PTK6 protein tyrosine kinase 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PTK6provided by HGNC
Official Full Name: protein tyrosine kinase 6provided by HGNC
Primary source: HGNC:HGNC:9617
See related: Ensembl:ENSG00000101213 MIM:602004; AllianceGenome:HGNC:9617
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]
Expression: Biased expression in esophagus (RPKM 27.3), skin (RPKM 21.0) and 9 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 20q13.33

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (63528001..63537376, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (65340691..65349973, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (62159354..62168729, complement)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

BRK confers tamoxifen-resistance in breast cancer via regulation of tyrosine phosphorylation of CDK1.
Title: BRK confers tamoxifen-resistance in breast cancer via regulation of tyrosine phosphorylation of CDK1.
Biochemical Studies of Systemic Lupus Erythematosus-Associated Mutations in Nonreceptor Tyrosine Kinases Ack1 and Brk.
Title: Biochemical Studies of Systemic Lupus Erythematosus-Associated Mutations in Nonreceptor Tyrosine Kinases Ack1 and Brk.
PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation.
Title: PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation.
Interference of PTK6/GAB1 signaling inhibits cell proliferation, invasion, and migration of cervical cancer cells.
Title: Interference of PTK6/GAB1 signaling inhibits cell proliferation, invasion, and migration of cervical cancer cells.
Breast Tumour Kinase (Brk/PTK6) Contributes to Breast Tumour Xenograft Growth and Modulates Chemotherapeutic Responses In Vitro.
Title: Breast Tumour Kinase (Brk/PTK6) Contributes to Breast Tumour Xenograft Growth and Modulates Chemotherapeutic Responses In Vitro.
Prognostic value of protein tyrosine kinase 6 overexpression in cancers: a meta-analysis.
Title: Prognostic value of protein tyrosine kinase 6 overexpression in cancers: a meta-analysis.
Targeting protein tyrosine kinase 6 in cancer.
Title: Targeting protein tyrosine kinase 6 in cancer.
BRK competitively binds and phosphorylates SMAD4 and regulates transforming growth factor-beta/SMAD4 signaling pathway. Activated BRK-mediated degradation of SMAD4 is associated with the repression of tumor suppressor gene FRK and increased expression of mesenchymal markers, SNAIL, and SLUG.
Title: BRK phosphorylates SMAD4 for proteasomal degradation and inhibits tumor suppressor FRK to control SNAIL, SLUG, and metastatic potential.
PSPC1, a nuclear substrate of PTK6, sequesters PTK6 in the nucleus and loses its metastasis driving capability in hepatocellular carcinoma. Conversely, PSPC1 upregulation or PSPC1-Y523F mutation promotes epithelial-mesenchymal transition, stemness, and metastasis via cytoplasmic translocation of active PTK6 and nuclear translocation of beta-catenin, which interacts with PSPC1 to augment Wnt3a autocrine signaling.
Title: PSPC1-interchanged interactions with PTK6 and β-catenin synergize oncogenic subcellular translocations and tumor progression.
Using saturation transfer difference NMR and molecular docking, we demonstrate that vemurafenib binds in the active site of PTK6, inhibiting its activation. These structural studies provide insight into the PTK6-vemurafenib complex, which can be utilized for further refinement chemistry, whereas functional studies demonstrate that active PTK6 is a viable drug target in prostate cancer
Title: Vemurafenib Inhibits Active PTK6 in PTEN-null Prostate Tumor Cells.

Submit: New GeneRIF Correction See all GeneRIFs (84)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

NoName (e-PCR)
- UniSTS:490261

PMC156606P1 (e-PCR)
- UniSTS:271408

D8S2279 (e-PCR)
- UniSTS:473907

sY3084 (e-PCR)
- UniSTS:515126

SHGC-35420 (e-PCR)
- UniSTS:33611

L18426 (e-PCR)
- UniSTS:34648

D11S3114 (e-PCR)
- UniSTS:152207

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables non-membrane spanning protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables non-membrane spanning protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase activity	EXP Inferred from Experiment more info	PubMed
enables protein tyrosine kinase activity	TAS Traceable Author Statement more info
enables signaling receptor binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in ERBB2 signaling pathway	TAS Traceable Author Statement more info
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to retinoic acid	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in innate immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in intestinal epithelial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of growth	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA replication	TAS Traceable Author Statement more info
involved_in positive regulation of cell cycle	TAS Traceable Author Statement more info
involved_in positive regulation of epidermal growth factor receptor signaling pathway	TAS Traceable Author Statement more info
involved_in positive regulation of neuron projection development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tyrosine phosphorylation of STAT protein	TAS Traceable Author Statement more info
involved_in protein autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein phosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in tyrosine phosphorylation of STAT protein	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in ruffle	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: protein-tyrosine kinase 6

Names: PTK6 protein tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kinase BRK

NP_001243287.1

EC 2.7.10.2

NP_005966.1

EC 2.7.10.2

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_001256358.2 → 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

Consensus CDS

CCDS74750.1

UniProtKB/Swiss-Prot

Q13882

Related

ENSP00000217185.3, ENST00000217185.3

Conserved Domains (1) summary

cd11847
Location:12 → 69

SH3_Brk; Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6
NM_005975.4 → NP_005966.1 protein-tyrosine kinase 6 isoform 1

See identical proteins and their annotated locations for NP_005966.1

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

B2RCR3, B4DW46, Q13882, Q58F01

Related

ENSP00000442460.2, ENST00000542869.3

Conserved Domains (4) summary

cd05148
Location:184 → 444

PTKc_Srm_Brk; Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk)

cd10358
Location:75 → 174

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

cd11847
Location:12 → 69

SH3_Brk; Src homology 3 domain of Brk (Breast tumor kinase) Protein Tyrosine Kinase (PTK), also called PTK6

smart00221
Location:192 → 441

STYKc; Protein kinase; unclassified specificity