P34925 (RYK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase RYK
EC=2.7.10.1

Gene names

Name:	RYK
Synonyms:	JTK5A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	604 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.5
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with DVL1 (via PDZ domain). Ref.5
Subcellular location	Membrane; 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.
Tissue specificity	Observed in all the tissues examined.
Domain	The extracellular WIF domain is responsible for Wnt binding By similarity.
Post-translational modification	Proteolytically cleaved, in part by presenilin, in response to WNT3 stimulation. Cleavage occurs during neuronal differentiation. Ref.6
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Contains 1 protein kinase domain. Contains 1 WIF domain.
Caution	According to some authors, has impaired kinase activity (Ref.4).

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW axon guidance Inferred from sequence or structural similarity. Source: UniProtKB commissural neuron axon guidance Inferred from electronic annotation. Source: Compara corpus callosum development Inferred from sequence or structural similarity. Source: UniProtKB negative chemotaxis Inferred from electronic annotation. Source: Compara negative regulation of axon extension involved in axon guidance Inferred from electronic annotation. Source: Compara positive regulation of MAPK cascade Inferred from direct assay Ref.4. Source: UniProtKB skeletal system morphogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW Wnt-activated receptor activity Inferred from electronic annotation. Source: Compara transmembrane receptor protein tyrosine kinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P34925-1)

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.

Isoform 2 (identifier: P34925-2)

The sequence of this isoform differs from the canonical sequence as follows:
     294-294: S → SSLG

