MP2K6_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: MP2K6_MOUSE
• UniProt AC: P70236
• Protein Name: Dual specificity mitogen-activated protein kinase kinase 6
• Gene Name: Map2k6
• Organism: Mus musculus (Mouse).
• Sequence Length: 334
• Subcellular Localization: Nucleus. Cytoplasm. Cytoplasm, cytoskeleton. Binds to microtubules..
• Protein Description: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases..
• Protein Sequence: MSQSKGKKRNPGLKIPKEAFEQPQTSSTPPRDLDSKACISIGNQNFEVKADDLEPIVELGRGAYGVVEKMRHVPSGQIMAVKRIRATVNSQEQKRLLMDLDVSMRTVDCPFTVTFYGALFREGDVWICMELMDTSLDKFYKQVIDKGQTIPEDILGKIAVSIVKALEHLHSKLSVIHRDVKPSNVLINTLGQVKMCDFGISGYLVDSVAKTIDAGCKPYMAPERINPELNQKGYSVKSDIWSLGITMIELAILRFPYDSWGTPFQQLKQVVEEPSPQLPADKFSADFVDFTSQCLKKNSKERPTYPELMQHPFFTVHESKAADVASFVKLILGD

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
25	Phosphorylation	EAFEQPQTSSTPPRD HHHCCCCCCCCCCCC	31.18	29899451
26	Phosphorylation	AFEQPQTSSTPPRDL HHCCCCCCCCCCCCC	27.28	25619855
27	Phosphorylation	FEQPQTSSTPPRDLD HCCCCCCCCCCCCCC	48.60	25619855
28	Phosphorylation	EQPQTSSTPPRDLDS CCCCCCCCCCCCCCC	36.76	28542873
35	Phosphorylation	TPPRDLDSKACISIG CCCCCCCCCEEEEEC	29.47	23984901
40	Phosphorylation	LDSKACISIGNQNFE CCCCEEEEECCCCEE	25.07	28464351
207	Phosphorylation	ISGYLVDSVAKTIDA CCCEEHHHHHHHHCC	19.25	22322096
211	Phosphorylation	LVDSVAKTIDAGCKP EHHHHHHHHCCCCCC	17.85	22322096
232	Ubiquitination	INPELNQKGYSVKSD CCHHHHHCCCCCHHH	59.76	22790023

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
207	S	Phosphorylation	Kinase	MAPK3	Q63844	Uniprot
211	T	Phosphorylation	Kinase	MAPK3	Q63844	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
207	S	Phosphorylation	Phosphorylated at Ser-207 and Thr-211 by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.	-
211	T	Phosphorylation	Phosphorylated at Ser-207 and Thr-211 by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of MP2K6_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MK14_MOUSE	Mapk14	physical	15644321

Drug and Disease Associations

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