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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

KIAA1804 Gene

protein-coding   GIFtS: 43
GCID: GC01P233463

Mixed Lineage Kinase 4


  Search for KIAA1804
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Mixed Lineage Kinase 42 3     dJ862P8.32
EC 2.7.11.253 8     Mitogen-Activated Protein Kinase Kinase Kinase MLK42
MLK42     EC 2.7.118
RP5-862P8.22     

External Ids:    Entrez Gene: 844512   Ensembl: ENSG000001436747   OMIM: 6147935   UniProtKB: Q5TCX83   

Export aliases for KIAA1804 gene to outside databases

Previous GC identifers: GC01P231725 GC01P229023 GC01P229791 GC01P230547 GC01P229770 GC01P231530 GC01P203953


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

GeneCards Summary for KIAA1804 Gene: 
KIAA1804 is a protein-coding gene. GO annotations related to this gene include MAP kinase kinase kinase activity and protein homodimerization activity. An important paralog of this gene is FPGT-TNNI3K.

UniProtKB/Swiss-Prot: M3KL4_HUMAN, Q5TCX8
Function: Negative regulator of TLR4 signaling. Does not activate JNK1/MAPK8 pathway, p38/MAPK14, nor ERK2/MAPK1
pathways




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000001.10  NC_018912.2  NT_167186.1  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the KIAA1804 gene promoter:
         AhR   ER-alpha   Tal-1   Lmo2   AP-4   NF-E2 p45   E47   Max   NF-E2   
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search SABiosciences Chromatin IP Primers for KIAA1804

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat KIAA1804


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

Entrez Gene cytogenetic band: 1q42   Ensembl cytogenetic band:  1q42.2   

KIAA1804 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
KIAA1804 gene location

GeneLoc information about chromosome 1         GeneLoc Exon Structure

GeneLoc location for GC01P233463:  view genomic region     (about GC identifiers)

Start:
233,463,514 bp from pter      End:
233,520,894 bp from pter
Size:
57,381 bases      Orientation:
plus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: M3KL4_HUMAN, Q5TCX8 (See protein sequence)
Recommended Name: Mitogen-activated protein kinase kinase kinase MLK4  
Size: 1036 amino acids; 113957 Da
Cofactor: Magnesium (By similarity)
Subunit: Homodimer (By similarity). Interacts with TLR4
Sequence caution: Sequence=BAB47433.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
Secondary accessions: B2RN34 Q5TCX7 Q5TCX9 Q8WWN1 Q8WWN2 Q96JM1
Alternative splicing: 3 isoforms:  Q5TCX8-1   Q5TCX8-2   Q5TCX8-3   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for KIAA1804: NX_Q5TCX8

Explore proteomics data for KIAA1804 at MOPED 

Post-translational modifications:

  • UniProtKB: Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation
    (By similarity)
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q5TCX8

  • 4/8 DME Specific Peptides for KIAA1804 (Q5TCX8) (see all 8)
     SGDEGWW  ILHRDLK  WMAPEVI  EARLFAML 

    KIAA1804 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    KIAA1804 Protein Expression
    REFSEQ proteins: NP_115811.2  
    ENSEMBL proteins: 
     ENSP00000355582   ENSP00000355583   ENSP00000355581  

    Human Recombinant Protein Products for KIAA1804: 
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    Browse Proteins at Cloud-Clone Corp. 

    Gene Ontology (GO): 1 cellular component term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005575cellular_component ND--

    KIAA1804 for ontologies           About GeneDecksing



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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    5/9 InterPro protein domains (see all 9):
     IPR017441 Protein_kinase_ATP_BS
     IPR016231 MAPKKK9/10/11
     IPR001245 Ser-Thr/Tyr_kinase_cat_dom
     IPR011009 Kinase-like_dom
     IPR008271 Ser/Thr_kinase_AS

    Graphical View of Domain Structure for InterPro Entry Q5TCX8

    ProtoNet protein and cluster: Q5TCX8

    UniProtKB/Swiss-Prot: M3KL4_HUMAN, Q5TCX8
    Similarity: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase
    subfamily
    Similarity: Contains 1 protein kinase domain
    Similarity: Contains 1 SH3 domain


