source: UniProtKB

commissural neuron axon guidance

Inferred from mutant phenotype Ref.9. Source: MGI

corpus callosum development

Inferred from mutant phenotype Ref.9. Source: UniProtKB

negative chemotaxis

Inferred from genetic interaction Ref.9. Source: MGI

negative regulation of axon extension involved in axon guidance

Inferred from genetic interaction Ref.9. Source: MGI

positive regulation of MAPK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

skeletal system morphogenesis

Inferred from mutant phenotype PubMed 10932185. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay Ref.10. Source: UniProtKB

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from direct assay Ref.10. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.4. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Wnt-activated receptor activity

Inferred from physical interaction Ref.7. Source: MGI

protein kinase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3434 Potential
Chain35 – 594560Tyrosine-protein kinase RYK
PRO_0000024465

Regions

Topological domain35 – 211177Extracellular Potential
Transmembrane212 – 23928Helical; Potential
Topological domain240 – 594355Cytoplasmic Potential
Domain50 – 178129WIF
Domain317 – 590274Protein kinase
Nucleotide binding323 – 3319ATP By similarity

Sites

Active site4521Proton acceptor By similarity
Binding site3511ATP By similarity

Amino acid modifications

Modified residue4821Phosphotyrosine; by autocatalysis By similarity
Glycosylation1231N-linked (GlcNAc...) Potential
Glycosylation1581N-linked (GlcNAc...) Potential
Glycosylation1621N-linked (GlcNAc...) Potential
Glycosylation1661N-linked (GlcNAc...) Potential
Glycosylation1931N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict171Missing in AAA02913. Ref.5
Sequence conflict201P → A in AAA40079. Ref.3
Sequence conflict311A → P in AAA40079. Ref.3
Sequence conflict35 – 362RS → V in AAA40079. Ref.3
Sequence conflict38 – 414ALAA → GPGR in AAA40079. Ref.3
Sequence conflict1121D → N in AAA40079. Ref.3
Sequence conflict1301V → G in AAA40079. Ref.3
Sequence conflict3111A → G in AAA40079. Ref.3
Sequence conflict316 – 3183RIT → GSH in AAA02913. Ref.5
Sequence conflict3271T → S in AAA40079. Ref.3
Sequence conflict3411D → R in AAA40079. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q01887 [UniParc].

Last modified June 1, 1994. Version 2.
Checksum: 5C7261A3F7824520

FASTA59466,285
        10         20         30         40         50         60 
MRAGRGGVPG SGGLRAPPPP LLLLLLAMLP AAAPRSPALA AAPAGPSVSL YLSEDEVRRL 

        70         80         90        100        110        120 
LGLDAELYYV RNDLISHYAL SFNLLVPSET NFLHFTWHAK SKVEYKLGFQ VDNFVAMGMP 

       130        140        150        160        170        180 
QVNISAQGEV PRTLSVFRVE LSCTGKVDSE VMILMQLNLT VNSSKNFTVL NFKRRKMCYK 

       190        200        210        220        230        240 
KLEEVKTSAL DKNTSRTIYD PVHAAPTTST RVFYISVGVC CAVIFLVAII LAVLHLHSMK 

       250        260        270        280        290        300 
RIELDDSISA SSSSQGLSQP STQTTQYLRA DTPNNATPIT SSSGYPTLRI EKNDLRSVTL 

       310        320        330        340        350        360 
LEAKAKVKDI AISRERITLK DVLQEGTFGR IFHGILVDEK DPNKEKQTFV KTVKDQASEV 

       370        380        390        400        410        420 
QVTMMLTESC KLRGLHHRNL LPITHVCIEE GEKPMVVLPY MNWGNLKLFL RQCKLVEANN 

       430        440        450        460        470        480 
PQAISQQDLV HMAIQIACGM SYLARREVIH RDLAARNCVI DDTLQVKITD NALSRDLFPM 

       490        500        510        520        530        540 
DYHCLGDNEN RPVRWMALES LVNNEFSSAS DVWAFGVTLW ELMTLGQTPY VDIDPFEMAA 

       550        560        570        580        590 
YLKDGYRIAQ PINCPDELFA VMACCWALDP EERPKFQQLV QCLTEFHAAL GAYV

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		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.
IPIIPI00128580.
PIRA47186.
I56248.
I58386.
RefSeqNP_001036072.1. NM_001042607.1.
NP_038677.3. NM_013649.3.
UniGeneMm.335391.

3D structure databases

ProteinModelPortalQ01887.
SMRQ01887. Positions 47-186, 317-585.
ModBaseSearch...

PTM databases

PhosphoSiteQ01887.

Proteomic databases

PRIDEQ01887.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000175883; ENSMUSP00000135858; ENSMUSG00000032547.
GeneID20187.
KEGGmmu:20187.
UCSCuc009rga.1. mouse.

Organism-specific databases

CTD6259.
MGIMGI:101766. Ryk.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00550000074361.
HOGENOMHOG000236284.
HOVERGENHBG047417.
InParanoidQ01887.
KOK05128.
OMATISSTAH.
OrthoDBEOG4W6NVZ.

Enzyme and pathway databases

BRENDA2.7.10.1. 3474.

Gene expression databases

ArrayExpressQ01887.
BgeeQ01887.
CleanExMM_RYK.
GenevestigatorQ01887.
GermOnlineENSMUSG00000032547. Mus musculus.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR003306. WIF.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF02019. WIF. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
ProDomPD013948. WIF. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00219. TyrKc. 1 hit.
SM00469. WIF. 1 hit.
[Graphical view]
SUPFAMSSF56112. Kinase_like. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50814. WIF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRYK. mouse.
NextBio297729.
SOURCESearch...

Entry information

Entry nameRYK_MOUSE
AccessionPrimary (citable) accession number: Q01887
Secondary accession number(s): Q61890
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: June 1, 1994
Last modified: May 1, 2013
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents