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    MAP4K5 mitogen-activated protein kinase kinase kinase kinase 5 [ Homo sapiens (human) ]

    Gene ID: 11183, updated on 10-Dec-2024

    Summary

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    Official Symbol
    MAP4K5provided by HGNC
    Official Full Name
    mitogen-activated protein kinase kinase kinase kinase 5provided by HGNC
    Primary source
    HGNC:HGNC:6867
    See related
    Ensembl:ENSG00000012983 MIM:604923; AllianceGenome:HGNC:6867
    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
    KHS; GCKR; KHS1; MAPKKKK5
    Summary
    This gene encodes a member of the serine/threonine protein kinase family, that is highly similar to yeast SPS1/STE20 kinase. Yeast SPS1/STE20 functions near the beginning of the MAP kinase signal cascades that is essential for yeast pheromone response. This kinase was shown to activate Jun kinase in mammalian cells, which suggested a role in stress response. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in endometrium (RPKM 13.1), ovary (RPKM 10.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MAP4K5 in Genome Data Viewer
    Location:
    14q22.1
    Exon count:
    36
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (50418521..50561126, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (44624744..44767297, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (50885239..50999287, complement)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene L-2-hydroxyglutarate dehydrogenase Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:50766206-50766899 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5720 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5721 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8355 Neighboring gene microRNA 4504 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:50802261-50802882 Neighboring gene distal membrane arm assembly component 2 like Neighboring gene Sharpr-MPRA regulatory region 14884 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8356 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8357 Neighboring gene ReSE screen-validated silencer GRCh37_chr14:50832542-50832707 Neighboring gene cyclin dependent kinase like 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:50838523-50839022 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:50838021-50838522 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:50863511-50864010 Neighboring gene zinc finger protein 678 pseudogene Neighboring gene uncharacterized LOC124903312 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8358 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8359 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5723 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:51026957-51027456 Neighboring gene atlastin GTPase 1 Neighboring gene small nuclear ribonucleoprotein polypeptide G pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8360 Neighboring gene RNA, 7SL, cytoplasmic 452, pseudogene Neighboring gene salvador family WW domain containing protein 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Prognostic and Functional Significance of MAP4K5 in Pancreatic Cancer. Wang OH, et al. PLoS One, 2016. PMID 27023625, Free PMC Article
    2. The -822G/A polymorphism in the promoter region of the MAP4K5 gene is associated with reduced risk of type 2 diabetes in Chinese Hans from Shanghai. Gu Y, et al. J Hum Genet, 2006. PMID 16699725
    3. A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase. Tung RM, et al. Oncogene, 1997 Feb 13. PMID 9038372
    4. TNF-mediated activation of the stress-activated protein kinase pathway: TNF receptor-associated factor 2 recruits and activates germinal center kinase related. Shi CS, et al. J Immunol, 1999 Sep 15. PMID 10477597
    5. GCKR links the Bcr-Abl oncogene and Ras to the stress-activated protein kinase pathway. Shi CS, et al. Blood, 1999 Feb 15. PMID 9949177

    See all (59) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MAP4K5 expression is decreased or lost in majority of pancreatic ductal adenocarcinoma.
      Title: Prognostic and Functional Significance of MAP4K5 in Pancreatic Cancer.
    2. TNF signaling leads to oligomerization, ubiquitination, and activation of GCKR and activation of the SAPK pathway in a manner that depends upon TRAF2 polyubiquitination and oligomerization and Ubc13 function
      Title: Tumor necrosis factor (TNF)-induced germinal center kinase-related (GCKR) and stress-activated protein kinase (SAPK) activation depends upon the E2/E3 complex Ubc13-Uev1A/TNF receptor-associated factor 2 (TRAF2).
    3. The -822G/A polymorphism in the promoter region of the MAP4K5 gene is associated with reduced risk of type 2 diabetes in Han Chinese from Shanghai.
      Title: The -822G/A polymorphism in the promoter region of the MAP4K5 gene is associated with reduced risk of type 2 diabetes in Chinese Hans from Shanghai.
    Submit: New GeneRIF Correction

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Common genetic variation and performance on standardized cognitive tests.
    EBI GWAS Catalog
    Genome-wide association study of periodontal health measured by probing depth in adults ages 18-49 years.
    EBI GWAS Catalog
    Lupus nephritis susceptibility Loci in women with systemic lupus erythematosus.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3-phosphoinositide-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables AMP-activated protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables MAP kinase kinase kinase kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables Rho-dependent protein serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables eukaryotic translation initiation factor 2alpha kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AS1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AS121 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AT120 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AXS139 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2BS14 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2BS36 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3S10 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3S28 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3S57 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T11 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T3 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T45 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3T6 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H4S1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ribosomal protein S6 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    mitogen-activated protein kinase kinase kinase kinase 5
    Names
    MAPK/ERK kinase kinase kinase 5
    MEK kinase kinase 5
    MEKKK 5
    germinal center kinase-related
    kinase homologous to SPS1/STE20
    NP_006566.2
    NP_942089.1
    XP_006720076.1
    XP_011534679.1
    XP_011534682.1
    XP_047286846.1
    XP_047286847.1
    XP_047286848.1
    XP_047286849.1
    XP_047286850.1
    XP_047286851.1
    XP_047286852.1
    XP_047286853.1
    XP_047286854.1
    XP_054231276.1
    XP_054231277.1
    XP_054231278.1
    XP_054231279.1
    XP_054231280.1
    XP_054231281.1
    XP_054231282.1
    XP_054231283.1

