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P45985

- MP2K4_HUMAN

UniProt

P45985 - MP2K4_HUMAN

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Protein
Dual specificity mitogen-activated protein kinase kinase 4
Gene
MAP2K4, JNKK1, MEK4, MKK4, PRKMK4, SEK1, SERK1, SKK1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Activated in response to a variety of cellular stresses, including UV and gamma-irradiation, heat shock, hyperosmolarity, T-cell receptor stimulation, peroxide and inflammatory cytokines. Also activated by developmental cues. MAP2K4/MKK4 is activated by the majority of MKKKs, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K7/TAK1, MAP3K10/MLK2, MAP3K11/MLK3, MAP3K12/DLK and MAP3K13/LZK.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei45 – 462Cleavage; by anthrax lethal factor
Sitei58 – 592Cleavage; by anthrax lethal factor
Binding sitei131 – 1311ATP By similarity
Active sitei229 – 2291Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi108 – 1169ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. JUN kinase kinase activity Source: Ensembl
  3. protein binding Source: IntAct
  4. protein kinase activity Source: ProtInc
  5. protein serine/threonine kinase activity Source: UniProtKB-KW
  6. protein tyrosine kinase activity Source: UniProtKB-KW

GO - Biological processi

  1. Fc-epsilon receptor signaling pathway Source: Reactome
  2. JNK cascade Source: Reactome
  3. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
  4. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  5. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
  6. apoptotic process Source: UniProtKB-KW
  7. cellular response to mechanical stimulus Source: UniProtKB
  8. cellular response to sorbitol Source: Ensembl
  9. innate immune response Source: Reactome
  10. positive regulation of DNA replication Source: Ensembl
  11. positive regulation of neuron apoptotic process Source: Ensembl
  12. signal transduction Source: ProtInc
  13. stress-activated MAPK cascade Source: Reactome
  14. toll-like receptor 10 signaling pathway Source: Reactome
  15. toll-like receptor 2 signaling pathway Source: Reactome
  16. toll-like receptor 3 signaling pathway Source: Reactome
  17. toll-like receptor 4 signaling pathway Source: Reactome
  18. toll-like receptor 5 signaling pathway Source: Reactome
  19. toll-like receptor 9 signaling pathway Source: Reactome
  20. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  21. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
  22. toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Apoptosis, Stress response

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 2681.
ReactomeiREACT_163701. FCERI mediated MAPK activation.
REACT_169436. Oxidative Stress Induced Senescence.
REACT_21368. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_22442. Interleukin-1 signaling.
SignaLinkiP45985.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 4 (EC:2.7.12.2)
Short name:
MAP kinase kinase 4
Short name:
MAPKK 4
Alternative name(s):
JNK-activating kinase 1
MAPK/ERK kinase 4
Short name:
MEK 4
SAPK/ERK kinase 1
Short name:
SEK1
Stress-activated protein kinase kinase 1
Short name:
SAPK kinase 1
Short name:
SAPKK-1
Short name:
SAPKK1
c-Jun N-terminal kinase kinase 1
Short name:
JNKK
Gene namesi
Name:MAP2K4
Synonyms:JNKK1, MEK4, MKK4, PRKMK4, SEK1, SERK1, SKK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:6844. MAP2K4.

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. dendrite cytoplasm Source: Ensembl
  3. nucleus Source: UniProtKB-SubCell
  4. perikaryon Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30589.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 399398Dual specificity mitogen-activated protein kinase kinase 4
PRO_0000086381Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei90 – 901Phosphoserine1 Publication
Modified residuei257 – 2571Phosphoserine; by MAP3K1 Publication
Modified residuei261 – 2611Phosphothreonine; by MAP3K1 Publication

Post-translational modificationi

Activated by phosphorylation on Ser-257 and Thr-261 by MAP kinase kinase kinases (MAP3Ks).

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP45985.
PaxDbiP45985.
PRIDEiP45985.

PTM databases

PhosphoSiteiP45985.

Miscellaneous databases

PMAP-CutDBP45985.

Expressioni

Tissue specificityi

Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.

Gene expression databases

ArrayExpressiP45985.
BgeeiP45985.
CleanExiHS_MAP2K4.
GenevestigatoriP45985.

