Protein MAP2K4

URN urn:agi-llid:6416
Total Entities 0
Connectivity 1225
Name MAP2K4
Description mitogen-activated protein kinase kinase 4
Notes This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Primary Cell Localization Cytoplasm
Class Protein kinase
ObjectType Protein

Pathway Osteoarthritis
Skin Aging
MTHFR Activity Regulation
Dopamine Receptors Signaling
Thrombopoietin Receptors Signaling in Platelet Maturation
Toll-like Receptors Act through MYD88-TIRAP Signaling
TLR4 Signaling in Leukocytes
Plasmin Effects in Inflammation
Scavenger Receptors in Platelet Activation
Toll-like Receptors in Sterile Inflammation
Basophil Activation
Eosinophil Survival by Cytokine Signaling
AXL Receptor Inhibits Macrophages and Dendritic Cells Function
Neutrophil Recruitment and Priming
Negative Acute Phase Proteins Synthesis
Positive Acute Phase Proteins Synthesis
Vascular Endothelial Cell Activation by Cytokines
Vascular Endothelial Cell Activation by Growth Factors
Nociception Expression Targets Signaling
EDNRA/B -> Vascular Motility
ADRA1A -> IL6 Production
CNR1/2 -> IL1B/2/4/6/10 Production
DRD2 Expression Targets
PTGER2/3 -> Inflammation-Related Expression Targets
Circadian Clock Genes in Suprachiasmatic Nuclei Neurons
Cardiomyocyte Dysfunction
Scavenger Receptor OLR1 in Inflammation Related Endothelial Dysfunction
Dendritic Cells Function in Atherosclerosis
Dilated Cardiomyopathy
Myocardial Remodeling
Myocardial Infarction
Inflammatory Reaction in Acne Vulgaris
Mast-Cells Activation in Atopic Dermatitis
IL17 Signaling in Psoriasis
Dendritic Cells Function in Psoriasis
Mesangial Cell Dysfunction in Diabetic Nephropathy
Insulin Resistance in Myocytes Induced by Obesity
Insulin Resistance in Hepatocytes
beta-Cell Destruction through Cytokines in Diabetes Mellitus
GNRH Signaling Impairment in Hypogonadotrophic Hypogonadism
OipA Signaling in Helicobacter Pylori Infection
Dendritic Cell Function in Ulcerative Colitis
Antiphospholipid Antibodies in Endothelial Cell
B-Cell Acute Lymphoblastic Leukemia
B-Cell Chronic Lymphocytic Leukemia
Chronic Myeloid Leukemia
Follicular Lymphoma
Osteoclast Activation in Multiple Myeloma
Multiple Myeloma
Antiphospholipid Antibodies and Endothelial Cell Interaction
T-Cell Acute Lymphoblastic Leukemia
Hepatocellular Carcinoma
Growth Factor Signaling in Hepatocellular Carcinoma
Proteins Involved in Pancreatic Cancer
Pancreatic Ductal Carcinoma
Growth Factor Signaling in Pancreatic Neoplasms
Mucin Production in Goblet Airway Epithelial Cells
CFTR Facilitates Oxidative Stress in Airway Epithelium in CF
Airway Epithelial Cell Dysfunction
Osteoclast Activation in Gout
Neutrophil Recruitment in Sinovium in Gout
Monocytes Function in Gout
TNF and IL1B Induce Metalloproteinase Synthesis in Osteoarthritis
Dendritic Cell Dysfunction in Psoriatic Arthritis
Synovial Fibroblast Activation in Psoriatic Arthritis
Keratinocyte Activation in Psoriatic Arthritis
Osteoclast Activation in Rheumatoid Arthritis
Synovial Fibroblast Activation by Citokines in Rheumatoid Arthritis
TLR2 Induced Synovial Fibroblast Activation in Rheumatoid Arthritis
Autocrine Cytokine/Chemokine Loops in Systemic Scleroderma
Skin Fibrosis
CCR5 Signaling in Macrophages
Majeed Syndrome
IL6 Promotes Inflammation in Muscular Dystrophies
Osteoclast Activation in Postmenopause
Glioma Invasion Signaling
Growth Factor Signaling in Neuroblastoma
Neuroblastoma
WNT Signaling in Breast Cancer
ESR1/ERBB Positive Luminal Breast Cancer
ESR1 Signaling in Breast Cancer
Endometrial Cancer
Endometrioid Endometrial Cancer
Proteins Involved in Endometrial Cancer
Clear Cell Endometrial Cancer and Papillary Serous Endometrial Cancer
Angiogenesis in Endometriosis
Proteins Involved in High-Grade Serous Ovarian Carcinoma
Endometrioid Ovarian Carcinoma
Proteins Involved in Endometrioid Ovarian Carcinoma
Clear Cell Ovarian Carcinoma
Proteins Involved in Mucinous Ovarian Carcinoma
High-Grade Serous Ovarian Carcinoma
Low-Grade Serous Ovarian Carcinoma
Proteins Involved in Low-Grade Serous Ovarian Carcinoma
Ovarian Cancer
Proteins Involved in Clear Cell Ovarian Carcinoma
Mucinous Ovarian Carcinoma
Subepithelial Fibroblasts in Middle Ear Cholesteatoma
HPV E5 Regulates EDNRA and EGFR Signaling Pathway in Keratinocytes
Androgen Receptor/Akt Signaling
Steroids Induced Cataract
VEGFA in Neovascular Glaucoma
Cytokines Trigger Otitis Media
Immune System Role in Otitis Media
Alveolar Macrophages Dysfunction in COPD
T-Cell Cytotoxic Activation
Mucin Hyperproduction in Goblet and Mucous Cells
WNT Signaling in Cystic Kidney Disease
Polycystins Mutation Effects in Cystic Kidney Disease
Plasmin Role in Glomerulonephritis
Endothelial Cell Dysfunction in Glomerulonephritis
Mesangial Cell Dysfunction in Glomerulonephritis
Interstitial Fibroblasts in Pyelonephritis
Apoptosis of Renal Tubule Epithelial Cell in Pyelonephritis
Endothelial Cell Dysfunction in Pyelonephritis
ANGPT1 -> CREB/CREBBP Expression Targets
ANGPT2 -> AP-1/CREBBP/MYC Expression Targets
AREG -> CREB/CREBBP Expression Targets
AREG -> AP-1 Expression Targets
Dopamine/Gi Expression Targets
BTC -> AP-1/ATF/CREB Expression Targets
Frizzled Receptors -> ARRB1/ARRB2 non-Canonical Signaling
AGTR1 -> ARRB1/ARRB2 Signaling
Sialophorin -> CTNNB/MYC/TP53 Signaling
CD72 -> NF-kB Expression Targets
CD8 -> NF-kB Expression Targets
CD80 -> NFATC Expression Targets
CD86 -> NFATC Expression Targets
EGF -> AP-1/ATF Expression Targets
EGF -> CREB/CREBBP/ELK/SRF/MYC Expression Targets
EGF -> TP53 Expression Targets
EGFR/ERBB2 -> TP53 Signaling
EGFR -> AP-1/ATF2 Signaling
EGFR -> AP-1/CREB/ELK/SRF/MYC Signaling
EREG -> CREB Expression Target
EREG -> AP-1/ATF Expression Targets
Erythropoietin -> AP-1/MYC/CREB Expression Targets
F2 -> AP-1/CREB/ELK/SRF/SP1 Expression Targets
PLG -> AP-1/CREB/ELK/SRF/SP1 Expression Targets
