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TNK2 Gene

protein-coding   GIFtS: 64
GCID: GC03M195590

Tyrosine Kinase, Non-Receptor, 2

  See TNK2-related disease
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Tyrosine Kinase, Non-Receptor, 21 2     ACK2 5
ACK12 3 5     Activated CDC42 Kinase 12
Activated Cdc42-Associated Kinase 11 2     Activated P21cdc42Hs Kinase2
Tyrosine Kinase Non-Receptor Protein 22 3     p21cdc42Hs2
ACK-12 3     EC 2.7.11.13
EC 2.7.10.23 8     EC 2.7.108

External Ids:    HGNC: 192971   Entrez Gene: 101882   Ensembl: ENSG000000619387   OMIM: 6069945   UniProtKB: Q079123   

Export aliases for TNK2 gene to outside databases

Previous GC identifers: GC03M197080 GC03M192870


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TNK2 Gene:
This gene encodes a tyrosine kinase that binds Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and
GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique
sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism
that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation
signal transduction pathway. Several alternatively spliced transcript variants have been identified from this
gene, but the full-length nature of only two transcript variants has been determined. (provided by RefSeq, Jul
2008)

GeneCards Summary for TNK2 Gene:
TNK2 (tyrosine kinase, non-receptor, 2) is a protein-coding gene. Diseases associated with TNK2 include infantile-onset mesial temporal lobe epilepsy with severe cognitive regression. GO annotations related to this gene include non-membrane spanning protein tyrosine kinase activity and protein serine/threonine kinase activity. An important paralog of this gene is SYK.

UniProtKB/Swiss-Prot: ACK1_HUMAN, Q07912
Function: Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading
and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and
nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated
endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and
mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR
at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell
migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in
brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and
'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on
'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF)
toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on
cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively
regulating pro-survival factors such as AKT1 and AR

Gene Wiki entry for TNK2 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000003.11  NT_005612.17  NC_018914.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the TNK2 gene promoter:
         AREB6   Pax-3   NF-1/L   NF-1   FOXC1   p300   Nkx2-5   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): TNK2 promoter sequence
   Search Chromatin IP Primers for TNK2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TNK2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 3q29   Ensembl cytogenetic band:  3q29   HGNC cytogenetic band: 3q29

TNK2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TNK2 gene location

GeneLoc information about chromosome 3         GeneLoc Exon Structure

GeneLoc location for GC03M195590:  view genomic region     (about GC identifiers)

Start:
195,590,235 bp from pter      End:
195,638,816 bp from pter
Size:
48,582 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: ACK1_HUMAN, Q07912 (See protein sequence)
Recommended Name: Activated CDC42 kinase 1  
Size: 1038 amino acids; 114569 Da
Cofactor: Magnesium
Subunit: Interacts with NEDD4 (via WW3 domain). NEDD4L and EGF promote association with NEDD4 (By similarity).
Homodimer. Interacts with AR, CDC42, WWASL and WWOX. Interacts with CSPG4 (activated). Interacts with MERTK
(activated); stimulates autophosphorylation. May interact (phosphorylated) with HSP90AB1; maintains kinase
activity. Interacts with NPHP1. Interacts with SNX9 (via SH3 domain). Interacts with SRC (via SH2 and SH3
domain). Interacts with EGFR, and this interaction is dependent on EGF stimulation and kinase activity of EGFR.
Interacts (via kinase domain) with AKT1. Part of a collagen stimulated complex involved in cell migration
composed of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with BCAR1/p130cas via SH3 domains. Forms complexes
with GRB2 and numerous receptor tyrosine kinases (RTK) including LTK, AXL or PDGFRL, in which GRB2 promotes RTK
recruitment by TNK2
Sequence caution: Sequence=AAH08884.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice
sites;
Selected PDB 3D structures from and Proteopedia for TNK2 (see all 10):
1CF4 (3D)        1U46 (3D)        1U4D (3D)        1U54 (3D)        3EQP (3D)        3EQR (3D)    
Secondary accessions: Q6ZMQ0 Q8N6U7 Q96H59
Alternative splicing: 3 isoforms:  Q07912-1   Q07912-2   Q07912-3   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for TNK2: NX_Q07912

