MAP2K1

Last updated
MAP2K1
Protein MAP2K1 PDB 1s9j.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases MAP2K1 , CFC3, MAPKK1, MEK1, MKK1, PRKMK1, mitogen-activated protein kinase kinase 1, MEL
External IDs OMIM: 176872; MGI: 1346866; HomoloGene: 2063; GeneCards: MAP2K1; OMA:MAP2K1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002755

NM_008927

RefSeq (protein)

NP_002746

NP_032953

Location (UCSC) Chr 15: 66.39 – 66.49 Mb Chr 9: 64.09 – 64.16 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the MAP2K1 gene. [5] [6]

Function

The protein encoded by this gene is a member of the dual-specificity protein kinase family that acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon activation by a wide variety of extra- and intracellular signals. As an essential component of the MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [7] MAP2K1 is altered in 1.05% of all human cancers. [8]

Meiosis

The genomes of diploid organisms in natural populations are highly polymorphic for insertions and deletions. During meiosis double-strand breaks (DSBs) that form within such polymorphic regions must be repaired by inter-sister chromatid exchange, rather than by inter-homolog exchange. Molecular-level studies of recombination during budding yeast meiosis have shown that recombination events initiated by DSBs in regions that lack corresponding sequences in the homolog are efficiently repaired by inter-sister chromatid recombination. [9] This recombination occurs with the same timing as inter-homolog recombination, but with reduced (2- to 3-fold) yields of joint molecules.

MAP2K1 is also known as MEK1 (see Mitogen-activated protein kinase kinase). MEK1 is a meiotic chromosome-axis-associated kinase that is thought to slow down, but not entirely block, sister chromatid recombination. Loss of MEK1 allows inter-sister DSB repair and also inter-sister Holliday junction intermediates to increase. Despite the normal activity of MEK1 in reducing inter-sister chromatid recombination, such recombination still occurs frequently during normal budding yeast meiosis (although not as frequently as during mitosis), and up to one-third of all recombination events are between sister chromatids. [9]

Interactions

MAP2K1 has been shown to interact with C-Raf, [10] Phosphatidylethanolamine binding protein 1, [10] MAP2K1IP1, [11] [12] GRB10, [13] MAPK3, [12] [14] [15] [16] MAPK8IP3, [17] [18] MAPK1 [10] [11] [19] [20] [21] [22] MP1, [12] and MAP3K1. [23]

Related Research Articles

Mitogen Activated Protein (MAP) kinase kinase kinase is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase. Subsequently, MAP kinase kinase activates MAP kinase. Several types of MAPKKK can exist but are mainly characterized by the MAP kinases they activate. MAPKKKs are stimulated by a large range of stimuli, primarily environmental and intracellular stressors. MAPKKK is responsible for various cell functions such as cell proliferation, cell differentiation, and apoptosis. The duration and intensity of signals determine which pathway ensues. Additionally, the use of protein scaffolds helps to place the MAPKKK in close proximity with its substrate to allow for a reaction. Lastly, because MAPKKK is involved in a series of several pathways, it has been used as a therapeutic target for cancer, amyloidosis, and neurodegenerative diseases. In humans, there are at least 19 genes which encode MAP kinase kinase kinases:

c-Raf Mammalian protein found in Homo sapiens

RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme that in humans is encoded by the RAF1 gene. The c-Raf protein is part of the ERK1/2 pathway as a MAP kinase (MAP3K) that functions downstream of the Ras subfamily of membrane associated GTPases. C-Raf is a member of the Raf kinase family of serine/threonine-specific protein kinases, from the TKL (Tyrosine-kinase-like) group of kinases.

<span class="mw-page-title-main">MAPK1</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 1, also known as ERK2, is an enzyme that in humans is encoded by the MAPK1 gene.

<span class="mw-page-title-main">MAPK3</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the MAPK3 gene.

<span class="mw-page-title-main">MAPK8</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 8 is a ubiquitous enzyme that in humans is encoded by the MAPK8 gene.

<span class="mw-page-title-main">MAP2K2</span> Protein-coding gene in the species Homo sapiens

Dual specificity mitogen-activated protein kinase kinase 2 is an enzyme that in humans is encoded by the MAP2K2 gene. It is more commonly known as MEK2, but has many alternative names including CFC4, MKK2, MAPKK2 and PRKMK2.

<span class="mw-page-title-main">MAP3K7</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, is an enzyme that in humans is encoded by the MAP3K7 gene.

<span class="mw-page-title-main">MAP2K6</span> Protein-coding gene in the species Homo sapiens

Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 or MAPK/ERK kinase 6 is an enzyme that in humans is encoded by the MAP2K6 gene, on chromosome 17.

<span class="mw-page-title-main">MAP2K3</span> Protein-coding gene in the species Homo sapiens

Dual specificity mitogen-activated protein kinase kinase 3 is an enzyme that in humans is encoded by the MAP2K3 gene.