FGF9 -> AP-1/CREB/MYC Expression Targets
FGF10 -> AP-1/CREB/CREBBP/MYC Expression Targets
FGF1 -> AP-1/CREB/ELK/SRF/MYC Expression Targets
FGF8 -> AP-1/CREB/MYC Expression Targets
FGF18 -> AP-1/CREB Expression Targets
FGF4 -> AP-1/MYC Expression Targets
FGF7 -> AP-1/CREB/CREBBP/MYC Expression Targets
FGF2 -> AP-1/CREB/CREBBP/ELK/SRF/MYC Expression Targets
FGFR -> AP-1/CREB/CREBBP/ELK/SRF/MYC Signaling
FrizzledR -> JUN/PAX2 Signaling
HBEGF -> AP-1/ATF Expression Targets
HBEGF -> TP53 Expression Targets
HBEGF -> CREB/MYC Expression Targets
HGF -> AP-1/CREB/ELK/SRF/MYC Expression Targets
HGFR -> AP-1/CREB/MYC Signaling
RAS/RAF/MAPK Signaling Activation in Cancer
RAS/RAF/MAPK Signaling Activation by Blocking of Tumor Suppressors
TGFB Signaling activation by Blocking of Tumor Suppressors
Apoptosis Block by Death Receptor Signaling in Cancer
Apoptosis Evasion in Cancer: Overview
VEGFA Dependent Angiogenesis in Cancer
Inhibition of THBS1 Activates Angiogenesis in Cancer
VEGF Independent Angiogenesis in Cancer
TGFB Family in Epithelial to Mesenchymal Transition in Cancer
FibronectinR -> NF-kB Signaling
FibronectinR -> AP-1/ELK/SRF/SREBF Signaling
Fibronectin Expression Targets
CTGF -> AP-1/CREB/MYC Expression Targets
IL1R -> STAT3 Signaling
IL16-> ATF/CREB/CREBBP Expression Target
PAF/Gq -> AP-1/ATF1/CREB/ERK/SRF Expression Targets
Dronabinol/Anandamide Expression Targets
S1P Expression Targets
NRG1 -> CREB/CREBBP/ELK/SRF/MYC Expression Targets
NRG1 -> TP53 Expression Target
NRG1 -> AP-1/ATF Expression Targets
NGF -> SMAD3/NF-kB Expression Targets
NGF -> AP-1/TP53/MYC Expression Targets
BDNF Expression Targets
NTF3 Expression Targets
NTF4 Expression Targets
NGF -> CREB/CEBPB/MEF2A Expression Targets
NOTCH -> TCF3 Signaling
NOTCH Expression Targets
PDGFB -> AP-1/CREB/MYC Expression Target
PDGFC -> CREB Expression Target
PDGFD -> AP-1 Expression Targets
PDGF -> AP-1/CREB/CREBBP/MYC Expression Targets
PDGFR -> AP-1/MYC Signaling
AVP/Gs -> CREB/ELK/SRF/AP-1/EGR Expression Targets
GNRH1 Expression Targets
GNRH2 Expression Targets
EDN1 Expression Targets
EDN3 Expression Targets
AVP/Gq -> CREB/ELK/SRF/AP-1/EGR Expression Targets
PDCD1 -> ATF/CREB/CREBBP Expression Targets
AngiopoietinR -> AP-1 Signaling
GDNF -> HSF1 Signaling
EphrinB -> MAPK/JUN/FOS Signaling
NTRK -> AP-1/CREB/ELK/SRF/MYC/SMAD3/TP53 Signaling
GAS6 -> AP-1/CREB Expression Targets
FIGF -> AP-1 Expression Target
KITLG -> AP-1/CREB/CREBBP/MYC Expression Targets
GDNF -> HSF1 Expression Targets
CSF1 -> AP-1/CREB/CREBBP/MYC Expression Targets
PGF -> AP-1/CREB/CREBBP/MYC Expression Targets
FLT3LG -> AP-1/CREB/CREBBP Expression Targets
TGFBR -> AP-1 Signaling
TGFBR -> CREB/ELK-SRF Signaling
TGFBR -> ATF/GADD/MAX/TP53 Signaling
TGFBR -> MEF/MYOD/MYOG Signaling
TNF-alpha/TNFRSF1A Signaling
JNK/MAPK Signaling
TGF-beta Signaling
P38 MAPK/MAPK14 Signaling
AXL Receptor Tyrosine Kinase Signaling
PI3K/RAC1 Signaling
