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P34925

- RYK_HUMAN

UniProt

P34925 - RYK_HUMAN

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Protein

Tyrosine-protein kinase RYK

Gene

RYK

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.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei361 – 3611ATPPROSITE-ProRule annotation
Active sitei462 – 4621Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi333 – 3419ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. transmembrane receptor protein tyrosine kinase activity Source: ProtInc
  3. transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

  1. axon guidance Source: UniProtKB
  2. corpus callosum development Source: UniProtKB
  3. neuron differentiation Source: UniProtKB
  4. neuron projection development Source: UniProtKB
  5. peptidyl-tyrosine phosphorylation Source: GOC
  6. positive regulation of MAPK cascade Source: UniProtKB
  7. signal transduction Source: ProtInc
  8. Wnt signaling pathway Source: UniProtKB-KW
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: Unplaced

Organism-specific databases

HGNCiHGNC:10481. RYK.

Subcellular locationi

Membrane By similarity; 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 – 224199ExtracellularSequence AnalysisAdd
BLAST
Transmembranei225 – 25228HelicalSequence AnalysisAdd
BLAST
Topological domaini253 – 604352CytoplasmicSequence AnalysisAdd
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 – 2525Sequence AnalysisAdd
BLAST
Chaini26 – 604579Tyrosine-protein kinase RYKPRO_0000024464Add
BLAST

Amino acid modifications

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

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. 72 interactions.
IntActiP34925. 1 interaction.
STRINGi9606.ENSP00000296084.

Structurei

3D structure databases

ProteinModelPortaliP34925.
SMRiP34925. Positions 60-193, 284-595.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini63 – 191129WIFPROSITE-ProRule annotationAdd
BLAST
Domaini327 – 600274Protein kinasePROSITE-ProRule annotationAdd
BLAST

Domaini

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

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.
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

        10         20         30         40         50
MRGAARLGRP GRSCLPGPAL RAAAAPALLL ARCAVAAAAG LRAAARPRPP
60 70 80 90 100
ELQSASAGPS VSLYLSEDEV RRLIGLDAEL YYVRNDLISH YALSFNLLVP
110 120 130 140 150
SETNFLHFTW HAKSKVEYKL GFQVDNVLAM DMPQVNISVQ GEVPRTLSVF
160 170 180 190 200
RVELSCTGKV DSEVMILMQL NLTVNSSKNF TVLNFKRRKM CYKKLEEVKT
210 220 230 240 250
SALDKNTSRT IYDPVHAAPT TSTRVFYISV GVCCAVIFLV AIILAVLHLH
260 270 280 290 300
NMKRIELDDS ISASSSSQGL SQPSTQTTQY LRADTPNNAT PITSYPTLRI
310 320 330 340 350
EKNDLRSVTL LEAKGKVKDI AISRERITLK DVLQEGTFGR IFHGILIDEK
360 370 380 390 400
DPNKEKQAFV KTVKDQASEI QVTMMLTESC KLRGLHHRNL LPITHVCIEE
410 420 430 440 450
GEKPMVILPY MNWGNLKLFL RQCKLVEANN PQAISQQDLV HMAIQIACGM
460 470 480 490 500
SYLARREVIH KDLAARNCVI DDTLQVKITD NALSRDLFPM DYHCLGDNEN
510 520 530 540 550
RPVRWMALES LVNNEFSSAS DVWAFGVTLW ELMTLGQTPY VDIDPFEMAA
560 570 580 590 600
YLKDGYRIAQ PINCPDELFA VMACCWALDP EERPKFQQLV QCLTEFHAAL

GAYV
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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti18 – 4629PALRA…RAAAR → RGLRAPPPPPLLLLLALLPL LPAPGAAAAPA(PubMed:8390040)CuratedAdd
BLAST
Sequence conflicti251 – 2511N → S in CAA49591. (PubMed:8390040)Curated
Sequence conflicti316 – 3161K → E in CAA49591. (PubMed:8390040)Curated
Sequence conflicti355 – 3551E → K(PubMed:8726462)Curated
Sequence conflicti437 – 4371Q → H in CAA49591. (PubMed:8390040)Curated
Sequence conflicti443 – 4431A → P in CAA49591. (PubMed:8390040)Curated
Sequence conflicti528 – 5281T → NS in AAB26341. (PubMed:8386829)Curated
Sequence conflicti541 – 5411V → TL in AAB26341. (PubMed:8386829)Curated
Sequence conflicti563 – 5631N → T in AAB26341. (PubMed:8386829)Curated
Sequence conflicti585 – 5851K → R in AAB26341. (PubMed:8386829)Curated

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. 1 PublicationVSP_005009

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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, 284-595.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112171. 72 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

ChiTaRSi RYK. human.
GeneWikii Related_to_receptor_tyrosine_kinase.
GenomeRNAii 6259.
NextBioi 24309.
PROi P34925.
SOURCEi Search...

Gene expression databases

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: November 26, 2014
This is version 143 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