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    MAP4K4 mitogen-activated protein kinase kinase kinase kinase 4 [ Homo sapiens (human) ]

    Gene ID: 9448, updated on 27-Nov-2024

    Summary

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    Official Symbol
    MAP4K4provided by HGNC
    Official Full Name
    mitogen-activated protein kinase kinase kinase kinase 4provided by HGNC
    Primary source
    HGNC:HGNC:6866
    See related
    Ensembl:ENSG00000071054 MIM:604666; AllianceGenome:HGNC:6866
    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
    HGK; NIK; MEKKK4; FLH21957; HEL-S-31
    Summary
    The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in brain (RPKM 42.7), fat (RPKM 25.1) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MAP4K4 in Genome Data Viewer
    Location:
    2q11.2
    Exon count:
    33
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (101697707..101894690)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (102156317..102352940)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (102314169..102511152)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:102150441-102151230 Neighboring gene uncharacterized LOC105373514 Neighboring gene PRCP pseudogene 1 Neighboring gene NANOG hESC enhancer GRCh37_chr2:102182961-102183536 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:102224391-102224936 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:102225481-102226024 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:102226025-102226568 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16302 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:102304849-102305051 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11827 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11828 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16303 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16304 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:102358485-102359214 Neighboring gene Sharpr-MPRA regulatory region 8953 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:102422933-102423868 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:102424513-102425121 Neighboring gene Sharpr-MPRA regulatory region 3767 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:102509916-102510686 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16305 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:102552199-102552715 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:102599375-102599875 Neighboring gene long intergenic non-protein coding RNA 1127 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:102637443-102637636 Neighboring gene interleukin 1 receptor type 2

    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. MAP4K4 negatively regulates CD8 T cell-mediated antitumor and antiviral immunity. Esen E, et al. Sci Immunol, 2020 Mar 27. PMID 32220977
    2. Lowered HGK expression inhibits cell invasion and adhesion in hepatocellular carcinoma cell line HepG2. Han SX, et al. World J Gastroenterol, 2010 Sep 28. PMID 20857524, Free PMC Article
    3. Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer. Zhang J, et al. Genes (Basel), 2022 Oct 3. PMID 36292671, Free PMC Article
    4. Integrated exome and transcriptome analysis prioritizes MAP4K4 de novo frameshift variants in autism spectrum disorder as a novel disease-gene association. Cesana M, et al. Hum Genet, 2023 Mar. PMID 36469137, Free PMC Article
    5. MAP4K4/JNK Signaling Pathway Stimulates Proliferation and Suppresses Apoptosis of Human Spermatogonial Stem Cells and Lower Level of MAP4K4 Is Associated with Male Infertility. Wan C, et al. Cells, 2022 Nov 28. PMID 36497065, Free PMC Article

    See all (159) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Role of Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Signaling in Liver and Metabolic Diseases.
      Title: Role of Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 Signaling in Liver and Metabolic Diseases.
    2. Syndromic craniosynostosis caused by a novel missense variant in MAP4K4: Expanding the genotype-phenotype relationship in RASopathies.
      Title: Syndromic craniosynostosis caused by a novel missense variant in MAP4K4: Expanding the genotype-phenotype relationship in RASopathies.
    3. MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.
      Title: MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1.
    4. FTO promotes gastric cancer progression by modulating MAP4K4 expression via demethylation in an m6A-dependent manner.
      Title: FTO promotes gastric cancer progression by modulating MAP4K4 expression via demethylation in an m6A-dependent manner.
    5. MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFbeta2-Smad2/3 signaling pathway in cervical cancer.
      Title: MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer.
    6. CircCPSF6 promotes hepatocellular carcinoma cancer progression by regulating MAP4K4 through sponging miR-145-5p.
      Title: CircCPSF6 promotes hepatocellular carcinoma cancer progression by regulating MAP4K4 through sponging miR-145-5p.
    7. Evaluation of the Role of MAP4K4 in Focal Adhesion Dynamics and Regulation of Cell Migration of Breast Cancer Cell Line MDA-MB-231.
      Title: Evaluation of the Role of MAP4K4 in Focal Adhesion Dynamics and Regulation of Cell Migration of Breast Cancer Cell Line MDA-MB-231.
    8. MAP4K4 promotes ovarian cancer metastasis through diminishing ADAM10-dependent N-cadherin cleavage.
      Title: MAP4K4 promotes ovarian cancer metastasis through diminishing ADAM10-dependent N-cadherin cleavage.
    9. Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish.
      Title: Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish.
    10. Integrated exome and transcriptome analysis prioritizes MAP4K4 de novo frameshift variants in autism spectrum disorder as a novel disease-gene association.
      Title: Integrated exome and transcriptome analysis prioritizes MAP4K4 de novo frameshift variants in autism spectrum disorder as a novel disease-gene association.
    Submit: New GeneRIF Correction See all GeneRIFs (51)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
    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

    Clone Names

    • FLJ10410, FLJ20373, FLJ90111, KIAA0687

    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables Rho-dependent protein serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables creatine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 microtubule binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT involved_in microvillus assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of cell-matrix adhesion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in neuron projection morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of ARF protein signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in positive regulation of GTPase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in positive regulation of cell migration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of focal adhesion assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in positive regulation of focal adhesion disassembly ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in positive regulation of hippo signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of keratinocyte migration ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of JNK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of MAPK cascade 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
    		  
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in focal adhesion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    mitogen-activated protein kinase kinase kinase kinase 4
    Names
    HPK/GCK-like kinase HGK
    MAPK/ERK kinase kinase kinase 4
    MEK kinase kinase 4
    Ste20 group protein kinase HGK
    epididymis secretory protein Li 31
    hepatocyte progenitor kinase-like/germinal center kinase-like kinase
    nck-interacting kinase
    NP_001229488.1
    NP_001229489.1
    NP_001371405.1
    NP_001371406.1
    NP_001371407.1
    NP_001371410.1
    NP_001371411.1
    NP_001371412.1
    NP_001371413.1
    NP_001371414.1
    NP_001371415.1
    NP_001371416.1
    NP_001371417.1
    NP_001371419.1
    NP_001371420.1
    NP_001371421.1
    NP_001371422.1
    NP_001371423.1
    NP_001371424.1
    NP_001371425.1
    NP_001371426.1
    NP_001371435.1
    NP_001371436.1
    NP_001371437.1
    NP_001371438.1
    NP_001371449.1
    NP_001371472.1
    NP_001371477.1
    NP_001371478.1
    NP_001371479.1
    NP_001371480.1
    NP_001371481.1
    NP_001371482.1
    NP_001371483.1
    NP_001371484.1
    NP_001371485.1
    NP_001371486.1
    NP_001371487.1
    NP_001371488.1
    NP_001371489.1
    NP_001371490.1
    NP_001371491.1
    NP_001371492.1
    NP_001371493.1
    NP_001371496.1
    NP_001371501.1
    NP_001371508.1
    NP_001381931.1
    NP_004825.3
    NP_663719.2
    NP_663720.1

    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_001242559.2 → NP_001229488.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 4

      See identical proteins and their annotated locations for NP_001229488.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses two alternate in-frame splice sites and lacks an alternate in-frame exon in the central coding region, compared to variant 2. The encoded isoform (4) is shorter than isoform 2. The 5' UTR of this variant is incomplete due to a lack of 5'-complete transcripts representing this variant, and the presence of splicing ambiguity in the 5' UTR.
      Source sequence(s)
      AC005035, AC007005, AY212247, BU625485, DB086475
      Consensus CDS
      CCDS56130.1
      UniProtKB/Swiss-Prot
      E7ESS2, O75172, O95819, Q9NST7
      UniProtKB/TrEMBL
      A0A0D9SEY1
      Related
      ENSP00000314363.6, ENST00000347699.8
      Conserved Domains (2) summary
      smart00036
      Location:921 → 1219
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    2. NM_001242560.2 → NP_001229489.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks two alternate in-frame exons but includes two different alternate in-frame exons in the central coding region, compared to variant 2. The encoded isoform (5) is shorter than isoform 2.
      Source sequence(s)
      AC005035, AC007005, AK296396, BU625485, DR002278
      Consensus CDS
      CCDS92823.1
      UniProtKB/TrEMBL
      B7Z3V5, E7EN19
      Related
      ENSP00000392830.2, ENST00000425019.6
      Conserved Domains (3) summary
      smart00036
      Location:917 → 1215
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      smart00220
      Location:25 → 289
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    3. NM_001384476.1 → NP_001371405.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:947 → 1245
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    4. NM_001384477.1 → NP_001371406.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:1010 → 1308
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    5. NM_001384478.1 → NP_001371407.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:840 → 1138
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06636
      Location:8 → 289
      STKc_MAP4K4_6_N; N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6

