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P34925

- RYK_HUMAN

UniProt

P34925 - RYK_HUMAN

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Protein
Tyrosine-protein kinase RYK
Gene
RYK, JTK5A
Organism
Homo sapiens (Human)
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.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei361 – 3611ATP By similarity
Active sitei462 – 4621Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi333 – 3419ATP By similarity

GO - Molecular functioni

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

GO - Biological processi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini26 – 224199Extracellular Reviewed prediction
Add
BLAST
Transmembranei225 – 25228Helical; Reviewed prediction
Add
BLAST
Topological domaini253 – 604352Cytoplasmic Reviewed prediction
Add
BLAST

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
Complete GO annotation...

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 – 2525 Reviewed prediction
Add
BLAST
Chaini26 – 604579Tyrosine-protein kinase RYK
PRO_0000024464Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi136 – 1361N-linked (GlcNAc...) Reviewed prediction
Glycosylationi171 – 1711N-linked (GlcNAc...) Reviewed prediction
Glycosylationi175 – 1751N-linked (GlcNAc...) Reviewed prediction
Glycosylationi179 – 1791N-linked (GlcNAc...) Reviewed prediction
Glycosylationi206 – 2061N-linked (GlcNAc...) Reviewed prediction
Modified residuei492 – 4921Phosphotyrosine; by autocatalysis By 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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini63 – 191129WIF
Add
BLAST
Domaini327 – 600274Protein kinase
Add
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 WIF domain.

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

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.
VSP_005009

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti18 – 4629PALRA…RAAAR → RGLRAPPPPPLLLLLALLPL LPAPGAAAAPA1 Publication
Add
BLAST
Sequence conflicti251 – 2511N → S in CAA49591. 1 Publication
Sequence conflicti316 – 3161K → E in CAA49591. 1 Publication
Sequence conflicti355 – 3551E → K1 Publication
Sequence conflicti437 – 4371Q → H in CAA49591. 1 Publication
Sequence conflicti443 – 4431A → P in CAA49591. 1 Publication
Sequence conflicti528 – 5281T → NS in AAB26341. 1 Publication
Sequence conflicti541 – 5411V → TL in AAB26341. 1 Publication
Sequence conflicti563 – 5631N → T in AAB26341. 1 Publication
Sequence conflicti585 – 5851K → R in AAB26341. 1 Publication

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...

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 140 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

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