Explore proteomics data for TNK2 at MOPED

Post-translational modifications: 

  • Autophosphorylation regulates kinase activity. Phosphorylation on Tyr-518 is required for interaction with SRC and
    is observed during association with clathrin-coated pits1
  • Polyubiquitinated by NEDD4 and NEDD4L. Degradation can be induced by EGF and is lysosome-dependent (By similarity)1
  • Ubiquitination2 at Lys1037
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for TNK2 (Q07912) (see all 13)
     FGVVRRG  GERLPRP  KVPFAWC  RDLAARN 


    See TNK2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_001010938.1  NP_005772.3  

    ENSEMBL proteins: 
     ENSP00000398614   ENSP00000371341   ENSP00000329425   ENSP00000392546   ENSP00000395588  
     ENSP00000390435   ENSP00000415126   ENSP00000392253   ENSP00000409462   ENSP00000393707  
     ENSP00000395154   ENSP00000390088   ENSP00000376201   ENSP00000323216  

    TNK2 Human Recombinant Protein Products:

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    Cloud-Clone Corp. Proteins for TNK2

     
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    TNK2 Assay Products:

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    Cloud-Clone Corp. ELISAs for TNK2
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    Search eBioscience for ELISAs for TNK2 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: tyrosine kinase, non-receptor, 2
    Ack family

    Selected InterPro protein domains (see all 9):
     IPR017441 Protein_kinase_ATP_BS
     IPR001245 Ser-Thr/Tyr_kinase_cat_dom
     IPR011009 Kinase-like_dom
     IPR001452 SH3_domain
     IPR021619 Inhibitor_Mig-6

    Graphical View of Domain Structure for InterPro Entry Q07912

    ProtoNet protein and cluster: Q07912

    3 Blocks protein domains:
    IPB000449 Ubiquitin-associated domain
    IPB001452 SH3 domain signature
    IPB008266 Tyrosine protein kinase


    UniProtKB/Swiss-Prot: ACK1_HUMAN, Q07912
    Domain: The EBD (EGFR-binding domain) domain is necessary for interaction with EGFR (By similarity)
    Domain: The SAM-like domain is necessary for NEDD4-mediated ubiquitination. Promotes membrane localization and
    dimerization to allow for autophosphorylation
    Domain: The UBA domain binds both poly- and mono-ubiquitin
    Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family
    Similarity: Contains 1 CRIB domain
    Similarity: Contains 1 protein kinase domain
    Similarity: Contains 1 SH3 domain
    Similarity: Contains 1 UBA domain


    Find genes that share domains with TNK2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ACK1_HUMAN, Q07912
    Function: Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading
    and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and
    nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated
    endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and
    mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR
    at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell
    migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in
    brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and
    'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on
    'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF)
    toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on
    cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively
    regulating pro-survival factors such as AKT1 and AR
    Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: Inhibited by AIM-100 (4-amino-5,6-biaryl-furo[2,3-d]pyrimidine), which suppresses activating
    phosphorylation at Tyr-284. Repressed by dasatinib

         Enzyme Numbers (IUBMB): EC 2.7.10.21 2 EC 2.7.102 EC 2.7.11.11

         Gene Ontology (GO): Selected molecular function terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004674protein serine/threonine kinase activity IEA--
    GO:0004712protein serine/threonine/tyrosine kinase activity IDA16257963
    GO:0004713protein tyrosine kinase activity IDA18993068
    GO:0004715non-membrane spanning protein tyrosine kinase activity IEA--
         
    Find genes that share ontologies with TNK2           About GenesLikeMe


    Phenotypes:
         7 GenomeRNAi human phenotypes for TNK2:
     Decreased influenza A H1N1 (A/  Decreased influenza A H1N1 (A/  Decreased influenza A/WSN/33 r  Increased apoptosis 
     Increased circadian period len  Increased gamma-H2AX phosphory  Increases Tamoxifen sensitivit 