Organism-specific databases

HPAiCAB007751.

Interactioni

Subunit structurei

Interacts with SPAG9 By similarity. Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAPK11 and MAPK14. Interacts (via its DVD domain) with MAP3Ks activators like MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with ARRB1, ARRB2 and MAPK8IP3/JIP3.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAP3K1Q132333EBI-447868,EBI-49776

Protein-protein interaction databases

BioGridi112315. 37 interactions.
IntActiP45985. 11 interactions.
MINTiMINT-151438.
STRINGi9606.ENSP00000262445.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi85 – 884
Beta strandi93 – 953
Beta strandi101 – 1033
Beta strandi107 – 1104
Beta strandi112 – 12110
Turni122 – 1243
Beta strandi127 – 1348
Helixi139 – 15315
Beta strandi164 – 1696
Beta strandi171 – 1788
Beta strandi182 – 1843
Helixi185 – 19410
Helixi202 – 22322
Helixi232 – 2343
Beta strandi235 – 2373
Beta strandi243 – 2453
Beta strandi249 – 2513
Beta strandi267 – 2704
Helixi272 – 2743
Helixi287 – 30216
Beta strandi312 – 3143
Beta strandi316 – 3216
Helixi338 – 34710
Helixi352 – 3543
Helixi358 – 3614
Helixi365 – 3728
Helixi377 – 38711

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3ALNX-ray2.30A/B/C80-399[»]
3ALOX-ray2.60A80-399[»]
3VUTX-ray3.50A/B80-399[»]
ProteinModelPortaliP45985.
SMRiP45985. Positions 95-388.

Miscellaneous databases

EvolutionaryTraceiP45985.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini102 – 367266Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni37 – 5216D domain
Add
BLAST
Regioni364 – 38724DVD domain
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi5 – 1915Gly/Ser-rich
Add
BLAST

Domaini

The DVD domain (residues 364-387) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.2 Publications
The D domain (residues 34-52) contains a conserved docking site and is required for the binding to MAPK substrates.2 Publications

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
HOVERGENiHBG108518.
InParanoidiP45985.
KOiK04430.
OMAiVMKSNDC.
OrthoDBiEOG7J9VPW.
PhylomeDBiP45985.
TreeFamiTF350701.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P45985-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MAAPSPSGGG GSGGGSGSGT PGPVGSPAPG HPAVSSMQGK RKALKLNFAN    50
PPFKSTARFT LNPNPTGVQN PHIERLRTHS IESSGKLKIS PEQHWDFTAE 100
DLKDLGEIGR GAYGSVNKMV HKPSGQIMAV KRIRSTVDEK EQKQLLMDLD 150
VVMRSSDCPY IVQFYGALFR EGDCWICMEL MSTSFDKFYK YVYSVLDDVI 200
PEEILGKITL ATVKALNHLK ENLKIIHRDI KPSNILLDRS GNIKLCDFGI 250
SGQLVDSIAK TRDAGCRPYM APERIDPSAS RQGYDVRSDV WSLGITLYEL 300
ATGRFPYPKW NSVFDQLTQV VKGDPPQLSN SEEREFSPSF INFVNLCLTK 350
DESKRPKYKE LLKHPFILMY EERAVEVACY VCKILDQMPA TPSSPMYVD 399
Length:399
Mass (Da):44,288
Last modified:November 1, 1995 - v1
Checksum:iA472537F2F26770B
GO
Isoform 2 (identifier: P45985-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     39-39: G → GFQINFCEKAQS

Note: No experimental confirmation available.