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 604	579	Tyrosine-protein kinase RYK		PRO_0000024464
Regions
	Topological domain	26 – 224	199	Extracellular Potential
	Transmembrane	225 – 252	28	Helical; Potential
	Topological domain	253 – 604	352	Cytoplasmic Potential
	Domain	63 – 191	129	WIF
	Domain	327 – 600	274	Protein kinase
	Nucleotide binding	333 – 341	9	ATP By similarity
Sites
	Active site	462	1	Proton acceptor By similarity
	Binding site	361	1	ATP By similarity
Amino acid modifications
	Modified residue	492	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	136	1	N-linked (GlcNAc...) Potential
	Glycosylation	171	1	N-linked (GlcNAc...) Potential
	Glycosylation	175	1	N-linked (GlcNAc...) Potential
	Glycosylation	179	1	N-linked (GlcNAc...) Potential
	Glycosylation	206	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	294	1	S → SSLG in isoform 2.		VSP_005009
	Natural variant	96	1	N → S. Ref.7		VAR_041800
	Natural variant	224	1	R → C. Ref.7		VAR_041801
	Natural variant	240	1	V → I in an ovarian mucinous carcinoma sample; somatic mutation. Ref.7		VAR_041802
Experimental info
	Mutagenesis	361	1	K → A: No induction of the MAPK pathway. Ref.4
	Mutagenesis	481	1	N → 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. Ref.4
	Mutagenesis	482	1	A → G: Gain of an autophosphorylation activity. Gain of an autophosphorylation activity; when associated with G-334 and F-481. Ref.4
	Sequence conflict	18 – 46	29	PALRA…RAAAR → RGLRAPPPPPLLLLLALLPL LPAPGAAAAPA Ref.2
	Sequence conflict	251	1	N → S in CAA49591. Ref.2
	Sequence conflict	316	1	K → E in CAA49591. Ref.2
	Sequence conflict	355	1	E → K Ref.3
	Sequence conflict	437	1	Q → H in CAA49591. Ref.2
	Sequence conflict	443	1	A → P in CAA49591. Ref.2
	Sequence conflict	528	1	T → NS in AAB26341. Ref.1
	Sequence conflict	541	1	V → TL in AAB26341. Ref.1
	Sequence conflict	563	1	N → T in AAB26341. Ref.1
	Sequence conflict	585	1	K → R in AAB26341. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 06D59C0FEAB63397	FASTA	604	67,507
	10 20 30 40 50 60 MRGAARLGRP GRSCLPGPAL RAAAAPALLL ARCAVAAAAG LRAAARPRPP ELQSASAGPS 70 80 90 100 110 120 VSLYLSEDEV RRLIGLDAEL YYVRNDLISH YALSFNLLVP SETNFLHFTW HAKSKVEYKL 130 140 150 160 170 180 GFQVDNVLAM DMPQVNISVQ GEVPRTLSVF RVELSCTGKV DSEVMILMQL NLTVNSSKNF 190 200 210 220 230 240 TVLNFKRRKM CYKKLEEVKT SALDKNTSRT IYDPVHAAPT TSTRVFYISV GVCCAVIFLV 250 260 270 280 290 300 AIILAVLHLH NMKRIELDDS ISASSSSQGL SQPSTQTTQY LRADTPNNAT PITSYPTLRI 310 320 330 340 350 360 EKNDLRSVTL LEAKGKVKDI AISRERITLK DVLQEGTFGR IFHGILIDEK DPNKEKQAFV 370 380 390 400 410 420 KTVKDQASEI QVTMMLTESC KLRGLHHRNL LPITHVCIEE GEKPMVILPY MNWGNLKLFL 430 440 450 460 470 480 RQCKLVEANN PQAISQQDLV HMAIQIACGM SYLARREVIH KDLAARNCVI DDTLQVKITD 490 500 510 520 530 540 NALSRDLFPM DYHCLGDNEN RPVRWMALES LVNNEFSSAS DVWAFGVTLW ELMTLGQTPY 550 560 570 580 590 600 VDIDPFEMAA YLKDGYRIAQ PINCPDELFA VMACCWALDP EERPKFQQLV QCLTEFHAAL GAYV
	Isoform 2 [UniParc]. Checksum: 9FA455AE7922F597	FASTA	607	67,764
	10 20 30 40 50 60 MRGAARLGRP GRSCLPGPAL RAAAAPALLL ARCAVAAAAG LRAAARPRPP ELQSASAGPS 70 80 90 100 110 120 VSLYLSEDEV RRLIGLDAEL YYVRNDLISH YALSFNLLVP SETNFLHFTW HAKSKVEYKL 130 140 150 160 170 180 GFQVDNVLAM DMPQVNISVQ GEVPRTLSVF RVELSCTGKV DSEVMILMQL NLTVNSSKNF 190 200 210 220 230 240 TVLNFKRRKM CYKKLEEVKT SALDKNTSRT IYDPVHAAPT TSTRVFYISV GVCCAVIFLV 250 260 270 280 290 300 AIILAVLHLH NMKRIELDDS ISASSSSQGL SQPSTQTTQY LRADTPNNAT PITSSLGYPT 310 320 330 340 350 360 LRIEKNDLRS VTLLEAKGKV KDIAISRERI TLKDVLQEGT FGRIFHGILI DEKDPNKEKQ 370 380 390 400 410 420 AFVKTVKDQA SEIQVTMMLT ESCKLRGLHH RNLLPITHVC IEEGEKPMVI LPYMNWGNLK 430 440 450 460 470 480 LFLRQCKLVE ANNPQAISQQ DLVHMAIQIA CGMSYLARRE VIHKDLAARN CVIDDTLQVK 490 500 510 520 530 540 ITDNALSRDL FPMDYHCLGD NENRPVRWMA LESLVNNEFS SASDVWAFGV TLWELMTLGQ 550 560 570 580 590 600 TPYVDIDPFE MAAYLKDGYR IAQPINCPDE LFAVMACCWA LDPEERPKFQ QLVQCLTEFH AALGAYV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S59184 mRNA. Translation: AAB26341.1. X69970 mRNA. Translation: CAA49591.1. X96588 mRNA. Translation: CAA65406.1.
IPI	IPI00219225. IPI00298345.
PIR	I37560.
RefSeq	NP_001005861.1. NM_001005861.2. NP_002949.2. NM_002958.3.
UniGene	Hs.654562.
3D structure databases
ProteinModelPortal	P34925.
ModBase	Search...
Protein-protein interaction databases
IntAct	P34925. 1 interaction.
STRING	9606.ENSP00000296084.
PTM databases
PhosphoSite	P34925.
Polymorphism databases
DMDM	1710811.
Proteomic databases
PaxDb	P34925.
PRIDE	P34925.
Protocols and materials databases
DNASU	6259.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296084; ENSP00000296084; ENSG00000163785.
GeneID	6259.
KEGG	hsa:6259.
Organism-specific databases
CTD	6259.
GeneCards	GC03M133794.
HGNC	HGNC:10481. RYK.
HPA	CAB034117.
MIM	600524. gene.
neXtProt	NX_P34925.
PharmGKB	PA34894.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000236284.
HOVERGEN	HBG047417.
InParanoid	P34925.
KO	K05128.
Enzyme and pathway databases
BRENDA	2.7.10.1. 2681.
Gene expression databases
ArrayExpress	P34925.
Bgee	P34925.
CleanEx	HS_RYK.
Genevestigator	P34925.
GermOnline	ENSG00000163785. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR003306. WIF. [Graphical view]
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF02019. WIF. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
ProDom	PD013948. WIF. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00219. TyrKc. 1 hit. SM00469. WIF. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS50814. WIF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	6259.
NextBio	24309.
SOURCE	Search...

Entry information

Entry name

RYK_HUMAN

Accession

Primary (citable) accession number: P34925
Secondary accession number(s): Q04696

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.