P42685 (FRK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase FRK
EC=2.7.10.2

Alternative name(s):
FYN-related kinase
Nuclear tyrosine protein kinase RAK
Protein-tyrosine kinase 5

Gene names

Name:	FRK
Synonyms:	PTK5, RAK

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	505 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents its ubiquitination and degradation, possibly by reducing its binding to NEDD4. May function as a tumor suppressor. Ref.9
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts (via the SH3-domain) with PTEN. Interacts with RB1. Ref.7 Ref.9
Subcellular location	Cytoplasm. Nucleus. Note: Predominantly found in the nucleus, with a small fraction found in the cell periphery. Ref.1
Tissue specificity	Predominantly expressed in epithelial derived cell lines and tissues, especially normal liver, kidney, breast and colon. Ref.1
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Tumor suppressor
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Traceable author statement Ref.7. Source: ProtInc
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Traceable author statement Ref.1. Source: ProtInc plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PTEN	P60484	7	EBI-1383583,EBI-696162
RB1	P06400	3	EBI-1383583,EBI-491274

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 505	505	Tyrosine-protein kinase FRK		PRO_0000088097
Regions
	Domain	42 – 110	69	SH3
	Domain	116 – 208	93	SH2
	Domain	234 – 491	258	Protein kinase
	Nucleotide binding	240 – 248	9	ATP By similarity
Sites
	Active site	354	1	Proton acceptor By similarity
	Binding site	262	1	ATP By similarity
Amino acid modifications
	Modified residue	37	1	Phosphoserine Ref.8
	Modified residue	387	1	Phosphotyrosine; by autocatalysis By similarity
Natural variations
	Natural variant	100	1	I → V. Ref.11 Corresponds to variant rs34704018 [ dbSNP | Ensembl ].		VAR_041702
	Natural variant	122	1	G → R. Ref.11 Corresponds to variant rs3756772 [ dbSNP | Ensembl ].		VAR_006283
	Natural variant	133	1	S → L. Ref.11 Corresponds to variant rs34064900 [ dbSNP | Ensembl ].		VAR_041703
Experimental info
	Mutagenesis	262	1	K → R: Loss of ability to phosphorylate PTEN. Ref.9
	Sequence conflict	115	1	P → A in AAC50116. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P42685 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 06EC050DDBCD930B	FASTA	505	58,254
	10 20 30 40 50 60 MSNICQRLWE YLEPYLPCLS TEADKSTVIE NPGALCSPQS QRHGHYFVAL FDYQARTAED 70 80 90 100 110 120 LSFRAGDKLQ VLDTLHEGWW FARHLEKRRD GSSQQLQGYI PSNYVAEDRS LQAEPWFFGA 130 140 150 160 170 180 IGRSDAEKQL LYSENKTGSF LIRESESQKG EFSLSVLDGA VVKHYRIKRL DEGGFFLTRR 190 200 210 220 230 240 RIFSTLNEFV SHYTKTSDGL CVKLGKPCLK IQVPAPFDLS YKTVDQWEID RNSIQLLKRL 250 260 270 280 290 300 GSGQFGEVWE GLWNNTTPVA VKTLKPGSMD PNDFLREAQI MKNLRHPKLI QLYAVCTLED 310 320 330 340 350 360 PIYIITELMR HGSLQEYLQN DTGSKIHLTQ QVDMAAQVAS GMAYLESRNY IHRDLAARNV 370 380 390 400 410 420 LVGEHNIYKV ADFGLARVFK VDNEDIYESR HEIKLPVKWT APEAIRSNKF SIKSDVWSFG 430 440 450 460 470 480 ILLYEIITYG KMPYSGMTGA QVIQMLAQNY RLPQPSNCPQ QFYNIMLECW NAEPKERPTF 490 500 ETLRWKLEDY FETDSSYSDA NNFIR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Rak, a novel nuclear tyrosine kinase expressed in epithelial cells." Cance W.G., Craven R.J., Bergman M., Xu L.H., Alitalo K., Liu E.T. Cell Growth Differ. 5:1347-1355(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[2]	"Cloning of FRK, a novel human intracellular SRC-like tyrosine kinase-encoding gene." Lee J., Wang Z., Luoh S.-M., Wood W.I., Scadden D.T. Gene 138:247-251(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lymphoid tissue.