VEGF Signaling
EGFR Signaling
WNT Planar Cell Polarity (PCP) non-Canonical Signaling
TCR -> CREB/CREBBP/ATF Expression Targets
T-Cell Receptor -> ATF/CREB Signaling
TGFA -> TP53 Expression Targets
TGFA/AP-1/ATF Expression Targets
TGFA -> CREB/CREBBP/ELK-SRF/MYC Expression Targets
TGFB3-TGFBR2 Expression Targets
TGFB2-TGFBR2 Expression Targets
TGFB1-TGFBR2 Expression Targets
FASLG Expression Targets
TNFSF10 Expression Targets
LTA Expression Targets
TNFSF14 Expression Targets
TNF -> AP-1 Expression Targets
CD72 -> AP-1 Expression Targets
CD40LG -> NF-kB/ELK/SRF -> CREB/NFATC Expression Targets
TNFSF13 Expression Targets
TNFSF13B Expression Targets
TNF -> ELK-SRF Expression Targets
TNF -> CREB Expression Targets
TNF -> TP53/ATF Expression Targets
EDA Expression Targets
EctodysplasinR -> AP-1 Signaling
TNFR -> CREB/ELK-SRF Signaling
TNFR -> AP-1/ATF/TP53 Signaling
NGFR -> AP-1/CEBPB/CREB/ELK/SRF/TP53 Signaling
NGFR -> MEF Signaling
TNFRSF6 -> DDIT3 Signaling
TNFRSF6 -> HSF1 Signaling
TNFRSF1A -> AP-1/ATF/TP53 Signaling
TNFRSF1A -> CREB/ELK-SRF Signaling
Thrombopoietin -> SPI1 Expression Targets
Thrombopoietin -> AP-1/CREB/CREBBP/MYC Expression Targets
TLR4 -> AP-1 Expression Targets
TLR5 Expression Targets
TLR7 Expression Targets
TLR4 -> AP-1/EGR1/HIF1A Expression Targets
IL1B -> PGE2 Expression Targets
TLR1 -> 2/6 Expression Targets
IL1B Expression Targets
IL1A Expression Targets
TLR9 Expression Targets
TLR -> AP-1 Signaling
ROS in Angiotensin Mediated Cardiovascular Remodeling and Hypertrophy
VEGFA -> ATF/CREB/ELK-SRF Expression Targets
VEGFC -> ATF Expression Target
VEGFA -> AP-1/CREBBP/MYC Expression Targets
VEGFR -> AP-1/CREB/MYC Signaling
VEGFR -> ATF/CREB/ELK-SRF Signaling
WNT1 Expression Targets
WNT3A Expression Targets
WNT4 Expression Targets
WNT5A Expression Targets
WNT7A Expression Targets
1_Inflammation in keratinocytes in the pathology of acne
2_Acute phase initiation in atopic dermatitis
2_Interleukin-17 and interleukin-22 signaling in psoriasis
1_TNF and IL1B provoke ECM degradation in osteoarthritis
1_Osteoclast-mediated bone resorption in postmenopausal women
1_Formation of cysts in polycystic kidney disease
2_The role of endothelial cells in pyelonephritis
3_The role of interstitial fibroblasts in pyelonephritis
3_Mesangial cell dysfunction in glomerulonephritis
1_Disruption of luteinizing hormone and follicle-stimulating hormone secretion in PCOS
2_Pathogens stimulate mucins expression in the middle ear
3_Cardiomyocyte dysfunction unrelated to cell junctions in ARVD
2_Intestine epithelial cells drive immunological responses in ulcerative colitis
6_p12I Viral protein promotes T-cell activation in HTLV-1 infection
4_2_Insulin resistance: inflammation-related insulin resistance
4_3_Insulin resistance: FFA-related insulin resistance
2_Neuron and Schwann cell death
mapk1 protein modificators
Interleukin-17 and interleukin-22 signaling in psoriasis

