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    MAP2K2 mitogen-activated protein kinase kinase 2 [ Homo sapiens (human) ]

    Gene ID: 5605, updated on 22-May-2013
    Official Symbol
    MAP2K2provided by HGNC
    Official Full Name
    mitogen-activated protein kinase kinase 2provided by HGNC
    Primary source
    HGNC:6842
    See related
    Ensembl:ENSG00000126934; HPRD:03164; MIM:601263; Vega:OTTHUMG00000134286
    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
    MEK2; MKK2; MAPKK2; PRKMK2
    Summary
    The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, mental retardation, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene. [provided by RefSeq, Jul 2008]
    Location :
    19p13.3
    Sequence :
    Chromosome: 19; NC_000019.9 (4090319..4124126, complement)
    See MAP2K2 in Epigenomics, MapViewer

    Chromosome 19 - NC_000019.9Genomic Context describing neighboring genes Neighboring gene protein inhibitor of activated STAT, 4 Neighboring gene zinc finger and BTB domain containing 7A Neighboring gene cAMP responsive element binding protein 3-like 3 Neighboring gene sirtuin 6

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details

    Related articles in PubMed

    1. Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass. Povlsen LK, et al. Nat Cell Biol, 2012 Oct. PMID 23000965.
    2. Charting the landscape of tandem BRCT domain-mediated protein interactions. Woods NT, et al. Sci Signal, 2012 Sep 18. PMID 22990118.
    3. Mitogen-activated protein kinase pathway in osteosarcoma. Na KY, et al. Pathology, 2012 Oct. PMID 22935974.
    4. IL1β down-regulation of sex hormone-binding globulin production by decreasing HNF-4α via MEK-1/2 and JNK MAPK pathways. Simó R, et al. Mol Endocrinol, 2012 Nov. PMID 22902540.
    5. MEK2 regulates ribonucleotide reductase activity through functional interaction with ribonucleotide reductase small subunit p53R2. Piao C, et al. Cell Cycle, 2012 Sep 1. PMID 22895183.

    See all (154) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

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

    1. osteosarcoma patients whose tumors expressed pMEK2 had a poorer clinical outcome than those whose tumors did not.
      Title: Mitogen-activated protein kinase pathway in osteosarcoma.
    2. IL1beta treatment reduces SHBG production in HepG2 cells by the down-regulation of HNF-4A via the MAPK kinase (MEK)-1/2 and c-Jun N-terminal kinase (JNK) MAPK signaling pathways.
      Title: IL1β down-regulation of sex hormone-binding globulin production by decreasing HNF-4α via MEK-1/2 and JNK MAPK pathways.
    3. MEK2 regulates ribonucleotide reductase activity through functional interaction with ribonucleotide reductase small subunit p53R2.
      Title: MEK2 regulates ribonucleotide reductase activity through functional interaction with ribonucleotide reductase small subunit p53R2.
    4. Data show substantial clinical activity of MEK1/2 inhibitor trametinib in melanoma and suggest that MEK is a valid therapeutic target.
      Title: Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial.
    5. Define the maximum tolerated dose and recommended phase 2 dose of MEK1/2 inhibitor trametinib and to assess its safety, pharmacokinetics, pharmacodynamics, and response rate in individuals with advanced solid tumours.
      Title: Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial.
    6. E-cadherin is necessary for localization of DLG1 but not phosphorylated MEK2 to the midbody ring during cytokinesis.
      Title: The MEK2-binding tumor suppressor hDlg is recruited by E-cadherin to the midbody ring.
    7. LPS increased IL-8 and IL-6 and decreased EVT invasion through activation of MEK1/2 MAPK signaling
      Title: Lipopolysaccharide induces cytokine production and decreases extravillous trophoblast invasion through a mitogen-activated protein kinase-mediated pathway: possible mechanisms of first trimester placental dysfunction.
    8. Findings indicate that Ras-induced nuclear accumulation of activated MEK1/2 was reliant on downregulation of the spatial regulator Sef.
      Title: Sef downregulation by Ras causes MEK1/2 to become aberrantly nuclear localized leading to polyploidy and neoplastic transformation.
    9. Screening a cohort of individuals with melanoma revealed the presence of recurring somatic MAP2K1 and MAP2K2 mutations, which occurred at an overall frequency of 8%.
      Title: Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma.
    10. Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b.
      Title: Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b.
    Submit: New GeneRIF Correction See all (67)

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

    Review eQTL and phenotype association data in this region using PheGenI

    Cardio-facio-cutaneous syndrome

    Summary from GeneReviews: Cardiofaciocutaneous Syndrome Go to GeneReviews

    Disease Characteristics
    Cardiofaciocutaneous (CFC) syndrome is characterized by cardiac abnormalities (pulmonic stenosis and other valve dysplasias, septal defects, hypertrophic cardiomyopathy, rhythm disturbances), distinctive craniofacial appearance, and cutaneous abnormalities (including xerosis, hyperkeratosis, ichthyosis, keratosis pilaris, ulerythema ophryogenes, eczema, pigmented moles, hemangiomas, and palmoplantar hyperkeratosis). The hair is typically sparse, curly, fine or thick, woolly or brittle; eyelashes and eyebrows may be absent or sparse. Nails may be dystrophic or fast growing. Some form of neurologic and/or cognitive delay (ranging from mild to severe) is seen in all affected individuals. Neoplasia, mostly acute lymphoblastic leukemia (ALL), has been reported in some individuals.
    Diagnosis Testing
    Diagnosis is based on clinical findings and molecular genetic testing. The four genes known to be associated with CFC syndrome are: BRAF (~75%), MAP2K1 and MAP2K2 (~25%), and KRAS (<2%). Molecular genetic testing is available clinically for all known genes.
    Genetic Counseling
    Cardiofaciocutaneous (CFC) syndrome is usually the result of a de novo dominant mutation. The risk to the sibs of a proband is small. To date, one family with transmission of an autosomal dominant germline mutation (MAP2K2) through multiple generations has been reported. Prenatal diagnosis for pregnancies at increased risk because of the theoretical possibility of germline mosaicism or for couples needing reassurance is possible if the disease-causing allele of the affected family member is known.
    References
    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env The transcription factors and kinases c-Jun, JNK, MEK, p38 MAPK, STAT-3, JAK-1, TFII D, TFII F, eIF-4E, and RNA polymerase II are induced by HIV-1 gp120 PubMed
    Nef, p27 nef HIV-1 Nef expression in primary T cells upregulates MEK1/2 activities, which induces the increased phosphorylation of ERK1/2 PubMed
    Tat, p14 tat Tat and IFN-gamma synergistically induce the expression of CXCL10, which is inhibited by MEK1/2 inhibitor and the p38 mitogen-activated protein kinase (MAPK) inhibitor PubMed
    tat MAP2K2 is downregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells PubMed
    tat HIV-1 Tat activates mitogen-activated protein kinases ERK1 and ERK2 through the activation of MEK1 and MEK2, leading to induction of IL-8, IL-10, IP-10, iNOS, superoxide and TNF-alpha, as well as the activation of CREB and increased albumin permeability PubMed
    Vpr, p15 vpr Inhibition of MEK1,2 impairs HIV-1 Vpr-induced BID cleavage PubMed
    vpr Overexpression of HIV-1 Vpr decreases phosphorylation of MEK2 PubMed
    vpr HIV-1 Vpr downregulates expression of genes involved in the MEK2-ERK pathway, including MAP2K2 (MEK2) and MKNK2 PubMed
    nucleocapsid gag Mitogen-activated protein kinase kinase 2 (MAP2K2) is downregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells PubMed

