Reactome | p-S218,S222-MAP2K1 [cytosol]

p-S218,S222-MAP2K1

Stable Identifier

R-HSA-109837

Type

Protein [EntityWithAccessionedSequence]

Species

Homo sapiens

Compartment

cytosol

Synonyms

p-S218,222-MEK1, Dual specificity mitogen-activated protein kinase kinase 1(phosphorylated), MAP kinase kinase 1(phosphorylated), p-S218,222-MAPKK 1, ERK activator kinase 1(phosphorylated), MAPK/ERK kinase 1

Locations in the PathwayBrowser

Expand all

Immune System (Homo sapiens)

- Cytokine Signaling in Immune system (Homo sapiens)
  - Signaling by Interleukins (Homo sapiens)
    - Interleukin-1 family signaling (Homo sapiens)
      - Interleukin-1 signaling (Homo sapiens)
        
        MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
        
        TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
        
        p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol] (Homo sapiens)
        
        p-S218,S222-MAP2K1 [cytosol] (Homo sapiens)
    - Interleukin-17 signaling (Homo sapiens)
      - MAP kinase activation (Homo sapiens)
        
        MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
        
        TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
        
        p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol] (Homo sapiens)
        
        p-S218,S222-MAP2K1 [cytosol] (Homo sapiens)
- Innate Immune System (Homo sapiens)
  - Toll-Like Receptors Cascades (Homo sapiens)
    - Toll Like Receptor 10 (TLR10) Cascade (Homo sapiens)
      - MyD88 cascade initiated on plasma membrane (Homo sapiens)
        
        MAP kinase activation (Homo sapiens)
        
        MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
        
        TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
        
        p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol] (Homo sapiens)
        
        p-S218,S222-MAP2K1 [cytosol] (Homo sapiens)
    - Toll Like Receptor 2 (TLR2) Cascade (Homo sapiens)
      - Toll Like Receptor TLR1:TLR2 Cascade (Homo sapiens)
        
        MyD88:Mal cascade initiated on plasma membrane (Homo sapiens)
        
        MAP kinase activation (Homo sapiens)
        
        MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
        
        TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
        
        p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol] (Homo sapiens)
        
        p-S218,S222-MAP2K1 [cytosol] (Homo sapiens)
      - Toll Like Receptor TLR6:TLR2 Cascade (Homo sapiens)
        
        MyD88:Mal cascade initiated on plasma membrane (Homo sapiens)
        
        MAP kinase activation (Homo sapiens)
        
        MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
        
        TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
        
        p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol] (Homo sapiens)
        
        p-S218,S222-MAP2K1 [cytosol] (Homo sapiens)
    - Toll Like Receptor 3 (TLR3) Cascade (Homo sapiens)
      - MAP kinase activation (Homo sapiens)
        
        MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
        
        TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
        
        p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol] (Homo sapiens)
        
        p-S218,S222-MAP2K1 [cytosol] (Homo sapiens)
    - Toll Like Receptor 4 (TLR4) Cascade (Homo sapiens)
      - MyD88-independent TLR4 cascade (Homo sapiens)
        
        TRIF(TICAM1)-mediated TLR4 signaling (Homo sapiens)
        
        MAP kinase activation (Homo sapiens)
        
        MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
        
        TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
        
        p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol] (Homo sapiens)
        
        p-S218,S222-MAP2K1 [cytosol] (Homo sapiens)
      - MyD88:Mal cascade initiated on plasma membrane (Homo sapiens)
        
        MAP kinase activation (Homo sapiens)
        
        MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
        
        TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
        
        p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol] (Homo sapiens)
        
        p-S218,S222-MAP2K1 [cytosol] (Homo sapiens)
    - Toll Like Receptor 5 (TLR5) Cascade (Homo sapiens)
      - MyD88 cascade initiated on plasma membrane (Homo sapiens)
        
        MAP kinase activation (Homo sapiens)
        
        MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
        
        TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
        
        p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol] (Homo sapiens)
        
        p-S218,S222-MAP2K1 [cytosol] (Homo sapiens)
    - Toll Like Receptor 7/8 (TLR7/8) Cascade (Homo sapiens)
      - MyD88 dependent cascade initiated on endosome (Homo sapiens)
        
        TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation (Homo sapiens)
        
        MAP kinase activation (Homo sapiens)
        
        MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
        
        TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
        
        p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol] (Homo sapiens)
        
        p-S218,S222-MAP2K1 [cytosol] (Homo sapiens)
    - Toll Like Receptor 9 (TLR9) Cascade (Homo sapiens)
      - MyD88 dependent cascade initiated on endosome (Homo sapiens)
        
        TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation (Homo sapiens)
        
        MAP kinase activation (Homo sapiens)
        
        MAP3K8 (TPL2)-dependent MAPK1/3 activation (Homo sapiens)
        
        TPL2 phosphorylates MEK1, SEK1 (Homo sapiens)
        
        p-S218,S222-MAP2K1,p-S257,T261-MAP2K4 [cytosol] (Homo sapiens)
        
        p-S218,S222-MAP2K1 [cytosol] (Homo sapiens)

External Reference Information

External Reference

UniProt:Q02750 MAP2K1

Gene Names

MAP2K1, MEK1, PRKMK1

Chain

chain:1-393

Reference Genes

BioGPS Gene:5604 MAP2K1

COSMIC (genes):MAP2K1 MAP2K1

CTD Gene:5604 MAP2K1

dbSNP Gene:5604 MAP2K1

ENSEMBL:ENSG00000169032 MAP2K1

HGNC:6840 MAP2K1

KEGG Gene (Homo sapiens):hsa:5604 MAP2K1

Monarch:5604 MAP2K1

NCBI Gene:5604 MAP2K1

OMIM:176872 MAP2K1

UCSC:Q02750 MAP2K1

Reference Transcript

Other Identifiers

0001740347

1130_at

11717291_a_at

11749555_a_at

11757478_s_at

16802190

1844_s_at

1S9J

202670_at

26430

2P55

3834

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

5604

5BX0

5EYM

5HZE

7984319

A4QPA9

A_23_P20248

AAA36318

AAI37460

AAI39730

AK291500

BAF84189

BC137459

BC139729

CAB003834

CCDS10216

CH471082

EAW77765

ENSG00000169032

ENSP00000302486

ENST00000307102

EntrezGene:5604

GE57608

GO:0000003

GO:0000165

GO:0000166

GO:0000187

GO:0000278

GO:0000902

GO:0001932

GO:0002376

GO:0003674

GO:0004672

GO:0004674

GO:0004708

GO:0004712

GO:0004713

GO:0004728

GO:0004871

GO:0005515

GO:0005524

GO:0005575

GO:0005576

GO:0005615

GO:0005622

GO:0005623

GO:0005634

GO:0005737

GO:0005739

GO:0005768

GO:0005769

GO:0005770

GO:0005783

GO:0005794

GO:0005815

GO:0005829

GO:0005856

GO:0005886

GO:0005925

GO:0006412

GO:0006464

GO:0006468

GO:0006810

GO:0006928

GO:0006935

GO:0006950

GO:0007049

GO:0007050

GO:0007165

GO:0007346

GO:0007507

GO:0007568

GO:0008022

GO:0008150

GO:0008219

GO:0008283

GO:0008285

GO:0009058

GO:0009790

GO:0010628

GO:0010629

GO:0016020

GO:0016192

GO:0016301

GO:0016310

GO:0016740

GO:0016791

GO:0018108

GO:0021697

GO:0030154

GO:0030182

GO:0030216

GO:0030234

GO:0030878

GO:0031410

GO:0032872

GO:0034641

GO:0035897

GO:0040011

GO:0042981

GO:0043167

GO:0043226

GO:0043539

GO:0045597

GO:0045893

GO:0047485

GO:0048538

GO:0048646

GO:0048679

GO:0048856

GO:0048870

GO:0050772

GO:0060020

GO:0060324

GO:0060425

