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Protein

Tyrosine-protein kinase FRK

Gene

FRK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei262ATPPROSITE-ProRule annotation1
Active sitei354Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi240 – 248ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: ProtInc
  • receptor binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS03471-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
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
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:3955. FRK.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: Predominantly found in the nucleus, with a small fraction found in the cell periphery.

GO - Cellular componenti

  • cytoplasm Source: HPA
  • extracellular exosome Source: UniProtKB
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • intracellular Source: ProtInc
  • intracellular membrane-bounded organelle Source: HPA
  • nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi262K → R: Loss of ability to phosphorylate PTEN. 1 Publication1

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi2444.
OpenTargetsiENSG00000111816.
PharmGKBiPA28373.

Chemistry databases

ChEMBLiCHEMBL4223.
DrugBankiDB08896. Regorafenib.
GuidetoPHARMACOLOGYi2025.

Polymorphism and mutation databases

BioMutaiFRK.
DMDMi1169745.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000880971 – 505Tyrosine-protein kinase FRKAdd BLAST505

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei37PhosphoserineCombined sources1
Modified residuei40PhosphoserineCombined sources1
Modified residuei178PhosphothreonineCombined sources1
Modified residuei387Phosphotyrosine; by autocatalysisBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP42685.
PaxDbiP42685.
PeptideAtlasiP42685.
PRIDEiP42685.
TopDownProteomicsiP42685-1. [P42685-1]

PTM databases

iPTMnetiP42685.
PhosphoSitePlusiP42685.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000111816.
CleanExiHS_FRK.
GenevisibleiP42685. HS.

Organism-specific databases

HPAiCAB025217.
HPA069346.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
BNIP2Q129824EBI-1383583,EBI-752094
PTENP604847EBI-1383583,EBI-696162
RB1P064003EBI-1383583,EBI-491274
SF3B4Q154274EBI-1383583,EBI-348469

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108726. 10 interactors.
IntActiP42685. 10 interactors.
MINTiMINT-3015573.
STRINGi9606.ENSP00000357615.

Chemistry databases

BindingDBiP42685.

Structurei

3D structure databases

ProteinModelPortaliP42685.
SMRiP42685.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 110SH3PROSITE-ProRule annotationAdd BLAST69
Domaini116 – 208SH2PROSITE-ProRule annotationAdd BLAST93
Domaini234 – 491Protein kinasePROSITE-ProRule annotationAdd BLAST258

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP42685.
KOiK08892.
OMAiIRTNKFS.
OrthoDBiEOG091G0D46.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P42685-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSNICQRLWE YLEPYLPCLS TEADKSTVIE NPGALCSPQS QRHGHYFVAL
60 70 80 90 100
FDYQARTAED LSFRAGDKLQ VLDTLHEGWW FARHLEKRRD GSSQQLQGYI
110 120 130 140 150
PSNYVAEDRS LQAEPWFFGA IGRSDAEKQL LYSENKTGSF LIRESESQKG
160 170 180 190 200
EFSLSVLDGA VVKHYRIKRL DEGGFFLTRR RIFSTLNEFV SHYTKTSDGL
210 220 230 240 250
CVKLGKPCLK IQVPAPFDLS YKTVDQWEID RNSIQLLKRL GSGQFGEVWE
260 270 280 290 300
GLWNNTTPVA VKTLKPGSMD PNDFLREAQI MKNLRHPKLI QLYAVCTLED
310 320 330 340 350
PIYIITELMR HGSLQEYLQN DTGSKIHLTQ QVDMAAQVAS GMAYLESRNY
360 370 380 390 400
IHRDLAARNV LVGEHNIYKV ADFGLARVFK VDNEDIYESR HEIKLPVKWT
410 420 430 440 450
APEAIRSNKF SIKSDVWSFG ILLYEIITYG KMPYSGMTGA QVIQMLAQNY
460 470 480 490 500
RLPQPSNCPQ QFYNIMLECW NAEPKERPTF ETLRWKLEDY FETDSSYSDA

NNFIR
Length:505
Mass (Da):58,254
Last modified:November 1, 1995 - v1
Checksum:i06EC050DDBCD930B
GO
Isoform 2 (identifier: P42685-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: MSNICQRLWEYLE → MDSTSLLPNPWIR
     14-155: Missing.