Group Metastasis Suppressors

MedScan ID 6416

LocusLink ID 6416
26398
287398

Alias SAPK/ERK kinase I
Dual specificity mitogen-activated protein kinase kinase IV
SAPK kinase 1
JNK-activated kinase 1
SEK1/MKK4/JNKK1/SKK1
JNKK1
MKK4
MAP2K4delta
MAPKK 4
SEK1
SAPK kinase I
SAPK/ERK kinase 1
JNK kinase 1
RP23-340L19.1
MAPK kinase IV
SKK1/MKK4
mitogen activated protein kinase kinase 4
MAPK/ERK kinase IV
SAPKK-1
c-Jun N- terminal kinase kinase 1
stress activated protein kinase kinase 1
SERK1
c-Jun N- terminal kinase kinase I
MAPK kinase 4
MEK4
Dual specificity mitogen-activated protein kinase kinase 4
JNKK I
mitogen activated protein kinase kinase 4, variant 1
OTTMUSP00000006102
SERK I
JNK activating kinase 1
MAPK/ERK kinase 4
JNK-activated kinase I
SKK1
PRKMK4
MAP kinase kinase 4
MAP2K4
mitogen-activated protein kinase kinase IV
MAP kinase kinase IV
SEK I
JNK activating kinase I
JNKK
MAPKK4
SAPKK1
JNK-activating kinase 1
MEK 4
c-Jun N-terminal kinase kinase 1
stress-activated protein kinase kinase 1
SAPK/Erk/kinase 1
JNKK 1
JNK kinase
mitogen-activated protein kinase kinase 4
PRKMK4s
MAPKK4s

EC Number 2.7.12.2
2.7.1.-

GO ID 0005524
0008545
0004708
0031435
0004672
0004674
0004713
0038095
0007254
0007257
0000187
0032147
0006915
0061049
0071260
0072709
2000672
0018108
0045740
0043525
0051770
0034393
0009611
0007165
0023014
0031098
0030424
0005737
0005829
0032839
0005634
0043204
0016301
0000166
0016740
0000165
0016310
0043065
0001934
0006468
0004702
0035897
0007346
0002755
0002756
0035666
0045087
0009405
0051403
0034166
0034134
0034138
0034142
0034146
0034162
0038123
0038124
0002224
0005622
0016772
0006950
0008063
0034130
0033267
0008152
0005515

KEGG ID hsa:6416
mmu:26398
rno:287398

Organism Homo sapiens {Organism urn:agi-taxid:9606}
Mus musculus {Organism urn:agi-taxid:10090}
Rattus norvegicus {Organism urn:agi-taxid:10116}
Homo sapiens
Mus musculus
Rattus norvegicus

Mouse chromosome position 11 40.53 cM
11 33.0 cM

OMIM ID 601335

Rat chromosome position 10q24

Hugo ID 6844
HGNC:6844

Human chromosome position 17p12
17p11.2

Swiss-Prot Accession P45985
P45985.1
Q543X6
P47809
Q8K2U0
P47809.2
Q4KSH6
B2R7N7
B3KYB2
D3DTS5
Q5U0B8
Q6FHX4
Q6P9H2
Q6PIE6
B7ZA62

