Dual-specificity mitogen-activated protein kinase kinase 3-like

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• ATP binding Source: UniProtKB-KW
• MAP kinase kinase activity Source: RGDInferred from sequence orthologyⁱ
  • "Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor necrosis factor-induced cytokine expression."
    Wysk M., Yang D.D., Lu H.T., Flavell R.A., Davis R.J.
    Proc. Natl. Acad. Sci. U.S.A. 96:3763-3768(1999) [PubMed] [Europe PMC] [Abstract]
  • "Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3 (Mkk3)-deficient mice."
    Lu H.T., Yang D.D., Wysk M., Gatti E., Mellman I., Davis R.J., Flavell R.A.
    EMBO J. 18:1845-1857(1999) [PubMed] [Europe PMC] [Abstract]
  • "Purification and identification of a major activator for p38 from osmotically shocked cells: activation of mitogen-activated protein kinase kinase 6 by osmotic shock, tumor necrosis factor-alpha, and H2O2."
    Moriguchi T., Toyoshima F., Gotoh Y., Iwamatsu A., Irie K., Mori E., Kuroyanagi N., Hagiwara M., Matsumoto K., Nishida E.
    J. Biol. Chem. 271:26981-26988(1996) [PubMed] [Europe PMC] [Abstract]
• protein kinase binding Source: RGDInferred from sequence orthologyⁱ
  • "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2."
    Chen Z., Cobb M.H.
    J. Biol. Chem. 276:16070-16075(2001) [PubMed] [Europe PMC] [Abstract]
  • "Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation."
    Jung H., Seong H.A., Ha H.
    J. Biol. Chem. 283:34541-34553(2008) [PubMed] [Europe PMC] [Abstract]
• protein serine/threonine kinase activity Source: UniProtKB-KW