    Go to the HIV-1, Human Protein Interaction Database

    Products Interactant Other Gene Complex Source Pubs Description
    NP_109587.1 NP_001645.1 ARAF    BIND  PubMed MEK2 interacts with A-Raf 
    NP_109587.1 NP_620407.1 MAPK1    BIND  PubMed MEK2 interacts with ERK2. This interaction is modeled on a demonstrated interaction between human MEK2 and rat ERK2. 
    NP_109587.1 AAH13992.1 MAPK3    BIND  PubMed MEK2 binds and activates ERK1. 
    NP_109587.1 NP_002871.1 RAF1    BIND  PubMed Raf interacts with Mek2. 
    P36507 P10398 ARAF    HPRD  PubMed  
    P36507 P15056 BRAF    HPRD  PubMed  
    P36507 P55211 CASP9    HPRD  PubMed  
    P36507 Q969H4 CNKSR1    HPRD  PubMed  
    P36507 P51452 DUSP3    HPRD  PubMed  
    P36507 Q05586 GRIN1    HPRD  PubMed  
    P36507 O15399 GRIN2D    HPRD  PubMed  
    P36507 Q9UHA4 LAMTOR3    HPRD  PubMed  
    P36507 P36507 MAP2K2    HPRD  PubMed  
    P36507 P36507 MAP2K2    HPRD  PubMed  
    P36507 P28482 MAPK1    HPRD  PubMed  
    P36507 P27361 MAPK3    HPRD  PubMed  
    P36507 P04049 RAF1    HPRD  PubMed  
    P36507 O14924 RGS12    HPRD  PubMed  
    BioGRID:111591 BioGRID:106864 ARAF    BioGRID  PubMed Reconstituted Complex; Two-hybrid 
    BioGRID:111591 BioGRID:107141 BRAF    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111591 BioGRID:116183 COPS5    BioGRID  PubMed Two-hybrid 
    BioGRID:111591 BioGRID:115098 FAM65B    BioGRID  PubMed Two-hybrid 
    BioGRID:111591 BioGRID:228662 Flna    BioGRID  PubMed Two-hybrid 
    BioGRID:111591 BioGRID:201048 Ksr1    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Co-fractionation 
    BioGRID:111591 BioGRID:110169 LIG4    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:111591 BioGRID:111590 MAP2K1    BioGRID  PubMed Co-fractionation 
    BioGRID:111591 BioGRID:111591 MAP2K2    BioGRID  PubMed Biochemical Activity 
    BioGRID:111591 BioGRID:111580 MAPK1    BioGRID  PubMed PCA; Two-hybrid 
    BioGRID:111591 BioGRID:111581 MAPK3    BioGRID  PubMed Biochemical Activity; Reconstituted Complex; Two-hybrid 
    BioGRID:111591 BioGRID:111585 MAPK8    BioGRID  PubMed Protein-peptide 
    BioGRID:111591 BioGRID:121122 MEPCE    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111591 BioGRID:111218 PEX14    BioGRID  PubMed Co-purification 
    BioGRID:111591 BioGRID:111831 RAF1    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:111591 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Co-purification; Reconstituted Complex 
    BioGRID:111591 BioGRID:124019 WDR83    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:111591 BioGRID:113361 YWHAB    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:111591 BioGRID:113540 ZNF207    BioGRID  PubMed Two-hybrid 
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      ARMS-mediated activation, organism-specific biosystemARMS (Ankyrin-Rich Membrane Spanning/Kidins 220) is a 220kD tetraspanning adaptor protein which becomes rapidly tyrosine phosphorylated by active Trk receptors. ARMS is another adaptor protein which ...
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    • Acute myeloid leukemia, organism-specific biosystem (from KEGG)
      Acute myeloid leukemia, organism-specific biosystemAcute myeloid leukemia (AML) is a disease that is characterized by uncontrolled proliferation of clonal neoplastic cells and accumulation in the bone marrow of blasts with an impaired differentiation...
    • Acute myeloid leukemia, conserved biosystem (from KEGG)
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    • Axon guidance, organism-specific biosystem (from REACTOME)
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      B Cell Receptor Signaling Pathway, organism-specific biosystemThe B cell receptor includes membrane ?? heavy chain molecules bound to a light chain and an Ig alpha (CD79A)/Ig beta (CD79B) heterodimer. Activation of the B cell receptor involves phosphorylation o...
    • B cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      B cell receptor signaling pathway, organism-specific biosystemB cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor...
    • B cell receptor signaling pathway, conserved biosystem (from KEGG)
      B cell receptor signaling pathway, conserved biosystemB cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor...
    • BDNF signaling pathway, organism-specific biosystem (from WikiPathways)
      BDNF signaling pathway, organism-specific biosystemBrain-derived neurotrophic factor (BDNF) is a neurotrophin essential for growth, differentiation, plasticity, and survival of neurons. BDNF is also required for processes such as energy metabolism, b...
    • Bladder cancer, organism-specific biosystem (from KEGG)
      Bladder cancer, organism-specific biosystemThe urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carc...
    • Bladder cancer, conserved biosystem (from KEGG)
      Bladder cancer, conserved biosystemThe urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carc...
    • CXCR3-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      CXCR3-mediated signaling events, organism-specific biosystem
      CXCR3-mediated signaling events
    • Cellular roles of Anthrax toxin, organism-specific biosystem (from Pathway Interaction Database)
      Cellular roles of Anthrax toxin, organism-specific biosystem
      Cellular roles of Anthrax toxin
    • Ceramide signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
      Ceramide signaling pathway, organism-specific biosystem
      Ceramide signaling pathway
    • Chronic myeloid leukemia, organism-specific biosystem (from KEGG)
      Chronic myeloid leukemia, organism-specific biosystemChronic myelogenous leukemia (CML) originates in a pluripotent hematopoetic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and ot...
    • Chronic myeloid leukemia, conserved biosystem (from KEGG)
      Chronic myeloid leukemia, conserved biosystemChronic myelogenous leukemia (CML) originates in a pluripotent hematopoetic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and ot...
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      Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
    • DAP12 interactions, organism-specific biosystem (from REACTOME)
      DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
    • DAP12 signaling, organism-specific biosystem (from REACTOME)
      DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
    • Developmental Biology, organism-specific biosystem (from REACTOME)
      Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Downstream signal transduction, organism-specific biosystem (from REACTOME)
      Downstream signal transduction, organism-specific biosystemThe role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of aro...
    • Downstream signaling in naive CD8+ T cells, organism-specific biosystem (from Pathway Interaction Database)
      Downstream signaling in naive CD8+ T cells, organism-specific biosystem
      Downstream signaling in naive CD8+ T cells
    • Downstream signaling of activated FGFR, organism-specific biosystem (from REACTOME)
      Downstream signaling of activated FGFR, organism-specific biosystemSignaling via FGFRs is mediated via direct recruitment of signaling proteins that bind to tyrosine auto-phosphorylation sites on the activated receptor and via closely linked docking proteins that be...
    • EGFR1 Signaling Pathway, organism-specific biosystem (from WikiPathways)
      EGFR1 Signaling Pathway, organism-specific biosystemThe androgen receptor is a member of the nuclear receptor family of ligand activated transcription factors. These receptors bind to steroid hormones, thyroid hormone, retinoids and vitamin D among ot...