GO:0060440

GO:0060502

GO:0060674

GO:0060711

GO:0070062

GO:0070371

GO:0070374

GO:0071902

GO:0090170

GO:0090398

GO:1903800

GO:2000641

HGNC:6840

HPA026430

Hs.3446.0.A2_3p_at

ILMN_1694240

IPR000719

IPR008271

IPR011009

IPR017441

L05624

L05624_s_at

L11284

L11284_at

LRG_725

LRG_725t1

MAP2K1

MAP2K1-201

MIM:163950

MIM:176872

MIM:615279

NM_002755

NP_002746

PF00069

PH_hs_0022483

SM00220

TC15000613.hg

uc010bhq.4

UPI000013EBC9

XM_011521783

XM_017022411

XM_017022412

XP_011520085

XP_016877900

XP_016877901

Participant Of

input

MAP2K1 binds MAPK3

hasMember

hasComponent

output

Dissociation of p-T,Y-MAPK3:MAP2K1

Other forms of this molecule

MAP2K1(9-393) [cytosol]

MAP2K1(2-8) [cytosol]

p-S,218, S222,T292 MAP2K1 [cytosol]

p-T286,T292-MAP2K1 [cytosol]

p-S218,S222,T286,T292-MAP2K1 [cytosol]

MAP2K1 [cytosol]

Inferred To

Homologues of p-S218,S222-MAP2K1 [cytosol] (Arabidopsis thaliana)

Homologues of p-S218,S222-MAP2K1 [cytosol] (Canis familiaris)

Homologues of p-S218,S222-MAP2K1 [cytosol] (Oryza sativa)

Homologues of p-S218,S222-MAP2K1 [cytosol] (Schizosaccharomyces pombe)

phospho-p-S218,S222-MAP2K1 [cytosol] (Arabidopsis thaliana)

phospho-p-S218,S222-MAP2K1 [cytosol] (Bos taurus)

phospho-p-S218,S222-MAP2K1 [cytosol] (Caenorhabditis elegans)

phospho-p-S218,S222-MAP2K1 [cytosol] (Canis familiaris)

phospho-p-S218,S222-MAP2K1 [cytosol] (Danio rerio)

phospho-p-S218,S222-MAP2K1 [cytosol] (Dictyostelium discoideum)

phospho-p-S218,S222-MAP2K1 [cytosol] (Drosophila melanogaster)

phospho-p-S218,S222-MAP2K1 [cytosol] (Gallus gallus)

phospho-p-S218,S222-MAP2K1 [cytosol] (Mus musculus)

phospho-p-S218,S222-MAP2K1 [cytosol] (Oryza sativa)

phospho-p-S218,S222-MAP2K1 [cytosol] (Rattus norvegicus)

phospho-p-S218,S222-MAP2K1 [cytosol] (Saccharomyces cerevisiae)

phospho-p-S218,S222-MAP2K1 [cytosol] (Schizosaccharomyces pombe)

phospho-p-S218,S222-MAP2K1 [cytosol] (Sus scrofa)

phospho-p-S218,S222-MAP2K1 [cytosol] (Taeniopygia guttata)

phospho-p-S218,S222-MAP2K1 [cytosol] (Xenopus tropicalis)

Modified Residues

Name

O-phospho-L-serine at 218

Coordinate

218

PsiMod Name

O-phospho-L-serine [MOD:00046]

PsiMod Definition

A protein modification that effectively converts an L-serine residue to O-phospho-L-serine.

Name

O-phospho-L-serine at 222

Coordinate

222

PsiMod Name

O-phospho-L-serine [MOD:00046]

PsiMod Definition

A protein modification that effectively converts an L-serine residue to O-phospho-L-serine.

Cross References

RefSeq

XP_016877900.1, NP_002746.1

ZINC - World Drugs

MP2K1_HUMAN

Brenda

2.7.12.2

ZINC - FDA approved

MP2K1_HUMAN

ZINC - Substances

MP2K1_HUMAN

ZINC - Biogenic

MP2K1_HUMAN

ZINC target

Q02750

PRO

Q02750

PDB

4U7Z, 3SLS, 3V01, 3DV3, 4U80, 3V04, 4U81, 3DY7, 3VVH, 3W8Q, 3E8N, 4ANB, 3MBL, 4ARK, 3ORN, 4LMN, 3OS3, 1S9J, 3PP1, 2P55, 4MNE, 3ZM4, 3EQF, 4AN2, 3EQG, 3EQD, 3ZLY, 3ZLX, 3EQC, 3ZLW, 5HZE, 5EYM, 3ZLS, 3EQB, 3WIG, 5BX0, 3EQI, 4AN9, 3EQH, 4AN3

