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

p-S218,S222-MAP2K1 [cytosol]

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

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Locations in the PathwayBrowser

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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 Receptor 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(TIRAP) 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(TIRAP) 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(TIRAP) 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

ENSEMBL_homo_sapiens_GENE:ENSG00000169032.11 MAP2K1

HGNC:6840 MAP2K1

KEGG Gene (Homo sapiens):5604 MAP2K1

Monarch:5604 MAP2K1

NCBI Gene:5604 MAP2K1

OMIM:176872 MAP2K1

UCSC:Q02750 MAP2K1

Reference Transcript

Other Identifiers

1130_at

11717291_a_at

11749555_a_at

11757478_s_at

16802190

1844_s_at

202670_PM_at

202670_at

3092255

3092256

3092264

3598663

3598664

3598670

3598671

3598672

3598673

3598688

3598690

3598691

3598692

3598696

3598697

3598700

3598701

3598702

5604

7984319

A_23_P20248

GE57608

GO:0000165

GO:0000166

GO:0002376

GO:0003824

GO:0004672

GO:0004674

GO:0004708

GO:0004712

GO:0004713

GO:0005078

GO:0005515

GO:0005524

GO:0005634

GO:0005737

GO:0005739

GO:0005768

GO:0005769

GO:0005770

GO:0005783

GO:0005794

GO:0005813

GO:0005815

GO:0005829

GO:0005856

GO:0005886

GO:0005925

GO:0006351

GO:0006355

GO:0006468

GO:0006935

GO:0007165

GO:0007507

GO:0008285

GO:0010628

GO:0014044

GO:0016020

GO:0016192

GO:0016301

GO:0016310

GO:0016740

GO:0021697

GO:0023052

GO:0030154

GO:0030182

GO:0030216

GO:0030295

GO:0030878

GO:0031410

GO:0032872

GO:0035987

GO:0036211

GO:0038133

GO:0042552

GO:0043226

GO:0043410

GO:0043539

GO:0044342

GO:0045893

GO:0048009

GO:0048538

GO:0048679

GO:0048856

GO:0048870

GO:0050772

GO:0060020

GO:0060090

GO:0060324

GO:0060425

GO:0060440

GO:0060502

GO:0060674

GO:0060711

GO:0070371

GO:0070374

GO:0071902

GO:0090170

GO:0090398

GO:0097110

GO:0098772

GO:0106310

GO:0140096

GO:1903226

GO:2000641

HMNXSV003018359

Hs.3446.0.A2_3p_at

ILMN_1694240

L05624_s_at

L11284_at

PH_hs_0022483

TC15000613.hg

Participates

as a member of

as an input of

MAP2K1 binds MAPK3 (Homo sapiens)

as a component of

as an output of

Dissociation of p-T,Y-MAPK3:MAP2K1 (Homo sapiens)

Other forms of this molecule

MAP2K1(9-393) [cytosol]

MAP2K1(2-8) [cytosol]

MAP2K1 F53S [cytosol]

MAP2K1 D67N [cytosol]

MAP2K1 Q56P [cytosol]

MAP2K1 E203K [cytosol]

MAP2K1 V60E [cytosol]

MAP2K1 P124S [cytosol]

MAP2K1 Y130C [cytosol]

MAP2K1 C121S [cytosol]

MAP2K1 G128V [cytosol]

MAP2K1 F53L [cytosol]

MAP2K1 K57N [cytosol]

MAP2K1 K57T [cytosol]

MAP2K1 F53V [cytosol]

MAP2K1 D67Y [cytosol]

MAP2K1 G128D [cytosol]

MAP2K1 P124L [cytosol]

MAP2K1 F53Y [cytosol]

MAP2K1 L42_K57del [cytosol]

MAP2K1 P124Q [cytosol]

MAP2K1 F53C [cytosol]

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

p-T286,T292-MAP2K1 [cytosol]

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

MAP2K1 [cytosol]

Inferred To

Phospho Mek1 [cytosol] (Mus musculus)

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

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

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] (Rattus norvegicus)

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

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

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

NP_002746.1, XP_016877900.1

ZINC - World Drugs

MP2K1_HUMAN

Guide to Pharmacology - Targets

2062

OpenTargets

ENSG00000169032

ZINC - FDA approved

MP2K1_HUMAN

ZINC - Substances

MP2K1_HUMAN

ZINC target

Q02750

ZINC - Biogenic

MP2K1_HUMAN

PRO

Q02750

PDB

9AXC, 3EQD, 6PP9, 3EQF, 3VVH, 6Q0J, 9AXH, 6X2P, 3EQG, 3DY7, 3EQH, 7B9L, 3PP1, 7B3M, 4LMN, 7MFD, 9AXX, 3W8Q, 7M0V, 5YT3, 3ORN, 7M0U, 3OS3, 3EQI, 7PQV, 3WIG, 7M0Z, 5BX0, 5EYM, 4AN3, 3DV3, 7UMB, 7M0Y, 8DGS, 6X2X, 3V04, 6U2G, 1S9J, 4ANB, 4AN9, 4U80, 3ZM4, 4U7Z, 4U81, 3ZLY, 7B94, 3V01, 7M0T, 4ARK, 5HZE, 2P55, 9AYA, 7B7R, 7F2X, 6Q0T, 9AXA, 3ZLS, 7XLP, 7M0W, 4AN2, 8DGT, 8CHF, 6NYB, 9AXY, 3MBL, 6V2W, 6X2S, 7XNC, 9AY7, 3ZLX, 3EQB, 9AXM, 3SLS, 3EQC, 3ZLW, 4MNE, 7M0X, 3E8N