    • EPO Receptor Signaling, organism-specific biosystem (from WikiPathways)
      EPO Receptor Signaling, organism-specific biosystemThe erythropoietin receptor is a 66 kDa peptide and is a member of the cytokine receptor family. The receptor is tyrosine phosphorylated upon binding by erythropoietin and associates with and activat...
    • ERK activation, organism-specific biosystem (from REACTOME)
      ERK activation, organism-specific biosystemActivated MEK phosphorylates and activates ERK.
    • ERK2 activation, organism-specific biosystem (from REACTOME)
      ERK2 activation, organism-specific biosystemActivated MEK2 phosphorylates and activates ERK2.
    • Endometrial cancer, organism-specific biosystem (from KEGG)
      Endometrial cancer, organism-specific biosystemEndometrial cancer (EC) is the most common gynaecological malignancy and the fourth most common malignancy in women in the developed world after breast, colorectal and lung cancer. Two types of endom...
    • Endometrial cancer, conserved biosystem (from KEGG)
      Endometrial cancer, conserved biosystemEndometrial cancer (EC) is the most common gynaecological malignancy and the fourth most common malignancy in women in the developed world after breast, colorectal and lung cancer. Two types of endom...
    • Endothelins, organism-specific biosystem (from Pathway Interaction Database)
      Endothelins, organism-specific biosystem
      Endothelins
    • ErbB signaling pathway, organism-specific biosystem (from KEGG)
      ErbB signaling pathway, organism-specific biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
    • ErbB signaling pathway, conserved biosystem (from KEGG)
      ErbB signaling pathway, conserved biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
    • ErbB1 downstream signaling, organism-specific biosystem (from Pathway Interaction Database)
      ErbB1 downstream signaling, organism-specific biosystem
      ErbB1 downstream signaling
    • ErbB2/ErbB3 signaling events, organism-specific biosystem (from Pathway Interaction Database)
      ErbB2/ErbB3 signaling events, organism-specific biosystem
      ErbB2/ErbB3 signaling events
    • Estrogen signaling pathway, organism-specific biosystem (from KEGG)
      Estrogen signaling pathway, organism-specific biosystemEstrogens are steroid hormones that regulate a plethora of physiological processes in mammals, including reproduction, cardiovascular protection, bone integrity, cellular homeostasis, and behavior. E...
    • Estrogen signaling pathway, conserved biosystem (from KEGG)
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    • FRS2-mediated cascade, organism-specific biosystem (from REACTOME)
      FRS2-mediated cascade, organism-specific biosystemThe FRS family of scaffolding adaptor proteins has two members, FRS2alpha and FRS2beta (also known as FRS3 or SNT-2). Activation of FGFR tyrosine kinase allows FRS2 proteins to become phosphorylated...
    • Fc epsilon RI signaling pathway, organism-specific biosystem (from KEGG)
      Fc epsilon RI signaling pathway, organism-specific biosystemFc epsilon RI-mediated signaling pathways in mast cells are initiated by the interaction of antigen (Ag) with IgE bound to the extracellular domain of the alpha chain of Fc epsilon RI. The activation...
    • Fc epsilon RI signaling pathway, conserved biosystem (from KEGG)
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    • Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem (from Pathway Interaction Database)
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    • Hepatitis B, organism-specific biosystem (from KEGG)
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    • Hypothetical Network for Drug Addiction, organism-specific biosystem (from WikiPathways)
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    • IGF1R signaling cascade, organism-specific biosystem (from REACTOME)
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    • IL-2 Signaling pathway, organism-specific biosystem (from WikiPathways)
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    • IL-5 Signaling Pathway, organism-specific biosystem (from WikiPathways)
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    • IL-7 Signaling Pathway, organism-specific biosystem (from WikiPathways)
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    • IL-9 Signaling Pathway, organism-specific biosystem (from WikiPathways)
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    • IL2-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      IL2-mediated signaling events, organism-specific biosystem
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    • IRS-related events, organism-specific biosystem (from REACTOME)
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    • IRS-related events triggered by IGF1R, organism-specific biosystem (from REACTOME)
      IRS-related events triggered by IGF1R, organism-specific biosystemThe phosphorylated type 1 insulin-like growth factor receptor phosphorylates IR1, IRS2, IRS4 and possibly other IRS/DOK family members (reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et a...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Influenza A, organism-specific biosystem (from KEGG)
      Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
    • Influenza A, conserved biosystem (from KEGG)
      Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • Insulin Signaling, organism-specific biosystem (from WikiPathways)
      Insulin Signaling, organism-specific biosystemInsulin signaling influences energy metabolism as well as growth. The presence of insulin signals the fed state, and this signal is passed via the AKT branch, which leads to the uptake of glucose fro...
    • Insulin receptor signalling cascade, organism-specific biosystem (from REACTOME)
      Insulin receptor signalling cascade, organism-specific biosystemAutophosphorylation of the insulin receptor triggers a series of signalling events, mediated by SHC or IRS, and resulting in activation of the Ras/RAF and MAP kinase cascades. A second effect of the ...
    • Insulin signaling pathway, organism-specific biosystem (from KEGG)
      Insulin signaling pathway, organism-specific biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • Insulin signaling pathway, conserved biosystem (from KEGG)
      Insulin signaling pathway, conserved biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • Integrin-mediated cell adhesion, organism-specific biosystem (from WikiPathways)
      Integrin-mediated cell adhesion, organism-specific biosystemIntegrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and ...
    • Interleukin-2 signaling, organism-specific biosystem (from REACTOME)
      Interleukin-2 signaling, organism-specific biosystemInterleukin-2 (IL-2) is a cytokine that is produced by T cells in response to antigen stimulation. Originally, IL-2 was discovered because of its potent growth factor activity on activated T cells in...
    • L1CAM interactions, organism-specific biosystem (from REACTOME)
      L1CAM interactions, organism-specific biosystemThe L1 family of cell adhesion molecules (L1CAMs) are a subfamily of the immunoglobulin superfamily of transmembrane receptors, comprised of four structurally related proteins: L1, Close Homolog of L...
    • Leptin signaling pathway, organism-specific biosystem (from WikiPathways)
      Leptin signaling pathway, organism-specific biosystemLeptin is a peptide hormone mainly synthesised and secreted from adipocytes. It is also expressed in other tissues including placenta, stomach and skeletal muscle. Leptin mediates its effects by bind...