ZINC - Metabolites

MP2K1_HUMAN

GeneCards

Q02750

DOCK Blaster

1S9J, 4AN9, 3DV3, 4AN2, 3SLS, 4AN3, 3VVH, 3DY7, 3PP1, 4ANB, 3W8Q, 3ORN, 5HZE, 2P55, 4U7Z, 4ARK, 4LMN, 3EQG, 5EYM, 3EQH, 3EQI, 3EQB, 3EQC, 3EQD, 4U81, 4U80, 3ZM4, 3V04, 3ZLS, 3V01, 3MBL, 3ZLY, 3ZLX, 3ZLW, 3OS3, 5BX0, 4MNE, 3WIG, 3E8N, 3EQF

ZINC - Predictions - Purchasable

MP2K1_HUMAN

Orphanet

16377

Interactors (19)

Accession	#Entities	Entities	Confidence Score	Evidence (IntAct)
UniProt:P15056 BRAF	35	p-BRAF-MACF1 fusion [cytosol] (R-HSA-6802536) BRAF-MACF1fusion [cytosol] (R-HSA-6802402) D594N BRAF [cytosol] (R-HSA-6802299) G596R BRAF [cytosol] (R-HSA-6802385) D594V BRAF [cytosol] (R-HSA-6802305) G466E BRAF [cytosol] (R-HSA-6802374) D594G BRAF [cytosol] (R-HSA-6802295) F595L BRAF [cytosol] (R-HSA-6802316) L597V BRAF [cytosol] (R-HSA-6802397) G464E BRAF [cytosol] (R-HSA-6802369) E586K BRAF [cytosol] (R-HSA-6802308) V600K BRAF [cytosol] (R-HSA-6802502) p-L597V BRAF [plasma membrane] (R-HSA-8936647) p-G464E BRAF [plasma membrane] (R-HSA-8936645) p-F595L BRAF [plasma membrane] (R-HSA-8936641) p-E586K BRAF [plasma membrane] (R-HSA-8936639) p-V600K BRAF [plasma membrane] (R-HSA-8936651) BRAF 599dupT [cytosol] (R-HSA-6802281) G469A BRAF [cytosol] (R-HSA-6802381) V600E BRAF [cytosol] (R-HSA-6802498) V600E BRAF V169_M438del [cytosol] (R-HSA-6802489) V600E BRAF V47_D380del [cytosol] (R-HSA-6802491) V600E BRAF V47_M438del [cytosol] (R-HSA-6802495) V600E BRAF V169_D380del [cytosol] (R-HSA-6802486) p-S445,S729-BRAF [plasma membrane] (R-HSA-8933622) p-S,T-BRAF [cytosol] (R-HSA-169856) BRAF [endosome] (R-HSA-190063) p-S338-BRAF [plasma membrane] (R-HSA-1063700) BRAF [plasma membrane] (R-HSA-934547) hyperphosphorylated BRAF [plasma membrane] (R-HSA-5675199) p-S365,S445,S729 BRAF [cytosol] (R-HSA-5672667) BRAF [cytosol] (R-HSA-167224) p-S445,T599,S602,S729 BRAF [plasma membrane] (R-HSA-5672679) p-S445,S729-BRAF [cytosol] (R-HSA-5672673) p-S445,T599,S602,S729 BRAF [cytosol] (R-HSA-5672676)	0.976	58
UniProt:P04049 RAF1	11	p-S338-RAF1 [cytosol] (R-HSA-5624469) p-S338,Y340,Y341-RAF1 [cytosol] (R-HSA-5624465) RAF1 [cytosol] (R-HSA-167205) p-S338-RAF1 [plasma membrane] (R-HSA-444236) p-S621-RAF1 [plasma membrane] (R-HSA-206222) hyperphosphorylated RAF1 [plasma membrane] (R-HSA-5675193) p-Y341,T491,S494,S621 RAF1 [plasma membrane] (R-HSA-5675420) p-S259,S621-RAF1 [cytosol] (R-HSA-109786) p-S621-RAF1 [cytosol] (R-HSA-206028) p-S338,Y341,T491,S494,S621 RAF1 [plasma membrane] (R-HSA-5672665) p-S338,Y341,T491,S494,S621 RAF1 [cytosol] (R-HSA-5672664)	0.952	35
