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P42685

- FRK_HUMAN

UniProt

P42685 - FRK_HUMAN

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Protein
Tyrosine-protein kinase FRK
Gene
FRK, PTK5, RAK
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei262 – 2621ATP By similarity
Active sitei354 – 3541Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi240 – 2489ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. non-membrane spanning protein tyrosine kinase activity Source: ProtInc
  3. protein binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. cell differentiation Source: Ensembl
  2. negative regulation of cell proliferation Source: ProtInc
  3. peptidyl-tyrosine phosphorylation Source: GOC
  4. protein phosphorylation Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
SignaLinkiP42685.

Names & Taxonomyi

Protein namesi
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 namesi
Name:FRK
Synonyms:PTK5, RAK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:3955. FRK.

Subcellular locationi

Cytoplasm. Nucleus
Note: Predominantly found in the nucleus, with a small fraction found in the cell periphery.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. extracellular vesicular exosome Source: UniProt
  3. intracellular Source: ProtInc
  4. nucleus Source: ProtInc
  5. plasma membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi262 – 2621K → R: Loss of ability to phosphorylate PTEN. 1 Publication

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

PharmGKBiPA28373.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 505505Tyrosine-protein kinase FRK
PRO_0000088097Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei37 – 371Phosphoserine1 Publication
Modified residuei387 – 3871Phosphotyrosine; by autocatalysis By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP42685.
PaxDbiP42685.
PRIDEiP42685.

PTM databases

PhosphoSiteiP42685.

Expressioni

Tissue specificityi

Predominantly expressed in epithelial derived cell lines and tissues, especially normal liver, kidney, breast and colon.1 Publication

Gene expression databases

ArrayExpressiP42685.
BgeeiP42685.
CleanExiHS_FRK.
GenevestigatoriP42685.

Organism-specific databases

HPAiCAB025217.

Interactioni

Subunit structurei

Interacts (via the SH3-domain) with PTEN. Interacts with RB1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PTENP604847EBI-1383583,EBI-696162
RB1P064003EBI-1383583,EBI-491274

Protein-protein interaction databases

BioGridi108726. 6 interactions.
IntActiP42685. 8 interactions.
MINTiMINT-3015573.
STRINGi9606.ENSP00000357615.

Structurei

3D structure databases

ProteinModelPortaliP42685.
SMRiP42685. Positions 17-499.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini42 – 11069SH3
Add
BLAST
Domaini116 – 20893SH2
Add
BLAST
Domaini234 – 491258Protein kinase
Add
BLAST

Sequence similaritiesi

Contains 1 SH2 domain.
Contains 1 SH3 domain.

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP42685.
KOiK08892.
OMAiVSHYTKT.
OrthoDBiEOG7GTT2V.
PhylomeDBiP42685.
TreeFamiTF351634.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. 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]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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]

Sequencei

Sequence statusi: Complete.

P42685-1 [UniParc]FASTAAdd to Basket

« Hide

MSNICQRLWE YLEPYLPCLS TEADKSTVIE NPGALCSPQS QRHGHYFVAL    50
FDYQARTAED LSFRAGDKLQ VLDTLHEGWW FARHLEKRRD GSSQQLQGYI 100
PSNYVAEDRS LQAEPWFFGA IGRSDAEKQL LYSENKTGSF LIRESESQKG 150
EFSLSVLDGA VVKHYRIKRL DEGGFFLTRR RIFSTLNEFV SHYTKTSDGL 200
CVKLGKPCLK IQVPAPFDLS YKTVDQWEID RNSIQLLKRL GSGQFGEVWE 250
GLWNNTTPVA VKTLKPGSMD PNDFLREAQI MKNLRHPKLI QLYAVCTLED 300
PIYIITELMR HGSLQEYLQN DTGSKIHLTQ QVDMAAQVAS GMAYLESRNY 350
IHRDLAARNV LVGEHNIYKV ADFGLARVFK VDNEDIYESR HEIKLPVKWT 400
APEAIRSNKF SIKSDVWSFG ILLYEIITYG KMPYSGMTGA QVIQMLAQNY 450
RLPQPSNCPQ QFYNIMLECW NAEPKERPTF ETLRWKLEDY FETDSSYSDA 500
NNFIR 505
Length:505
Mass (Da):58,254
Last modified:November 1, 1995 - v1
Checksum:i06EC050DDBCD930B
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti100 – 1001I → V.1 Publication
Corresponds to variant rs34704018 [ dbSNP | Ensembl ].
VAR_041702
Natural varianti122 – 1221G → R.1 Publication
Corresponds to variant rs3756772 [ dbSNP | Ensembl ].
VAR_006283
Natural varianti133 – 1331S → L.1 Publication
Corresponds to variant rs34064900 [ dbSNP | Ensembl ].
VAR_041703

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti115 – 1151P → A in AAC50116. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS5103.1.
PIRiI38396.
RefSeqiNP_002022.1. NM_002031.2.
XP_005266937.1. XM_005266880.2.
XP_005266938.1. XM_005266881.1.
XP_005266939.1. XM_005266882.2.
UniGeneiHs.89426.

Genome annotation databases

EnsembliENST00000606080; ENSP00000476145; ENSG00000111816.
GeneIDi2444.
KEGGihsa:2444.
UCSCiuc003pwi.1. human.

Polymorphism databases

DMDMi1169745.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS5103.1.
PIRi I38396.
RefSeqi NP_002022.1. NM_002031.2.
XP_005266937.1. XM_005266880.2.
XP_005266938.1. XM_005266881.1.
XP_005266939.1. XM_005266882.2.
UniGenei Hs.89426.

3D structure databases

ProteinModelPortali P42685.
SMRi P42685. Positions 17-499.
ModBasei Search...

Protein-protein interaction databases

BioGridi 108726. 6 interactions.
IntActi P42685. 8 interactions.
MINTi MINT-3015573.
STRINGi 9606.ENSP00000357615.

Chemistry

BindingDBi P42685.
ChEMBLi CHEMBL2363074.
GuidetoPHARMACOLOGYi 2025.

PTM databases

PhosphoSitei P42685.

Polymorphism databases

DMDMi 1169745.

Proteomic databases

MaxQBi P42685.
PaxDbi P42685.
PRIDEi P42685.

Protocols and materials databases

DNASUi 2444.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000606080 ; ENSP00000476145 ; ENSG00000111816 .
GeneIDi 2444.
KEGGi hsa:2444.
UCSCi uc003pwi.1. human.

Organism-specific databases

CTDi 2444.
GeneCardsi GC06M116308.
HGNCi HGNC:3955. FRK.
HPAi CAB025217.
MIMi 606573. gene.
neXtProti NX_P42685.
PharmGKBi PA28373.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233858.
HOVERGENi HBG008761.
InParanoidi P42685.
KOi K08892.
OMAi VSHYTKT.
OrthoDBi EOG7GTT2V.
PhylomeDBi P42685.
TreeFami TF351634.

Enzyme and pathway databases

BRENDAi 2.7.10.2. 2681.
SignaLinki P42685.

Miscellaneous databases

GeneWikii Fyn-related_kinase.
GenomeRNAii 2444.
NextBioi 9741.
PROi P42685.
SOURCEi Search...

Gene expression databases

ArrayExpressi P42685.
Bgeei P42685.
CleanExi HS_FRK.
Genevestigatori P42685.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR011009. 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 ]
Pfami PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view ]
PRINTSi PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTi SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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.

Entry informationi

Entry nameiFRK_HUMAN
AccessioniPrimary (citable) accession number: P42685
Secondary accession number(s): Q13128, Q9NTR5
Entry historyi
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 statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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