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P34925 (RYK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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
Gene names
Name:RYK
Synonyms:JTK5A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length604 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.5

Catalytic activity

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

Subunit structure

Interacts with DVL1 (via PDZ domain). Ref.5

Subcellular location

Membrane; 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.

Tissue specificity

Observed in all the tissues examined.

Domain

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

Post-translational modification

Proteolytically cleaved, in part by presenilin, in response to WNT3 stimulation. Cleavage occurs during neuronal differentiation. Ref.6

Sequence similarities

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

Contains 1 protein kinase domain.

Contains 1 WIF domain.

Caution

According to some authors, has impaired kinase activity (Ref.4).

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCytoplasm
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   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 signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

axon guidance

Inferred from sequence or structural similarity. Source: UniProtKB

commissural neuron axon guidance

Inferred from electronic annotation. Source: Ensembl

corpus callosum development

Inferred from sequence or structural similarity. Source: UniProtKB

negative chemotaxis

Inferred from electronic annotation. Source: Ensembl

negative regulation of axon extension involved in axon guidance

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Traceable author statement Ref.1. Source: GOC

positive regulation of MAPK cascade

Inferred from direct assay Ref.4. Source: UniProtKB

signal transduction

Traceable author statement Ref.1. Source: ProtInc

skeletal system morphogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of membrane

Non-traceable author statement Ref.3. Source: UniProtKB

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Wnt-activated receptor activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction Ref.5. Source: UniProtKB

transmembrane receptor protein tyrosine kinase activity

Traceable author statement Ref.1. Source: ProtInc

transmembrane signaling receptor activity

Inferred from direct assay Ref.4. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P34925-1)

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.
Isoform 2 (identifier: P34925-2)

The sequence of this isoform differs from the canonical sequence as follows:
     294-294: S → SSLG
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 604579Tyrosine-protein kinase RYK
PRO_0000024464

Regions

Topological domain26 – 224199Extracellular Potential
Transmembrane225 – 25228Helical; Potential
Topological domain253 – 604352Cytoplasmic Potential
Domain63 – 191129WIF
Domain327 – 600274Protein kinase
Nucleotide binding333 – 3419ATP By similarity

Sites

Active site4621Proton acceptor By similarity
Binding site3611ATP By similarity

Amino acid modifications

Modified residue4921Phosphotyrosine; by autocatalysis By similarity
Glycosylation1361N-linked (GlcNAc...) Potential
Glycosylation1711N-linked (GlcNAc...) Potential
Glycosylation1751N-linked (GlcNAc...) Potential
Glycosylation1791N-linked (GlcNAc...) Potential
Glycosylation2061N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence2941S → SSLG in isoform 2.
VSP_005009
Natural variant961N → S. Ref.7
VAR_041800
Natural variant2241R → C. Ref.7
VAR_041801
Natural variant2401V → I in an ovarian mucinous carcinoma sample; somatic mutation. Ref.7
VAR_041802

Experimental info

Mutagenesis3611K → A: No induction of the MAPK pathway. Ref.4
Mutagenesis4811N → 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. Ref.4
Mutagenesis4821A → G: Gain of an autophosphorylation activity. Gain of an autophosphorylation activity; when associated with G-334 and F-481. Ref.4
Sequence conflict18 – 4629PALRA…RAAAR → RGLRAPPPPPLLLLLALLPL LPAPGAAAAPA Ref.2
Sequence conflict2511N → S in CAA49591. Ref.2
Sequence conflict3161K → E in CAA49591. Ref.2
Sequence conflict3551E → K Ref.3
Sequence conflict4371Q → H in CAA49591. Ref.2
Sequence conflict4431A → P in CAA49591. Ref.2
Sequence conflict5281T → NS in AAB26341. Ref.1
Sequence conflict5411V → TL in AAB26341. Ref.1
Sequence conflict5631N → T in AAB26341. Ref.1
Sequence conflict5851K → R in AAB26341. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: 06D59C0FEAB63397

FASTA60467,507
        10         20         30         40         50         60 
MRGAARLGRP GRSCLPGPAL RAAAAPALLL ARCAVAAAAG LRAAARPRPP ELQSASAGPS 

        70         80         90        100        110        120 
VSLYLSEDEV RRLIGLDAEL YYVRNDLISH YALSFNLLVP SETNFLHFTW HAKSKVEYKL 

       130        140        150        160        170        180 
GFQVDNVLAM DMPQVNISVQ GEVPRTLSVF RVELSCTGKV DSEVMILMQL NLTVNSSKNF 

       190        200        210        220        230        240 
TVLNFKRRKM CYKKLEEVKT SALDKNTSRT IYDPVHAAPT TSTRVFYISV GVCCAVIFLV 

       250        260        270        280        290        300 
AIILAVLHLH NMKRIELDDS ISASSSSQGL SQPSTQTTQY LRADTPNNAT PITSYPTLRI 

       310        320        330        340        350        360 
EKNDLRSVTL LEAKGKVKDI AISRERITLK DVLQEGTFGR IFHGILIDEK DPNKEKQAFV 

       370        380        390        400        410        420 
KTVKDQASEI QVTMMLTESC KLRGLHHRNL LPITHVCIEE GEKPMVILPY MNWGNLKLFL 

       430        440        450        460        470        480 
RQCKLVEANN PQAISQQDLV HMAIQIACGM SYLARREVIH KDLAARNCVI DDTLQVKITD 

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

       550        560        570        580        590        600 
VDIDPFEMAA YLKDGYRIAQ PINCPDELFA VMACCWALDP EERPKFQQLV QCLTEFHAAL 


GAYV 

« Hide

Isoform 2 [UniParc].

Checksum: 9FA455AE7922F597
Show »

FASTA60767,764

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S59184 mRNA. Translation: AAB26341.1.
X69970 mRNA. Translation: CAA49591.1.
X96588 mRNA. Translation: CAA65406.1.
PIRI37560.
RefSeqNP_001005861.1. NM_001005861.2.
NP_002949.2. NM_002958.3.
UniGeneHs.654562.

3D structure databases

ProteinModelPortalP34925.
SMRP34925. Positions 60-193, 327-595.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112171. 70 interactions.
IntActP34925. 1 interaction.
STRING9606.ENSP00000296084.

PTM databases

PhosphoSiteP34925.

Polymorphism databases

DMDM1710811.

Proteomic databases

PaxDbP34925.
PRIDEP34925.

Protocols and materials databases

DNASU6259.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296084; ENSP00000296084; ENSG00000163785.
GeneID6259.
KEGGhsa:6259.

Organism-specific databases

CTD6259.
GeneCardsGC03M133794.
HGNCHGNC:10481. RYK.
HPACAB034117.
HPA045503.
MIM600524. gene.
neXtProtNX_P34925.
PharmGKBPA34894.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000236284.
HOVERGENHBG047417.
InParanoidP34925.
KOK05128.
PhylomeDBP34925.
TreeFamTF317402.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
ReactomeREACT_111102. Signal Transduction.
SignaLinkP34925.

Gene expression databases

ArrayExpressP34925.
BgeeP34925.
CleanExHS_RYK.
GenevestigatorP34925.

Family and domain databases

InterProIPR011009. 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]
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. SSF56112. 1 hit.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50814. WIF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiRelated_to_receptor_tyrosine_kinase.
GenomeRNAi6259.
NextBio24309.
PROP34925.
SOURCESearch...

Entry information

Entry nameRYK_HUMAN
AccessionPrimary (citable) accession number: P34925
Secondary accession number(s): Q04696
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: October 1, 1996
Last modified: June 11, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM