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

Gene ID: 11183, updated on 3-Apr-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_2023_10 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (50418521..50561126, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (44624744..44767297, complement)
105.20220307 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. 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
  4. A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase. Tung RM, et al. Oncogene, 1997 Feb 13. PMID 9038372
  5. Adaptor proteins CRK and CRKL associate with the serine/threonine protein kinase GCKR promoting GCKR and SAPK activation. Shi CS, et al. Blood, 2000 Feb 1. PMID 10648385

See all (53) 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)

Genotypes

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 ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables MAP kinase kinase kinase kinase activity IBA
Inferred from Biological aspect of Ancestor
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 
Process Evidence Code Pubs
involved_in MAPK cascade 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 
involved_in phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in protein phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
  
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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NEW Try the new Transcript table

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, Q8IYF6, Q9Y4K4
    UniProtKB/TrEMBL
    A0A804HIS2, 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, Q8IYF6, Q9Y4K4
    UniProtKB/TrEMBL
    A0A804HIS2, 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_2023_10

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

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

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

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

  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, Q8IYF6, Q9Y4K4
    UniProtKB/TrEMBL
    A0A804HIS2, 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

  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/Swiss-Prot
    A0A0A0MQR1, Q8IYF6, Q9Y4K4
    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

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

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

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

  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

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

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

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

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

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

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

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

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y4K4.2 GenPept UniProtKB/Swiss-Prot:Q9Y4K4

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