RYK

Protein identityUniProt · HPA

UniProt accession

P34925

Gene

RYK

Ensembl

ENSG00000163785

Chromosome

3

Canonical length

607 aa

Protein class

Enzymes, Predicted membrane proteins

Subcellular location

Golgi apparatus,Cytosol

OverviewNCBI Gene

The protein encoded by this gene is an atypical member of the family of growth factor receptor protein tyrosine kinases, differing from other members at a number of conserved residues in the activation and nucleotide binding domains. This gene product belongs to a subfamily whose members do not appear to be regulated by phosphorylation in the activation segment. It has been suggested that mediation of biological activity by recruitment of a signaling-competent auxiliary protein may occur through an as yet uncharacterized mechanism. The encoded protein has a leucine-rich extracellular domain with a WIF-type Wnt binding region, a single transmembrane domain, and an intracellular tyrosine kinase domain. This protein is involved in stimulating Wnt signaling pathways such as the regulation of axon pathfinding. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2012]

Canonical amino-acid sequenceUniProt

607 residues, UniProt reviewed canonical sequence.

>P34925|RYK
     1  MRGAARLGRP GRSCLPGARG LRAPPPPPLL LLLALLPLLP APGAAAAPAP RPPELQSASA
    61  GPSVSLYLSE DEVRRLIGLD AELYYVRNDL ISHYALSFSL LVPSETNFLH FTWHAKSKVE
   121  YKLGFQVDNV LAMDMPQVNI SVQGEVPRTL SVFRVELSCT GKVDSEVMIL MQLNLTVNSS
   181  KNFTVLNFKR RKMCYKKLEE VKTSALDKNT SRTIYDPVHA APTTSTRVFY ISVGVCCAVI
   241  FLVAIILAVL HLHSMKRIEL DDSISASSSS QGLSQPSTQT TQYLRADTPN NATPITSYPT
   301  LRIEKNDLRS VTLLEAKGKV KDIAISRERI TLKDVLQEGT FGRIFHGILI DEKDPNKEKQ
   361  AFVKTVKDQA SEIQVTMMLT ESCKLRGLHH RNLLPITHVC IEEGEKPMVI LPYMNWGNLK
   421  LFLRQCKLVE ANNPQAISQQ DLVHMAIQIA CGMSYLARRE VIHKDLAARN CVIDDTLQVK
   481  ITDNALSRDL FPMDYHCLGD NENRPVRWMA LESLVNNEFS SASDVWAFGV TLWELMTLGQ
   541  TPYVDIDPFE MAAYLKDGYR IAQPINCPDE LFAVMACCWA LDPEERPKFQ QLVQCLTEFH
   601  AALGAYV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RYK can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

79 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.29

gnomAD pLI

0.99

gnomAD missense Z

1.81

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 10% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axon extension involved in axon guidance
• axon guidance
• axonogenesis
• canonical Wnt signaling pathway
• cell surface receptor protein tyrosine kinase signaling pathway
• chemorepulsion of dopaminergic neuron axon
• commissural neuron axon guidance
• corpus callosum development
• midbrain dopaminergic neuron differentiation
• negative regulation of axon extension involved in axon guidance
• neurogenesis
• neuron differentiation
• neuron projection development
• non-canonical Wnt signaling pathway
• positive regulation of cell proliferation in midbrain
• positive regulation of MAPK cascade
• positive regulation of neuron projection development
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• signal transduction
• skeletal system morphogenesis
• synapse assembly
• Wnt signaling pathway, planar cell polarity pathway

Molecular functions

• ATP binding
• coreceptor activity
• frizzled binding
• protein kinase activity
• transmembrane signaling receptor activity
• Wnt receptor activity
• Wnt-protein binding

Cellular components

• cytoplasm
• glutamatergic synapse
• membrane
• nucleus
• plasma membrane
• postsynaptic density membrane
• presynaptic active zone membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• WIF domain
• Tyrosine-protein kinase, active site
• Protein kinase-like domain superfamily
• WIF domain superfamily
• Receptor Tyrosine Kinase
• WIF domain
• Protein tyrosine and serine/threonine kinase

KeywordsUniProt

• ATP-binding
• Cytoplasm
• Disulfide bond
• Glycoprotein
• Kinase
• Membrane
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Receptor
• Signal
• Transferase
• Transmembrane
• Transmembrane helix
• Tyrosine-protein kinase
• Wnt signaling pathway

InteractionsUniProt · HPA

Protein binding partners of RYK in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DVL1