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Protein

Tyrosine-protein kinase RYK

Gene

Ryk

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei351 – 3511ATPPROSITE-ProRule annotation
Active sitei452 – 4521Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi323 – 3319ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. frizzled binding Source: UniProtKB
  3. protein kinase activity Source: InterPro
  4. transmembrane signaling receptor activity Source: MGI
  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.

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 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:101766. Ryk.

Subcellular locationi

  1. Membrane 1 Publication; Single-pass type I membrane protein 1 Publication
  2. Nucleus 1 Publication
  3. Cytoplasm 1 Publication

  4. Note: In cells that have undergone neuronal differentiation, the C-terminal cleaved part is translocated from the cytoplasm to the nucleus.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini35 – 211177ExtracellularSequence AnalysisAdd
BLAST
Transmembranei212 – 23928HelicalSequence AnalysisAdd
BLAST
Topological domaini240 – 594355CytoplasmicSequence AnalysisAdd
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 – 3434Sequence AnalysisAdd
BLAST
Chaini35 – 594560Tyrosine-protein kinase RYKPRO_0000024465Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi123 – 1231N-linked (GlcNAc...)Sequence Analysis
Glycosylationi158 – 1581N-linked (GlcNAc...)Sequence Analysis
Glycosylationi162 – 1621N-linked (GlcNAc...)Sequence Analysis
Glycosylationi166 – 1661N-linked (GlcNAc...)Sequence Analysis
Glycosylationi193 – 1931N-linked (GlcNAc...)Sequence Analysis
Modified residuei482 – 4821Phosphotyrosine; by autocatalysisBy 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

BgeeiQ01887.
CleanExiMM_RYK.
ExpressionAtlasiQ01887. baseline and differential.
GenevestigatoriQ01887.

Interactioni

Subunit structurei

Interacts with DVL1 (via PDZ domain).1 Publication

Protein-protein interaction databases

BioGridi203044. 11 interactions.
DIPiDIP-61011N.

Structurei

3D structure databases

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

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini50 – 178129WIFPROSITE-ProRule annotationAdd
BLAST
Domaini317 – 590274Protein kinasePROSITE-ProRule annotationAdd
BLAST

Domaini

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

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.
GeneTreeiENSGT00770000120499.
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

        10         20         30         40         50
MRAGRGGVPG SGGLRAPPPP LLLLLLAMLP AAAPRSPALA AAPAGPSVSL
60 70 80 90 100
YLSEDEVRRL LGLDAELYYV RNDLISHYAL SFNLLVPSET NFLHFTWHAK
110 120 130 140 150
SKVEYKLGFQ VDNFVAMGMP QVNISAQGEV PRTLSVFRVE LSCTGKVDSE
160 170 180 190 200
VMILMQLNLT VNSSKNFTVL NFKRRKMCYK KLEEVKTSAL DKNTSRTIYD
210 220 230 240 250
PVHAAPTTST RVFYISVGVC CAVIFLVAII LAVLHLHSMK RIELDDSISA
260 270 280 290 300
SSSSQGLSQP STQTTQYLRA DTPNNATPIT SSSGYPTLRI EKNDLRSVTL
310 320 330 340 350
LEAKAKVKDI AISRERITLK DVLQEGTFGR IFHGILVDEK DPNKEKQTFV
360 370 380 390 400
KTVKDQASEV QVTMMLTESC KLRGLHHRNL LPITHVCIEE GEKPMVVLPY
410 420 430 440 450
MNWGNLKLFL RQCKLVEANN PQAISQQDLV HMAIQIACGM SYLARREVIH
460 470 480 490 500
RDLAARNCVI DDTLQVKITD NALSRDLFPM DYHCLGDNEN RPVRWMALES
510 520 530 540 550
LVNNEFSSAS DVWAFGVTLW ELMTLGQTPY VDIDPFEMAA YLKDGYRIAQ
560 570 580 590
PINCPDELFA VMACCWALDP EERPKFQQLV QCLTEFHAAL GAYV
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. Curated
The sequence AAA40079.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti17 – 171Missing in AAA02913 (PubMed:8394755).Curated
Sequence conflicti20 – 201P → A in AAA40079 (PubMed:1334548).Curated
Sequence conflicti31 – 311A → P in AAA40079 (PubMed:1334548).Curated
Sequence conflicti35 – 362RS → V in AAA40079 (PubMed:1334548).Curated
Sequence conflicti38 – 414ALAA → GPGR in AAA40079 (PubMed:1334548).Curated
Sequence conflicti112 – 1121D → N in AAA40079 (PubMed:1334548).Curated
Sequence conflicti130 – 1301V → G in AAA40079 (PubMed:1334548).Curated
Sequence conflicti311 – 3111A → G in AAA40079 (PubMed:1334548).Curated
Sequence conflicti316 – 3183RIT → GSH in AAA02913 (PubMed:8394755).Curated
Sequence conflicti327 – 3271T → S in AAA40079 (PubMed:1334548).Curated
Sequence conflicti341 – 3411D → R in AAA40079 (PubMed:1334548).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi203044. 11 interactions.
DIPiDIP-61011N.

PTM databases

PhosphoSiteiQ01887.

Proteomic databases

PRIDEiQ01887.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi6259.
MGIiMGI:101766. Ryk.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00770000120499.
HOGENOMiHOG000236284.
HOVERGENiHBG047417.
InParanoidiQ01887.
KOiK05128.
OMAiDHASEVQ.
OrthoDBiEOG7M98KK.
PhylomeDBiQ01887.
TreeFamiTF317402.

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.

Miscellaneous databases

ChiTaRSiRyk. mouse.
NextBioi297729.
PROiQ01887.
SOURCEiSearch...

Gene expression databases

BgeeiQ01887.
CleanExiMM_RYK.
ExpressionAtlasiQ01887. baseline and differential.
GenevestigatoriQ01887.

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]
ProtoNetiSearch...

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: April 1, 2015
This is version 145 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.