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    BMX BMX non-receptor tyrosine kinase [ Homo sapiens (human) ]

    Gene ID: 660, updated on 2-Nov-2024

    Summary

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    Official Symbol
    BMXprovided by HGNC
    Official Full Name
    BMX non-receptor tyrosine kinaseprovided by HGNC
    Primary source
    HGNC:HGNC:1079
    See related
    Ensembl:ENSG00000102010 MIM:300101; AllianceGenome:HGNC:1079
    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
    ETK; PSCTK2; PSCTK3
    Summary
    This gene encodes a non-receptor tyrosine kinase belonging to the Tec kinase family. The protein contains a PH-like domain, which mediates membrane targeting by binding to phosphatidylinositol 3,4,5-triphosphate (PIP3), and a SH2 domain that binds to tyrosine-phosphorylated proteins and functions in signal transduction. The protein is implicated in several signal transduction pathways including the Stat pathway, and regulates differentiation and tumorigenicity of several types of cancer cells. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]
    Expression
    Broad expression in bone marrow (RPKM 2.4), placenta (RPKM 2.2) and 21 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See BMX in Genome Data Viewer
    Location:
    Xp22.2
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (15500807..15556519)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (15083780..15139496)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (15518930..15574642)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene PIR-FIGF readthrough Neighboring gene vascular endothelial growth factor D Neighboring gene pirin Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20672 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:15510866-15511368 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:15511369-15511872 Neighboring gene ReSE screen-validated silencer GRCh37_chrX:15537807-15538079 Neighboring gene angiotensin converting enzyme 2 Neighboring gene HNRNPDL pseudogene 5 Neighboring gene dACE2 interferon-inducible promoter region Neighboring gene BRD4-independent group 4 enhancer GRCh37_chrX:15617708-15618907 Neighboring gene ACE2 promoter region Neighboring gene ACE2 divergent transcript Neighboring gene collectrin, amino acid transport regulator Neighboring gene prothymosin alpha pseudogene 14

    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. Non-receptor tyrosine kinase Etk is involved in the apoptosis of small cell lung cancer cells. Guo L, et al. Exp Mol Pathol, 2010 Jun. PMID 20206622
    2. BMX, a novel nonreceptor tyrosine kinase gene of the BTK/ITK/TEC/TXK family located in chromosome Xp22.2. Tamagnone L, et al. Oncogene, 1994 Dec. PMID 7970727
    3. A tyrosine kinase profile of prostate carcinoma. Robinson D, et al. Proc Natl Acad Sci U S A, 1996 Jun 11. PMID 8650201, Free PMC Article
    4. BMX tyrosine kinase gene is expressed in granulocytes and myeloid leukaemias. Kaukonen J, et al. Br J Haematol, 1996 Sep. PMID 8790141
    5. Etk/Bmx, a tyrosine kinase with a pleckstrin-homology domain, is an effector of phosphatidylinositol 3'-kinase and is involved in interleukin 6-induced neuroendocrine differentiation of prostate cancer cells. Qiu Y, et al. Proc Natl Acad Sci U S A, 1998 Mar 31. PMID 9520419, Free PMC Article

    See all (84) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Preclinical spheroid models identify BMX as a therapeutic target for metastatic MYCN nonamplified neuroblastoma.
      Title: Preclinical spheroid models identify BMX as a therapeutic target for metastatic MYCN nonamplified neuroblastoma.
    2. BMX controls 3betaHSD1 and sex steroid biosynthesis in cancer.
      Title: BMX controls 3βHSD1 and sex steroid biosynthesis in cancer.
    3. Linc00173 upregulated Etk through functioning as a competitive endogenous RNA (ceRNA) by "sponging" miRNA-218 and led to the upregulation of GSKIP and NDRG1, resulting in the translocation of beta-catenin. Importantly, expression analysis revealed that both Linc00173 and Etk were upregulated in SCLC patient samples and exhibiting positive Linc00173/Etk correlation
      Title: Linc00173 promotes chemoresistance and progression of small cell lung cancer by sponging miR-218 to regulate Etk expression.
    4. tyrosine kinase BMX is negatively regulated by androgen and contributes to castration-resistant prostate cancer by enhancing the phosphorylation and activation of multiple receptor tyrosine kinases following androgen deprivation therapy
      Title: BMX-Mediated Regulation of Multiple Tyrosine Kinases Contributes to Castration Resistance in Prostate Cancer.
    5. Epithelial and endothelial tyrosine kinase (Etk) interacts with 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) to promote small-cell lung cancer (SCLC) chemoresistance through regulation of autophagy.
      Title: Etk Interaction with PFKFB4 Modulates Chemoresistance of Small-cell Lung Cancer by Regulating Autophagy.
    6. results demonstrate that hypoxia-dependent upregulation of BMX contributes to therapeutic resistance through a compensatory prosurvival signaling mechanism. These results also reveal the role of off-target drug effects on tumor microenvironment and development of acquired drug resistance.
      Title: Hypoxia-induced upregulation of BMX kinase mediates therapeutic resistance in acute myeloid leukemia.
    7. These results suggested that BMX can promote cell proliferation through PI3K/AKT/mTOR and STAT3 signaling pathways in cervical cancer cells.
      Title: BMX/Etk promotes cell proliferation and tumorigenicity of cervical cancer cells through PI3K/AKT/mTOR and STAT3 pathways.
    8. The studies suggested that BMXDeltaN might play roles in lung tumorigenicity, with expression of BMXDeltaN promoting cell growth, cell migration, and cell transformation.
      Title: A novel BMX variant promotes tumor cell growth and migration in lung adenocarcinoma.
    9. results demonstrate that cleaved BMX is a novel N-end rule substrate, and its degradation exhibits a novel interplay between substrate phosphorylation and N-end rule degradation, revealing an increasing complex regulatory network of apoptotic proteolytic signaling cascades.
      Title: Phosphorylation Impacts N-end Rule Degradation of the Proteolytically Activated Form of BMX Kinase.
    10. Data indicate that EPHA3 is involved in regulating the multidrug resistance (MDR) of small cell lung cancer (SCLC) via PI3K/BMX/STAT3 signaling and may be a therapeutic target in SCLC.
      Title: EPHA3 regulates the multidrug resistance of small cell lung cancer via the PI3K/BMX/STAT3 signaling pathway.
    Submit: New GeneRIF Correction See all GeneRIFs (41)

