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

    Gene ID: 5753, updated on 28-Oct-2024

    Summary

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    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
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    Genomic context

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    See PTK6 in Genome Data Viewer
    Location:
    20q13.33
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (63528001..63537376, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (65340691..65349973, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (62159354..62168729, complement)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102723814 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:62149497-62150374 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:62150375-62151251 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:62151252-62152128 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13157 Neighboring gene pancreatic progenitor cell differentiation and proliferation factor Neighboring gene Sharpr-MPRA regulatory region 4884 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18226 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13158 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13159 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_61036 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13160 Neighboring gene src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18227 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:62175449-62176002 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:62178175-62178816 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18228 Neighboring gene Sharpr-MPRA regulatory region 13995 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13164 Neighboring gene fibronectin type III domain containing 11

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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

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    Related articles in PubMed

    1. Downregulated expression of PTK6 is correlated with poor survival in esophageal squamous cell carcinoma. Chen YF, et al. Med Oncol, 2014 Dec. PMID 25377660
    2. Role of the Brk SH3 domain in substrate recognition. Qiu H, et al. Oncogene, 2004 Mar 18. PMID 14676834
    3. Co-crystal structures of PTK6: With Dasatinib at 2.24 Å, with novel imidazo[1,2-a]pyrazin-8-amine derivative inhibitor at 1.70 Å resolution. Thakur MK, et al. Biochem Biophys Res Commun, 2017 Jan 22. PMID 27993680
    4. Crystal structure of the kinase domain of human protein tyrosine kinase 6 (PTK6) at 2.33 Å resolution. Thakur MK, et al. Biochem Biophys Res Commun, 2016 Sep 16. PMID 27480927
    5. The expression and prognostic value of protein tyrosine kinase 6 in early-stage cervical squamous cell cancer. Wang XJ, et al. Chin J Cancer, 2016 Jun 16. PMID 27311570, Free PMC Article

    See all (134) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Circular RNA hsa_circ_0001610 promotes prostate cancer progression by sponging miR-1324 and upregulating PTK6.
      Title: Circular RNA hsa_circ_0001610 promotes prostate cancer progression by sponging miR-1324 and upregulating PTK6.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. Targeting protein tyrosine kinase 6 in cancer.
      Title: Targeting protein tyrosine kinase 6 in cancer.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (85)

    Phenotypes

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    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ42088

    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 receptor signaling pathway via JAK-STAT TAS
    Traceable Author Statement
    more info
    		  
    involved_in protein autophosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    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

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    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
    NP_005966.1

    NCBI Reference Sequences (RefSeq)

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    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)

    1. 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

    2. 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

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

      Range
      63528001..63537376 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060944.1 Alternate T2T-CHM13v2.0

      Range
      65340691..65349973 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13882.1 GenPept UniProtKB/Swiss-Prot:Q13882

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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