    • Long-term depression, organism-specific biosystem (from KEGG)
      Long-term depression, organism-specific biosystemCerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and...
    • Long-term depression, conserved biosystem (from KEGG)
      Long-term depression, conserved biosystemCerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and...
    • Long-term potentiation, organism-specific biosystem (from KEGG)
      Long-term potentiation, organism-specific biosystemHippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippo...
    • Long-term potentiation, conserved biosystem (from KEGG)
      Long-term potentiation, conserved biosystemHippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippo...
    • MAP kinase activation in TLR cascade, organism-specific biosystem (from REACTOME)
      MAP kinase activation in TLR cascade, organism-specific biosystemThe mitogen activated protein kinase (MAPK) cascade, one of the most ancient and evolutionarily conserved signaling pathways, is involved in many processes of immune responses. The MAP kinases cascad...
    • MAPK Cascade, organism-specific biosystem (from WikiPathways)
      MAPK Cascade, organism-specific biosystem
      MAPK Cascade
    • MAPK signaling pathway, organism-specific biosystem (from WikiPathways)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MAPK signaling pathway, organism-specific biosystem (from KEGG)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MAPK signaling pathway, conserved biosystem (from KEGG)
      MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MEK activation, organism-specific biosystem (from REACTOME)
      MEK activation, organism-specific biosystemMEK is phosphorylated and activated by RAF.
    • Melanogenesis, organism-specific biosystem (from KEGG)
      Melanogenesis, organism-specific biosystemCutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory cont...
    • Melanogenesis, conserved biosystem (from KEGG)
      Melanogenesis, conserved biosystemCutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory cont...
    • Melanoma, organism-specific biosystem (from KEGG)
      Melanoma, organism-specific biosystemMelanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes...
    • Melanoma, conserved biosystem (from KEGG)
      Melanoma, conserved biosystemMelanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes...
    • MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystem (from WikiPathways)
      MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystemThis pathway shows the role of microRNAs in the process of cardiac hypertrophy. MicroRNA targets were predicted by the TargetScan algorithm, and the predicted interactions are shown in red dashed lin...
    • MyD88 cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
      MyD88 cascade initiated on plasma membrane, organism-specific biosystemMammalian myeloid differentiation factor 88 (MyD88) is Toll/interleukin (IL)-1 (TIR)-domain containing adapter protein which plays crucial role in TLR signaling. All TLRs, with only one exception of...
    • MyD88 dependent cascade initiated on endosome, organism-specific biosystem (from REACTOME)
      MyD88 dependent cascade initiated on endosome, organism-specific biosystemUpon binding of their ligands, TLR7/8 and TLR9 recruit a cytoplasmic adaptor MyD88 and IRAKs, downstream of which the signaling pathways are divided to induce either inflammatory cytokines or type I ...
    • MyD88-independent cascade, organism-specific biosystem (from REACTOME)
      MyD88-independent cascade, organism-specific biosystemMyD88-independent signaling route utilizes TRAM and TRIF adapters, that are essential for production of both type 1 interferons(IFNs) and pro-inflammatory cytokines. TRAM is thought to bridge between...
    • MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystem (from REACTOME)
      MyD88:Mal cascade initiated on plasma membrane, organism-specific biosystemThe first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also b...
    • NCAM signaling for neurite out-growth, organism-specific biosystem (from REACTOME)
      NCAM signaling for neurite out-growth, organism-specific biosystemThe neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the n...
    • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
      NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
    • Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Neurotrophin signaling pathway, organism-specific biosystem (from KEGG)
      Neurotrophin signaling pathway, organism-specific biosystemNeurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic facto...
    • Neurotrophin signaling pathway, conserved biosystem (from KEGG)
      Neurotrophin signaling pathway, conserved biosystemNeurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic facto...
    • Non-small cell lung cancer, organism-specific biosystem (from KEGG)
      Non-small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heter...
    • Non-small cell lung cancer, conserved biosystem (from KEGG)
      Non-small cell lung cancer, conserved biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heter...
    • Nongenotropic Androgen signaling, organism-specific biosystem (from Pathway Interaction Database)
      Nongenotropic Androgen signaling, organism-specific biosystem
      Nongenotropic Androgen signaling
    • Oncostatin M Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Oncostatin M Signaling Pathway, organism-specific biosystemOncostatin M (OSM) is a member of the multifunctional cytokine interleukin 6 (IL6) - type cytokine family. It is mainly produced in cell types such as activated T lymphocytes, macrophages, monocytes,...
    • PI3K-Akt signaling pathway, organism-specific biosystem (from KEGG)
      PI3K-Akt signaling pathway, organism-specific biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
    • PI3K-Akt signaling pathway, conserved biosystem (from KEGG)
      PI3K-Akt signaling pathway, conserved biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
    • Pathways in cancer, organism-specific biosystem (from KEGG)
      Pathways in cancer, organism-specific biosystem
      Pathways in cancer
    • Prion diseases, organism-specific biosystem (from KEGG)
      Prion diseases, organism-specific biosystemPrion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of ...
    • Prion diseases, conserved biosystem (from KEGG)
      Prion diseases, conserved biosystemPrion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of ...
    • Prolactin Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Prolactin Signaling Pathway, organism-specific biosystemProlactin (PRL), a pleiotropic polypeptide hormone, mostly secreted by the lactotrophic cells of anterior pituitary gland and to a lesser extent expressed in numerous extra pituitary tissues such as ...
    • Prolonged ERK activation events, organism-specific biosystem (from REACTOME)
      Prolonged ERK activation events, organism-specific biosystemAfter NGF binding, activated Trk receptors provide multiple docking sites for adaptor proteins and enzymes. Two docking proteins, the Ankyrin-Rich Membrane Spanning protein (ARMS/Kidins220) and Fibro...
    • Prostate Cancer, organism-specific biosystem (from WikiPathways)
      Prostate Cancer, organism-specific biosystem
      Prostate Cancer
    • Prostate cancer, organism-specific biosystem (from KEGG)
      Prostate cancer, organism-specific biosystemProstate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of...
    • Prostate cancer, conserved biosystem (from KEGG)