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Urinary bladder.
[6]	"Novel protein kinases expressed in human breast cancer." Cance W.G., Craven R.J., Weiner T.M., Liu E.T. Int. J. Cancer 54:571-577(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
[7]	"The nuclear tyrosine kinase Rak associates with the retinoblastoma protein pRb." Craven R.J., Cance W.G., Liu E.T. Cancer Res. 55:3969-3972(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RB1.
[8]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Rak functions as a tumor suppressor by regulating PTEN protein stability and function." Yim E.-K., Peng G., Dai H., Hu R., Li K., Lu Y., Mills G.B., Meric-Bernstam F., Hennessy B.T., Craven R.J., Lin S.-Y. Cancer Cell 15:304-314(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PTEN, MUTAGENESIS OF LYS-262.
[10]	"RAKing in AKT: a tumor suppressor function for the intracellular tyrosine kinase FRK." Brauer P.M., Tyner A.L. Cell Cycle 8:2728-2732(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[11]	"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] VAL-100; ARG-122 AND LEU-133.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U22322 mRNA. Translation: AAC50116.1. U00803 mRNA. Translation: AAA18284.1. AL121963, AL357141 Genomic DNA. Translation: CAB87592.2. AL357141, AL121963 Genomic DNA. Translation: CAI16469.1. CH471051 Genomic DNA. Translation: EAW48241.1. BC012916 mRNA. Translation: AAH12916.1.
IPI	IPI00000885.
PIR	I38396.
RefSeq	NP_002022.1. NM_002031.2.
UniGene	Hs.89426.
3D structure databases
ProteinModelPortal	P42685.
ModBase	Search...
Protein-protein interaction databases
IntAct	P42685. 4 interactions.
MINT	MINT-3015573.
STRING	9606.ENSP00000357615.
PTM databases
PhosphoSite	P42685.
Polymorphism databases
DMDM	1169745.
Proteomic databases
PaxDb	P42685.
PRIDE	P42685.
Protocols and materials databases
DNASU	2444.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368626; ENSP00000357615; ENSG00000111816.
GeneID	2444.
KEGG	hsa:2444.
UCSC	uc003pwi.1. human.
Organism-specific databases
CTD	2444.
GeneCards	GC06M116308.
HGNC	HGNC:3955. FRK.
HPA	CAB025217.
MIM	606573. gene.
neXtProt	NX_P42685.
PharmGKB	PA28373.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233858.
HOVERGEN	HBG008761.
InParanoid	P42685.
KO	K08892.
OMA	SHYTKTS.
OrthoDB	EOG4FJ88S.
PhylomeDB	P42685.
Enzyme and pathway databases
BRENDA	2.7.10.2. 2681.
Gene expression databases
ArrayExpress	P42685.
Bgee	P42685.
CleanEx	HS_FRK.
Genevestigator	P42685.
GermOnline	ENSG00000111816. Homo sapiens.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR000980. SH2. IPR001452. SH3_domain. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. [Graphical view]
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00452. SH3DOMAIN. PR00109. TYRKINASE.
SMART	SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50044. SH3. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS50001. SH2. 1 hit. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P42685.
ChEMBL	CHEMBL4223.
GenomeRNAi	2444.
NextBio	9741.
SOURCE	Search...

Entry information

Entry name

FRK_HUMAN

Accession

Primary (citable) accession number: P42685
Secondary accession number(s): Q13128, Q9NTR5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 136 of the entry and version 1 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.