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FLASH GENE
Symbol MAP3K11 contributors: mct/ - updated : 20-05-2016
HGNC name mitogen-activated protein kinase kinase kinase 11
HGNC id 6850
Location 11q13.1      Physical location : 65.365.226 - 65.381.720
Synonym name
  • mixed lineage kinase 3
  • dual (tyr and Ser/thr) specificity src-homology three (SH3) domain-containing proline-rich kinase
  • SH3 domain-containing proline-rich kinase
  • Src-homology 3 domain-containing proline-rich kinase
  • Synonym symbol(s) PTK1, MLK3, SPRK, MLK-3, MEKK11, MGC17114
    EC.number 2.7.11.25
    DNA
    TYPE functioning gene
    STRUCTURE 16.50 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - PGA@ - FTH1 - SCGB1A1 - AHNAK - ROM1 - SLC3A2 - CHRM1 - COX8A - MARK2 - FKBP2 - PLCB2 - [PYGM PYGM ,SF1 ] - FAU - CAPN1 - [MAP3K11 ,RELA ] - (D11S1956E ,D11S951E ) - FOSL1 - (SLC29A2 ,D11S913 ) - ACTN3 - PC - D11S703 - GSTP1 - D11S987 - qter
    Physical map
    TM7SF2 11q13 transmembrane 7 superfamily member 2 C11orf5 11q13 chromosome 11 open reading frame 5 FAU 11q12-q13.1 Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV) ubiquitously expressed (fox derived); ribosomal protein S30 MRPL49 11q13 mitochondrial ribosomal protein L49 HRD1 11q13 HRD1 protein LOC387778 11 similar to p33 ringo LOC387779 11 similar to Phosphoglycerate mutase 1 (Phosphoglycerate mutase isozyme B) (PGAM-B) (BPG-dependent PGAM 1) CAPN1 11q13 calpain 1, (mu/I) large subunit LOC387780 11 similar to solute carrier family 22 member 6; organic cationic transporter-like 1; solute carrier family 22 (organic anion transporter), member 6 POLA2 11q13.1 polymerase (DNA-directed), alpha (70kD) CDC42EP2 11q13 CDC42 effector protein (Rho GTPase binding) 2 DPF2 11q13 D4, zinc and double PHD fingers family 2 TIGD3 11q13.2 tigger transposable element derived 3 LOC283130 11q13.1 hypothetical protein LOC283130 FKSG44 11q13 hypothetical protein FKSG44 LOC387781 11 similar to UBIQUITIN-LIKE PROTEIN FUBI SCYL1 11q11-q12 SCY1-like 1 (S. cerevisiae) LTBP3 11q12 latent transforming growth factor beta binding protein 3 MTVR1 11q23 Mouse Mammary Turmor Virus Receptor homolog 1 SSSCA1 11q13.1 Sjogren's syndrome/scleroderma autoantigen 1 DKFZp762C186 11q13.1 tangerin KCNK7 11q13 potassium channel, subfamily K, member 7 MAP3K11 11q13.3 mitogen-activated protein kinase kinase kinase 11 RELA 11q13 v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) SIPA1 11q13.3 signal-induced proliferation-associated gene 1 LOC387782 11 LOC387782 HTATIP 11q13 HIV-1 Tat interactive protein, 60kDa AYP1 11q13.1 AYP1 protein LOC390211 11 similar to Keratin, type II cytoskeletal 8 (Cytokeratin 8) (K8) (CK 8) LOC91056 11q13.1 hypothetical protein BC004895 OVOL1 11q13 ovo-like 1(Drosophila) FLJ30934 11q13.1 hypothetical protein FLJ30934 CFL1 11q13 cofilin 1 (non-muscle) MUS81 11q13 MUS81 endonuclease homolog (yeast) EFEMP2 11q13 EGF-containing fibulin-like extracellular matrix protein 2 CTSW 11q13.1 cathepsin W (lymphopain) FIBP 11q13.1 fibroblast growth factor (acidic) intracellular binding protein DIPA 11q12.1 hepatitis delta antigen-interacting protein A FOSL1 11q13 FOS-like antigen 1 P5326 11q13.1 hypothetical protein p5326 DRAP1 11q13.3 DR1-associated protein 1 (negative cofactor 2 alpha) FLJ32880 11q13.1 hypothetical protein FLJ32880 SART1 11q12-q13 squamous cell carcinoma antigen recognised by T cells MGC11102 11q13.1 hypothetical protein MGC11102 BANF1 11q13.1 barrier to autointegration factor 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3574 92 847 - 2010 20514022
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
     salivary gland   highly
    Lymphoid/Immunespleen   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES basic
    STRUCTURE
    motifs/domains
  • glycine rich and N-terminal Src-homology 3 (SH3) domain (is autoinhibited through its SH3 domain)
  • a kinase domain
  • a leucine zipper
  • a Cdc42/Rac interactive binding (CRIB) motif
  • a catalytic domain (in MLK1 domain)
  • C-terminal proline–serine–threonine rich domain, with signature sequences of both Ser/Thr and Tyr kinases in the catalytic domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Map3k11