<span class="mw-page-title-main">MAP3K11</span> Protein-coding gene in humans

Mitogen-activated protein kinase kinase kinase 11 is an enzyme that in humans is encoded by the MAP3K11 gene.

<span class="mw-page-title-main">YWHAQ</span> Protein-coding gene in the species Homo sapiens

14-3-3 protein theta is a protein that in humans is encoded by the YWHAQ gene.

<span class="mw-page-title-main">RPS6KA5</span> Enzyme

Ribosomal protein S6 kinase alpha-5 is an enzyme that in humans is encoded by the RPS6KA5 gene. This kinase, together with RPS6KA4, are thought to mediate the phosphorylation of histone H3, linked to the expression of immediate early genes.

<span class="mw-page-title-main">RPS6KA2</span> Enzyme found in humans

Ribosomal protein S6 kinase alpha-2 is an enzyme that in humans is encoded by the RPS6KA2 gene.

<span class="mw-page-title-main">MAP2K5</span> Protein-coding gene in the species Homo sapiens

Dual specificity mitogen-activated protein kinase kinase 5 is an enzyme that in humans is encoded by the MAP2K5 gene.

<span class="mw-page-title-main">MAPK8IP3</span> Protein-coding gene in the species Homo sapiens

C-jun-amino-terminal kinase-interacting protein 3 is an enzyme that in humans is encoded by the MAPK8IP3 gene.

<span class="mw-page-title-main">MAP3K12</span>

Mitogen-activated protein kinase 12 is an enzyme that in humans is encoded by the MAP3K12 gene.

<span class="mw-page-title-main">PTPRR</span> Protein-coding gene in the species Homo sapiens

Protein tyrosine phosphatase receptor-type R is an enzyme that in humans is encoded by the PTPRR gene.

<span class="mw-page-title-main">MAPKAPK3</span> Protein-coding gene in the species Homo sapiens

MAP kinase-activated protein kinase 3 is an enzyme that in humans is encoded by the MAPKAPK3 gene.

<span class="mw-page-title-main">MAP2K1IP1</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase scaffold protein 1 is a scaffold protein that in humans is encoded by the MAPKSP1 gene.

<span class="mw-page-title-main">MAPK12</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 12, also known as extracellular signal-regulated kinase 6 (ERK6) or stress-activated protein kinase 3 (SAPK3), is an enzyme that in humans is encoded by the MAPK12 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000169032 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000004936 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Rampoldi L, Zimbello R, Bortoluzzi S, Tiso N, Valle G, Lanfranchi G, Danieli GA (Mar 1998). "Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5". Cytogenet Cell Genet. 78 (3–4): 301–3. doi:10.1159/000134677. PMID   9465908.
  6. Zheng CF, Guan KL (Jun 1993). "Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2". J Biol Chem. 268 (15): 11435–9. doi: 10.1016/S0021-9258(18)82142-1 . PMID   8388392.
  7. "Entrez Gene: MAP2K1 mitogen-activated protein kinase kinase 1".
  8. "MAP2K1 - My Cancer Genome".
  9. 1 2 Goldfarb T, Lichten M (2010). "Frequent and efficient use of the sister chromatid for DNA double-strand break repair during budding yeast meiosis". PLOS Biol. 8 (10): e1000520. doi: 10.1371/journal.pbio.1000520 . PMC   2957403 . PMID   20976044.
  10. 1 2 3 Yeung, K; Janosch P; McFerran B; Rose D W; Mischak H; Sedivy J M; Kolch W (May 2000). "Mechanism of Suppression of the Raf/MEK/Extracellular Signal-Regulated Kinase Pathway by the Raf Kinase Inhibitor Protein". Mol. Cell. Biol. 20 (9). UNITED STATES: 3079–85. doi:10.1128/MCB.20.9.3079-3085.2000. PMC   85596 . PMID   10757792.
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  14. Marti, A; Luo Z; Cunningham C; Ohta Y; Hartwig J; Stossel T P; Kyriakis J M; Avruch J (Jan 1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. 272 (5). UNITED STATES: 2620–8. doi: 10.1074/jbc.272.5.2620 . PMID   9006895.
  15. Butch, E R; Guan K L (Feb 1996). "Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2". J. Biol. Chem. 271 (8). UNITED STATES: 4230–5. doi: 10.1074/jbc.271.8.4230 . PMID   8626767.
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  19. Sanz-Moreno, Victoria; Casar Berta; Crespo Piero (May 2003). "p38α Isoform Mxi2 Binds to Extracellular Signal-Regulated Kinase 1 and 2 Mitogen-Activated Protein Kinase and Regulates Its Nuclear Activity by Sustaining Its Phosphorylation Levels". Mol. Cell. Biol. 23 (9). United States: 3079–90. doi:10.1128/MCB.23.9.3079-3090.2003. PMC   153192 . PMID   12697810.
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Further reading