Show »
Length:410
Mass (Da):45,584
Checksum:i097F8966398DD6C0
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti16 – 161S → R.1 Publication
Corresponds to variant rs17855590 [ dbSNP | Ensembl ].
VAR_062963
Natural varianti142 – 1421Q → L in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication
VAR_040818
Natural varianti154 – 1541R → W in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication
VAR_040819
Natural varianti234 – 2341N → I in an ovarian serous carcinoma sample; somatic mutation. 1 Publication
VAR_040820
Natural varianti251 – 2511S → N in a metastatic melanoma sample; somatic mutation. 1 Publication
VAR_040821
Natural varianti279 – 2791A → T in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication
VAR_040822

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei39 – 391G → GFQINFCEKAQS in isoform 2.
VSP_038838

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti118 – 1181K → R in CAG38801. 1 Publication
Sequence conflicti179 – 1791E → G in BAG35884. 1 Publication
Sequence conflicti356 – 3561P → L in AAH60764. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L36870 mRNA. Translation: AAC41719.1.
U17743 mRNA. Translation: AAC50127.1.
AF070090
, AF070080, AF070081, AF070082, AF070083, AF070084, AF070085, AF070086, AF070087, AF070088, AF070089 Genomic DNA. Translation: AAC24130.1.
CR536564 mRNA. Translation: CAG38801.1.
BT019676 mRNA. Translation: AAV38482.1.
AK131544 mRNA. Translation: BAG54774.1.
AK313053 mRNA. Translation: BAG35884.1.
DQ015703 Genomic DNA. Translation: AAY22176.1.
AC005244 Genomic DNA. No translation available.
AC005410 Genomic DNA. No translation available.
CH471108 Genomic DNA. Translation: EAW89975.1.
CH471108 Genomic DNA. Translation: EAW89974.1.
CH471108 Genomic DNA. Translation: EAW89976.1.
BC036032 mRNA. Translation: AAH36032.1.
BC060764 mRNA. Translation: AAH60764.1.
CCDSiCCDS11162.1. [P45985-1]
CCDS62095.1. [P45985-2]
PIRiI38901.
RefSeqiNP_001268364.1. NM_001281435.1. [P45985-2]
NP_003001.1. NM_003010.3. [P45985-1]
UniGeneiHs.514681.

Genome annotation databases

EnsembliENST00000353533; ENSP00000262445; ENSG00000065559. [P45985-1]
ENST00000415385; ENSP00000410402; ENSG00000065559. [P45985-2]
GeneIDi6416.
KEGGihsa:6416.
UCSCiuc002gnj.3. human. [P45985-1]
uc002gnk.3. human. [P45985-2]

Polymorphism databases

DMDMi1170596.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L36870 mRNA. Translation: AAC41719.1 .
U17743 mRNA. Translation: AAC50127.1 .
AF070090
, AF070080 , AF070081 , AF070082 , AF070083 , AF070084 , AF070085 , AF070086 , AF070087 , AF070088 , AF070089 Genomic DNA. Translation: AAC24130.1 .
CR536564 mRNA. Translation: CAG38801.1 .
BT019676 mRNA. Translation: AAV38482.1 .
AK131544 mRNA. Translation: BAG54774.1 .
AK313053 mRNA. Translation: BAG35884.1 .
DQ015703 Genomic DNA. Translation: AAY22176.1 .
AC005244 Genomic DNA. No translation available.
AC005410 Genomic DNA. No translation available.
CH471108 Genomic DNA. Translation: EAW89975.1 .
CH471108 Genomic DNA. Translation: EAW89974.1 .
CH471108 Genomic DNA. Translation: EAW89976.1 .
BC036032 mRNA. Translation: AAH36032.1 .
BC060764 mRNA. Translation: AAH60764.1 .
CCDSi CCDS11162.1. [P45985-1 ]
CCDS62095.1. [P45985-2 ]
PIRi I38901.
RefSeqi NP_001268364.1. NM_001281435.1. [P45985-2 ]
NP_003001.1. NM_003010.3. [P45985-1 ]
UniGenei Hs.514681.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3ALN X-ray 2.30 A/B/C 80-399 [» ]
3ALO X-ray 2.60 A 80-399 [» ]
3VUT X-ray 3.50 A/B 80-399 [» ]
ProteinModelPortali P45985.
SMRi P45985. Positions 95-388.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112315. 37 interactions.
IntActi P45985. 11 interactions.
MINTi MINT-151438.
STRINGi 9606.ENSP00000262445.

Chemistry

BindingDBi P45985.
ChEMBLi CHEMBL2897.
GuidetoPHARMACOLOGYi 2065.