    6. NM_001384481.1 → NP_001371410.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 9

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      A0A0D9SEY1
      Conserved Domains (2) summary
      smart00036
      Location:986 → 1292
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    7. NM_001384482.1 → NP_001371411.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 10

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Related
      ENSP00000389752.1, ENST00000413150.6
      Conserved Domains (2) summary
      smart00036
      Location:837 → 1135
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06636
      Location:8 → 289
      STKc_MAP4K4_6_N; N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6

    8. NM_001384483.1 → NP_001371412.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 11

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:931 → 1229
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06636
      Location:8 → 289
      STKc_MAP4K4_6_N; N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6

    9. NM_001384484.1 → NP_001371413.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 12

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:948 → 1246
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    10. NM_001384485.1 → NP_001371414.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 13

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:948 → 1254
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    11. NM_001384486.1 → NP_001371415.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 14

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      A0A0D9SEY1
      Conserved Domains (2) summary
      smart00036
      Location:989 → 1287
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    12. NM_001384487.1 → NP_001371416.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 15

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:978 → 1276
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    13. NM_001384488.1 → NP_001371417.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 16

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      A0A0D9SEY1
      Conserved Domains (2) summary
      smart00036
      Location:988 → 1286
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    14. NM_001384490.1 → NP_001371419.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 18

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:871 → 1169
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06636
      Location:8 → 289
      STKc_MAP4K4_6_N; N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6

    15. NM_001384491.1 → NP_001371420.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 19

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:916 → 1214
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    16. NM_001384492.1 → NP_001371421.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 20

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      A0A0D9SEY1
      Conserved Domains (2) summary
      smart00036
      Location:1034 → 1332
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    17. NM_001384493.1 → NP_001371422.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 21

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:1012 → 1310
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    18. NM_001384494.1 → NP_001371423.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 22

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Related
      ENSP00000387370.1, ENST00000456652.5
      Conserved Domains (2) summary
      smart00036
      Location:870 → 1168
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06636
      Location:8 → 289
      STKc_MAP4K4_6_N; N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6

    19. NM_001384495.1 → NP_001371424.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 23

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:904 → 1202
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06636
      Location:8 → 289
      STKc_MAP4K4_6_N; N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6

    20. NM_001384496.1 → NP_001371425.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 24

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:932 → 1238
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    21. NM_001384497.1 → NP_001371426.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 25

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      A0A0D9SEY1
      Conserved Domains (2) summary
      smart00036
      Location:1063 → 1361
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    22. NM_001384506.1 → NP_001371435.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 27

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      A0A0D9SEY1
      Conserved Domains (2) summary
      smart00036
      Location:1002 → 1300
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    23. NM_001384507.1 → NP_001371436.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 28

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      A0A0D9SEY1
      Conserved Domains (2) summary
      smart00036
      Location:925 → 1223
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    24. NM_001384508.1 → NP_001371437.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 29

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:946 → 1244
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    25. NM_001384509.1 → NP_001371438.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 30

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:977 → 1275
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    26. NM_001384520.1 → NP_001371449.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 31

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      A0A0D9SEY1
      Conserved Domains (2) summary
      smart00036
      Location:968 → 1266
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    27. NM_001384543.1 → NP_001371472.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 32

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      A0A0D9SEY1
      Conserved Domains (2) summary
      smart00036
      Location:971 → 1269
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    28. NM_001384548.1 → NP_001371477.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 35

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:983 → 1281
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    29. NM_001384549.1 → NP_001371478.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 36

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z388
      Conserved Domains (2) summary
      smart00036
      Location:895 → 1193
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    30. NM_001384550.1 → NP_001371479.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 37

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:910 → 1208
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    31. NM_001384551.1 → NP_001371480.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 38

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      H7C360
      Conserved Domains (2) summary
      smart00036
      Location:885 → 1183
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    32. NM_001384552.1 → NP_001371481.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 39

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:938 → 1236
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    33. NM_001384553.1 → NP_001371482.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 40

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z388
      Conserved Domains (2) summary
      smart00036
      Location:1001 → 1299
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    34. NM_001384554.1 → NP_001371483.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 41

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:905 → 1211
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    35. NM_001384555.1 → NP_001371484.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 42

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z388
      Conserved Domains (2) summary
      smart00036
      Location:1003 → 1301
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    36. NM_001384556.1 → NP_001371485.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 43

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:936 → 1234
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    37. NM_001384557.1 → NP_001371486.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 44

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      H7C360
      Related
      ENSP00000409720.1, ENST00000417294.5
      Conserved Domains (2) summary
      smart00036
      Location:882 → 1180
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    38. NM_001384558.1 → NP_001371487.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 45

