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Reviewed, UniProtKB/Swiss-Prot P42685 (FRK_HUMAN)

Last modified November 3, 2009. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length505 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 505505Tyrosine-protein kinase FRK
PRO_0000088097

Regions

Domain42 – 11069SH3
Domain116 – 20893SH2
Domain234 – 491258Protein kinase
Nucleotide binding240 – 2489ATP By similarity

Sites

Active site3541Proton acceptor By similarity
Binding site2621ATP By similarity

Amino acid modifications

Modified residue371Phosphoserine Ref.9
Modified residue461Phosphotyrosine Ref.8 Ref.11
Modified residue621Phosphoserine Ref.9
Modified residue3871Phosphotyrosine; by autocatalysis By similarity
Modified residue4971Phosphotyrosine Ref.8 Ref.7

Natural variations

Natural variant1001I → V
VAR_041702
Natural variant1221G → R: dbSNP rs3756772. Ref.12
VAR_006283
Natural variant1331S → L: dbSNP rs34064900. Ref.12
VAR_041703

Experimental info

Mutagenesis2621K → R: Loss of ability to phosphorylate PTEN. Ref.10
Sequence conflict1151P → A in AAC50116. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P42685-1 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 06EC050DDBCD930B

FASTA50558,254
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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

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.
IPIIPI00000885.
PIRI38396.
RefSeqNP_002022.1.
UniGeneHs.89426

3D structure databases

HSSPHSSP built from PDB template 2PTK based on UniProtKB P00523.
ModBaseSearch...

Protein-protein interaction databases

STRINGP42685.

PTM databases

PhosphoSiteP42685.

Proteomic databases

PRIDEP42685.

Genome annotation databases

EnsemblENST00000368626; ENSP00000357615; ENSG00000111816; Homo sapiens. [Genome view]
GeneID2444.
KEGGhsa:2444.
UCSCuc003pwi.1. human.

Organism-specific databases

CTD2444.
GeneCardsGC06M116369.
H-InvDBHIX0006158.
HGNCHGNC:3955. FRK.
HPACAB025217.
MIM606573. gene.
PharmGKBPA28373.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP42685.
HOVERGENP42685.
OMAEYLQNDA.

Enzyme and pathway databases

BRENDA2.7.10.2. 247.

Gene expression databases

ArrayExpressP42685.
BgeeP42685.
CleanExHS_FRK.
GenevestigatorP42685.
GermOnlineENSG00000111816. Homo sapiens.

Family and domain databases

InterProIPR000719. 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]
Gene3DG3DSA:3.30.505.10. SH2. 1 hit.
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
ProDomPD000001. Prot_kinase. 1 hit.
PD000093. SH2. 1 hit.
PD000066. SH3. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
PROSITEPS00107. 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]
ProtoNetSearch...

Other Resources

NextBio9741.
SOURCESearch...

Entry information

Entry nameFRK_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents