MAP2K1 (mitogen-activated protein kinase kinase 1)

Gene

• Entrez ID: 5604
• Gene name: Mitogen-activated protein kinase kinase 1
• Gene symbol: MAP2K1
• Synonyms: CFC3, MAPKK1, MEK1, MEL, MKK1, PRKMK1
• Chromosome: 15
• Chromosome location: 15q22.31
• Summary: The protein encoded by this gene is a member of the dual specificity protein kinase family, which 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 wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121908594	T>C	Pathogenic	Missense variant, genic upstream transcript variant, coding sequence variant
rs121908595	A>G	Pathogenic	Missense variant, genic upstream transcript variant, coding sequence variant
rs121908596	G>A,T	Likely-pathogenic, pathogenic-likely-pathogenic, pathogenic	Missense variant, genic upstream transcript variant, coding sequence variant
rs397516789	C>T	Likely-pathogenic	Coding sequence variant, missense variant, genic upstream transcript variant
rs397516790	A>C,G	Likely-pathogenic	Coding sequence variant, missense variant, genic upstream transcript variant
rs397516791	T>G	Likely-pathogenic	Coding sequence variant, missense variant, genic upstream transcript variant
rs397516792	C>A,G,T	Likely-pathogenic, pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, missense variant, genic upstream transcript variant
rs397516793	T>A,C	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant, genic upstream transcript variant
rs727503996	A>G	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs727504317	G>A	Pathogenic, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs727504819	G>A,T	Uncertain-significance, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs730880502	T>A,G	Uncertain-significance, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs730880503	C>T	Pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs730880507	T>G	Likely-pathogenic	Coding sequence variant, missense variant
rs730880508	GC>TT	Pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs797044593	A>G	Pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs869025339	AAG>-	Likely-pathogenic	Genic upstream transcript variant, coding sequence variant, inframe deletion
rs869025608	G>C,T	Pathogenic, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs876657651	A>G	Uncertain-significance, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057518078	TGGGAGAACTGAAGG>-	Likely-pathogenic	Genic upstream transcript variant, inframe deletion, coding sequence variant
rs1057518080	ACTGAAGGATGACGA>-	Likely-pathogenic	Genic upstream transcript variant, inframe deletion, coding sequence variant
rs1057519728	T>A,C,G	Pathogenic, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057519729	A>C	Pathogenic, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057519730	T>A,G	Pathogenic, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057519731	G>C	Pathogenic, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057519732	C>A,T	Uncertain-significance, pathogenic, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057519733	G>A	Pathogenic	Coding sequence variant, missense variant
rs1057519734	C>T	Pathogenic	Coding sequence variant, missense variant
rs1057519805	T>C	Likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057519819	T>C	Likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057519820	A>C	Likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057519821	G>C,T	Likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057519822	T>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1057519823	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1057519856	T>A	Likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057519908	T>G	Likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1057519909	A>C	Likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs1595860875	A>T	Likely-pathogenic	Coding sequence variant, missense variant, genic upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003226	hsa-miR-424-5p	Luciferase reporter assay	20065103
MIRT003226	hsa-miR-424-5p	Immunohistochemistry, qRT-PCR, Western blot	21179471
MIRT004483	hsa-miR-34a-5p	qRT-PCR, Luciferase reporter assay, Western blot, Northern blot	20299489
MIRT006601	hsa-miR-1826	Luciferase reporter assay, Western blot	22049531
MIRT006601	hsa-miR-1826	Luciferase reporter assay, Western blot	22180573
MIRT007165	hsa-miR-497-5p	Luciferase reporter assay, qRT-PCR, Western blot	23092882
MIRT022002	hsa-miR-128-3p	Sequencing	20371350
MIRT025120	hsa-miR-181a-5p	Sequencing	20371350
MIRT025120	hsa-miR-181a-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23911747
MIRT027265	hsa-miR-101-3p	Sequencing	20371350
MIRT038788	hsa-miR-93-3p	CLASH	23622248
MIRT047918	hsa-miR-30c-5p	CLASH	23622248
MIRT281791	hsa-miR-142-5p	PAR-CLIP	20371350
MIRT281792	hsa-miR-559	PAR-CLIP	20371350
MIRT281793	hsa-miR-548b-5p	PAR-CLIP	20371350
MIRT281794	hsa-miR-548a-5p	PAR-CLIP	20371350
MIRT281795	hsa-miR-548c-5p	PAR-CLIP	20371350
MIRT281796	hsa-miR-548d-5p	PAR-CLIP	20371350
MIRT281797	hsa-miR-548j-5p	PAR-CLIP	20371350
MIRT281798	hsa-miR-548k	PAR-CLIP	20371350
MIRT281799	hsa-miR-548l	PAR-CLIP	20371350
MIRT281800	hsa-miR-548h-5p	PAR-CLIP	20371350
MIRT281801	hsa-miR-548i	PAR-CLIP	20371350
MIRT281802	hsa-miR-548w	PAR-CLIP	20371350
MIRT281803	hsa-miR-548y	PAR-CLIP	20371350
MIRT281804	hsa-miR-548o-5p	PAR-CLIP	20371350
MIRT281805	hsa-miR-548ab	PAR-CLIP	20371350
MIRT281806	hsa-miR-548ad-5p	PAR-CLIP	20371350
MIRT281807	hsa-miR-548ae-5p	PAR-CLIP	20371350
MIRT281808	hsa-miR-548ak	PAR-CLIP	20371350
MIRT281809	hsa-miR-548am-5p	PAR-CLIP	20371350
MIRT281810	hsa-miR-451b	PAR-CLIP	20371350
MIRT281811	hsa-miR-548ap-5p	PAR-CLIP	20371350
MIRT281812	hsa-miR-548aq-5p	PAR-CLIP	20371350
MIRT281813	hsa-miR-548ar-5p	PAR-CLIP	20371350
MIRT281814	hsa-miR-548as-5p	PAR-CLIP	20371350
MIRT281815	hsa-miR-548au-5p	PAR-CLIP	20371350
MIRT281816	hsa-miR-5590-3p	PAR-CLIP	20371350
MIRT281817	hsa-miR-548av-5p	PAR-CLIP	20371350
MIRT281818	hsa-miR-548ay-5p	PAR-CLIP	20371350
MIRT281819	hsa-miR-6507-5p	PAR-CLIP	20371350
MIRT281820	hsa-miR-8054	PAR-CLIP	20371350
MIRT281821	hsa-miR-548bb-5p	PAR-CLIP	20371350
MIRT342789	hsa-miR-624-5p	PAR-CLIP	20371350
MIRT403875	hsa-miR-181b-5p	Luciferase reporter assay	23645289
MIRT438770	hsa-miR-494-3p	qRT-PCR, Western blot	24960059
MIRT438774	hsa-miR-34c-5p	qRT-PCR, Western blot	24960059
MIRT438775	hsa-miR-34b-3p	qRT-PCR, Western blot	24960059
MIRT438778	hsa-miR-449a	qRT-PCR, Western blot	24960059
MIRT438778	hsa-miR-449a	Luciferase reporter assay, qRT-PCR, Western blot	26609480
MIRT438779	hsa-miR-448	qRT-PCR, Western blot	24960059
MIRT438782	hsa-miR-211-5p	qRT-PCR, Western blot	24960059
MIRT438783	hsa-miR-204-5p	qRT-PCR, Western blot	24960059
MIRT450208	hsa-miR-889-3p	PAR-CLIP	22100165
MIRT574078	hsa-miR-6856-5p	PAR-CLIP	20371350
MIRT574079	hsa-miR-6758-5p	PAR-CLIP	20371350

