Human Gene MAP3K1 (ENST00000399503.4_4) from GENCODE V47lift37
  Description: mitogen-activated protein kinase kinase kinase 1 (from RefSeq NM_005921.2)
Gencode Transcript: ENST00000399503.4_4
Gencode Gene: ENSG00000095015.6_7
Transcript (Including UTRs)
   Position: hg19 chr5:56,111,376-56,191,979 Size: 80,604 Total Exon Count: 20 Strand: +
Coding Region
   Position: hg19 chr5:56,111,401-56,189,507 Size: 78,107 Coding Exon Count: 20 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:56,111,376-56,191,979)mRNA (may differ from genome)Protein (1512 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: M3K1_HUMAN
DESCRIPTION: RecName: Full=Mitogen-activated protein kinase kinase kinase 1; EC=2.7.11.25; AltName: Full=MAPK/ERK kinase kinase 1; Short=MEK kinase 1; Short=MEKK 1;
FUNCTION: Component of a protein kinase signal transduction cascade. Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
COFACTOR: Magnesium.
ENZYME REGULATION: Activated by autophosphorylation on Thr-1400 and Thr-1412 following oligomerization.
SUBUNIT: Binds both upstream activators and downstream substrates in multimolecular complexes through its N-terminus. Oligomerizes after binding MAP4K2 or TRAF2. Interacts with AXIN1. Interacts (via the kinase catalytic domain) with STK38.
INTERACTION: P45985:MAP2K4; NbExp=3; IntAct=EBI-49776, EBI-447868; Q12851:MAP4K2; NbExp=2; IntAct=EBI-49776, EBI-49783;
PTM: Autophosphorylated (By similarity).
DISEASE: Defects in MAP3K1 are the cause of 46,XY sex reversal type 6 (SRXY6) [MIM:613762]. SRXY6 is a disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.
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 RING-type zinc finger.
SIMILARITY: Contains 1 SWIM-type zinc finger.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: MAP3K1
Diseases sorted by gene-association score: 46xy sex reversal 6* (1200), map3k1-related 46,xy dsd and 46,xy cgd* (500), 46 xy gonadal dysgenesis* (163), 46,xy partial gonadal dysgenesis* (143)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 14.74 RPKM in Skin - Not Sun Exposed (Suprapubic)
Total median expression: 204.62 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -2.3025-0.092 Picture PostScript Text
3' UTR -551.902472-0.223 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS
IPR001841 - Znf_RING
IPR013083 - Znf_RING/FYVE/PHD
IPR007527 - Znf_SWIM

Pfam Domains:
PF00069 - Protein kinase domain
PF07714 - Protein tyrosine and serine/threonine kinase
PF17667 - Fungal protein kinase

SCOP Domains:
48371 - ARM repeat
56112 - Protein kinase-like (PK-like)
57850 - RING/U-box
57903 - FYVE/PHD zinc finger

ModBase Predicted Comparative 3D Structure on Q13233
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004709 MAP kinase kinase kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008270 zinc ion binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0019901 protein kinase binding
GO:0046872 metal ion binding

Biological Process:
GO:0000165 MAPK cascade
GO:0000186 activation of MAPKK activity
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0006468 protein phosphorylation
GO:0007346 regulation of mitotic cell cycle
GO:0016310 phosphorylation
GO:0023014 signal transduction by protein phosphorylation
GO:0031098 stress-activated protein kinase signaling cascade
GO:0032147 activation of protein kinase activity
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0042981 regulation of apoptotic process
GO:0071260 cellular response to mechanical stimulus

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  LF213333 - JP 2014500723-A/20836: Polycomb-Associated Non-Coding RNAs.
AK307828 - Homo sapiens cDNA, FLJ97776.
LF209910 - JP 2014500723-A/17413: Polycomb-Associated Non-Coding RNAs.
AF042838 - Homo sapiens MEK kinase 1 (MEKK1) mRNA, partial cds.
JD475102 - Sequence 456126 from Patent EP1572962.
JD338803 - Sequence 319827 from Patent EP1572962.
JD094080 - Sequence 75104 from Patent EP1572962.
JD230844 - Sequence 211868 from Patent EP1572962.
JD521715 - Sequence 502739 from Patent EP1572962.
JD150497 - Sequence 131521 from Patent EP1572962.
JD404685 - Sequence 385709 from Patent EP1572962.
JD181143 - Sequence 162167 from Patent EP1572962.
JD347109 - Sequence 328133 from Patent EP1572962.
LF332613 - JP 2014500723-A/140116: Polycomb-Associated Non-Coding RNAs.
LF332612 - JP 2014500723-A/140115: Polycomb-Associated Non-Coding RNAs.
LF332611 - JP 2014500723-A/140114: Polycomb-Associated Non-Coding RNAs.
LF332609 - JP 2014500723-A/140112: Polycomb-Associated Non-Coding RNAs.
LF332608 - JP 2014500723-A/140111: Polycomb-Associated Non-Coding RNAs.
LF332607 - JP 2014500723-A/140110: Polycomb-Associated Non-Coding RNAs.
LF332604 - JP 2014500723-A/140107: Polycomb-Associated Non-Coding RNAs.
LF332603 - JP 2014500723-A/140106: Polycomb-Associated Non-Coding RNAs.
LF332602 - JP 2014500723-A/140105: Polycomb-Associated Non-Coding RNAs.
LF332601 - JP 2014500723-A/140104: Polycomb-Associated Non-Coding RNAs.
BX537527 - Homo sapiens mRNA; cDNA DKFZp686I17101 (from clone DKFZp686I17101).
LF332600 - JP 2014500723-A/140103: Polycomb-Associated Non-Coding RNAs.
LF332599 - JP 2014500723-A/140102: Polycomb-Associated Non-Coding RNAs.
JD483602 - Sequence 464626 from Patent EP1572962.
JD091891 - Sequence 72915 from Patent EP1572962.
JD261049 - Sequence 242073 from Patent EP1572962.
LF332598 - JP 2014500723-A/140101: Polycomb-Associated Non-Coding RNAs.
U56433 - Human HeLa mRNA isolated as a false positive in a two-hybrid-screen.
LF332597 - JP 2014500723-A/140100: Polycomb-Associated Non-Coding RNAs.
LF332596 - JP 2014500723-A/140099: Polycomb-Associated Non-Coding RNAs.
LF332595 - JP 2014500723-A/140098: Polycomb-Associated Non-Coding RNAs.
MA568190 - JP 2018138019-A/140116: Polycomb-Associated Non-Coding RNAs.
MA568189 - JP 2018138019-A/140115: Polycomb-Associated Non-Coding RNAs.
MA568188 - JP 2018138019-A/140114: Polycomb-Associated Non-Coding RNAs.
MA568186 - JP 2018138019-A/140112: Polycomb-Associated Non-Coding RNAs.
MA568185 - JP 2018138019-A/140111: Polycomb-Associated Non-Coding RNAs.
MA568184 - JP 2018138019-A/140110: Polycomb-Associated Non-Coding RNAs.
MA568181 - JP 2018138019-A/140107: Polycomb-Associated Non-Coding RNAs.
MA568180 - JP 2018138019-A/140106: Polycomb-Associated Non-Coding RNAs.
MA568179 - JP 2018138019-A/140105: Polycomb-Associated Non-Coding RNAs.
MA568178 - JP 2018138019-A/140104: Polycomb-Associated Non-Coding RNAs.
MA568177 - JP 2018138019-A/140103: Polycomb-Associated Non-Coding RNAs.
MA568176 - JP 2018138019-A/140102: Polycomb-Associated Non-Coding RNAs.
MA568175 - JP 2018138019-A/140101: Polycomb-Associated Non-Coding RNAs.
MA568174 - JP 2018138019-A/140100: Polycomb-Associated Non-Coding RNAs.
MA568173 - JP 2018138019-A/140099: Polycomb-Associated Non-Coding RNAs.
MA568172 - JP 2018138019-A/140098: Polycomb-Associated Non-Coding RNAs.
MA448910 - JP 2018138019-A/20836: Polycomb-Associated Non-Coding RNAs.
MA445487 - JP 2018138019-A/17413: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_At1rPathway - Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling
h_fMLPpathway - fMLP induced chemokine gene expression in HMC-1 cells
h_egfPathway - EGF Signaling Pathway
h_fasPathway - FAS signaling pathway ( CD95 )
h_gleevecpathway - Inhibition of Cellular Proliferation by Gleevec
h_keratinocytePathway - Keratinocyte Differentiation
h_HivnefPathway - HIV-I Nef: negative effector of Fas and TNF
h_bcrPathway - BCR Signaling Pathway
h_rac1Pathway - Rac 1 cell motility signaling pathway
h_41bbPathway - The 4-1BB-dependent immune response
h_ceramidePathway - Ceramide Signaling Pathway
h_fcer1Pathway - Fc Epsilon Receptor I Signaling in Mast Cells
h_hcmvPathway - Human Cytomegalovirus and Map Kinase Pathways
h_mapkPathway - MAPKinase Signaling Pathway
h_vipPathway - Neuropeptides VIP and PACAP inhibit the apoptosis of activated T cells
h_cd40Pathway - CD40L Signaling Pathway
h_tcrPathway - T Cell Receptor Signaling Pathway
h_il1rPathway - Signal transduction through IL1R
h_malPathway - Role of MAL in Rho-Mediated Activation of SRF
h_nfkbPathway - NF-kB Signaling Pathway
h_pdgfPathway - PDGF Signaling Pathway
h_stressPathway - TNF/Stress Related Signaling
h_egfr_smrtePathway - Map Kinase Inactivation of SMRT Corepressor
h_p38mapkPathway - p38 MAPK Signaling Pathway
h_pyk2Pathway - Links between Pyk2 and Map Kinases
h_tnfr1Pathway - TNFR1 Signaling Pathway
h_tnfr2Pathway - TNFR2 Signaling Pathway
h_tollPathway - Toll-Like Receptor Pathway

Reactome (by CSHL, EBI, and GO)

Protein Q13233 (Reactome details) participates in the following event(s):

R-HSA-166869 TRAF6 binds MEKK1
R-HSA-933528 Interaction of MEKK1 with TRAF6
R-HSA-2730887 Autophosphorylation and activation of MEKK1
R-HSA-2730868 Phosphorylation of MEK7 by MEKK1
R-HSA-2730896 Phosphorylation of MEK4 by MEKK1
R-HSA-933530 Activation of IKK by MEKK1
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975871 MyD88 cascade initiated on plasma membrane
R-HSA-933542 TRAF6 mediated NF-kB activation
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-975155 MyD88 dependent cascade initiated on endosome
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168249 Innate Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000399503.1, ENST00000399503.2, ENST00000399503.3, M3K1_HUMAN, MAPKKK1, MEKK, MEKK1, NM_005921, Q13233, uc319ajl.1, uc319ajl.2
UCSC ID: ENST00000399503.4_4
RefSeq Accession: NM_005921.2
Protein: Q13233 (aka M3K1_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene MAP3K1:
gonad-dys-46xy (Nonsyndromic Disorders of Testicular Development Overview)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.