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Protein

Tyrosine-protein kinase RYK

Gene

RYK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Caution

According to some authors, has impaired kinase activity.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 sitei364ATPPROSITE-ProRule annotation1
Active sitei465Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi336 – 344ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processWnt signaling pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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 RYKCurated (EC:2.7.10.1PROSITE-ProRule annotation)
Gene namesi
Name:RYKImported
Synonyms:JTK5A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000163785.12
HGNCiHGNC:10481 RYK
MIMi600524 gene
neXtProtiNX_P34925

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 227ExtracellularSequence analysisAdd BLAST202
Transmembranei228 – 248HelicalSequence analysisAdd BLAST21
Topological domaini249 – 607CytoplasmicSequence analysisAdd BLAST359

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi364K → A: No induction of the MAPK pathway. 1 Publication1
Mutagenesisi484N → 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
Mutagenesisi485A → 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
OpenTargetsiENSG00000163785
PharmGKBiPA34894

Polymorphism and mutation databases

BioMutaiRYK
DMDMi1710811

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000002446426 – 607Tyrosine-protein kinase RYKAdd BLAST582

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi139N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi159 ↔ 194PROSITE-ProRule annotation
Glycosylationi174N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi178N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi182N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi209N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei495Phosphotyrosine; 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

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP34925
PaxDbiP34925
PeptideAtlasiP34925
PRIDEiP34925
ProteomicsDBi54954
54955 [P34925-2]

PTM databases

iPTMnetiP34925
PhosphoSitePlusiP34925

Expressioni

Tissue specificityi

Observed in all the tissues examined.

Gene expression databases

BgeeiENSG00000163785
CleanExiHS_RYK

Organism-specific databases

HPAiHPA045503
HPA075430

Interactioni

Subunit structurei

Interacts with DVL1 (via PDZ domain).1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112171, 86 interactors
IntActiP34925, 1 interactor
STRINGi9606.ENSP00000296084

Structurei

3D structure databases

ProteinModelPortaliP34925
SMRiP34925
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini66 – 194WIFPROSITE-ProRule annotationAdd BLAST129
Domaini330 – 603Protein kinasePROSITE-ProRule annotationAdd BLAST274

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi24 – 53Pro-richPROSITE-ProRule annotationAdd BLAST30

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1024 Eukaryota
ENOG410XSKI LUCA
GeneTreeiENSGT00810000125384
HOGENOMiHOG000236284
HOVERGENiHBG047417
InParanoidiP34925
KOiK05128
OMAiEYKLGFQ
OrthoDBiEOG091G0353
PhylomeDBiP34925
TreeFamiTF317402

Family and domain databases

Gene3Di2.60.40.2170, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR003306 WIF
IPR038677 WIF_sf
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF02019 WIF, 1 hit
PRINTSiPR00109 TYRKINASE
ProDomiView protein in ProDom or Entries sharing at least one domain
PD013948 WIF, 1 hit
SMARTiView protein in SMART
SM00469 WIF, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS50814 WIF, 1 hit

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 GRSCLPGARG LRAPPPPPLL LLLALLPLLP APGAAAAPAP
60 70 80 90 100
RPPELQSASA GPSVSLYLSE DEVRRLIGLD AELYYVRNDL ISHYALSFSL
110 120 130 140 150
LVPSETNFLH FTWHAKSKVE YKLGFQVDNV LAMDMPQVNI SVQGEVPRTL
160 170 180 190 200
SVFRVELSCT GKVDSEVMIL MQLNLTVNSS KNFTVLNFKR RKMCYKKLEE
210 220 230 240 250
VKTSALDKNT SRTIYDPVHA APTTSTRVFY ISVGVCCAVI FLVAIILAVL
260 270 280 290 300
HLHSMKRIEL DDSISASSSS QGLSQPSTQT TQYLRADTPN NATPITSYPT
310 320 330 340 350
LRIEKNDLRS VTLLEAKGKV KDIAISRERI TLKDVLQEGT FGRIFHGILI
360 370 380 390 400
DEKDPNKEKQ AFVKTVKDQA SEIQVTMMLT ESCKLRGLHH RNLLPITHVC
410 420 430 440 450
IEEGEKPMVI LPYMNWGNLK LFLRQCKLVE ANNPQAISQQ DLVHMAIQIA
460 470 480 490 500
CGMSYLARRE VIHKDLAARN CVIDDTLQVK ITDNALSRDL FPMDYHCLGD
510 520 530 540 550
NENRPVRWMA LESLVNNEFS SASDVWAFGV TLWELMTLGQ TPYVDIDPFE
560 570 580 590 600
MAAYLKDGYR IAQPINCPDE LFAVMACCWA LDPEERPKFQ QLVQCLTEFH

