MP2K1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: MP2K1_MOUSE
• UniProt AC: P31938
• Protein Name: Dual specificity mitogen-activated protein kinase kinase 1
• Gene Name: Map2k1
• Organism: Mus musculus (Mouse).
• Sequence Length: 393
• Subcellular Localization: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome . Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body . Cytoplasm . Nucleus . Membrane ; Peripheral membrane protein . Localizes at centrosomes during prometapha
• Protein Description: 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..
• Protein Sequence: MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKVGELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELLFGCHVEGDAAETPPRPRTPGRPLSSYGMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAFIKRSDAEEVDFAGWLCSTIGLNQPSTPTHAASI

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
7	Phosphorylation	-MPKKKPTPIQLNPA -CCCCCCCCCCCCCC	41.73	25619855
24	Phosphorylation	GSAVNGTSSAETNLE CCCCCCCCCHHHHHH	29.02	25338131
25	Phosphorylation	SAVNGTSSAETNLEA CCCCCCCCHHHHHHH	29.93	22942356
72	Phosphorylation	DDDFEKISELGAGNG CCCHHHHHHCCCCCC	37.52	21454597
104	Ubiquitination	KLIHLEIKPAIRNQI EEHHHHCCHHHHHHH	21.01	22790023
168	Ubiquitination	IPEQILGKVSIAVIK CCHHHHHHHHHHHHH	29.39	22790023
175	Ubiquitination	KVSIAVIKGLTYLRE HHHHHHHHCHHHHHH	41.07	22790023
192	Ubiquitination	KIMHRDVKPSNILVN CCCCCCCCHHHEEEC	47.20	22790023
207	Glutathionylation	SRGEIKLCDFGVSGQ CCCCEEECCCCCCHH	3.28	24333276
212	Phosphorylation	KLCDFGVSGQLIDSM EECCCCCCHHHHHHH	22.62	15358159
218	Phosphorylation	VSGQLIDSMANSFVG CCHHHHHHHHHHCCC	16.89	22322096
222	Phosphorylation	LIDSMANSFVGTRSY HHHHHHHHCCCCCCC	16.27	22322096
226	Phosphorylation	MANSFVGTRSYMSPE HHHHCCCCCCCCCHH	15.90	26643407
231	Phosphorylation	VGTRSYMSPERLQGT CCCCCCCCHHHHCCC	18.51	22942356
286	Phosphorylation	VEGDAAETPPRPRTP EECCCCCCCCCCCCC	33.59	26824392
292	Phosphorylation	ETPPRPRTPGRPLSS CCCCCCCCCCCCCHH	32.55	26239621
298	Phosphorylation	RTPGRPLSSYGMDSR CCCCCCCHHCCCCCC	24.97	26239621
299	Phosphorylation	TPGRPLSSYGMDSRP CCCCCCHHCCCCCCC	33.13	26239621
300	Phosphorylation	PGRPLSSYGMDSRPP CCCCCHHCCCCCCCC	17.06	26239621
304	Phosphorylation	LSSYGMDSRPPMAIF CHHCCCCCCCCCHHH	37.48	26239621
316	Phosphorylation	AIFELLDYIVNEPPP HHHHHHHHHHCCCCC	13.51	26239621
353	Ubiquitination	PAERADLKQLMVHAF HHHHCCHHHHHHHHH	41.77	22790023
377	Phosphorylation	DFAGWLCSTIGLNQP CCHHHHHHHHCCCCC	22.38	23649490
385	Phosphorylation	TIGLNQPSTPTHAAS HHCCCCCCCCCCCCC	36.94	26239621
386	Phosphorylation	IGLNQPSTPTHAASI HCCCCCCCCCCCCCC	38.60	26239621
388	Phosphorylation	LNQPSTPTHAASI-- CCCCCCCCCCCCC--	25.00	26239621
392	Phosphorylation	STPTHAASI------ CCCCCCCCC------	29.61	26239621

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
218	S	Phosphorylation	Kinase	RAF	-	Uniprot
222	S	Phosphorylation	Kinase	RAF	-	Uniprot
286	T	Phosphorylation	Kinase	CDK5	P49615	PSP
292	T	Phosphorylation	Kinase	MAP3K1	Q13233	GPS
292	T	Phosphorylation	Kinase	M3K1	P53349	PhosphoELM
292	T	Phosphorylation	Kinase	MEKK1	Q62925	PSP
292	T	Phosphorylation	Kinase	ERK2	P63085	PSP
292	T	Phosphorylation	Kinase	MAPK3	Q63844	GPS
298	S	Phosphorylation	Kinase	PAK	-	Uniprot
386	T	Phosphorylation	Kinase	MAPK1	P63085	GPS
386	T	Phosphorylation	Kinase	MAPK3	Q63844	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
218	S	Phosphorylation	Autophosphorylated at Ser-218 and Ser-222, autophosphosphorylation is promoted by NEK10 following UV irradiation (By similarity).	10409742
218	S	Phosphorylation	Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (BRAF or MEKK1) positively regulates kinase activity.	10409742
222	S	Phosphorylation	Autophosphorylated at Ser-218 and Ser-222, autophosphosphorylation is promoted by NEK10 following UV irradiation (By similarity).	8385802
222	S	Phosphorylation	Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (BRAF or MEKK1) positively regulates kinase activity.	8385802
292	T	Phosphorylation	Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK.	19219045
292	T	Phosphorylation	MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK.	19219045
298	S	Phosphorylation	Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK.	19219045
298	S	Phosphorylation	MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK.	19219045

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of MP2K1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CPNE1_HUMAN	CPNE1	physical	12522145
CPNE4_HUMAN	CPNE4	physical	12522145
MYOD1_MOUSE	Myod1	physical	21454680
AXIN1_MOUSE	Axin1	physical	12223491
MK01_MOUSE	Mapk1	physical	21144847
PAXI_MOUSE	Pxn	physical	14636584
MK01_MOUSE	Mapk1	physical	11435472
AXIN1_MOUSE	Axin1	physical	18316368

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.