RYK receptor like tyrosine kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: RYKprovided by HGNC
Official Full Name: receptor like tyrosine kinaseprovided by HGNC
Primary source: HGNC:HGNC:10481
See related: Ensembl:ENSG00000163785 MIM:600524; AllianceGenome:HGNC:10481
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: JTK5; RYK1; JTK5A; D3S3195
Summary: 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]
Expression: Ubiquitous expression in ovary (RPKM 32.1), testis (RPKM 26.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q22.2

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (134157133..134250859, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (136902246..136995998, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (133875977..133969701, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Downregulation of exosomal miR-7-5p promotes breast cancer migration and invasion by targeting RYK and participating in the atypical WNT signalling pathway.
Title: Downregulation of exosomal miR-7-5p promotes breast cancer migration and invasion by targeting RYK and participating in the atypical WNT signalling pathway.
Comprehensive analysis reveals COPB2 and RYK associated with tumor stages of larynx squamous cell carcinoma.
Title: Comprehensive analysis reveals COPB2 and RYK associated with tumor stages of larynx squamous cell carcinoma.
WNT/RYK signaling functions as an antiinflammatory modulator in the lung mesenchyme.
Title: WNT/RYK signaling functions as an antiinflammatory modulator in the lung mesenchyme.
PAX7, PAX9 and RYK Expression in Cleft Affected Tissue.
Title: PAX7, PAX9 and RYK Expression in Cleft Affected Tissue.
Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases.
Title: Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases.
RYK is highly correlated with gastric cancer tumorigenesis and the potential of liver metastasis, suggesting it may be a novel oncogenic factor of the noncanonical Wnt signaling pathway
Title: RYK, a receptor of noncanonical Wnt ligand Wnt5a, is positively correlated with gastric cancer tumorigenesis and potential of liver metastasis.
appears to signal predominantly through non-canonical WNT-triggered pathways including the PCP and WNT/Ca2+ pathways [review]
Title: The biochemistry, signalling and disease relevance of RYK and other WNT-binding receptor tyrosine kinases.
our findings demonstrate that Ryk promotes stem cell-like and tumorigenic features to glioma cells its essential for the maintenance of glioblastoma stem cells
Title: RYK promotes the stemness of glioblastoma cells via the WNT/ β-catenin pathway.
Wnt5A/Ryk signaling might provide novel therapeutic strategies to prevent capillary leakage in systemic inflammation and septic shock.
Title: Wnt5A/Ryk signaling critically affects barrier function in human vascular endothelial cells.
results corroborated previous findings of Ryk-mediated Wnt5a effect, and suggested a role for Ror2 in the Wnt5a machinery in glioblastoma
Title: Wnt5a, Ryk and Ror2 expression in glioblastoma subgroups.

Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of RYK	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70882 (e-PCR)
- UniSTS:53251

SHGC-132301 (e-PCR)
- UniSTS:170770

GDB:568595 (e-PCR)
- UniSTS:157728

D14S567 (e-PCR)
- UniSTS:149808

RH81074 (e-PCR)
- UniSTS:86329

RH69892 (e-PCR)
- UniSTS:91726

SHGC-112408 (e-PCR)
- UniSTS:183648

D3S1238 (e-PCR), detects polymorphism
- UniSTS:70250

SHGC-150765 (e-PCR)
- UniSTS:173678

WI-12317 (e-PCR)
- UniSTS:82038

D3S4192 (e-PCR)
- UniSTS:7552

SHGC-143452 (e-PCR)
- UniSTS:171914

SHGC-77367 (e-PCR)
- UniSTS:21162

D3S3684 (e-PCR), detects polymorphism
- UniSTS:5363

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables Wnt receptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables Wnt-protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables Wnt-protein binding	NAS Non-traceable Author Statement more info	PubMed
enables coreceptor activity	TAS Traceable Author Statement more info	PubMed
enables frizzled binding	ISS Inferred from Sequence or Structural Similarity more info
enables frizzled binding	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
NOT enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
NOT enables transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane signaling receptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Wnt signaling pathway, planar cell polarity pathway	TAS Traceable Author Statement more info	PubMed
involved_in axon extension involved in axon guidance	IEA Inferred from Electronic Annotation more info
involved_in axon guidance	ISS Inferred from Sequence or Structural Similarity more info
involved_in axon guidance	NAS Non-traceable Author Statement more info	PubMed
involved_in axonogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in axonogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in axonogenesis	TAS Traceable Author Statement more info	PubMed
involved_in canonical Wnt signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in chemorepulsion of dopaminergic neuron axon	ISS Inferred from Sequence or Structural Similarity more info
involved_in commissural neuron axon guidance	ISS Inferred from Sequence or Structural Similarity more info
involved_in corpus callosum development	ISS Inferred from Sequence or Structural Similarity more info
involved_in midbrain dopaminergic neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of axon extension involved in axon guidance	IEA Inferred from Electronic Annotation more info
involved_in neurogenesis	NAS Non-traceable Author Statement more info	PubMed
involved_in neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron projection development	ISS Inferred from Sequence or Structural Similarity more info
involved_in non-canonical Wnt signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell proliferation in midbrain	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of neuron projection development	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IBA Inferred from Biological aspect of Ancestor more info
NOT involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in skeletal system morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in synapse assembly	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic density membrane	IEA Inferred from Electronic Annotation more info
located_in presynaptic active zone membrane	IEA Inferred from Electronic Annotation more info
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: tyrosine-protein kinase RYK

Names: JTK5A protein tyrosine kinase; hydroxyaryl-protein kinase

NP_001005861.1

EC 2.7.10.1

NP_002949.2

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_032937.1 RefSeqGene

Range

4886..98612

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001005861.3 → NP_001005861.1 tyrosine-protein kinase RYK isoform 1 precursor

See identical proteins and their annotated locations for NP_001005861.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AB209405, AC096967, AC108742, BC021700, CN309980, X69970

Consensus CDS

CCDS75016.1

Related

ENSP00000478721.1, ENST00000620660.4

Conserved Domains (3) summary

smart00469
Location:63 → 196

WIF; Wnt-inhibitory factor-1 like domain

cd05043
Location:326 → 606

PTK_Ryk; Pseudokinase domain of Ryk (Receptor related to tyrosine kinase)

pfam07714
Location:333 → 599

Pkinase_Tyr; Protein tyrosine kinase
NM_002958.4 → NP_002949.2 tyrosine-protein kinase RYK isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the coding region, compared to variant 1, resulting in a shorter protein (isoform 2).

Source sequence(s)

AB209405, AC096967, AC108742, BC021700, CN309980, X69970

Consensus CDS

CCDS77820.1

UniProtKB/Swiss-Prot

A0A087WUK1, A0A096LNL3, P34925, Q04696

Related

ENSP00000485095.1, ENST00000623711.4

Conserved Domains (2) summary

smart00469
Location:63 → 196

WIF; Wnt-inhibitory factor-1 like domain

cd05043
Location:323 → 603

PTK_Ryk; Pseudokinase domain of Ryk (Receptor related to tyrosine kinase)