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	TAS
GO:0000187	Process	Activation of MAPK activity	IBA	21873635
GO:0000187	Process	Activation of MAPK activity	IDA	10644344
GO:0000187	Process	Activation of MAPK activity	TAS	19565474
GO:0004672	Function	Protein kinase activity	TAS	10570282
GO:0004674	Function	Protein serine/threonine kinase activity	IMP	18305109
GO:0004674	Function	Protein serine/threonine kinase activity	TAS
GO:0004708	Function	MAP kinase kinase activity	IBA	21873635
GO:0004708	Function	MAP kinase kinase activity	IDA	8388392, 28166211
GO:0004712	Function	Protein serine/threonine/tyrosine kinase activity	TAS	19565474
GO:0004713	Function	Protein tyrosine kinase activity	IEA
GO:0005078	Function	MAP-kinase scaffold activity	IMP	29433126
GO:0005515	Function	Protein binding	IPI	15299019, 17110930, 17255949, 17724343, 17979178, 18329369, 19197339, 20179161, 20554783, 20679487, 21441104, 22752157, 23241949, 23934108, 24211253, 24746704, 25155755, 25416956, 25437913, 25600339, 26496610, 29433126, 31980649, 32296183
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	TAS	19565474
GO:0005739	Component	Mitochondrion	TAS	19565474
GO:0005769	Component	Early endosome	TAS	19565474
GO:0005770	Component	Late endosome	TAS	19565474
GO:0005783	Component	Endoplasmic reticulum	IDA	22572157
GO:0005794	Component	Golgi apparatus	TAS	19565474
GO:0005815	Component	Microtubule organizing center	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS	19565474
GO:0005886	Component	Plasma membrane	IDA
GO:0005925	Component	Focal adhesion	TAS	19565474
GO:0006468	Process	Protein phosphorylation	IDA	28166211
GO:0006935	Process	Chemotaxis	TAS	10570282
GO:0007050	Process	Cell cycle arrest	IMP	9765203
GO:0007165	Process	Signal transduction	TAS	10570282
GO:0007507	Process	Heart development	IEA
GO:0008022	Function	Protein C-terminus binding	IDA	22572157
GO:0008285	Process	Negative regulation of cell population proliferation	IDA	9765203
GO:0010628	Process	Positive regulation of gene expression	IMP	15155804
GO:0010629	Process	Negative regulation of gene expression	IGI	23626836
GO:0018107	Process	Peptidyl-threonine phosphorylation	IMP	18305109
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IEA
GO:0021697	Process	Cerebellar cortex formation	IEA
GO:0030182	Process	Neuron differentiation	IBA	21873635
GO:0030216	Process	Keratinocyte differentiation	IEA
GO:0030878	Process	Thyroid gland development	IEA
GO:0032872	Process	Regulation of stress-activated MAPK cascade	TAS	19565474
GO:0043539	Function	Protein serine/threonine kinase activator activity	IDA	8388392
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	24375836, 26514923
GO:0047485	Function	Protein N-terminus binding	IDA	22572157
GO:0048538	Process	Thymus development	IEA
GO:0048679	Process	Regulation of axon regeneration	IEA
GO:0048870	Process	Cell motility	IEA
GO:0050772	Process	Positive regulation of axonogenesis	IEA
GO:0060020	Process	Bergmann glial cell differentiation	IEA
GO:0060324	Process	Face development	IEA
GO:0060440	Process	Trachea formation	IEA
GO:0060502	Process	Epithelial cell proliferation involved in lung morphogenesis	IEA
GO:0060674	Process	Placenta blood vessel development	IEA
GO:0060711	Process	Labyrinthine layer development	IEA
GO:0070371	Process	ERK1 and ERK2 cascade	IMP	18305109
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IMP	24375836
GO:0071902	Process	Positive regulation of protein serine/threonine kinase activity	IDA	8388392
GO:0090170	Process	Regulation of Golgi inheritance	TAS	19565474
GO:0090398	Process	Cellular senescence	IMP	9765203
GO:0097110	Function	Scaffold protein binding	IPI	10409742
GO:1903800	Process	Positive regulation of production of miRNAs involved in gene silencing by miRNA	IMP	24375836
GO:2000641	Process	Regulation of early endosome to late endosome transport	TAS	19565474

Other IDs

• MIM: 176872
• HGNC: 6840
• e!Ensembl: ENSG00000169032

Protein

• UniProt ID: Q02750
• Protein name: Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (MKK1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
• Protein function: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.
• PDB: 1S9J, 2P55, 3DV3, 3DY7, 3E8N, 3EQB, 3EQC, 3EQD, 3EQF, 3EQG, 3EQH, 3EQI, 3MBL, 3ORN, 3OS3, 3PP1, 3SLS, 3V01, 3V04, 3VVH, 3W8Q, 3WIG, 3ZLS, 3ZLW, 3ZLX, 3ZLY, 3ZM4, 4AN2, 4AN3, 4AN9, 4ANB, 4ARK, 4LMN, 4MNE, 4U7Z, 4U80, 4U81, 5BX0, 5EYM, 5HZE, 5YT3, 6NYB, 6PP9, 6Q0J, 6Q0T, 6U2G, 6V2V, 6V2W, 6V2X, 6V2Y, 6V2Z
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	68 → 361	Protein kinase domain	Domain

• Sequence:

  MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKV
  GELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHE
  CNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYL
  REKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHY
  SVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSY
  GMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAF
  IKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAGV

• Sequence length: 393