dbPTM

MP2K1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MP2K1_HUMAN
UniProt AC	Q02750
Protein Name	Dual specificity mitogen-activated protein kinase kinase 1
Gene Name	MAP2K1
Organism	Homo sapiens (Human).
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	MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKVGELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSYGMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAFIKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAGV

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
18	Phosphorylation	LNPAPDGSAVNGTSS CCCCCCCCCCCCCCC	36.10	28555341
23	Phosphorylation	DGSAVNGTSSAETNL CCCCCCCCCCHHHHH	17.82	7873542
24	Phosphorylation	GSAVNGTSSAETNLE CCCCCCCCCHHHHHH	29.02	29523821
25	Phosphorylation	SAVNGTSSAETNLEA CCCCCCCCHHHHHHH	29.93	29523821
28	Phosphorylation	NGTSSAETNLEALQK CCCCCHHHHHHHHHH	44.83	25022875
36	Ubiquitination	NLEALQKKLEELELD HHHHHHHHHHHCCCH	48.44	21890473
55	Phosphorylation	KRLEAFLTQKQKVGE HHHHHHHHHHHHHCC	27.54	-
57	Ubiquitination	LEAFLTQKQKVGELK HHHHHHHHHHHCCCC	47.02	21890473
64	Ubiquitination	KQKVGELKDDDFEKI HHHHCCCCCCCHHHH	55.60	21890473
64	Acetylation	KQKVGELKDDDFEKI HHHHCCCCCCCHHHH	55.60	23236377
70	Ubiquitination	LKDDDFEKISELGAG CCCCCHHHHHHCCCC	52.07	-
72	Phosphorylation	DDDFEKISELGAGNG CCCHHHHHHCCCCCC	37.52	25159151
88	Ubiquitination	VVFKVSHKPSGLVMA EEEEEECCCCCEEEE	33.11	-
97	Ubiquitination	SGLVMARKLIHLEIK CCEEEEEEEHHHHCC	42.10	-
104	Sumoylation	KLIHLEIKPAIRNQI EEHHHHCCHHHHHHH	21.01	-
104	Sumoylation	KLIHLEIKPAIRNQI EEHHHHCCHHHHHHH	21.01	-
104	Ubiquitination	KLIHLEIKPAIRNQI EEHHHHCCHHHHHHH	21.01	21890473
168	Ubiquitination	IPEQILGKVSIAVIK CCHHHHHHHHHHHHH	29.39	-
175	Ubiquitination	KVSIAVIKGLTYLRE HHHHHHHHCHHHHHH	41.07	21890473
175	Acetylation	KVSIAVIKGLTYLRE HHHHHHHHCHHHHHH	41.07	70960685
192	Ubiquitination	KIMHRDVKPSNILVN CCCCCCCCHHHEEEC	47.20	21890473
194	Phosphorylation	MHRDVKPSNILVNSR CCCCCCHHHEEECCC	30.68	21406692
200	Phosphorylation	PSNILVNSRGEIKLC HHHEEECCCCCEEEC	33.90	21406692
205	Ubiquitination	VNSRGEIKLCDFGVS ECCCCCEEECCCCCC	38.47	21890473
212	Phosphorylation	KLCDFGVSGQLIDSM EECCCCCCHHHHHHH	22.62	22322096
218	Phosphorylation	VSGQLIDSMANSFVG CCHHHHHHHHHHCCC	16.89	21487005
222	Phosphorylation	LIDSMANSFVGTRSY HHHHHHHHCCCCCCC	16.27	21487005
226	Phosphorylation	MANSFVGTRSYMSPE HHHHCCCCCCCCCHH	15.90	29255136
228	Phosphorylation	NSFVGTRSYMSPERL HHCCCCCCCCCHHHH	25.65	26074081
229	Phosphorylation	SFVGTRSYMSPERLQ HCCCCCCCCCHHHHC	9.79	26074081
231	Phosphorylation	VGTRSYMSPERLQGT CCCCCCCCHHHHCCC	18.51	17192257
238	Phosphorylation	SPERLQGTHYSVQSD CHHHHCCCCCCHHHH	12.51	26074081
277	Glutathionylation	ELELMFGCQVEGDAA HHHHHEECEEECCCC	2.54	22555962
286	Phosphorylation	VEGDAAETPPRPRTP EECCCCCCCCCCCCC	33.59	25159151
292	Phosphorylation	ETPPRPRTPGRPLSS CCCCCCCCCCCCCHH	32.55	25159151
298	Phosphorylation	RTPGRPLSSYGMDSR CCCCCCCHHCCCCCC	24.97	18042262
299	Phosphorylation	TPGRPLSSYGMDSRP CCCCCCHHCCCCCCC	33.13	25159151
300	Phosphorylation	PGRPLSSYGMDSRPP CCCCCHHCCCCCCCC	17.06	29496963
304	Phosphorylation	LSSYGMDSRPPMAIF CHHCCCCCCCCCHHH	37.48	29496963
316	Phosphorylation	AIFELLDYIVNEPPP HHHHHHHHHHCCCCC	13.51	17192257
344	Ubiquitination	FVNKCLIKNPAERAD HHHHHHCCCHHHHCC	43.88	-
353	Ubiquitination	PAERADLKQLMVHAF HHHHCCHHHHHHHHH	41.77	21890473
353	Acetylation	PAERADLKQLMVHAF HHHHCCHHHHHHHHH	41.77	25953088
362	Acetylation	LMVHAFIKRSDAEEV HHHHHHHCCCCHHHC	39.12	70960691
377	Phosphorylation	DFAGWLCSTIGLNQP CCHHHHHHHHCCCCC	22.38	29514088
378	Phosphorylation	FAGWLCSTIGLNQPS CHHHHHHHHCCCCCC	20.33	29514088
385	Phosphorylation	TIGLNQPSTPTHAAG HHCCCCCCCCCCCCC	36.94	25159151
386	Phosphorylation	IGLNQPSTPTHAAGV HCCCCCCCCCCCCCC	38.60	25159151
388	Phosphorylation	LNQPSTPTHAAGV-- CCCCCCCCCCCCC--	25.00	30183078

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
23	T	Phosphorylation	Kinase	MAP2K_GROUP	-	PhosphoELM
23	T	Phosphorylation	Kinase	MAP2K-FAMILY	-	GPS
24	S	Phosphorylation	Kinase	MAP2K_GROUP	-	PhosphoELM
24	S	Phosphorylation	Kinase	MAP2K-FAMILY	-	GPS
25	S	Phosphorylation	Kinase	MAP2K_GROUP	-	PhosphoELM
25	S	Phosphorylation	Kinase	MAP2K-FAMILY	-	GPS
55	T	Phosphorylation	Kinase	CHEK1	O14757	GPS
218	S	Phosphorylation	Kinase	ARAF	P10398	PSP
218	S	Phosphorylation	Kinase	MAP3K_GROUP	-	PhosphoELM
218	S	Phosphorylation	Kinase	MAP2K_GROUP	-	PhosphoELM
218	S	Phosphorylation	Kinase	MAP3K-FAMILY	-	GPS
218	S	Phosphorylation	Kinase	MAP2K-FAMILY	-	GPS
218	S	Phosphorylation	Kinase	RAF1	Q99N57	PSP
218	S	Phosphorylation	Kinase	RAF1	P04049	Uniprot
218	S	Phosphorylation	Kinase	PLK1	P53350	PSP
218	S	Phosphorylation	Kinase	MOS	P00536	PSP
218	S	Phosphorylation	Kinase	BRAF	P15056	Uniprot
218	S	Phosphorylation	Kinase	MAP3K8	P41279	GPS
222	S	Phosphorylation	Kinase	MAP3K_GROUP	-	PhosphoELM
222	S	Phosphorylation	Kinase	PDK1	Q15118	GPS
222	S	Phosphorylation	Kinase	PDPK1	O15530	PhosphoELM
222	S	Phosphorylation	Kinase	PLK1	P53350	PSP
222	S	Phosphorylation	Kinase	MAP3K-FAMILY	-	GPS
222	S	Phosphorylation	Kinase	ARAF	P10398	PSP
222	S	Phosphorylation	Kinase	RAF1	P04049	Uniprot
222	S	Phosphorylation	Kinase	RAF1	Q99N57	PSP
222	S	Phosphorylation	Kinase	BRAF	P15056	Uniprot
222	S	Phosphorylation	Kinase	MAP3K8	P41279	GPS
222	S	Phosphorylation	Kinase	MOS	P00536	PSP
286	T	Phosphorylation	Kinase	CDK1	P06493	PSP
286	T	Phosphorylation	Kinase	CDK_GROUP	-	PhosphoELM
286	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
286	T	Phosphorylation	Kinase	CDK-FAMILY	-	GPS
286	T	Phosphorylation	Kinase	MAPK3	P27361	GPS
292	T	Phosphorylation	Kinase	CDK1	P06493	PSP
292	T	Phosphorylation	Kinase	MK01	P28482	PhosphoELM
292	T	Phosphorylation	Kinase	CDK5	Q00535	PSP
292	T	Phosphorylation	Kinase	MAPK3	P27361	GPS
298	S	Phosphorylation	Kinase	MAP2K_GROUP	-	PhosphoELM
298	S	Phosphorylation	Kinase	PAK	-	Uniprot
298	S	Phosphorylation	Kinase	MAP2K-FAMILY	-	GPS
298	S	Phosphorylation	Kinase	PAK1	Q13153	PSP
386	T	Phosphorylation	Kinase	MAPK1	P28482	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
218	S	Phosphorylation	10409742
Autophosphorylated at Ser-218 and Ser-222, autophosphosphorylation is promoted by NEK10 following UV irradiation.
218	S	Phosphorylation	10409742
Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (BRAF or MEKK1) positively regulates kinase activity.
222	S	Phosphorylation	8131746
Autophosphorylated at Ser-218 and Ser-222, autophosphosphorylation is promoted by NEK10 following UV irradiation.
222	S	Phosphorylation	8131746
Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (BRAF or MEKK1) positively regulates kinase activity.
292	T	Phosphorylation	16129686
Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK.
292	T	Phosphorylation	16129686
MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK.
298	S	Phosphorylation	16129686
Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK.
298	S	Phosphorylation	16129686
MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of MP2K1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
KSR2_HUMAN	KSR2	physical	12975377
MK01_HUMAN	MAPK1	physical	12697810
FLNA_MOUSE	Flna	physical	9006895
MK03_HUMAN	MAPK3	physical	9006895
MK01_HUMAN	MAPK1	physical	11823456
RAF1_HUMAN	RAF1	physical	10757792
PEBP1_HUMAN	PEBP1	physical	10757792
MK01_HUMAN	MAPK1	physical	10757792
LTOR2_HUMAN	LAMTOR2	physical	11266467
LTOR3_HUMAN	LAMTOR3	physical	11266467
MK03_HUMAN	MAPK3	physical	8626767
LTOR3_HUMAN	LAMTOR3	physical	9733512
M3K1_HUMAN	MAP3K1	physical	10969079
GRB10_HUMAN	GRB10	physical	9553107
MP2K1_HUMAN	MAP2K1	physical	8226933
MK03_HUMAN	MAPK3	physical	8226933
MK01_HUMAN	MAPK1	physical	11352917
MK01_HUMAN	MAPK1	physical	11279118
WNK1_HUMAN	WNK1	physical	20936779
RAF1_HUMAN	RAF1	physical	15485920
KSR1_MOUSE	Ksr1	physical	10409742
MP2K2_HUMAN	MAP2K2	physical	10409742
BRAF_HUMAN	BRAF	physical	16888650
WDR83_HUMAN	WDR83	physical	15118098
LSP1_HUMAN	LSP1	physical	15090600
KSR1_HUMAN	KSR1	physical	15090600
MP2K1_HUMAN	MAP2K1	physical	17979178
ARAF_HUMAN	ARAF	physical	17979178
BRAF_HUMAN	BRAF	physical	17979178
KSR1_HUMAN	KSR1	physical	17979178
RAF1_HUMAN	RAF1	physical	17979178
1433B_HUMAN	YWHAB	physical	17979178
1433Z_HUMAN	YWHAZ	physical	17979178
HSP7C_HUMAN	HSPA8	physical	17979178
1433E_HUMAN	YWHAE	physical	17979178
MK01_HUMAN	MAPK1	physical	12788955
RAF1_HUMAN	RAF1	physical	16093354
FBW1A_HUMAN	BTRC	physical	24211253
BANP_HUMAN	BANP	physical	25416956
PPARG_HUMAN	PPARG	physical	17101779
PTN11_HUMAN	PTPN11	physical	26344197
ARAF_HUMAN	ARAF	physical	26496610
BRAF_HUMAN	BRAF	physical	26496610
RAF1_HUMAN	RAF1	physical	26496610
KSR1_HUMAN	KSR1	physical	26496610
ZN277_HUMAN	ZNF277	physical	26496610
RBM33_HUMAN	RBM33	physical	26496610
VHL_HUMAN	VHL	genetic	28319113
TUSC3_HUMAN	TUSC3	genetic	27453043
MTOR_HUMAN	MTOR	genetic	27453043
TITIN_HUMAN	TTN	genetic	27453043
FUMH_HUMAN	FH	genetic	27453043
ING5_HUMAN	ING5	genetic	27453043
BLM_HUMAN	BLM	genetic	27453043
ATAD5_HUMAN	ATAD5	genetic	27453043
STK11_HUMAN	STK11	genetic	27453043

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
615279	Cardiofaciocutaneous syndrome 3 (CFC3)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB06616	Bosutinib
DB08911	Trametinib

Regulatory Network of MP2K1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-385, AND MASSSPECTROMETRY.	19369195 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231; THR-286 ANDTHR-386, AND MASS SPECTROMETRY.	18691976 [Abstract]
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry."; Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.; Mol. Cell. Proteomics 6:537-547(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-222, AND MASSSPECTROMETRY.	17192257 [Abstract]
"Activation of MEK family kinases requires phosphorylation of twoconserved Ser/Thr residues."; Zheng C.-F., Guan K.-L.; EMBO J. 13:1123-1131(1994). Cited for: PHOSPHORYLATION AT SER-218 AND SER-222, AND MUTAGENESIS.	8131746 [Abstract]

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