    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TNK2
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TNK2
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for TNK2

    miRNA
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    miRTarBase miRNAs that target TNK2:
    hsa-mir-484 (MIRT041931)

    Block miRNA regulation of human, mouse, rat TNK2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TNK2 (see all 18):
    hsa-miR-875-3p hsa-miR-330-5p hsa-miR-149 hsa-miR-326 hsa-miR-3121-3p hsa-miR-1299 hsa-miR-3155b hsa-miR-761
    SwitchGear 3'UTR luciferase reporter plasmidTNK2 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat TNK2

    Gene Editing
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    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TNK2
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    Addgene plasmids for TNK2 

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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    ACK1_HUMAN, Q07912: Cell membrane. Nucleus. Endosome. Cell junction, adherens junction (By similarity).
    Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmic vesicle, clathrin-coated
    vesicle. Membrane, clathrin-coated pit. Note=The Tyr-284 phosphorylated form is found both in the membrane and
    nucleus. Colocalizes with EGFR on endosomes. Nuclear translocation is CDC42-dependent
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endosome5
    nucleus5
    plasma membrane5
    cytosol3
    cytoskeleton1

    Gene Ontology (GO): Selected cellular component terms (see all 13):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA--
    GO:0005737cytoplasm IDA--
    GO:0005768endosome ISS--
    GO:0005886plasma membrane IDA--
    GO:0005905coated pit IDA--

    Find genes that share ontologies with TNK2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for TNK2 About   (see all 7)  
    See pathways by source

    SuperPathContained pathways About
    1Focal adhesion
    Focal Adhesion0.65
    2CDC42 signaling events
    CDC42 signaling events0.34
    3Tyrosine Kinases / Adaptors
    Tyrosine Kinases / Adaptors
    4G protein signaling Regulation of RAC1 activity
    G protein signaling Regulation of RAC1 activity
    5G protein signaling Regulation of CDC42 activity
    G protein signaling Regulation of CDC42 activity


    Find genes that share SuperPaths with TNK2           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for TNK2
        CDC42 Pathway

    1 Cell Signaling Technology (CST) Pathway for TNK2
        Tyrosine Kinases / Adaptors

    2 GeneGo (Thomson Reuters) Pathways for TNK2
        G-protein signaling Regulation of RAC1 activity
    G-protein signaling Regulation of CDC42 activity

    4 BioSystems Pathways for TNK2
        Focal Adhesion
    EGFR1 Signaling Pathway
    G13 Signaling Pathway
    CDC42 signaling events



        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for TNK2
    Interactions:

        GeneGlobe Interaction Network for TNK2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for TNK2 (Q079121, 2, 3 ENSP000003713414) via UniProtKB, MINT, STRING, and/or I2D (see all 55)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    BCAR1P569451, 2, 3, ENSP000001623304EBI-603457,EBI-702093 MINT-7104409 MINT-7104436 MINT-7104364 MINT-7104381 MINT-7104396 I2D: score=1 STRING: ENSP00000162330
    SNX9Q9Y5X12, 3, ENSP000003760244MINT-62874 MINT-62879 MINT-62873 MINT-62880 I2D: score=3 STRING: ENSP00000376024
    CLTCQ006102, 3, ENSP000002691224MINT-7983409 MINT-62881 I2D: score=4 STRING: ENSP00000269122
    ITFG2Q969R82, 3, ENSP000002287994MINT-64707 I2D: score=2 STRING: ENSP00000228799
    CRKP461082, 3, ENSP000003005744MINT-7104372 I2D: score=1 STRING: ENSP00000300574
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006468protein phosphorylation ----
    GO:0006897endocytosis IEA--
    GO:0007166cell surface receptor signaling pathway TAS--
    GO:0007264small GTPase mediated signal transduction TAS8497321
    GO:0016310phosphorylation IDA--

    Find genes that share ontologies with TNK2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for TNK2 (ACK1)