Note: No experimental confirmation available.
Show »
Length:363
Mass (Da):41,980
Checksum:iE1A26410F13F6232
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti115P → A in AAC50116 (PubMed:7696183).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041702100I → V.1 PublicationCorresponds to variant rs34704018dbSNPEnsembl.1
Natural variantiVAR_006283122G → R.1 PublicationCorresponds to variant rs3756772dbSNPEnsembl.1
Natural variantiVAR_041703133S → L.1 PublicationCorresponds to variant rs34064900dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0564961 – 13MSNIC…WEYLE → MDSTSLLPNPWIR in isoform 2. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_05649714 – 155Missing in isoform 2. 1 PublicationAdd BLAST142

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U22322 mRNA. Translation: AAC50116.1.
U00803 mRNA. Translation: AAA18284.1.
AK302264 mRNA. Translation: BAG63611.1.
AL021451 Genomic DNA. No translation available.
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. [P42685-1]
PIRiI38396.
RefSeqiNP_002022.1. NM_002031.2. [P42685-1]
XP_005266937.1. XM_005266880.4. [P42685-1]
XP_005266938.1. XM_005266881.2. [P42685-1]
XP_005266939.1. XM_005266882.4. [P42685-1]
XP_011533955.1. XM_011535653.2. [P42685-1]
XP_011533956.1. XM_011535654.2. [P42685-1]
XP_011533957.1. XM_011535655.2. [P42685-1]
XP_016866134.1. XM_017010645.1. [P42685-1]
UniGeneiHs.89426.

Genome annotation databases

EnsembliENST00000606080; ENSP00000476145; ENSG00000111816. [P42685-1]
GeneIDi2444.
KEGGihsa:2444.
UCSCiuc003pwi.2. human. [P42685-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U22322 mRNA. Translation: AAC50116.1.
U00803 mRNA. Translation: AAA18284.1.
AK302264 mRNA. Translation: BAG63611.1.
AL021451 Genomic DNA. No translation available.
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. [P42685-1]
PIRiI38396.
RefSeqiNP_002022.1. NM_002031.2. [P42685-1]
XP_005266937.1. XM_005266880.4. [P42685-1]
XP_005266938.1. XM_005266881.2. [P42685-1]
XP_005266939.1. XM_005266882.4. [P42685-1]
XP_011533955.1. XM_011535653.2. [P42685-1]
XP_011533956.1. XM_011535654.2. [P42685-1]
XP_011533957.1. XM_011535655.2. [P42685-1]
XP_016866134.1. XM_017010645.1. [P42685-1]
UniGeneiHs.89426.

3D structure databases

ProteinModelPortaliP42685.
SMRiP42685.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108726. 10 interactors.
IntActiP42685. 10 interactors.
MINTiMINT-3015573.
STRINGi9606.ENSP00000357615.

Chemistry databases

BindingDBiP42685.
ChEMBLiCHEMBL4223.
DrugBankiDB08896. Regorafenib.
GuidetoPHARMACOLOGYi2025.

PTM databases

iPTMnetiP42685.
PhosphoSitePlusiP42685.

Polymorphism and mutation databases

BioMutaiFRK.
DMDMi1169745.

Proteomic databases

MaxQBiP42685.
PaxDbiP42685.
PeptideAtlasiP42685.
PRIDEiP42685.
TopDownProteomicsiP42685-1. [P42685-1]

Protocols and materials databases

DNASUi2444.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000606080; ENSP00000476145; ENSG00000111816. [P42685-1]
GeneIDi2444.
KEGGihsa:2444.
UCSCiuc003pwi.2. human. [P42685-1]

Organism-specific databases

CTDi2444.
DisGeNETi2444.
GeneCardsiFRK.
HGNCiHGNC:3955. FRK.
HPAiCAB025217.
HPA069346.
MIMi606573. gene.
neXtProtiNX_P42685.
OpenTargetsiENSG00000111816.
PharmGKBiPA28373.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP42685.
KOiK08892.
OMAiIRTNKFS.
OrthoDBiEOG091G0D46.
PhylomeDBiP42685.
TreeFamiTF351634.

Enzyme and pathway databases

BioCyciZFISH:HS03471-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
SignaLinkiP42685.

Miscellaneous databases

ChiTaRSiFRK. human.
GeneWikiiFyn-related_kinase.
GenomeRNAii2444.
PROiP42685.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111816.
CleanExiHS_FRK.
GenevisibleiP42685. HS.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiFRK_HUMAN
AccessioniPrimary (citable) accession number: P42685
Secondary accession number(s): B4DY49, Q13128, Q9NTR5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 30, 2016
This is version 174 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.