    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

    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Nef nef A cell-based bimolecular fluorescence complementation assay demonstrates that HIV-1 Nef interacts with the Tec family members Bmx, Btk, and Itk, but not with Tec or Txk in 293T cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 non-membrane spanning protein tyrosine kinase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein tyrosine kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in B cell receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in adaptive immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell adhesion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mesoderm development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in phosphatidylinositol biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein phosphorylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    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 membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    cytoplasmic tyrosine-protein kinase BMX
    Names
    BTK-like on X chromosome
    Etk/Bmx cytosolic tyrosine kinase
    NTK38 tyrosine kinase
    bone marrow tyrosine kinase gene in chromosome X protein
    epithelial and endothelial tyrosine kinase
    NP_001307795.1
    NP_001712.1
    NP_975010.1
    XP_016885241.1
    XP_054183595.1

    NCBI Reference Sequences (RefSeq)

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    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.

    Genomic

    1. NG_013227.1 RefSeqGene

      Range
      5031..60743
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001320866.2 → NP_001307795.1  cytoplasmic tyrosine-protein kinase BMX isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate in-frame acceptor splice site in the mid-coding region compared to variant 1. The resulting isoform (2) is 1 aa shorter than isoform 1.
      Source sequence(s)
      AF045459, BC016652, BP236451, X83107
      UniProtKB/TrEMBL
      A8K709, B2R8Z4
      Conserved Domains (5) summary
      cd05113
      Location:411 → 666
      PTKc_Btk_Bmx; Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome
      cd10399
      Location:288 → 393
      SH2_Tec_Bmx; Src homology 2 (SH2) domain found in Tec protein, Bmx
      cd01238
      Location:7 → 147
      PH_Btk; Bruton's tyrosine kinase pleckstrin homology (PH) domain
      pfam00169
      Location:6 → 111
      PH; PH domain
      pfam07714
      Location:416 → 665
      Pkinase_Tyr; Protein tyrosine kinase

    2. NM_001721.7 → NP_001712.1  cytoplasmic tyrosine-protein kinase BMX isoform 1

      See identical proteins and their annotated locations for NP_001712.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an alternate 5' non-coding exon compared to variant 1. Variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AF045459, BC016652, BQ226991
      Consensus CDS
      CCDS14168.1
      UniProtKB/Swiss-Prot
      A6NIH9, O60564, P51813, Q12871
      UniProtKB/TrEMBL
      A8K709, B2R8Z4
      Related
      ENSP00000340082.6, ENST00000342014.6
      Conserved Domains (3) summary
      cd05113
      Location:412 → 667
      PTKc_Btk_Bmx; Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome
      cd10399
      Location:289 → 394
      SH2_Tec_Bmx; Src homology 2 (SH2) domain found in Tec protein, Bmx
      cd01238
      Location:7 → 147
      PH_Btk; Bruton's tyrosine kinase pleckstrin homology (PH) domain

    3. NM_203281.3 → NP_975010.1  cytoplasmic tyrosine-protein kinase BMX isoform 1

      See identical proteins and their annotated locations for NP_975010.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Variants 1 and 2 encode the same isoform.
      Source sequence(s)
      AF045459, BC016652, BP236451, X83107
      Consensus CDS
      CCDS14168.1
      UniProtKB/Swiss-Prot
      A6NIH9, O60564, P51813, Q12871
      UniProtKB/TrEMBL
      A8K709, B2R8Z4
      Related
      ENSP00000308774.6, ENST00000348343.11
      Conserved Domains (3) summary
      cd05113
      Location:412 → 667
      PTKc_Btk_Bmx; Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome
      cd10399
      Location:289 → 394
      SH2_Tec_Bmx; Src homology 2 (SH2) domain found in Tec protein, Bmx
      cd01238
      Location:7 → 147
      PH_Btk; Bruton's tyrosine kinase pleckstrin homology (PH) domain

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      15500807..15556519
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017029752.3 → XP_016885241.1  cytoplasmic tyrosine-protein kinase BMX isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      15083780..15139496
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054327620.1 → XP_054183595.1  cytoplasmic tyrosine-protein kinase BMX isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P51813.1 GenPept UniProtKB/Swiss-Prot:P51813

    Gene LinkOut

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

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