    3 HMDB Compounds for TNK2    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    MagnesiumMagnesium (see all 2)7439-95-4--

    2 DrugBank Compounds for TNK2    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Adenosine triphosphate5'-ATP (see all 8)56-65-5target--17139284 17016423
    Debromohymenialdisine-- --target--17139284 17016423

    2 Novoseek inferred chemical compound relationships for TNK2 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 65.8 61 16288044 (7), 16777958 (5), 14506255 (4), 17494760 (3) (see all 22)
    serine 12.8 2 16257963 (2)



    Find genes that share compounds with TNK2           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for TNK2 gene (2 alternative transcripts): 
    NM_001010938.1  NM_005781.4  

    Unigene Cluster for TNK2:

    Tyrosine kinase, non-receptor, 2
    Hs.518513  [show with all ESTs]
    Unigene Representative Sequence: AB209338
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 24):
    ENST00000416152 ENST00000381916(uc003fvt.1 uc010hzw.1) ENST00000333602(uc003fvu.1)
    ENST00000420716(uc003fvq.1) ENST00000428187(uc003fvs.1) ENST00000495247
    ENST00000464041 ENST00000439230 ENST00000481865(uc003fvv.1) ENST00000424563
    ENST00000478623 ENST00000411741 ENST00000489628 ENST00000478715 ENST00000468680
    ENST00000486523 ENST00000438207 ENST00000430929
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    hsa-miR-875-3p hsa-miR-330-5p hsa-miR-149 hsa-miR-326 hsa-miR-3121-3p hsa-miR-1299 hsa-miR-3155b hsa-miR-761
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    Additional mRNA sequence: 

    AB209338.1 AK126712.1 AK127455.1 AK131539.1 AK225786.1 AK309332.1 BC008884.2 BC020389.1 
    BC028164.1 L13738.2 

    24 DOTS entries:

    DT.91875210  DT.97780847  DT.101983760  DT.101983759  DT.99967159  DT.40208268  DT.120927703  DT.91695164 
    DT.100751739  DT.100751737  DT.120927389  DT.95241216  DT.95355848  DT.97818466  DT.100009087  DT.120927805 
    DT.120927670  DT.120927822  DT.75189040  DT.95217433  DT.95241213  DT.95241214  DT.95241217  DT.99935113 

    Selected AceView cDNA sequences (see all 181):

    BF058375 AI950554 BI905791 AI859326 BQ436053 AW072953 CD675663 BU183396 
    AI440501 AI873679 BC028164 CD675007 BG742978 BC020395 BM668122 BQ066273 
    BU579620 CD673649 BC020389 BC008884 BI324840 AW206140 C02015 H02127 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for TNK2 (see all 24)    About this scheme

    ExUns: 1 ^ 2 ^ 3a · 3b · 3c ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13a · 13b · 13c ^ 14a · 14b · 14c ^ 15 ^ 16a · 16b ^ 17a ·
    SP1:                                      -     -     -     -     -     -                       -                                         -                     
    SP2:                                                        -     -                             -                                                               
    SP3:                                                                    -                       -                                         -                     
    SP4:        -     -     -     -     -     -     -     -     -     -     -                       -                                         -                     
    SP5:                                -     -     -     -     -     -     -                       -                                                               

    ExUns: 17b · 17c ^ 18 ^ 19a · 19b ^ 20a · 20b · 20c · 20d ^ 21 ^ 22a · 22b ^ 23a · 23b · 23c · 23d · 23e · 23f ^ 24 ^ 25 ^ 26 ^ 27a · 27b ^ 28 ^ 29a · 29b ^
    SP1:                                -     -     -     -     -                                                                                                   
    SP2:                                                                                                                                                            
    SP3:                                                                                                                                                            
    SP4:                                                                                                                                                            
    SP5:                                                                                                                                                            

    ExUns: 30 ^ 31 ^ 32 ^ 33a · 33b ^ 34
    SP1:                                    
    SP2:                                    
    SP3:                                    
    SP4:                                    
    SP5:                                    


    ECgene alternative splicing isoforms for TNK2

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    TNK2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    TNK2 Expression
    About this image


    TNK2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Ovary (Reproductive System)
             Oviduct
     
     Testis (Reproductive System)
             Leydig Cells Testis Interstitium
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Brain (Nervous System)
             Cerebral Cortex
    TNK2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TNK2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.518513

    UniProtKB/Swiss-Prot: ACK1_HUMAN, Q07912
    Tissue specificity: The Tyr-284 phosphorylated form shows a significant increase in expression in breast cancers
    during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal
    carcinoma (IDC) and lymph node metastatic (LNMM) stages. It also shows a significant increase in expression in
    prostate cancers during the progressive stages

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of animals.

    Orthologs for TNK2 gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tnk21 , 5 tyrosine kinase, non-receptor, 21, 5 87.7(n)1
    94.61(a)1
      16 (23.16 cM)5
    517891  NM_016788.31  NP_058068.21 
     326438745 
    chicken
    (Gallus gallus)
    Aves TNK21 tyrosine kinase, non-receptor, 2 75.03(n)
    75(a)
      431014  XM_004943344.1  XP_004943401.1 
    African clawed frog
    (Xenopus laevis)
    Amphibia 480610082   -- 77.5(n)    48061008 
    zebrafish
    (Danio rerio)
    Actinopterygii LOC5591191 activated CDC42 kinase 1-like 67.53(n)
    67.83(a)
      559119  XM_005163683.1  XP_005163740.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Ack6
    Ack
    34(a)
    1 → many
    3L(4108186-4114157)
    worm
    (Caenorhabditis elegans)
    Secernentea sid-36
    Protein SID-3, isoform a (sid-3) mRNA, complete cd...
    24(a)
    1 → many
    X(17186140-17193293) WBGene00002207


    ENSEMBL Gene Tree for TNK2 (if available)
    TreeFam Gene Tree for TNK2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TNK2 gene
    SYK2  TNK12  JAK32  JAK22  TYK22  ERBB42  JAK12  ERBB32  
    PTK22  ERBB22  ZAP702  EGFR2  PTK2B2  
    Selected SIMAP similar genes for TNK2 using alignment to 10 protein entries:     ACK1_HUMAN (see all proteins) (see all similar genes):
    SRC    TNK1    PTK2    FRK    EPHA2    FYN
    HCK    ERBB2    EGFR    ERBB4    EPHA5    JAK2
    FES    EPHA3    EPHA6    EZR-ROS1    FGR    LRIG3(NM_001136051)-ROS1

    Find genes that share paralogs with TNK2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for TNK2 (see all 1435)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 3 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0327924
    A lung adenocarcinoma sample4--see VAR_0327922 R L mis40--------
    VAR_0327974
    An ovarian endometrioid cancer sample4--see VAR_0327972 E K mis40--------
    VAR_0327944
    An ovarian mucinous carcinoma sample4--see VAR_0327942 R Q mis40--------
    VAR_0327984
    A gastric adenocarcinoma sample4--see VAR_0327982 M I mis40--------
    rs67737021,2
    C,F,A,H--195589762(+) CAGGCG/ATCTCT 2 -- ds500118Minor allele frequency- A:0.12EA NS NA CSA WA 2116
    rs23446541,2
    C,F,A,H--195589770(-) CCCAGC/TGCAGA 2 -- ds500124Minor allele frequency- T:0.26EA NS NA WA CSA 2124
    rs738911591,2
    C,F--195589790(+) GGCCGC/TGGTGG 2 -- ds50016Minor allele frequency- T:0.11WA NA CSA EA 364
    rs1879762271,2
    C--195589816(+) TTCACC/TGTACA 2 -- ds50010--------
    rs1402404561,2
    --195589832(+) CAGTGC/TCTTTT 2 -- ds50010--------
    rs1452388711,2
    --195590185(+) TTGGGA/GCCTGG 2 -- ds50010--------

