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P42685 (FRK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

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
Protein-tyrosine kinase 5
Gene names
Name:FRK
Synonyms:PTK5, RAK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length505 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Binary interactions

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.8
Modified residue3871Phosphotyrosine; by autocatalysis By similarity

Natural variations

Natural variant1001I → V. Ref.11
Corresponds to variant rs34704018 [ dbSNP | Ensembl ].
VAR_041702
Natural variant1221G → R. Ref.11
Corresponds to variant rs3756772 [ dbSNP | Ensembl ].
VAR_006283
Natural variant1331S → L. Ref.11
Corresponds to variant rs34064900 [ dbSNP | Ensembl ].
VAR_041703

Experimental info

Mutagenesis2621K → R: Loss of ability to phosphorylate PTEN. Ref.9
Sequence conflict1151P → A in AAC50116. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P42685 [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] [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. 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] [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. 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] [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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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. 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] [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.
CCDSCCDS5103.1.
PIRI38396.
RefSeqNP_002022.1. NM_002031.2.
XP_005266937.1. XM_005266880.2.
XP_005266938.1. XM_005266881.1.
XP_005266939.1. XM_005266882.2.
UniGeneHs.89426.

3D structure databases

ProteinModelPortalP42685.
SMRP42685. Positions 17-499.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108726. 6 interactions.
IntActP42685. 8 interactions.
MINTMINT-3015573.
STRING9606.ENSP00000357615.

Chemistry

BindingDBP42685.
ChEMBLCHEMBL2363074.
GuidetoPHARMACOLOGY2025.

PTM databases

PhosphoSiteP42685.

Polymorphism databases

DMDM1169745.

Proteomic databases

MaxQBP42685.
PaxDbP42685.
PRIDEP42685.

Protocols and materials databases

DNASU2444.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000606080; ENSP00000476145; ENSG00000111816.
GeneID2444.
KEGGhsa:2444.
UCSCuc003pwi.1. human.

Organism-specific databases

CTD2444.
GeneCardsGC06M116308.
HGNCHGNC:3955. FRK.
HPACAB025217.
MIM606573. gene.
neXtProtNX_P42685.
PharmGKBPA28373.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233858.
HOVERGENHBG008761.
InParanoidP42685.
KOK08892.
OMAVSHYTKT.
OrthoDBEOG7GTT2V.
PhylomeDBP42685.
TreeFamTF351634.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
SignaLinkP42685.

Gene expression databases

ArrayExpressP42685.
BgeeP42685.
CleanExHS_FRK.
GenevestigatorP42685.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
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

GeneWikiFyn-related_kinase.
GenomeRNAi2444.
NextBio9741.
PROP42685.
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: July 9, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM