InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MAP2K1

Summary

InnateDB Protein

IDBP-18021.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MAP2K1

Protein Name

mitogen-activated protein kinase kinase 1

Synonyms

CFC3; MAPKK1; MEK1; MKK1; PRKMK1;

Species

Homo sapiens

Ensembl Protein

ENSP00000302486

InnateDB Gene

IDBG-18019 (MAP2K1)

Protein Structure

UniProt Annotation

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. 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. {ECO:0000269PubMed:14737111, ECO:0000269PubMed:17101779}.

Subcellular Localization

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body. Cytoplasm. Nucleus. Note=Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis.

Disease Associations

Cardiofaciocutaneous syndrome 3 (CFC3) [MIM:615279]: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures. {ECO:0000269PubMed:16439621, ECO:0000269PubMed:18042262}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Widely expressed, with extremely low levels in brain. {ECO:0000269PubMed:1281467}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 80 experimentally validated interaction(s) in this database.
They are also associated with 13 interaction(s) predicted by orthology.

Experimentally validated
Total	80 [view]
Protein-Protein	77 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	1 [view]
DNA-RNA	0

Predicted by orthology
Total	13 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004708	MAP kinase kinase activity
GO:0004712	protein serine/threonine/tyrosine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004728	receptor signaling protein tyrosine phosphatase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0017016	Ras GTPase binding
GO:0019901	protein kinase binding
GO:0031435	mitogen-activated protein kinase kinase kinase binding
GO:0043539	protein serine/threonine kinase activator activity

Biological Process

GO:0000165	MAPK cascade
GO:0000186	activation of MAPKK activity
GO:0000187	activation of MAPK activity
GO:0002224	toll-like receptor signaling pathway
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0003056	regulation of vascular smooth muscle contraction
GO:0006468	protein phosphorylation
GO:0006928	cellular component movement
GO:0006935	chemotaxis
GO:0006979	response to oxidative stress
GO:0007050	cell cycle arrest
GO:0007067	mitotic nuclear division
GO:0007165	signal transduction
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007264	small GTPase mediated signal transduction
GO:0007265	Ras protein signal transduction
GO:0007411	axon guidance
GO:0008283	cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0010628	positive regulation of gene expression
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030182	neuron differentiation
GO:0030216	keratinocyte differentiation
GO:0030335	positive regulation of cell migration
GO:0032320	positive regulation of Ras GTPase activity
GO:0032402	melanosome transport
GO:0032872	regulation of stress-activated MAPK cascade
GO:0032968	positive regulation of transcription elongation from RNA polymerase II promoter
GO:0034111	negative regulation of homotypic cell-cell adhesion
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0045087	innate immune response (InnateDB)
GO:0045597	positive regulation of cell differentiation
GO:0046579	positive regulation of Ras protein signal transduction
GO:0047496	vesicle transport along microtubule
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048313	Golgi inheritance
GO:0048678	response to axon injury
GO:0048812	neuron projection morphogenesis
GO:0048870	cell motility
GO:0051291	protein heterooligomerization
GO:0051384	response to glucocorticoid
GO:0051403	stress-activated MAPK cascade
GO:0060674	placenta blood vessel development
GO:0060711	labyrinthine layer development
GO:0071902	positive regulation of protein serine/threonine kinase activity
GO:0090170	regulation of Golgi inheritance
GO:0090398	cellular senescence
GO:2000641	regulation of early endosome to late endosome transport

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005769	early endosome
GO:0005770	late endosome
GO:0005794	Golgi apparatus
GO:0005815	microtubule organizing center
GO:0005829	cytosol
GO:0005874	microtubule
GO:0005886	plasma membrane
GO:0005925	focal adhesion
GO:0005938	cell cortex
GO:0030424	axon
GO:0030425	dendrite
GO:0032839	dendrite cytoplasm
GO:0043204	perikaryon
GO:0048471	perinuclear region of cytoplasm
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt