Q922K9 (FRK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase FRK
EC=2.7.10.2

Alternative name(s):
Beta-cell Src-homology tyrosine kinase
Short name=BSK
FYN-related kinase
Intestine tyrosine kinase

Gene names

Name:	Frk
Synonyms:	Bsk, Iyk

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	512 AA.
Sequence status	Complete.
Protein existence	Evidence 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 By similarity.
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 By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Predominantly found in the nucleus, with a small fraction found in the cell periphery By similarity.
Tissue specificity	Expressed in intestinal tract, fetal and adult islets of Langerhans, kidney, liver and lung. Ref.1 Ref.2
Disruption phenotype	Mice are viable and do not show any histological abnormalities in epithelial tissues or develop any pathological and/or metabolic disorders associated with the failure of epithelial organs. Ref.5
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

Keywords
Cellular component	Cytoplasm Nucleus
Disease	Tumor suppressor
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 512

512

Tyrosine-protein kinase FRK

PRO_0000260826

Regions

Domain

42 – 117

76

SH3

Domain

123 – 215

93

SH2

Domain

241 – 498

258

Protein kinase

Nucleotide binding

247 – 255

9

ATP By similarity

Sites

Active site

361

1

Proton acceptor By similarity

Binding site

269

1

ATP By similarity

Amino acid modifications

Modified residue

394

1

Phosphotyrosine; by autocatalysis

Experimental info

Sequence conflict

154

1

S → T in CAA88658. Ref.1

Sequence conflict

237

1

D → H in CAA88658. Ref.1

Sequence conflict

335

1

L → F in CAA88658. Ref.1

Sequence conflict

335

1

L → F in AAA65197. Ref.2

Sequence conflict

509

1

N → K in CAA88658. Ref.1

Sequence conflict

509

1

N → K in AAA65197. Ref.2

Secondary structure

1

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512

Helix Strand Turn

Details...

Beta strand

52 – 58

7

Beta strand

63 – 67

5

Beta strand

76 – 80

5

Beta strand

83 – 91

9

Beta strand

103 – 108

6

Turn

109 – 111

3

Beta strand

112 – 114

3

Helix

116 – 120

5

Beta strand

122 – 124

3

Helix

130 – 137

8

Beta strand

138 – 141

4

Beta strand

147 – 151

5

Beta strand

153 – 157

5

Beta strand

159 – 167

9

Beta strand

169 – 176

8

Beta strand

178 – 180

3

Beta strand

182 – 185

4

Beta strand

188 – 192

5

Helix

193 – 200

8

Beta strand

205 – 209

5

Sequences

	Sequence		Length	Mass (Da)
	Q922K9 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: B79A0BC07B9EC5F8	FASTA	512	58,844
	10 20 30 40 50 60 MGSVCVRLWA YLQPFLPCWS QEADKSVVIE NPGAFCPPEA PRSQEPERSH GQYFVALFDY 70 80 90 100 110 120 QARTAEDLSF RAGDKLQVLD TSHEGWWLAR HLEKKGTGLG QQLQGYIPSN YVAEDRSLQA 130 140 150 160 170 180 EPWFFGAIKR ADAEKQLLYS ENQTGAFLIR ESESQKGDFS LSVLDEGVVK HYRIRRLDEG 190 200 210 220 230 240 GFFLTRRKVF STLNEFVNYY TTTSDGLCVK LEKPCLKIQV PTPFDLSYKT ADQWEIDRNS 250 260 270 280 290 300 IQLLKRLGSG QFGEVWEGLW NNTTPVAVKT LKPGSMDPND FLREAQIMKS LRHPKLIQLY 310 320 330 340 350 360 AVCTLEDPIY IITELMRHGS LQEYLQNDGG SKIHLIQQVD MAAQVASGMA YLESQNYIHR 370 380 390 400 410 420 DLAARNVLVG EHNIYKVADF GLARVFKVDN EDIYESKHEI KLPVKWTAPE AIRTNKFSIK 430 440 450 460 470 480 SDVWSFGILL YEIITYGKMP YSGMTGAQVI QMLSQNYRLP QPSNCPQQFY SIMLECWNVE 490 500 510 PKQRPTFETL HWKLEDYFET DCSYSDTNNF IN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"iyk, a novel intracellular protein tyrosine kinase differentially expressed in the mouse mammary gland and intestine." Thuveson M., Albrecht D., Zuercher G., Andres A., Ziemiecki A. Biochem. Biophys. Res. Commun. 209:582-589(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Strain: BALB/c. Tissue: Mammary gland.
[2]	"Cloning of BSK, a murine FRK homologue with a specific pattern of tissue distribution." Oberg-Welsh C., Welsh M. Gene 152:239-242(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Kidney, Mammary gland and Skin.
[4]	"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]. Strain: FVB/N. Tissue: Mammary tumor.
[5]	"Characterization of mice deficient in the Src family nonreceptor tyrosine kinase Frk/rak." Chandrasekharan S., Qiu T.H., Alkharouf N., Brantley K., Mitchell J.B., Liu E.T. Mol. Cell. Biol. 22:5235-5247(2002) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[6]	"The tyrosine kinase FRK/RAK participates in cytokine-induced islet cell cytotoxicity." Welsh M., Welsh C., Ekman M., Dixelius J., Hagerkvist R., Anneren C., Akerblom B., Mahboobi S., Chandrasekharan S., Liu E.T. Biochem. J. 382:261-268(2004) [PubMed] [Europe PMC] [Abstract] Cited for: AUTOPHOSPHORYLATION.
[7]	"Solution structure of the SH3 and SH2 domains of FYN-related kinase." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 50-220.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z48757 mRNA. Translation: CAA88658.1.
L36132 mRNA. Translation: AAA65197.1.
AK028855 mRNA. Translation: BAC26155.1.
AK052614 mRNA. Translation: BAC35063.1.
AK166379 mRNA. Translation: BAE38741.1.
BC007137 mRNA. Translation: AAH07137.1.

IPI

IPI00462777.

PIR

I49552.

RefSeq

NP_001153016.1. NM_001159544.1.
NP_034367.2. NM_010237.3.

UniGene

Mm.332432.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2D8J	NMR	-	A	51-115	[»]
2DLY	NMR	-	A	113-220	[»]

ProteinModelPortal

Q922K9.

SMR

Q922K9. Positions 49-510.

ModBase

Search...

Protein-protein interaction databases

STRING

10090.ENSMUSP00000019913.

PTM databases

PhosphoSite

Q922K9.

Proteomic databases

PaxDb

Q922K9.

PRIDE

Q922K9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000019913; ENSMUSP00000019913; ENSMUSG00000019779.
ENSMUST00000170771; ENSMUSP00000130289; ENSMUSG00000019779.

GeneID

14302.

KEGG

mmu:14302.

UCSC

uc007euy.2. mouse.

Organism-specific databases

CTD

2444.

MGI

MGI:103265. Frk.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00620000087702.

HOGENOM

HOG000233858.

HOVERGEN

HBG008761.

InParanoid

Q922K9.

KO

K08892.

OMA

SHYTKTS.

OrthoDB

EOG4FJ88S.

Gene expression databases

Bgee

Q922K9.

CleanEx

MM_FRK.

Genevestigator

Q922K9.

GermOnline

ENSMUSG00000019779. Mus musculus.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_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]

Pfam

PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.
SSF50044. SH3. 1 hit.

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.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q922K9.

NextBio

285723.

SOURCE

Search...

Entry information

Entry name

FRK_MOUSE

Accession

Primary (citable) accession number: Q922K9
Secondary accession number(s): Q61364, Q61745

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 99 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program