      Prostate cancer, conserved biosystemProstate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of...
    • Proteoglycans in cancer, organism-specific biosystem (from KEGG)
      Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
    • Proteoglycans in cancer, conserved biosystem (from KEGG)
      Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
    • RAF phosphorylates MEK, organism-specific biosystem (from REACTOME)
      RAF phosphorylates MEK, organism-specific biosystemActive Raf-1 phosphorylates MEK-1/2 on Serine residues, converting ATP to ADP. The MEK-1/2 kinase is now active.
    • RAF/MAP kinase cascade, organism-specific biosystem (from REACTOME)
      RAF/MAP kinase cascade, organism-specific biosystemThe MAP kinase cascade describes a sequence of phosphorylation events involving serine/threonine-specific protein kinases. Used by various signal transduction pathways, this cascade constitutes a com...
    • Regulation of Actin Cytoskeleton, organism-specific biosystem (from WikiPathways)
      Regulation of Actin Cytoskeleton, organism-specific biosystemhttp://www.genome.jp/kegg/pathway/hsa/hsa04810.html
    • Regulation of actin cytoskeleton, organism-specific biosystem (from KEGG)
      Regulation of actin cytoskeleton, organism-specific biosystem
      Regulation of actin cytoskeleton
    • Regulation of actin cytoskeleton, conserved biosystem (from KEGG)
      Regulation of actin cytoskeleton, conserved biosystem
      Regulation of actin cytoskeleton
    • Renal cell carcinoma, organism-specific biosystem (from KEGG)
      Renal cell carcinoma, organism-specific biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...
    • Renal cell carcinoma, conserved biosystem (from KEGG)
      Renal cell carcinoma, conserved biosystemRenal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal canc...
    • SHC-mediated signalling, organism-specific biosystem (from REACTOME)
      SHC-mediated signalling, organism-specific biosystemRelease of phospho-SHC from the insulin receptor triggers a cascade of signalling events via SOS, RAF and the MAP kinases.
    • SHC-related events, organism-specific biosystem (from REACTOME)
      SHC-related events, organism-specific biosystemSHC is one of the mediators of insulin signalling events. It is activated by phosphorylation and triggers a cascade of events involving SOS, RAF and the MAP kinases.
    • SHC-related events triggered by IGF1R, organism-specific biosystem (from REACTOME)
      SHC-related events triggered by IGF1R, organism-specific biosystemPhosphorylated IGF1R binds and phosphorylates SHC1 (reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et al. 2010, Parrella et al. 2010, Siddle et al. 2012). Phosphorylated SHC then binds GR...
    • SHC1 events in EGFR signaling, organism-specific biosystem (from REACTOME)
      SHC1 events in EGFR signaling, organism-specific biosystemGRB2 can bind EGFR directly or through another SH2-containing protein, SHC1. This association leads to RAS activation.
    • SHC1 events in ERBB2 signaling, organism-specific biosystem (from REACTOME)
      SHC1 events in ERBB2 signaling, organism-specific biosystemAll ERBB2 heterodimers, ERBB2:EGFR, ERBB2:ERBB3 and ERBB2:ERBB4, are able to activate RAF/MAP kinase cascade by recruiting SHC1 (Pinkas-Kramarski et al. 1996, Sepp-Lorenzino et al. 1996) to phosphory...
    • SHC1 events in ERBB4 signaling, organism-specific biosystem (from REACTOME)
      SHC1 events in ERBB4 signaling, organism-specific biosystemAll splicing isoforms of ERBB4 possess two tyrosine residues in the C-tail that serve as docking sites for SHC1 (Kaushansky et al. 2008, Pinkas-Kramarski et al. 1996, Cohen et al. 1996). Once bound t...
    • SOS-mediated signalling, organism-specific biosystem (from REACTOME)
      SOS-mediated signalling, organism-specific biosystemSOS is recruited to the plasma membrane and mediates activation of Ras.
    • Serotonin Receptor 2 and ELK-SRF/GATA4 signaling, organism-specific biosystem (from WikiPathways)
      Serotonin Receptor 2 and ELK-SRF/GATA4 signaling, organism-specific biosystemThis pathway is courtesy of Ariadne Genomics Pathway Studio.
    • Serotonin Receptor 4/6/7 and NR3C Signaling, organism-specific biosystem (from WikiPathways)
      Serotonin Receptor 4/6/7 and NR3C Signaling, organism-specific biosystemThis pathway is courtesy of Ariadne Genomics Pathway Studio.
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signal transduction by L1, organism-specific biosystem (from REACTOME)
      Signal transduction by L1, organism-specific biosystemBesides adhesive roles in cell cell interaction, L1 functions as a signal transducing receptor providing neurons with cues from their environment for axonal growth and guidance. L1 associates with be...
    • Signaling Pathways in Glioblastoma, organism-specific biosystem (from WikiPathways)
      Signaling Pathways in Glioblastoma, organism-specific biosystemThe most frequently altered genes in glioblastoma. This pathway originally accompanied the 2008 Nature publication on the comprehensive genomic characterization of human glioblastoma genes and core p...
    • Signaling by EGFR, organism-specific biosystem (from REACTOME)
      Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
    • Signaling by EGFR in Cancer, organism-specific biosystem (from REACTOME)
      Signaling by EGFR in Cancer, organism-specific biosystemThe pathway "Signaling by EGFR in Cancer" shows "Signaling by constitutively active EGFR" in parallel with "Signaling by EGFR". This allows users to compare signaling by constitutively active EGFR ca...
    • Signaling by ERBB2, organism-specific biosystem (from REACTOME)
      Signaling by ERBB2, organism-specific biosystemERBB2, also known as HER2 or NEU, is a receptor tyrosine kinase (RTK) belonging to the EGFR family. ERBB2 possesses an extracellular domain that does not bind any known ligand, contrary to other EGFR...
    • Signaling by ERBB4, organism-specific biosystem (from REACTOME)
      Signaling by ERBB4, organism-specific biosystemERBB4, also known as HER4, belongs to the ERBB family of receptors, which also includes ERBB1 (EGFR i.e. HER1), ERBB2 (HER2 i.e. NEU) and ERBB3 (HER3). Similar to EGFR, ERBB4 has an extracellular lig...
    • Signaling by FGFR, organism-specific biosystem (from REACTOME)
      Signaling by FGFR, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
    • Signaling by FGFR in disease, organism-specific biosystem (from REACTOME)
      Signaling by FGFR in disease, organism-specific biosystemThe pathway 'Signaling by FGFR in disease' shows 'Signaling by FGFR mutants' in parallel with the wild-type pathway 'Signaling by FGFR', allowing users to compare disease and normal events. FGFR mut...
    • Signaling by GPCR, organism-specific biosystem (from REACTOME)
      Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
    • Signaling by Insulin receptor, organism-specific biosystem (from REACTOME)
      Signaling by Insulin receptor, organism-specific biosystemInsulin binding to its receptor results in receptor autophosphorylation on tyrosine residues and the tyrosine phosphorylation of insulin receptor substrates (e.g. IRS and Shc) by the insulin receptor...
    • Signaling by Interleukins, organism-specific biosystem (from REACTOME)
      Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...
    • Signaling by PDGF, organism-specific biosystem (from REACTOME)
      Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
    • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
      Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
    • Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystem (from REACTOME)
      Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystemBinding of IGF1 (IGF-I) or IGF2 (IGF-II) to the extracellular alpha peptides of the type 1 insulin-like growth factor receptor (IGF1R) triggers the activation of two major signaling pathways: the SOS...
    • Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem
      Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
    • Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem
      Signaling events mediated by Stem cell factor receptor (c-Kit)
    • Signaling of Hepatocyte Growth Factor Receptor, organism-specific biosystem (from WikiPathways)
      Signaling of Hepatocyte Growth Factor Receptor, organism-specific biosystem
      Signaling of Hepatocyte Growth Factor Receptor
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • Signalling to ERKs, organism-specific biosystem (from REACTOME)
      Signalling to ERKs, organism-specific biosystemNeurotrophins utilize multiple pathways to activate ERKs (ERK1 and ERK2), a subgroup of the large MAP kinase (MAPK) family, from the plasma membrane. The major signalling pathways to ERKs are via RAS...
    • Signalling to RAS, organism-specific biosystem (from REACTOME)
      Signalling to RAS, organism-specific biosystemSignalling through Shc adaptor proteins appears to be identical for both NGF and EGF. It leads to a fast, but transient, MAPK/ERK activation, which is insufficient to explain the prolonged activation...
    • Signalling to p38 via RIT and RIN, organism-specific biosystem (from REACTOME)
      Signalling to p38 via RIT and RIN, organism-specific biosystemRIT and RIN are two small guanine nucleotide binding proteins that share more than 50% sequence identity with RAS, including highly conserved core effector domains. Unlike RAS, the C termini of RIT a...
    • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • T cell receptor signaling pathway, conserved biosystem (from KEGG)
      T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • TCR Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TCR Signaling Pathway, organism-specific biosystemThe T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the ? and ? chains, and a signaling subunit, namely the CD3?, ? and ? chains and the TCR? chain. This complex partic...
    • TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystem (from REACTOME)
      TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystemTRAF6 mediates NFkB activation via canonical phosphorylation of IKK complex by TAK1. TRAF6 and TAK1 also regulate MAPK cascades leading to the activation of AP-1.
    • TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystem (from REACTOME)
      TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystemTRIF was shown to induce IRF3/7 and NF-?B activation and apoptosis through distinct intracellular signaling pathways [Han KJ et al 2004; Kaiser WJ and Offermann MK et al 2005]. TRIF consists of an N...
    • TSLP Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TSLP Signaling Pathway, organism-specific biosystemThymic stromal lymphopoietin (TSLP) is a type I cytokine member of interleukin-2 cytokine family. TSLP signals through interleukin-7 receptor a chain (IL-7Ra) and the TSLP receptor subunit (TSLPR), h...
    • Thyroid cancer, organism-specific biosystem (from KEGG)
      Thyroid cancer, organism-specific biosystemThyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer- related deaths each year. More than 95% of thyroid carcinomas are derived from follicular cel...
    • Thyroid cancer, conserved biosystem (from KEGG)
      Thyroid cancer, conserved biosystemThyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer- related deaths each year. More than 95% of thyroid carcinomas are derived from follicular cel...
    • Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 10 (TLR10) Cascade, organism-specific biosystemLittle is known about TLR10 ligands. It has been established that the receptor homodimerizes upon binding and signals in an MyD88-dependent manner (Hasan U et al 2005; Nyman T et al 2008). It may als...
    • Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 2 (TLR2) Cascade, organism-specific biosystemTLR2 is involved in recognition of peptidoglycan from gram-positive bacteria, bacterial lipoproteins, mycoplasma lipoprotein and mycobacterial products. It is quite possible that recognition of at le...
    • Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemToll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and in...
    • Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystemToll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria,...
    • Toll Like Receptor 5 (TLR5) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 5 (TLR5) Cascade, organism-specific biosystemTLR5 is the receptor for flagellin, the protein that forms bacterial flagella. Unlike most other Pathogen-Associated Molecular Patterns (PAMPs), flagellin does not undergo any posttranslational modif...
    • Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystemRNA can serve as a danger signal, both in its double-stranded form (that is associated with viral infection), as well as single-stranded RNA (ssRNA). Specifically, guanosine (G)- and uridine (U)-rich...
    • Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystemCpG DNA is an unusual Pathogen-Associated Molecular Pattern (PAMP). Cytosine methylation exists in mammalian but not bacterial cells, and most (but not all) CpG in the mammalian genome is methylated....
    • Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor TLR1:TLR2 Cascade, organism-specific biosystemTLR1 is expressed by monocytes. TLR1 and TLR2 cotranslationally form heterodimeric complexes on the cell surface and in the cytosol. The TLR2:TLR1 complex recognizes Neisserial PorB and Mycobacterial...
    • Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor TLR6:TLR2 Cascade, organism-specific biosystemTLR2 and TLR4 recognize different bacterial cell wall components. While TLR4 is trained onto Gram-negative lipopolysaccharide components, TLR2 - in combination with TLR6 - plays a major role in recog...
    • Toll-Like Receptors Cascades, organism-specific biosystem (from REACTOME)
      Toll-Like Receptors Cascades, organism-specific biosystemIn human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) doma...
    • Toll-like receptor signaling pathway, organism-specific biosystem (from KEGG)
      Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
    • Toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
      Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
    • Toll-like receptor signaling pathway, conserved biosystem (from KEGG)
      Toll-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
    • VEGF signaling pathway, organism-specific biosystem (from KEGG)
      VEGF signaling pathway, organism-specific biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
    • VEGF signaling pathway, conserved biosystem (from KEGG)
      VEGF signaling pathway, conserved biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
    • Vascular smooth muscle contraction, organism-specific biosystem (from KEGG)
      Vascular smooth muscle contraction, organism-specific biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...
    • Vascular smooth muscle contraction, conserved biosystem (from KEGG)
      Vascular smooth muscle contraction, conserved biosystemThe vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regula...
    • mTOR signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
      mTOR signaling pathway, organism-specific biosystem
      mTOR signaling pathway