    KIAA1804 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: M3KL4_HUMAN, Q5TCX8
    Function: Negative regulator of TLR4 signaling. Does not activate JNK1/MAPK8 pathway, p38/MAPK14, nor ERK2/MAPK1
    pathways
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Enzyme regulation: Homodimerization via the leucine zipper domains is required for autophosphorylation and
    subsequent activation (By similarity)

         Enzyme Numbers (IUBMB): EC 2.7.11.251 2 EC 2.7.112

         Gene Ontology (GO): 5/7 molecular function terms (GO ID links to tree view) (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004709MAP kinase kinase kinase activity IEA--
    GO:0004713protein tyrosine kinase activity IEA--
    GO:0005515protein binding ----
    GO:0005524ATP binding IEA--
         
    KIAA1804 for ontologies           About GeneDecksing


    Phenotypes:
         5 GenomeRNAi human phenotypes for KIAA1804:
     Decreased focal adhesion (FA)   Decreased substrate adherent c  Increased G1 DNA content  Increased cell death in HCC-19 
     Increased colony dispersion (i 

    Animal Models:
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    SwitchGear 3'UTR luciferase reporter plasmidKIAA1804 3' UTR sequence
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    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
    About This Section



    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for KIAA1804

    STRING Interaction Network Preview (showing 2 interactants - click image to see more details)

    2 Interacting proteins for KIAA1804 (Q5TCX83 ENSP000003555834) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    MAP3K10Q027793, ENSP000002530554I2D: score=3 STRING: ENSP00000253055
    YWHABP319463, ENSP000003001614I2D: score=1 STRING: ENSP00000300161
    About this table

    Gene Ontology (GO): 3 biological process terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006468protein phosphorylation ISS--
    GO:0007257activation of JUN kinase activity ISS--
    GO:0046777protein autophosphorylation ISS--

    KIAA1804 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section
    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for KIAA1804 (M3KL4)

    Search CenterWatch for drugs/clinical trials and news about KIAA1804 / M3KL4

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for KIAA1804 gene: 
    NM_032435.2  

    Unigene Cluster for KIAA1804:

    Mixed lineage kinase 4
    Hs.547779  [show with all ESTs]
    Unigene Representative Sequence: NM_032435
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000366623(uc001hvs.1) ENST00000366624(uc001hvt.4) ENST00000366622(uc001hvu.4)

    miRNA
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    hsa-miR-411* hsa-miR-379* hsa-miR-15a hsa-miR-30d hsa-miR-570 hsa-miR-10b* hsa-miR-374c hsa-miR-30a
    SwitchGear 3'UTR luciferase reporter plasmidKIAA1804 3' UTR sequence
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    Additional mRNA sequence: 

    AB058707.1 AJ311797.1 AJ311798.1 AK309811.1 BC136648.1 BC136649.1 

    3 DOTS entries:

    DT.408499  DT.100747405  DT.97838553 

    24/55 AceView cDNA sequences (see all 55):

    AW296283 BE464090 AI522215 AL135712 BU679677 AL710353 BX281297 AI671270 
    AW241601 AI936383 BG824246 BU685509 AI809005 AJ311798 AA961822 BI963837 
    NM_032435 BQ776861 AA459127 AW473218 AW241448 BM788456 BU619993 AA458908 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    KIAA1804 expression in normal human tissues (normalized intensities)      KIAA1804 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    KIAA1804 Expression
    About this image


    KIAA1804 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/2 selected tissues (see all 2) fully expand
     
     Testis (Reproductive System)
             Pre-Sertoli Cells Testis Cord
     
     Kidney (Urinary System)
             Ureteric Bud

    See KIAA1804 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for KIAA1804

    SOURCE GeneReport for Unigene cluster: Hs.547779
        SABiosciences Custom PCR Arrays for KIAA1804
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    In Situ
    Assay Products:
     

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

    This gene was present in the common ancestor of animals.