PIR ID I38901
S52423

GenBank ID NC_000017
XR_934080
XR_001752584
XM_005256755
XP_005256812
XM_011523977
XP_011522279
XM_011523976
XP_011522278
NM_001281435
NP_001268364
NM_003010
NP_003001
XM_005256753
XP_005256810
NG_033952
AC005244
AC005410
AH006187
AAC24130
CH471108
EAW89973
EAW89974
EAW89975
EAW89976
DQ015703
AAY22176
AA293365
AK122997
AK131544
BAG54774
AK294923
BAG58005
AK313053
BAG35884
AK316100
BAH14471
AK316177
BAH14548
AU150695
BC036032
AAH36032
BC050386
BC060764
AAH60764
BQ028457
BT019676
AAV38482
CR536564
CAG38801
L31902
L36870
AAC41719
U17743
AAC50127
P45985
NC_000077
NM_001316369
NP_001303298
NM_009157
NP_033183
NM_001316368
NP_001303297
NM_001316367
NP_001303296
XM_006533370
XP_006533433
XM_017314561
XP_017170050
XM_011249033
XP_011247335
NM_001362739
NM_001362740
AL662895
AL663069
CH466601
EDL10407
AK036928
BAC29642
AK044534
BAC31968
AK044698
BAC32038
AK139777
AK187893
BC029833
AAH29833
BY244326
BY277234
CB723868
U18310
AAB81554
P47809
NC_005109
NM_001030023
NP_001025194
AC_000078
AABR07029803
AABR07029804
AABR07029805
AABR07029806
AAHX01064427
AAHX01064428
AAHX01064429
CH473948
EDM04764
AY880882
AAX61181
KC795688
AGO65350
NC_018928
AF070080
AF070081
AF070082
AF070083
AF070084
AF070085
AF070086
AF070087
AF070088
AF070089
AF070090
AMYH02032997
XM_006533369
XP_006533432
XM_006533373
XP_006533436
XM_006533372
XP_006533435
AC_000033
AAHY01093964
AAHY01093965
AAHY01093966
AAHY01093967
AAHY01093968
XM_006721568
XP_006721631
AC_000149
ABBA01054999
ABBA01055000
XM_006533374
XP_006533437
XM_006533371
XP_006533434
XM_005256754
XP_005256811
AABR06064274
AABR06064275
AABR06064276
AABR06064277
AABR06064278
CAM21549
CAM21550
CAM23607
CAM23608
NT_010718
NW_926584
NW_001838403
AC_000060
CR600508
CR601866
NT_096135
NW_001030477
Q543X6
Q8K2U0
NW_001084656
NW_047334
Q4KSH6
Q6FHX4
Q6P9H2
Q6PIE6

Swiss-Prot ID MP2K4_HUMAN
MP2K4_MOUSE
Q543X6_MOUSE
Q4KSH6_RAT
D3DTS5_HUMAN

Cell Localization Cytoplasm
Nucleus

Ensembl ID ENSG00000065559
ENSP00000410402.3
ENST00000415385.7
ENSP00000262445.5
ENST00000353533.10
ENSMUSG00000033352
ENSMUSP00000041282.3
ENSMUST00000046963.9
ENSRNOG00000003834
ENSRNOP00000005293.6
ENSRNOT00000005293.7
ENSP00000410402
ENST00000415385
ENSP00000262445
ENST00000353533
ENSMUSP00000041282
ENSMUST00000046963
ENSRNOP00000005293
ENSRNOT00000005293

MGI ID MGI:1346869
1346869

RGD ID 1307040

Unigene ID Hs.514681
Mm.412922
Rn.198875

Homologene ID 48159

Shape Sickle-vertex

IPI ID IPI00024674
IPI00942214
IPI00112335
IPI00369884
IPI00794157
IPI00875050
IPI00649311

Ensembl Gene ID ENSG00000065559

ProteinAtlas NormalTissue Tissue: cerebral cortex; Cell type: glial cells; Level: Negative; Expression type: Staining; Reliability: Uncertain
Tissue: cervix
uterine; Cell type: glandular cells; Level: Weak; Expression type: Staining; Reliability: Uncertain
Tissue: thyroid gland; Cell type: glandular cells; Level: Moderate; Expression type: Staining; Reliability: Uncertain
Tissue: vulva/anal skin; Cell type: epidermal cells; Level: Weak; Expression type: Staining; Reliability: Uncertain
Tissue: salivary gland; Cell type: glandular cells; Level: Negative; Expression type: Staining; Reliability: Uncertain
Tissue: appendix; Cell type: glandular cells; Level: Negative; Expression type: Staining; Reliability: Uncertain
Tissue: testis; Cell type: Leydig cells; Level: Weak; Expression type: Staining; Reliability: Uncertain
Tissue: nasopharynx; Cell type: respiratory epithelial cells; Level: Weak; Expression type: Staining; Reliability: Uncertain
Tissue: rectum; Cell type: glandular cells; Level: Weak; Expression type: Staining; Reliability: Uncertain