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Protein

Tyrosine-protein kinase FRK

Gene

FRK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-6798695 Neutrophil degranulation
R-HSA-8948751 Regulation of PTEN stability and activity
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

EuPathDBiHostDB:ENSG00000111816.7
HGNCiHGNC:3955 FRK
MIMi606573 gene
neXtProtiNX_P42685

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

EPDiP42685
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
HPA057484

Interactioni

Subunit structurei

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

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108726, 10 interactors
IntActiP42685, 10 interactors
MINTiP42685
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

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

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

Family and domain databases

CDDicd10369 SH2_Src_Frk, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR035805 SH2_Frk
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00452 SH3DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

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 → V1 PublicationCorresponds to variant dbSNP:rs34704018Ensembl.1
Natural variantiVAR_006283122G → R1 PublicationCorresponds to variant dbSNP:rs3756772Ensembl.1
Natural variantiVAR_041703133S → L1 PublicationCorresponds to variant dbSNP:rs34064900Ensembl.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 Genomic DNA No translation available.
AL357141 Genomic DNA No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiFRK_HUMAN
AccessioniPrimary (citable) accession number: P42685
Secondary accession number(s): B4DY49, Q13128, Q9NTR5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: May 23, 2018
This is version 185 of the entry and version 1 of the sequence. See 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

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