PTK6 PTK6 protein tyrosine kinase 6 [Homo sapiens] - Gene

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Summary

Official Symbol: PTK6provided by HGNC
Official Full Name: PTK6 protein tyrosine kinase 6provided by HGNC
Primary source: HGNC:9617
See related: Ensembl:ENSG00000101213; HPRD:03594; MIM:602004; Vega:OTTHUMG00000033039
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BRK
Summary: The protein encoded by this gene is a cytoplasmic nonreceptor protein kinase which may function as an intracellular signal transducer in epithelial tissues. Overexpression of this gene in mammary epithelial cells leads to sensitization of the cells to epidermal growth factor and results in a partially transformed phenotype. Expression of this gene has been detected at low levels in some breast tumors but not in normal breast tissue. The encoded protein has been shown to undergo autophosphorylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

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Genomic context

Location :: 20q13.3

Sequence :: Chromosome: 20; NC_000020.10 (62159766..62168707, complement)

See PTK6 in Epigenomics, MapViewer

Chromosome 20 - NC_000020.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

show that as primary human keratinocytes are induced to differentiate in vitro, Brk levels decrease
Title: Breast tumor kinase (Brk/PTK6) plays a role in the differentiation of primary keratinocytes.
present findings indicate an increase of cytoplasmic Brk expression in non-small cell lung cancer
Title: Detection of Brk expression in non-small cell lung cancer: clinicopathological relevance.
Data suggest that since PTK6 plays an important role in HER receptor signal transduction, its down-regulation might be suitable for future therapy approaches in breast cancer.
Title: Impact of protein tyrosine kinase 6 (PTK6) on human epidermal growth factor receptor (HER) signalling in breast cancer.
Alternative transcript-PTK6 is able to negatively regulate growth and modulate PTK6 activity, protein-protein associations and/or subcellular localization.
Title: The alternative splice variant of protein tyrosine kinase 6 negatively regulates growth and enhances PTK6-mediated inhibition of β-catenin.
Results identified Brk and ERK5 as important downstream effectors of Met signaling to cell migration.
Title: Breast tumor kinase and extracellular signal-regulated kinase 5 mediate Met receptor signaling to cell migration in breast cancer cells.
Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells.
Title: Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells.
Brk antagonizes the transcriptional activity of the transcription factor FoxO family of proteins by inhibiting its nuclear localization. As a result, the cell cycle inhibitor p27, a FoxO target gene, is down-regulated.
Title: Deregulation of the cell cycle by breast tumor kinase (Brk).
PTK6 enhances EGFR signaling by inhibition of EGFR down-regulation through phosphorylation of ARAP1 in breast cancer cells.
Title: PTK6 inhibits down-regulation of EGF receptor through phosphorylation of ARAP1.
AKT is a direct substrate of PTK6 and AKT tyrosine residues 315 and 326 are phosphorylated by PTK6.
Title: Protein tyrosine kinase 6 directly phosphorylates AKT and promotes AKT activation in response to epidermal growth factor.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.

Submit: New GeneRIF Correction See all (35)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
Q13882	P00533	EGFR	HPRD	PubMed
Q13882	P21860	ERBB3	HPRD	PubMed
Q13882	Q07666	KHDRBS1	HPRD	PubMed
Q13882	Q13882	PTK6	HPRD	PubMed
Q13882	Signal-transducing adaptor protein-2	STAP2	HPRD	PubMed
BioGRID:111720	BioGRID:108276	EGFR	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111720	BioGRID:108377	ERBB3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111720	BioGRID:115900	KHDRBS1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:111720	BioGRID:120759	STAP2	BioGRID	PubMed	Reconstituted Complex; Two-hybrid

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
non-membrane spanning protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cell migration	IDA Inferred from Direct Assay more info	PubMed
cellular response to retinoic acid	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of neuron projection development	IMP Inferred from Mutant Phenotype more info	PubMed
protein autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
protein phosphorylation	TAS Traceable Author Statement more info	PubMed
tyrosine phosphorylation of Stat3 protein	IDA Inferred from Direct Assay more info	PubMed
tyrosine phosphorylation of Stat5 protein	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
NOT nucleolus	IDA Inferred from Direct Assay more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
ruffle	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: protein-tyrosine kinase 6

Names: protein-tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kinase BRK

NP_005966.1

EC 2.7.10.2

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001256358.1 → NP_001243287.1 protein-tyrosine kinase 6 Isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the 5' coding region which results in a frameshift and early stop codon, compared to variant 1. The resulting protein (isoform 2) has a shorter and distinct C-terminus, compared to isoform 1. This variant is also known as lambdaM5 and Alt-PTK6.

Source sequence(s)

AK301364, AL121829, X78549

UniProtKB/Swiss-Prot

Q13882

Conserved Domains (1) summary

cd00174
Location:12 – 69
Blast Score: 137

SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...
NM_005975.3 → NP_005966.1 protein-tyrosine kinase 6 Isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer protein (isoform 1).

Source sequence(s)

AL121829, BC035843, DA762278, X78549

Consensus CDS

CCDS13524.1

UniProtKB/Swiss-Prot

Q13882

Related

ENSP00000217185, OTTHUMP00000031656, ENST00000217185, OTTHUMT00000080313

Conserved Domains (4) summary

cd00174
Location:12 – 69
Blast Score: 136

SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...

cd05148
Location:184 – 444
Blast Score: 1305

PTKc_Srm_Brk; Catalytic domain of the Protein Tyrosine Kinases, Srm and Brk

smart00221
Location:192 – 441
Blast Score: 951

STYKc; Protein kinase; unclassified specificity.

cd10358
Location:75 – 174
Blast Score: 407

SH2_PTK6_Brk; Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast tumor kinase (Brk)

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000020.10 Reference GRCh37.p5 Primary Assembly

Range

62159766..62168707, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000152.1 Alternate HuRef

Range

58889971..58898912, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL121829.30	CAC15525.1
genomic	CH471077.2	EAW75262.1
		EAW75263.1
genomic	U61412.1	AAC34935.1
mRNA	AK124082.1	None
mRNA	AK301364.1	BAG62908.1
mRNA	AK301691.1	BAG63163.1
mRNA	AK315232.1	BAG37660.1
mRNA	BC035843.1	AAH35843.1
mRNA	DA762278.1	None
mRNA	X78549.1	CAA55295.1