    Homologene
    FAMILY
  • protein kinase superfamily
  • STE Ser/Thr protein kinase family
  • MAP (mitogen activated protein) kinase family
  • mixed-lineage kinase family
  • CATEGORY enzyme , receptor membrane serine/threonine kinase
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    basic FUNCTION
  • serine/threonine protein kinase that may contribute to promoting microtubule instability, a hallmark of M phase entry
  • contributing to the TNF signaling pathway that activates JNK
  • required for mitogen activation of BRAF and cell proliferation
  • activates multiple mitogen-activated protein kinase (MAPK) pathways in response to growth factors, stresses and the pro-inflammatory cytokine, tumor necrosis factor (TNF)
  • regulates the MAPKinase pathway activating ERK, MAPK14 and JNK, in response to extracellular signals
  • scaffolding protein, involved in the formation of a multiprotein complex containing MAP3K11/BRAF/RAF1
  • required for optimal activation of stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) signaling by TNFA
  • activates multiple MAPK pathways, including the JNK (c-Jun N-terminal kinase) pathway
  • crucial requirement in the migration of invasive breast cancer cells
  • induces luminal repopulation and suppresses the expression of the pro-apoptotic protein BCL2L11 in breast cancer
  • having both a proliferative and antiapoptotic role in the acquisition of a malignant phenotype in mammary epithelial cells
  • is an important regulator of MMP expression and invasion in ovarian cancer cells
  • plays a crucial role in compromising mitochondrial integrity and functions as a proapoptotic competence factor in the early stages of cytokine-induced pancreatic beta cell death
  • promotes saturated fatty acid-induced JNK activation and diet-induced metabolic dysfunction.
  • mitogen-activated protein kinase kinase kinase that activates multiple mitogen-activated protein kinase pathways and has been implicated in regulating proliferation in several cell types
  • is a critical factor controlling the activity of kinase networks that control the cellular responses to different concentrations of ROS
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • JNK cascade
  • MAP3K11-PIN1 signaling cascade plays a critical role in regulating the cell cycle, centrosome numbers, and oncogenesis
  • a component
  • MAP3K11-JNK-AP1 signaling is critical for breast cancer cell migration and invasion
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting specifically with the GTP bound form of RAC and CDC42, regulators of JNK pathway
  • interacting with GSK3B (cell death induced by GSK3B was mediated by MAP3K11 in a manner dependent on its phosphorylation of the specific residues within the C-terminal domain by GSK3B)
  • activation of MAP3K11 specifically by FGD1/CDC42 is important for skeletal mineralization
  • associates with and uniquely phosphorylates S138 within the PPIase domain of PIN1
  • promotes neointima formation through increased activation of the RHOA pathway in vascular smooth muscle cells
  • direct interaction between PRKAA1 subunit and MAP3K11, and MAP3K11 serves as a common upstream kinase of AMPK and JNK and functions as a direct upstream kinase for AMPK independent of STK11
  • serves as a common upstream kinase of PRKAA1 and JNK and functions as a direct upstream kinase for PRKAA1 independent of STK11
  • ERBB2 activation inhibits the pro-apoptotic function of MAP3K11, which plays a mechanistic role in mediating anti-tumor activities of ERBB2-directed therapies
  • cell & other
    REGULATION
    activated by phosphorylation
    Other activation of MAP3K11 specifically by FGD1/CDC42 is important for skeletal mineralization
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in MSI gastrointestinal carcinomas
    tumoral     --over  
    in breast cancer cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    therapeutics that target MAP3K11 or PIN1 could prove beneficial for a subset of cancers where the MAP3K11-PIN1 pathway is dysregulated
    cancerreproductivebreast
    may be an important therapeutic target for the treatment of invasive breast cancer
    ANIMAL & CELL MODELS