UniProt:P10398 ARAF	4	p-S299,S302,T452,T455,S576 ARAF [plasma membrane] (R-HSA-5672648) p-S299,S302,T452,T455,S576 ARAF [cytosol] (R-HSA-5672646) p-S576 ARAF [cytosol] (R-HSA-5672681) p-S214,S576 ARAF [cytosol] (R-HSA-5672639)	0.69	5
UniProt:Q8IVT5 KSR1	5	p-S311,S406 KSR1 [cytosol] (R-HSA-5672654) KSR1 [cytosol] (R-HSA-5672587) p-S311 KSR1 [cytosol] (R-HSA-5672652) p-S311,Y552 KSR1 [plasma membrane] (R-HSA-5672659) p-S311,Y552 KSR1 [cytosol] (R-HSA-5672656)	0.643	7
UniProt:P28482 MAPK1	7	MAPK1 [extracellular region] (R-HSA-6806250) MAPK1 [ficolin-1-rich granule lumen] (R-HSA-6800964) MAPK1 [azurophil granule lumen] (R-HSA-6799225) MAPK1 [nucleoplasm] (R-HSA-199960) MAPK1 [cytosol] (R-HSA-59282) p-T185,Y187-MAPK1 [nucleoplasm] (R-HSA-112354) p-T185,Y187-MAPK1 [cytosol] (R-HSA-109853)	0.609	2
UniProt:Q8N9N5 BANP	1	BANP [nucleoplasm] (R-HSA-3221973)	0.556	3
UniProt:Q9Y297 BTRC	2	BTRC [nucleoplasm] (R-HSA-3361753) BTRC [cytosol] (R-HSA-174237)	0.556	3
UniProt:P46937 YAP1	7	p-5S-YAP1 [cytosol] (R-HSA-2028554) p-S127-YAP1 [cytosol] (R-HSA-2028553) p-Y407-YAP1 [nucleoplasm] (R-HSA-8956661) YAP1 [nucleoplasm] (R-HSA-1253322) YAP1 [cytosol] (R-HSA-1253345) p-Y-YAP1 [cytosol] (R-HSA-8937843) p-Y-YAP1 [nucleoplasm] (R-HSA-8937857)	0.556	3
UniProt:P31946 YWHAB	2	YWHAB [endosome] (R-HSA-190058) YWHAB [cytosol] (R-HSA-48888)	0.527	2
UniProt:Q86Y07 VRK2			0.524	2
UniProt:Q61097	5	phospho-p-S311,S406 KSR1 [cytosol] (R-MMU-5672654) KSR1 [cytosol] (R-MMU-5672587) phospho-p-S311 KSR1 [cytosol] (R-MMU-5672652) phospho-p-S311,Y552 KSR1 [plasma membrane] (R-MMU-5672659) phospho-p-S311,Y552 KSR1 [cytosol] (R-MMU-5672656)	0.508	2
UniProt:Q13526 PIN1	1	PIN1 [nucleoplasm] (R-HSA-936016)	0.508	5
UniProt:P27361 MAPK3	4	p-T202,Y204-MAPK3 [nucleoplasm] (R-HSA-112359) p-T202,Y204-MAPK3 [cytosol] (R-HSA-109842) MAPK3 [cytosol] (R-HSA-59284) MAPK3 [nucleoplasm] (R-HSA-73724)	0.499	2
UniProt:Q86Y07-1 VRK2			0.499	2
UniProt:Q8N9N5-2 BANP			0.488	2
UniProt:Q9H8W4 PKHF2			0.488	4
UniProt:Q49A26-4 GLYR1			0.488	2
UniProt:Q96S96 PEBP4			0.462	3
UniProt:O75832 PSMD10	2	PSMD10 [cytosol] (R-HSA-68788) PSMD10 [nucleoplasm] (R-HSA-174322)	0.462	2