GO - Biological processⁱ

• activation of MAPK activity Source: RGDInferred from sequence orthologyⁱ
  • "The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy."
    Liao P., Georgakopoulos D., Kovacs A., Zheng M., Lerner D., Pu H., Saffitz J., Chien K., Xiao R.P., Kass D.A., Wang Y.
    Proc. Natl. Acad. Sci. U.S.A. 98:12283-12288(2001) [PubMed] [Europe PMC] [Abstract]
  • "Role of the JIP4 scaffold protein in the regulation of mitogen-activated protein kinase signaling pathways."
    Kelkar N., Standen C.L., Davis R.J.
    Mol. Cell. Biol. 25:2733-2743(2005) [PubMed] [Europe PMC] [Abstract]
• cardiac muscle contraction Source: RGDInferred from sequence orthologyⁱ
  • "The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy."
    Liao P., Georgakopoulos D., Kovacs A., Zheng M., Lerner D., Pu H., Saffitz J., Chien K., Xiao R.P., Kass D.A., Wang Y.
    Proc. Natl. Acad. Sci. U.S.A. 98:12283-12288(2001) [PubMed] [Europe PMC] [Abstract]
• cellular response to lipopolysaccharide Source: RGD <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Lipopolysaccharide induces CYP2E1 in astrocytes through MAP kinase kinase-3 and C/EBPbeta and -delta."
    Kelicen P., Tindberg N.
    J. Biol. Chem. 279:15734-15742(2004) [PubMed] [Europe PMC] [Abstract]
• cellular response to sorbitol Source: RGD <p>Inferred from Expression Pattern</p> <p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "Activation of ASK1, downstream MAPKK and MAPK isoforms during cardiac ischaemia."
    Harding S.J., Browne G.J., Miller B.W., Prigent S.A., Dickens M.
    Biochim. Biophys. Acta 1802:733-740(2010) [PubMed] [Europe PMC] [Abstract]
• cellular response to vascular endothelial growth factor stimulus Source: RGDInferred from sequence orthologyⁱ
  • "miR-20a represses endothelial cell migration by targeting MKK3 and inhibiting p38 MAP kinase activation in response to VEGF."
    Pin A.L., Houle F., Guillonneau M., Paquet E.R., Simard M.J., Huot J.
    Angiogenesis 15:593-608(2012) [PubMed] [Europe PMC] [Abstract]
• heart development Source: RGDInferred from expression patternⁱ
  • "Expression of mitogen-activated protein kinase pathways during postnatal development of rat heart."
    Kim S.O., Irwin P., Katz S., Pelech S.L.
    J. Cell. Biochem. 71:286-301(1998) [PubMed] [Europe PMC] [Abstract]
• inflammatory response Source: RGDInferred from sequence orthologyⁱ
  • "Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor necrosis factor-induced cytokine expression."
    Wysk M., Yang D.D., Lu H.T., Flavell R.A., Davis R.J.
    Proc. Natl. Acad. Sci. U.S.A. 96:3763-3768(1999) [PubMed] [Europe PMC] [Abstract]
  • "Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3 (Mkk3)-deficient mice."
    Lu H.T., Yang D.D., Wysk M., Gatti E., Mellman I., Davis R.J., Flavell R.A.
    EMBO J. 18:1845-1857(1999) [PubMed] [Europe PMC] [Abstract]
• MAPK cascade Source: RGDInferred from sequence orthologyⁱ
  • "Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor necrosis factor-induced cytokine expression."
    Wysk M., Yang D.D., Lu H.T., Flavell R.A., Davis R.J.
    Proc. Natl. Acad. Sci. U.S.A. 96:3763-3768(1999) [PubMed] [Europe PMC] [Abstract]
  • "Purification and identification of a major activator for p38 from osmotically shocked cells: activation of mitogen-activated protein kinase kinase 6 by osmotic shock, tumor necrosis factor-alpha, and H2O2."
    Moriguchi T., Toyoshima F., Gotoh Y., Iwamatsu A., Irie K., Mori E., Kuroyanagi N., Hagiwara M., Matsumoto K., Nishida E.
    J. Biol. Chem. 271:26981-26988(1996) [PubMed] [Europe PMC] [Abstract]
• negative regulation of hippo signaling Source: RGDInferred from sequence orthologyⁱ
  • "Regulation of Hippo signalling by p38 signalling."
    Huang D., Li X., Sun L., Huang P., Ying H., Wang H., Wu J., Song H.
    J Mol Cell Biol 8:328-337(2016) [PubMed] [Europe PMC] [Abstract]
• p38MAPK cascade Source: RGDInferred from sequence orthologyⁱ
  • "miR-20a represses endothelial cell migration by targeting MKK3 and inhibiting p38 MAP kinase activation in response to VEGF."
    Pin A.L., Houle F., Guillonneau M., Paquet E.R., Simard M.J., Huot J.
    Angiogenesis 15:593-608(2012) [PubMed] [Europe PMC] [Abstract]
• positive regulation of blood vessel endothelial cell migration Source: RGDInferred from sequence orthologyⁱ
  • "miR-20a represses endothelial cell migration by targeting MKK3 and inhibiting p38 MAP kinase activation in response to VEGF."
    Pin A.L., Houle F., Guillonneau M., Paquet E.R., Simard M.J., Huot J.
    Angiogenesis 15:593-608(2012) [PubMed] [Europe PMC] [Abstract]
• positive regulation of nitric-oxide synthase biosynthetic process Source: RGD <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Both p38alpha(MAPK) and JNK/SAPK pathways are important for induction of nitric-oxide synthase by interleukin-1beta in rat glomerular mesangial cells."
    Guan Z., Buckman S.Y., Springer L.D., Morrison A.R.
    J. Biol. Chem. 274:36200-36206(1999) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein kinase activity Source: RGDInferred from sequence orthologyⁱ
  • "Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha."
    Lim S., Jin K., Friedman E.
    J. Biol. Chem. 277:25040-25046(2002) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein phosphorylation Source: RGDInferred from direct assayⁱ
  • "Activation of ASK1, downstream MAPKK and MAPK isoforms during cardiac ischaemia."
    Harding S.J., Browne G.J., Miller B.W., Prigent S.A., Dickens M.
    Biochim. Biophys. Acta 1802:733-740(2010) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription, DNA-templated Source: RGDInferred from sequence orthologyⁱ
  • "Mirk protein kinase is activated by MKK3 and functions as a transcriptional activator of HNF1alpha."
    Lim S., Jin K., Friedman E.
    J. Biol. Chem. 277:25040-25046(2002) [PubMed] [Europe PMC] [Abstract]
• regulation of cytokine biosynthetic process Source: RGDInferred from sequence orthologyⁱ
  • "Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for tumor necrosis factor-induced cytokine expression."
    Wysk M., Yang D.D., Lu H.T., Flavell R.A., Davis R.J.
    Proc. Natl. Acad. Sci. U.S.A. 96:3763-3768(1999) [PubMed] [Europe PMC] [Abstract]
• response to ischemia Source: RGDInferred from expression patternⁱ
  • "Activation of ASK1, downstream MAPKK and MAPK isoforms during cardiac ischaemia."
    Harding S.J., Browne G.J., Miller B.W., Prigent S.A., Dickens M.
    Biochim. Biophys. Acta 1802:733-740(2010) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Proteomic databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

GO - Molecular functionⁱ

• protein kinase binding Source: RGDInferred from sequence orthologyⁱ
  • "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2."
    Chen Z., Cobb M.H.
    J. Biol. Chem. 276:16070-16075(2001) [PubMed] [Europe PMC] [Abstract]
  • "Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation."
    Jung H., Seong H.A., Ha H.
    J. Biol. Chem. 283:34541-34553(2008) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Region

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequenceⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

        10         20         30         40         50
MESPAASPPA SLPQTKGKSK RKRDLRISCV SKPPVSNPTP PRNLDSRTFI 
        60         70         80         90        100
TIGDRNFEVE ADDLVTISEL GRGAYGVVEK VRHAQSGTIM AVKRIRATVN 
       110        120        130        140        150
SQEQKRLLMD LDINMRTVDC FYTVTFYGAL FREGDVWICM ELMDTSLDKF 
       160        170        180        190        200
YRKVLEKNMK IPEDILGEIA VSIVRALEHL HSKLSVIHRD VKPSNVLINK 
       210        220        230        240        250
EGHVKMCDFG ISGYLVDSVA KTMDAGCKPY MAPERINPEL NQKGYNVKSD 
       260        270        280        290        300
VWSLGITMIE MAILRFPYES WGTPFQQLKQ VVEEPSPQLP ADQFSPEFVD 
       310        320        330        340 
FTSQCLRKNP AERMSYLELM EHPFFTLHKT KKTDIAAFVK EILGEDS    

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