    NCBI Reference Sequences (RefSeq)

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    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.

    mRNA and Protein(s)

    1. NM_006575.6 → NP_006566.2  mitogen-activated protein kinase kinase kinase kinase 5

      See identical proteins and their annotated locations for NP_006566.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 2. Variants 1 and 2 encode the same isoform.
      Source sequence(s)
      AK124738, BC036013, CN343360
      Consensus CDS
      CCDS91875.1
      UniProtKB/Swiss-Prot
      A0A0A0MQR1, A0A804HIS2, Q8IYF6, Q9Y4K4
      UniProtKB/TrEMBL
      B2R928
      Related
      ENSP00000507200.1, ENST00000682126.1
      Conserved Domains (2) summary
      smart00036
      Location:511 → 826
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06646
      Location:10 → 277
      STKc_MAP4K5; Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5

    2. NM_198794.4 → NP_942089.1  mitogen-activated protein kinase kinase kinase kinase 5

      See identical proteins and their annotated locations for NP_942089.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform.
      Source sequence(s)
      AK124738, BC036013, CB990293
      Consensus CDS
      CCDS91875.1
      UniProtKB/Swiss-Prot
      A0A0A0MQR1, A0A804HIS2, Q8IYF6, Q9Y4K4
      UniProtKB/TrEMBL
      B2R928
      Related
      ENSP00000013125.5, ENST00000013125.9
      Conserved Domains (2) summary
      smart00036
      Location:511 → 826
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06646
      Location:10 → 277
      STKc_MAP4K5; Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      50418521..50561126 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047430898.1 → XP_047286854.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X5

      UniProtKB/TrEMBL
      B2R928

    2. XM_047430897.1 → XP_047286853.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X4

      UniProtKB/TrEMBL
      B2R928

    3. XM_047430893.1 → XP_047286849.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X1

      UniProtKB/TrEMBL
      B2R928

    4. XM_047430896.1 → XP_047286852.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X4

      UniProtKB/TrEMBL
      B2R928

    5. XM_006720013.5 → XP_006720076.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X3

      See identical proteins and their annotated locations for XP_006720076.1

      UniProtKB/Swiss-Prot
      A0A0A0MQR1, A0A804HIS2, Q8IYF6, Q9Y4K4
      UniProtKB/TrEMBL
      B2R928
      Conserved Domains (2) summary
      smart00036
      Location:511 → 826
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06646
      Location:10 → 277
      STKc_MAP4K5; Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5

    6. XM_047430891.1 → XP_047286847.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X1

      UniProtKB/TrEMBL
      B2R928

    7. XM_011536377.4 → XP_011534679.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X4

      See identical proteins and their annotated locations for XP_011534679.1

      UniProtKB/TrEMBL
      B2R928
      Conserved Domains (3) summary
      smart00036
      Location:511 → 825
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      smart00220
      Location:20 → 277
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06646
      Location:10 → 277
      STKc_MAP4K5; Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5

    8. XM_047430892.1 → XP_047286848.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X1

      UniProtKB/TrEMBL
      B2R928

    9. XM_047430895.1 → XP_047286851.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X4

      UniProtKB/TrEMBL
      B2R928

    10. XM_047430894.1 → XP_047286850.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X2

      UniProtKB/TrEMBL
      B2R928

    11. XM_047430890.1 → XP_047286846.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X1

      UniProtKB/TrEMBL
      B2R928

    12. XM_011536380.4 → XP_011534682.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X6

      UniProtKB/TrEMBL
      B3KWC4
      Conserved Domains (1) summary
      smart00036
      Location:222 → 537
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      44624744..44767297 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054375305.1 → XP_054231280.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X4

      UniProtKB/TrEMBL
      B2R928

    2. XM_054375302.1 → XP_054231277.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X3

      UniProtKB/TrEMBL
      B2R928

    3. XM_054375306.1 → XP_054231281.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X4

      UniProtKB/TrEMBL
      B2R928

    4. XM_054375301.1 → XP_054231276.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X3

      UniProtKB/TrEMBL
      B2R928

    5. XM_054375303.1 → XP_054231278.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X4

      UniProtKB/TrEMBL
      B2R928

    6. XM_054375304.1 → XP_054231279.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X4

      UniProtKB/TrEMBL
      B2R928

    7. XM_054375307.1 → XP_054231282.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X7

      UniProtKB/TrEMBL
      B2R928

    8. XM_054375308.1 → XP_054231283.1  mitogen-activated protein kinase kinase kinase kinase 5 isoform X6

      UniProtKB/TrEMBL
      B3KWC4
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y4K4.3 GenPept UniProtKB/Swiss-Prot:Q9Y4K4

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