Reviewed, UniProtKB/Swiss-Prot P42685 (FRK_HUMAN)

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

Gene names

Name:	FRK
Synonyms:	PTK5, RAK

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	505 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.10
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts (via the SH3-domain) with PTEN. Ref.10
Subcellular location	Cytoplasm Probable.
Tissue specificity	Restricted to cells lines derived from tissues of lymphoid, brain, breast, colon and bladder origin. 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
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
Gene Ontology (GO)
Biological process	negative regulation of cell proliferation Traceable author statement. Source: ProtInc protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Ref.2 Traceable author statement. Source: ProtInc protein binding Ref.10 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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.9
	Modified residue	46	1	Phosphotyrosine Ref.8 Ref.11
	Modified residue	62	1	Phosphoserine Ref.9
	Modified residue	387	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	497	1	Phosphotyrosine Ref.8 Ref.7
Natural variations
	Natural variant	100	1	I → V		VAR_041702
	Natural variant	122	1	G → R: dbSNP rs3756772. Ref.12		VAR_006283
	Natural variant	133	1	S → L: dbSNP rs34064900. Ref.12		VAR_041703
Experimental info
	Mutagenesis	262	1	K → R: Loss of ability to phosphorylate PTEN. Ref.10
	Sequence conflict	115	1	P → A in AAC50116. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P42685-1 [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: 7696183] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[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: 7510261] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lymphoid.
[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: 14574404] [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: 15489334] [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: 8099900] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
[7]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-497, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-46; TYR-387 AND TYR-497, MASS SPECTROMETRY.
[9]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; SER-62 AND TYR-387, MASS SPECTROMETRY.
[10]	"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: 19345329] [Abstract] Cited for: FUNCTION, INTERACTION WITH PTEN, MUTAGENESIS OF LYS-262.
[11]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-46, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[12]	"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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-100; ARG-122 AND LEU-133.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
UniGene	Hs.89426
3D structure databases
HSSP	HSSP built from PDB template 2PTK based on UniProtKB P00523.
ModBase	Search...
Protein-protein interaction databases
STRING	P42685.
PTM databases
PhosphoSite	P42685.
Proteomic databases
PRIDE	P42685.
Genome annotation databases
Ensembl	ENST00000368626; ENSP00000357615; ENSG00000111816; Homo sapiens. [Genome view]
GeneID	2444.
KEGG	hsa:2444.
UCSC	uc003pwi.1. human.
Organism-specific databases
CTD	2444.
GeneCards	GC06M116369.
H-InvDB	HIX0006158.
HGNC	HGNC:3955. FRK.
HPA	CAB025217.
MIM	606573. gene.
PharmGKB	PA28373.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P42685.
HOVERGEN	P42685.
OMA	EYLQNDA.
Enzyme and pathway databases
BRENDA	2.7.10.2. 247.
Gene expression databases
ArrayExpress	P42685.
Bgee	P42685.
CleanEx	HS_FRK.
Genevestigator	P42685.
GermOnline	ENSG00000111816. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR000980. SH2. IPR001452. SH3_domain. IPR020473. SH3_region. IPR001245. Tyr_pkinase. IPR008266. Tyr_pkinase_AS. [Graphical view]
Gene3D	G3DSA:3.30.505.10. SH2. 1 hit.
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00452. SH3DOMAIN. PR00109. TYRKINASE.
ProDom	PD000001. Prot_kinase. 1 hit. PD000093. SH2. 1 hit. PD000066. SH3. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
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 Resources
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:	November 3, 2009
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.