ZINC - Investigational

MP2K1_HUMAN

ZINC - Metabolites

MP2K1_HUMAN

GeneCards

Q02750

HPA

ENSG00000169032-MAP2K1

Ensembl

ENSG00000169032, ENSP00000302486, ENST00000307102

Pharos - Targets

Q02750

ZINC - Predictions - Purchasable

MP2K1_HUMAN

Orphanet

16377

Interactors (26)

Accession	#Entities	Entities	Confidence Score	Evidence (IntAct)
UniProt:P15056 BRAF	20	BRAF(1-380)-MACF1(600-7388)fusion [cytosol] (R-HSA-6802402) p-BRAF(1-380)-MACF1(600-7388) fusion [cytosol] (R-HSA-6802536) BRAF E501G [cytosol] (R-HSA-9651132) BRAF D594N [cytosol] (R-HSA-6802299) BRAF D638E [cytosol] (R-HSA-9651125) BRAF G596R [cytosol] (R-HSA-6802385) BRAF D594V [cytosol] (R-HSA-6802305) BRAF G596V [cytosol] (R-HSA-9651138) BRAF G466E [cytosol] (R-HSA-6802374) BRAF D594G [cytosol] (R-HSA-6802295) BRAF L505H [cytosol] (R-HSA-9648845) BRAF F595L [cytosol] (R-HSA-6802316) BRAF L597V [cytosol] (R-HSA-6802397) BRAF G464E [cytosol] (R-HSA-6802369) BRAF N581D [cytosol] (R-HSA-9651152) BRAF E586K [cytosol] (R-HSA-6802308) BRAF V600K [cytosol] (R-HSA-6802502) BRAF A246P [cytosol] (R-HSA-9651123) BRAF G469V [cytosol] (R-HSA-9648620) BRAF T244P [cytosol] (R-HSA-9651165)	0.978	63
UniProt:P04049 RAF1	20	p-S338,Y340,Y341-RAF1 [cytosol] (R-HSA-5624465) p-S338-RAF1 [cytosol] (R-HSA-5624469) p-S621-RAF1 S259F [cytosol] (R-HSA-9656124) p-S621-RAF1 S257L [cytosol] (R-HSA-9656121) p-S621-RAF1 P261L [cytosol] (R-HSA-9656106) p-S621-RAF1 N262K [cytosol] (R-HSA-9656101) p-S621-RAF1 P261A [cytosol] (R-HSA-9656103) p-S621-RAF1 P261S [cytosol] (R-HSA-9656113) p-S621-RAF1 S259T [cytosol] (R-HSA-9656130) p-S621-RAF1 P261T [cytosol] (R-HSA-9656115) p-S621-RAF1 P261R [cytosol] (R-HSA-9656110) p-S621-RAF1 S259P [cytosol] (R-HSA-9656127) p-S621-RAF1 T260I [cytosol] (R-HSA-9656136) p-S621-RAF1 T260R [cytosol] (R-HSA-9656139) p-S621-RAF1 V263A [cytosol] (R-HSA-9656148) p-S621-RAF1 R256S [cytosol] (R-HSA-9656119) p-S621-RAF1 T491I [cytosol] (R-HSA-9656143) p-S621-RAF1 D486N [cytosol] (R-HSA-9656088) p-S621-RAF1 S427G [cytosol] (R-HSA-9656134) p-S621-RAF1 L613V [cytosol] (R-HSA-9656098)	0.96	39
UniProt:P10398 ARAF	4	p-S299,S302,T452,T455,S582 ARAF [cytosol] (R-HSA-5672646) p-S299,S302,T452,T455,S582 ARAF [plasma membrane] (R-HSA-5672648) p-S582 ARAF [cytosol] (R-HSA-5672681) p-S214,S582 ARAF [cytosol] (R-HSA-5672639)	0.855	10
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,Y602 KSR1 [plasma membrane] (R-HSA-5672659) p-S311,Y602 KSR1 [cytosol] (R-HSA-5672656)	0.837	11
UniProt:Q04917 YWHAH	1	YWHAH [cytosol] (R-HSA-1445107)	0.837	8
UniProt:P61981 YWHAG	1	YWHAG [cytosol] (R-HSA-380312)	0.837	8
UniProt:P31946 YWHAB	1	YWHAB [cytosol] (R-HSA-48888)	0.788	7
UniProt:P27348 YWHAQ	1	YWHAQ [cytosol] (R-HSA-1445116)	0.725	5
UniProt:Q6VAB6 KSR2	1	KSR2 [cytosol] (R-HSA-5672589)	0.643	9
UniProt:P63104 YWHAZ	2	YWHAZ [nucleoplasm] (R-HSA-450469) YWHAZ [cytosol] (R-HSA-206099)	0.643	6
UniProt:P62258 YWHAE	1	YWHAE [cytosol] (R-HSA-194368)	0.643	5
UniProt:P36507 MAP2K2	12	MAP2K2(1-10) [cytosol] (R-HSA-5211334) MAP2K2(11-400) [cytosol] (R-HSA-5211337) MAP2K2 C125S [cytosol] (R-HSA-9652070) MAP2K2 P128Q [cytosol] (R-HSA-9652082) MAP2K2 V35M [cytosol] (R-HSA-9652086) MAP2K2 Y134C [cytosol] (R-HSA-9652089) p-S222,S226-MAP2K2 [cytosol] (R-HSA-169292) MAP2K2 [cytosol] (R-HSA-59504) p-S,T-MAP2K2 [cytosol] (R-HSA-109848) MAP2K2 N126D [cytosol] (R-HSA-9652079) MAP2K2 L46F [cytosol] (R-HSA-9652076) MAP2K2 F57C [cytosol] (R-HSA-9652073)	0.643	5
UniProt:P28482 MAPK1	18	MAPK1 [endoplasmic reticulum lumen] (R-HSA-9636293) MAPK1 [ficolin-1-rich granule lumen] (R-HSA-6800964) MAPK1 [extracellular region] (R-HSA-6806250) MAPK1 [azurophil granule lumen] (R-HSA-6799225) p-T185,Y187 MAPK1 E322V [cytosol] (R-HSA-9652797) p-T185,Y187 MAPK1 E322K [cytosol] (R-HSA-9652175) p-T185,Y187 MAPK1 E81K [cytosol] (R-HSA-9652799) p-T185,Y187 MAPK1 S142L [cytosol] (R-HSA-9652808) p-T185,Y187 MAPK1 P58L [cytosol] (R-HSA-9652806) p-T185,Y187 MAPK1 D321V [cytosol] (R-HSA-9652791) p-T185,Y187 MAPK1 D321N [cytosol] (R-HSA-9652785) p-T185,Y187 MAPK1 E322A [cytosol] (R-HSA-9652794) p-T185,Y187 MAPK1 P58G [cytosol] (R-HSA-9652802) p-T185-MAPK1 [cytosol] (R-HSA-9635773) MAPK1 [nucleoplasm] (R-HSA-199960) MAPK1 [cytosol] (R-HSA-59282) p-T185,Y187-MAPK1 [cytosol] (R-HSA-109853) p-T185,Y187-MAPK1 [nucleoplasm] (R-HSA-112354)	0.609	2
UniProt:Q8N9N5 BANP	1	BANP [nucleoplasm] (R-HSA-3221973)	0.556	3
UniProt:P46937 YAP1	8	p-Y407-YAP1 [cytosol] (R-HSA-9865208) p-S127-YAP1 [cytosol] (R-HSA-2028553) p-5S-YAP1 [cytosol] (R-HSA-2028554) p-Y407-YAP1 [nucleoplasm] (R-HSA-8956661) p-Y-YAP1 [cytosol] (R-HSA-8937843) p-Y-YAP1 [nucleoplasm] (R-HSA-8937857) YAP1 [cytosol] (R-HSA-1253345) YAP1 [nucleoplasm] (R-HSA-1253322)	0.556	3
UniProt:Q8WWU5-7 TCP11			0.556	3
UniProt:Q8N9N5-2 BANP			0.556	3
UniProt:Q9H8W4 PKHF2			0.556	3
UniProt:Q9Y297 BTRC	2	BTRC [cytosol] (R-HSA-174237) BTRC [nucleoplasm] (R-HSA-3361753)	0.556	3
UniProt:Q86Y07 VRK2	2	VRK2 [mitochondrial outer membrane] (R-HSA-9715102) VRK2 [endoplasmic reticulum membrane] (R-HSA-9714457)	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,Y602 KSR1 [plasma membrane] (R-MMU-5672659) phospho-p-S311,Y602 KSR1 [cytosol] (R-MMU-5672656)	0.508	2
UniProt:Q13526 PIN1	2	PIN1 [cytosol] (R-HSA-9626823) PIN1 [nucleoplasm] (R-HSA-936016)	0.508	5
UniProt:P27361 MAPK3	6	MAPK3 [endoplasmic reticulum lumen] (R-HSA-9636295) p-T202-MAPK3 [cytosol] (R-HSA-9635775) MAPK3 [nucleoplasm] (R-HSA-73724) MAPK3 [cytosol] (R-HSA-59284) p-T202,Y204-MAPK3 [cytosol] (R-HSA-109842) p-T202,Y204-MAPK3 [nucleoplasm] (R-HSA-112359)	0.499	2
UniProt:Q86Y07-1 VRK2			0.499	2
UniProt:Q96S96 PEBP4			0.462	3
UniProt:O75832 PSMD10	1	PSMD10 [cytosol] (R-HSA-68788)	0.462	2

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