    Markers

    Genotypes

    Homology

    Clone Names

    • FLJ26075

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding NAS
    Non-traceable Author Statement
    more info
    		  
    MAP kinase kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    PDZ domain binding IDA
    Inferred from Direct Assay
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein complex scaffold IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein serine/threonine kinase activator activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein serine/threonine kinase activity NAS
    Non-traceable Author Statement
    more info
    		  
    protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
    		  
    protein serine/threonine/tyrosine kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    protein tyrosine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    scaffold protein binding IPI
    Inferred from Physical Interaction
    more info
    		  
    Process Evidence Code Pubs
    ERK1 and ERK2 cascade TAS
    Traceable Author Statement
    more info
    		  
    MAPK cascade TAS
    Traceable Author Statement
    more info
    		  
    MyD88-dependent toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    MyD88-independent toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    Ras protein signal transduction TAS
    Traceable Author Statement
    more info
    		  
    TRIF-dependent toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    activation of MAPK activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    activation of MAPKK activity TAS
    Traceable Author Statement
    more info
    		  
    axon guidance TAS
    Traceable Author Statement
    more info
    		  
    epidermal growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    fibroblast growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    innate immune response TAS
    Traceable Author Statement
    more info
    		  
    insulin receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    neurotrophin TRK receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    peptidyl-serine autophosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    positive regulation of cell motility IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein phosphorylation NAS
    Non-traceable Author Statement
    more info
    		  
    regulation of Golgi inheritance TAS
    Traceable Author Statement
    more info
    		 PubMed 
    regulation of early endosome to late endosome transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    regulation of stress-activated MAPK cascade TAS
    Traceable Author Statement
    more info
    		 PubMed 
    small GTPase mediated signal transduction TAS
    Traceable Author Statement
    more info
    		  
    stress-activated MAPK cascade TAS
    Traceable Author Statement
    more info
    		  
    toll-like receptor 10 signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    toll-like receptor 2 signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    toll-like receptor 3 signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    toll-like receptor 4 signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    toll-like receptor 5 signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    toll-like receptor 9 signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    toll-like receptor TLR1:TLR2 signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    toll-like receptor TLR6:TLR2 signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		  
    Golgi apparatus TAS
    Traceable Author Statement
    more info
    		 PubMed 
    cell cortex IEA
    Inferred from Electronic Annotation
    more info
    		  
    cell-cell junction IDA
    Inferred from Direct Assay
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		 PubMed 
    early endosome TAS
    Traceable Author Statement
    more info
    		 PubMed 
    endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		  
    extracellular region NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    focal adhesion TAS
    Traceable Author Statement
    more info
    		 PubMed 
    internal side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  
    late endosome TAS
    Traceable Author Statement
    more info
    		 PubMed 
    microtubule IDA
    Inferred from Direct Assay
    more info
    		  
    mitochondrion TAS
    Traceable Author Statement
    more info
    		 PubMed 
    nucleus TAS
    Traceable Author Statement
    more info
    		 PubMed 
    perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    peroxisomal membrane IDA
    Inferred from Direct Assay
    more info
    		  