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:908 → 1206
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    39. NM_001384559.1 → NP_001371488.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 46

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z388
      Conserved Domains (2) summary
      smart00036
      Location:894 → 1192
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    40. NM_001384560.1 → NP_001371489.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 47

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      H7C360
      Conserved Domains (2) summary
      smart00036
      Location:859 → 1157
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    41. NM_001384561.1 → NP_001371490.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 48

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:831 → 1129
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    42. NM_001384562.1 → NP_001371491.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 49

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:937 → 1235
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    43. NM_001384563.1 → NP_001371492.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 50

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z388
      Conserved Domains (2) summary
      smart00036
      Location:1000 → 1298
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    44. NM_001384564.1 → NP_001371493.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 51

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      A0A0D9SEY1
      Conserved Domains (2) summary
      smart00036
      Location:1023 → 1321
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    45. NM_001384567.1 → NP_001371496.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 52

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z388
      Conserved Domains (2) summary
      smart00036
      Location:972 → 1270
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    46. NM_001384572.1 → NP_001371501.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 53

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      B7Z3V5
      Conserved Domains (2) summary
      smart00036
      Location:939 → 1237
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    47. NM_001384579.1 → NP_001371508.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 54

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      UniProtKB/TrEMBL
      H7C360
      Conserved Domains (2) summary
      smart00036
      Location:916 → 1214
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:6 → 280
      PKc_like; Protein Kinases, catalytic domain

    48. NM_001395002.1 → NP_001381931.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 55

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005
      Consensus CDS
      CCDS92821.1
      UniProtKB/TrEMBL
      A0A0D9SEY1, G5E948
      Related
      ENSP00000313644.6, ENST00000324219.9
      Conserved Domains (2) summary
      smart00036
      Location:1066 → 1364
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    49. NM_004834.5 → NP_004825.3  mitogen-activated protein kinase kinase kinase kinase 4 isoform 1

      See identical proteins and their annotated locations for NP_004825.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) lacks two alternate in-frame exons but includes a different in-frame exon in the central coding region, and uses an alternate in-frame splice site in both the central and 3' coding regions, compared to variant 2. The encoded isoform (1) is shorter than isoform 2.
      Source sequence(s)
      AC005035, AC007005, AF096300, BU625485, DR002278
      Consensus CDS
      CCDS82487.1
      UniProtKB/TrEMBL
      B7Z3V5
      Related
      ENSP00000489579.1, ENST00000634702.1
      Conserved Domains (2) summary
      smart00036
      Location:839 → 1145
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cd06636
      Location:8 → 289
      STKc_MAP4K4_6_N; N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6

    50. NM_145686.4 → NP_663719.2  mitogen-activated protein kinase kinase kinase kinase 4 isoform 2

      See identical proteins and their annotated locations for NP_663719.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2).
      Source sequence(s)
      AC005035, AC007005, BC064691, BU625485, DR002278
      Consensus CDS
      CCDS74546.1
      UniProtKB/TrEMBL
      H7C360
      Related
      ENSP00000343658.5, ENST00000350878.9
      Conserved Domains (2) summary
      smart00036
      Location:955 → 1253
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    51. NM_145687.4 → NP_663720.1  mitogen-activated protein kinase kinase kinase kinase 4 isoform 3

      See identical proteins and their annotated locations for NP_663720.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon but includes a different in-frame exon in the central coding region, compared to variant 2. The encoded isoform (3) is shorter than isoform 2. The 5' UTR of this variant is incomplete due to a lack of 5'-complete transcripts representing this variant, and the presence of splicing ambiguity in the 5' UTR.
      Source sequence(s)
      AB014587, AC005035, AC007005, BU625485, DB086475
      Consensus CDS
      CCDS92822.1
      UniProtKB/TrEMBL
      H7C360, V9HWH3
      Related
      ENSP00000486116.2, ENST00000625522.3
      Conserved Domains (2) summary
      smart00036
      Location:894 → 1192
      CNH; Domain found in NIK1-like kinases, mouse citron and yeast ROM1, ROM2
      cl21453
      Location:8 → 289
      PKc_like; Protein Kinases, catalytic domain

    RNA

    1. NR_169279.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005

    2. NR_169280.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005

    3. NR_169281.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005

    4. NR_169282.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC005035, AC007005

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      101697707..101894690
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      102156317..102352940
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O95819.2 GenPept UniProtKB/Swiss-Prot:O95819

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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