    HapMap Linkage Disequilibrium report for TNK2 (195590235 - 195638816 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for TNK2 (see all 30):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2726528CNV Deletion23290073
    esv2726527CNV Deletion23290073
    esv2726526CNV Deletion23290073
    esv2726538CNV Deletion23290073
    esv2726533CNV Deletion23290073
    esv2726532CNV Deletion23290073
    dgv835e201CNV Deletion23290073
    esv2726539CNV Deletion23290073
    dgv834e201CNV Deletion23290073
    esv2726531CNV Deletion23290073

    Human Gene Mutation Database (HGMD): TNK2
    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 606994    OMIM disorders: --

    1 disease for TNK2:    
    About MalaCards
    infantile-onset mesial temporal lobe epilepsy with severe cognitive regression


    Find genes that share disorders with TNK2           About GenesLikeMe

    5 Novoseek inferred disease relationships for TNK2 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    wiskott-aldrich syndrome 54.4 2 9422512 (1), 16257963 (1)
    prostate cancer 20 5 17494760 (2), 18190847 (2), 16288044 (1)
    cancer 3.92 6 20432460 (2), 15886301 (1), 19815557 (1)
    shock 0 2 8647288 (2)
    tumors 0 11 16288044 (3), 17494760 (2), 18190847 (2), 19144635 (1) (see all 5)

    Human Genome Epidemiology (HuGE) Navigator: TNK2 (2 documents)

    Export disorders for TNK2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

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    PubMed articles for TNK2 gene, integrated from 10 sources (see all 101):
    (articles sorted by number of sources associating them with TNK2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42. (PubMed id 8497321)1, 2, 3 Manser E.... Lim L. (Nature 1993)
    2. Biochemical properties of the Cdc42-associated tyrosine kinase ACK1. Substrate specificity, authphosphorylation, and interaction with Hck. (PubMed id 14506255)1, 3, 9 Yokoyama N. and Miller W.T. (J. Biol. Chem. 2003)
    3. Down-regulation of active ACK1 is mediated by association with the E3 ubiquitin ligase Nedd4-2. (PubMed id 19144635)1, 2, 9 Chan W.... Manser E. (J. Biol. Chem. 2009)
    4. Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling. (PubMed id 19815557)1, 2, 9 Pao-Chun L.... Manser E. (J. Biol. Chem. 2009)
    5. Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. (PubMed id 16288044)1, 2, 9 Mahajan N.P.... Earp H.S. (Cancer Res. 2005)
    6. Dysregulation of Ack1 inhibits down-regulation of the EGF receptor. (PubMed id 18262180)1, 2, 9 Groevdal L.M....Stang E. (Exp. Cell Res. 2008)
    7. SNX9 as an adaptor for linking synaptojanin-1 to the Cdc42 effector ACK1. (PubMed id 16137687)1, 2, 9 Yeow-Fong L.... Manser E. (FEBS Lett. 2005)
    8. Phosphorylation of WASP by the Cdc42-associated kinase ACK1: dual hydroxyamino acid specificity in a tyrosine kinase. (PubMed id 16257963)1, 2, 9 Yokoyama N.... Miller W.T. (J. Biol. Chem. 2005)
    9. Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation. (PubMed id 17494760)1, 2, 9 Mahajan N.P.... Whang Y.E. (Proc. Natl. Acad. Sci. U.S.A. 2007)
    10. Shepherding AKT and androgen receptor by Ack1 tyrosine kinase. (PubMed id 20432460)1, 2, 9 Mahajan K. and Mahajan N.P. (J. Cell. Physiol. 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 10188 HGNC: 19297 AceView: ACK1 Ensembl:ENSG00000061938 euGenes: HUgn10188
    ECgene: TNK2 H-InvDB: TNK2

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for TNK2 Pharmacogenomics, SNPs, Pathways
    CGP resequencing studieshttp://www.sanger.ac.uk/perl/genetics/CGP/cgp_viewer?action=gene&ln=ACK1

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for TNK2 gene:
    Search GeneIP for patents involving TNK2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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