AALGAYV
Length:607
Mass (Da):67,815
Last modified:March 28, 2018 - v3
Checksum:i3AFAE21A2680F400
GO
Isoform 2 (identifier: P34925-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     297-297: S → SSLG

Note: No experimental confirmation available.
Show »
Length:610
Mass (Da):68,072
Checksum:iB7B48282565CE05B
GO

Sequence cautioni

The sequence AAB26341 differs from that shown. Reason: Frameshift at several positions.Curated
The sequence CAA65406 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti26P → R in AAB26341 (PubMed:8386829).Curated1
Sequence conflicti33L → V in AAB26341 (PubMed:8386829).Curated1
Sequence conflicti254S → N in AAB26341 (PubMed:8386829).Curated1
Sequence conflicti254S → N in CAA65406 (PubMed:8726462).Curated1
Sequence conflicti319K → E in CAA49591 (PubMed:8390040).Curated1
Sequence conflicti358E → K in CAA65406 (PubMed:8726462).Curated1
Sequence conflicti440Q → H in CAA49591 (PubMed:8390040).Curated1
Sequence conflicti446A → P in CAA49591 (PubMed:8390040).Curated1
Sequence conflicti531T → NS in AAB26341 (PubMed:8386829).Curated1
Sequence conflicti544V → TL in AAB26341 (PubMed:8386829).Curated1
Sequence conflicti566N → T in AAB26341 (PubMed:8386829).Curated1
Sequence conflicti588K → R in AAB26341 (PubMed:8386829).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04180099S → N4 PublicationsCorresponds to variant dbSNP:rs1131262Ensembl.1
Natural variantiVAR_041801227R → C1 PublicationCorresponds to variant dbSNP:rs55740278Ensembl.1
Natural variantiVAR_041802243V → I in an ovarian mucinous carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs746238409Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005009297S → SSLG in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S59184 mRNA Translation: AAB26341.1 Frameshift.
X69970 mRNA Translation: CAA49591.1
AC096967 Genomic DNA No translation available.
AC107310 Genomic DNA No translation available.
AC108742 Genomic DNA No translation available.
AMYH02007719 Genomic DNA No translation available.
X96588 mRNA Translation: CAA65406.1 Different initiation.
CCDSiCCDS75016.1 [P34925-2]
CCDS77820.1 [P34925-1]
PIRiI37560
RefSeqiNP_001005861.1, NM_001005861.2 [P34925-2]
NP_002949.2, NM_002958.3 [P34925-1]
UniGeneiHs.654562

Genome annotation databases

EnsembliENST00000620660; ENSP00000478721; ENSG00000163785 [P34925-2]
ENST00000623711; ENSP00000485095; ENSG00000163785 [P34925-1]
GeneIDi6259
KEGGihsa:6259

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiRYK_HUMAN
AccessioniPrimary (citable) accession number: P34925
Secondary accession number(s): A0A087WUK1, A0A096LNL3, Q04696
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: March 28, 2018
Last modified: July 18, 2018
This is version 173 of the entry and version 3 of the sequence. See 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

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