    Preferred Names
    dual specificity mitogen-activated protein kinase kinase 2
    Names
    dual specificity mitogen-activated protein kinase kinase 2
    MAPK/ERK kinase 2
    MAP kinase kinase 2
    ERK activator kinase 2
    mitogen-activated protein kinase kinase 2, p45
    NP_109587.1

    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_007996.1 RefSeqGene

      Range
      5001..38808
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_030662.3 → NP_109587.1  dual specificity mitogen-activated protein kinase kinase 2

      Status: REVIEWED

      Source sequence(s)
      AA312322, BC000471
      Consensus CDS
      CCDS12120.1
      UniProtKB/Swiss-Prot
      P36507
      Related
      ENSP00000262948, OTTHUMP00000165826, ENST00000262948, OTTHUMT00000258957
      Conserved Domains (2) summary
      smart00220
      Location:72 – 369
      Blast Score: 617
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl09925
      Location:66 – 396
      Blast Score: 1627
      PKc_like; Protein Kinases, catalytic domain

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000019.9 Reference GRCh37.p10 Primary Assembly

      Range
      4090319..4124126, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000151.1 Alternate HuRef

      Range
      3854052..3888086, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018930.1 Alternate CHM1_1.0

      Range
      4014707..4048001, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    genomic ABBA01056089.1 (22626..56660) None
    genomic AC016586.9 (115357..149164) None
    genomic AMYH01009327.1 (7447..40741) None
    genomic CH471139.2 EAW69262.1
      EAW69263.1
      EAW69264.1
      EAW69265.1
    mRNA AA312322.1 None
    mRNA AK093125.1 BAG52659.1
    mRNA AK126446.1 None
    mRNA AK129586.1 BAC85187.1
    mRNA BC000471.2 AAH00471.1
    mRNA BC018645.2 AAH18645.1
    mRNA BX538081.1 CAD98005.1
    mRNA L11285.1 None
    other-genetic DQ893601.2 ABM84527.1
    other-genetic DQ895060.2 ABM85986.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P36507.1 GenPept UniProtKB/Swiss-Prot:P36507

    Additional Links

    Gene LinkOut

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

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

      Related information

      • Order cDNA clone
        Order cDNA clone
      • 3D structures
        3D structure of a gene
      • BioAssay
        Related PubChem BioAssays
      • BioAssay, by Gene target
        PubChem BioAssays done on the Gene target
      • BioAssay, by Protein Target
        BioAssay, by Protein Target
      • BioProjects
        BioProjects related to a gene
      • BioSystems
        BioSystems
      • Books
        Links between Entrez Gene and 'Books' are established if a GeneID is explicitly referenced in a book.
      • CCDS
        Links from Gene to CCDS are established if a gene encodes a protein sequence that is a member of a Consensus CDS (CCDS).
      • ClinVar
        Related medical variations
      • Conserved Domains
        Conserved Domain Database Links between Entrez Gene and Conserved Domain Database (CDD) are calculated from the domains annotated by the CDD group on Reference Sequence proteins.
      • dbVar
        Link from Gene to dbVar
      • EST
        Link to related EST entry
      • Full text in PMC
        PMC links
      • Full text in PMC_nucleotide
        Full text in PubMedCentral identified from shared sequence links
      • Genome
        Genome records having the gene annotated on corresponding genomic reference sequence.
      • GEO Profiles
        Related GEO
      • GTR
        GTR associated with a gene
      • HomoloGene
        Links between HomoloGene and Gene are provided by the HomoloGene group when a gene is included in a HomoloGene record.
      • Map Viewer
        These links are maintained by the Map Viewer group and are provided when a GeneID is annotated on a map for the same species.
      • MedGen
        Related information in MedGen
      • Nucleotide
        Link to related Nucleotide entry
      • OMIM
        Links between OMIM and Gene are calculated by Gene based on MIM numbers included in the summary and phenotype sections of the Gene record.
      • Probe
        Related Probe entry
      • Protein
        Link to related protein entry
      • PubChem Compound
        PubChem Compounds
      • PubChem Substance
        PubChem Substances
      • PubMed
        Links between Gene and PubMed are the result of the following: 1. Manual curation within NCBI. Part of the process of generating a REVIEWED RefSeq is an analysis of the current literature. Papers that are seminal in defining the gene, its sequence, and its function are added to the record at that time. Alert users point out gaps or errors in papers associated with a Gene record. These messages are reviewed and implemented as required. 2. Integration of information from other public databases. Gene integrates gene-citation from resources external to NCBI such as model organism-specific databases, Gene Ontology (GO), groups curating interactions, and sequence databases. The assumption in using these source is that they report citations specific to a gene in a known species. Gene does not process citations from OMIM automatically, because many of citations in OMIM refer to studies of genes in species other than human.
      • PubMed (GeneRIF)
        GeneRIF -- Gene Reference Into Function Staff of the Index Section in the National Library of Medicine review the current literature. When they find articles focused on the structure and function of a gene, they write a brief summary of the impact of the paper and make the connection between the citation (PubMed) and Gene. An interface exists for interested users to submit such data as well. http://www.ncbi.nlm.nih.gov/projects/GeneRIF/GeneRIFhelp.html
      • PubMed (OMIM)
        Links are provided when Gene has a link to a record in OMIM, and OMIM explicitly cites these publications in PubMed.
      • PubMed(nucleotide/PMC)
        Citations in PubMed identified from shared sequence and PMC links.
      • RefSeq Proteins
        Link to Protein RefSeqs
      • RefSeq RNAs
        Link to Nucleotide RefSeq RNAs
      • RefSeqGene
        Link to Nucleotide RefSeqGenes
      • SNP
        Related SNP records
      • SNP: GeneView
        SNPs linked from GeneView
      • SNP: Genotype
        Gene Genotype Report
      • SNP: VarView
        Related Clinical SNP
      • Taxonomy
        Link to related taxonomy entry
      • UniGene
        Links are provided between Gene and UniGene when both databases calculate links to the same mRNA record (gi).
      • UniSTS
        Related UniSTS records

      Links to other resources

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