    Orthologs for KIAA1804 gene from 5/13 species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia BC0218911 , 5 cDNA sequence BC0218911, 5 74.76(n)1
    72.61(a)1
      8 (73.65 cM)5
    2348781  NM_145608.21  NP_663583.21 
     1259104505 
    chicken
    (Gallus gallus)
    Aves LOC4285861 mitogen-activated protein kinase kinase kinase MLK4-like 71.53(n)
    69.96(a)
      428586  XM_003640952.1  XP_003641000.1 
    lizard
    (Anolis carolinensis)
    Reptilia --
    --
    64(a)
    1 ↔ 1
    1(220625817-220682809)
    zebrafish
    (Danio rerio)
    Actinopterygii si:ch211-120p12.31 si:ch211-120p12.3 63.92(n)
    64.84(a)
      561518  XM_684924.2  XP_690016.2 
    fruit fly
    (Drosophila melanogaster)
    Insecta slpr3 JNK cascade protein kinase 49(a)   7D17   --


    ENSEMBL Gene Tree for KIAA1804 (if available)
    TreeFam Gene Tree for KIAA1804 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for KIAA1804 gene
    FPGT-TNNI3K2  MAP3K122  MAP3K112  RAF12  KSR22  KSR12  MOS2  BRAF2  
    MAP3K92  MAP3K102  ARAF2  MAP3K72  TNNI3K2  ZAK2  MAP3K132  ILK2  

    KIAA1804 for paralogs           About GeneDecksing



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

    10/1410 SNPs in KIAA1804 are shown (see all 1410)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 1 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1919259531,2
    --233461597(+) TCCAAA/TTTTGA 1 -- us2k10--------
    rs1843096671,2
    --233461724(+) CCATAA/GCCACT 1 -- us2k10--------
    rs1510517151,2
    --233461890(+) AGACAC/TAATGC 1 -- us2k10--------
    rs351769431,2
    C,F--233461946(+) ATATAT/CATGCA 1 -- us2k18Minor allele frequency- C:0.16NA WA 250
    rs1905838801,2
    --233462038(+) TACTTC/TAAATA 1 -- us2k10--------
    rs1402973991,2
    --233462068(+) CTAATA/GTAATG 1 -- us2k10--------
    rs1822992651,2
    --233462153(+) AAACAC/TTTTTG 1 -- us2k10--------
    rs1844891221,2
    --233462233(+) AAAAAC/TCCTAT 1 -- us2k10--------
    rs1503418491,2
    --233462416(+) TCCTAG/TCCTCA 1 -- us2k10--------
    rs1451044611,2
    --233462512(+) TTTTAG/TAATTT 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for KIAA1804 (233463514 - 233520894 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for KIAA1804:    About this table     
    Variant IDTypeSubtypePubMed ID
    esv273887CNV Insertion20981092
    esv2431778CNV Insertion19546169
    esv269665CNV Insertion20981092
    esv22442CNV Gain19812545

    SABiosciences Cancer Mutation PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

    KIAA1804 for disorders           About MalaCards
    OMIM gene information: 614793    OMIM disorders: --


    KIAA1804 for disorders           About GeneDecksing

    Genetic Association Database (GAD): KIAA1804
    Human Genome Epidemiology (HuGE) Navigator: KIAA1804 (1 document)

    Export disorders for KIAA1804 gene to outside databases

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

    PubMed articles for KIAA1804 gene, integrated from 9 sources (see all 18):
    (articles sorted by number of sources associating them with KIAA1804)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. MLK4 has negative effect on TLR4 signaling. (PubMed id 21602844)1, 2 Seit-Nebi A....Han J. (2012)
    2. The DNA sequence and biological annotation of human chromosome 1. (PubMed id 16710414)1, 2 Gregory S.G.... Bentley D.R. (2006)
    3. Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. (PubMed id 11347906)1, 2 Nagase T.... Ohara O. (2001)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 84451 AceView: KIAA1804 Ensembl:ENSG00000143674 euGenes: HUgn84451

    (According to HUGE)
    About This Section
    HUGE: KIAA1804

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

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for KIAA1804 gene:
    Search GeneIP for patents involving KIAA1804

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



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
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    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 3 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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