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Protein

Tyrosine-protein kinase RYK

Gene

RYK

Organism
Homo sapiens (Human)
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.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei361ATPPROSITE-ProRule annotation1
Active sitei462Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi333 – 341ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway Source: ParkinsonsUK-UCL
  • frizzled binding Source: ParkinsonsUK-UCL
  • transmembrane receptor protein tyrosine kinase activity Source: ProtInc
  • transmembrane signaling receptor activity Source: UniProtKB
  • Wnt-activated receptor activity Source: ParkinsonsUK-UCL
  • Wnt-protein binding Source: ParkinsonsUK-UCL

GO - Biological processi

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

BioCyciZFISH:HS08934-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-4086400. PCP/CE pathway.
SignaLinkiP34925.
SIGNORiP34925.

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
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:10481. RYK.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 224ExtracellularSequence analysisAdd BLAST199
Transmembranei225 – 252HelicalSequence analysisAdd BLAST28
Topological domaini253 – 604CytoplasmicSequence analysisAdd BLAST352

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi361K → A: No induction of the MAPK pathway. 1 Publication1
Mutagenesisi481N → 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 Publication1
Mutagenesisi482A → G: Gain of an autophosphorylation activity. Gain of an autophosphorylation activity; when associated with G-334 and F-481. 1 Publication1

Organism-specific databases

DisGeNETi6259.
PharmGKBiPA34894.

Polymorphism and mutation databases

BioMutaiRYK.
DMDMi1710811.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000002446426 – 604Tyrosine-protein kinase RYKAdd BLAST579

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi136N-linked (GlcNAc...)Sequence analysis1
Glycosylationi171N-linked (GlcNAc...)Sequence analysis1
Glycosylationi175N-linked (GlcNAc...)Sequence analysis1
Glycosylationi179N-linked (GlcNAc...)Sequence analysis1
Glycosylationi206N-linked (GlcNAc...)Sequence analysis1
Modified residuei492Phosphotyrosine; by autocatalysisBy similarity1

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

EPDiP34925.
PaxDbiP34925.
PeptideAtlasiP34925.
PRIDEiP34925.

PTM databases

iPTMnetiP34925.
PhosphoSitePlusiP34925.

Expressioni

Tissue specificityi

Observed in all the tissues examined.

Gene expression databases

BgeeiENSG00000163785.
CleanExiHS_RYK.

Organism-specific databases

HPAiHPA045503.

Interactioni

Subunit structurei

Interacts with DVL1 (via PDZ domain).1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112171. 82 interactors.
IntActiP34925. 1 interactor.
STRINGi9606.ENSP00000296084.

Structurei

3D structure databases

ProteinModelPortaliP34925.
SMRiP34925.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini63 – 191WIFPROSITE-ProRule annotationAdd BLAST129
Domaini327 – 600Protein kinasePROSITE-ProRule annotationAdd BLAST274

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

eggNOGiKOG1024. Eukaryota.
ENOG410XSKI. LUCA.
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.
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]
SMARTiSM00469. 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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti18 – 46PALRA…RAAAR → RGLRAPPPPPLLLLLALLPL LPAPGAAAAPA (PubMed:8390040).CuratedAdd BLAST29
Sequence conflicti251N → S in CAA49591 (PubMed:8390040).Curated1
Sequence conflicti316K → E in CAA49591 (PubMed:8390040).Curated1
Sequence conflicti355E → K (PubMed:8726462).Curated1
Sequence conflicti437Q → H in CAA49591 (PubMed:8390040).Curated1
Sequence conflicti443A → P in CAA49591 (PubMed:8390040).Curated1
Sequence conflicti528T → NS in AAB26341 (PubMed:8386829).Curated1
Sequence conflicti541V → TL in AAB26341 (PubMed:8386829).Curated1
Sequence conflicti563N → T in AAB26341 (PubMed:8386829).Curated1
Sequence conflicti585K → R in AAB26341 (PubMed:8386829).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04180096N → S.1 Publication1
Natural variantiVAR_041801224R → C.1 Publication1
Natural variantiVAR_041802240V → I in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005009294S → SSLG in isoform 2. 1 Publication1

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.

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.
PIRiI37560.
RefSeqiNP_001005861.1. NM_001005861.2.
NP_002949.2. NM_002958.3.
UniGeneiHs.654562.

3D structure databases

ProteinModelPortaliP34925.
SMRiP34925.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112171. 82 interactors.
IntActiP34925. 1 interactor.
STRINGi9606.ENSP00000296084.

PTM databases

iPTMnetiP34925.
PhosphoSitePlusiP34925.

Polymorphism and mutation databases

BioMutaiRYK.
DMDMi1710811.

Proteomic databases

EPDiP34925.
PaxDbiP34925.
PeptideAtlasiP34925.
PRIDEiP34925.

Protocols and materials databases

DNASUi6259.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296084; ENSP00000296084; ENSG00000163785.
GeneIDi6259.
KEGGihsa:6259.

Organism-specific databases

CTDi6259.
DisGeNETi6259.
GeneCardsiRYK.
HGNCiHGNC:10481. RYK.
HPAiHPA045503.
MIMi600524. gene.
neXtProtiNX_P34925.
PharmGKBiPA34894.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1024. Eukaryota.
ENOG410XSKI. LUCA.
HOGENOMiHOG000236284.
HOVERGENiHBG047417.
InParanoidiP34925.
KOiK05128.
PhylomeDBiP34925.
TreeFamiTF317402.

Enzyme and pathway databases

BioCyciZFISH:HS08934-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-4086400. PCP/CE pathway.
SignaLinkiP34925.
SIGNORiP34925.

Miscellaneous databases

ChiTaRSiRYK. human.
GeneWikiiRelated_to_receptor_tyrosine_kinase.
GenomeRNAii6259.
PROiP34925.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163785.
CleanExiHS_RYK.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
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]
SMARTiSM00469. 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...

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 2, 2016
This is version 161 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

Caution

According to some authors, has impaired kinase activity.1 Publication

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

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 one 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.