PTM databases

PhosphoSitei P45985.

Polymorphism databases

DMDMi 1170596.

Proteomic databases

MaxQBi P45985.
PaxDbi P45985.
PRIDEi P45985.

Protocols and materials databases

DNASUi 6416.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000353533 ; ENSP00000262445 ; ENSG00000065559 . [P45985-1 ]
ENST00000415385 ; ENSP00000410402 ; ENSG00000065559 . [P45985-2 ]
GeneIDi 6416.
KEGGi hsa:6416.
UCSCi uc002gnj.3. human. [P45985-1 ]
uc002gnk.3. human. [P45985-2 ]

Organism-specific databases

CTDi 6416.
GeneCardsi GC17P011864.
HGNCi HGNC:6844. MAP2K4.
HPAi CAB007751.
MIMi 601335. gene.
neXtProti NX_P45985.
PharmGKBi PA30589.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOVERGENi HBG108518.
InParanoidi P45985.
KOi K04430.
OMAi VMKSNDC.
OrthoDBi EOG7J9VPW.
PhylomeDBi P45985.
TreeFami TF350701.

Enzyme and pathway databases

BRENDAi 2.7.12.2. 2681.
Reactomei REACT_163701. FCERI mediated MAPK activation.
REACT_169436. Oxidative Stress Induced Senescence.
REACT_21368. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
REACT_22442. Interleukin-1 signaling.
SignaLinki P45985.

Miscellaneous databases

ChiTaRSi MAP2K4. human.
EvolutionaryTracei P45985.
GeneWikii MAP2K4.
GenomeRNAii 6416.
NextBioi 24922.
PMAP-CutDB P45985.
PROi P45985.
SOURCEi Search...

Gene expression databases

ArrayExpressi P45985.
Bgeei P45985.
CleanExi HS_MAP2K4.
Genevestigatori P45985.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms."
    Derijard B., Raingeaud J., Barrett T., Wu I.-H., Han J., Ulevitch R.J., Davis R.J.
    Science 267:682-685(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Brain.
  2. "Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2."
    Lin A., Minden A., Martinetto H., Claret F.-X., Lange-Carter C., Mercurio F., Johnson G.L., Karin M.
    Science 268:286-290(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
  3. "Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene."
    Su G.H., Hilgers W., Shekher M.C., Tang D.J., Yeo C.J., Hruban R.H., Kern S.E.
    Cancer Res. 58:2339-2342(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  5. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Brain and Thalamus.
  7. NIEHS SNPs program
    Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  8. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  10. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-16.
    Tissue: Brain and Testis.
  11. "MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/6."
    Tibbles L.A., Ing Y.L., Kiefer F., Chan J., Iscove N., Woodgett J.R., Lassam N.J.
    EMBO J. 15:7026-7035(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-261, ENZYME REGULATION, INTERACTION WITH MAP3K11/MLK3.
  12. "Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor."
    Vitale G., Bernardi L., Napolitani G., Mock M., Montecucco C.
    Biochem. J. 352:739-745(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY ANTHRAX LETHAL FACTOR.
  13. "Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3."
    McDonald P.H., Chow C.W., Miller W.E., Laporte S.A., Field M.E., Lin F.-T., Davis R.J., Lefkowitz R.J.
    Science 290:1574-1577(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ARRB2.
  14. "Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade."
    Matsuura H., Nishitoh H., Takeda K., Matsuzawa A., Amagasa T., Ito M., Yoshioka K., Ichijo H.
    J. Biol. Chem. 277:40703-40709(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAPK8IP3/JIP3.
  15. "A docking site in MKK4 mediates high affinity binding to JNK MAPKs and competes with similar docking sites in JNK substrates."
    Ho D.T., Bardwell A.J., Abdollahi M., Bardwell L.
    J. Biol. Chem. 278:32662-32672(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN, INTERACTION WITH MAPK8/JNK1; MAPK9/JNK2; MAPK10/JNK3; MAPK11 AND MAPK14.
  16. "Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases."
    Takekawa M., Tatebayashi K., Saito H.
    Mol. Cell 18:295-306(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN.
  17. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  18. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  19. "A scanning peptide array approach uncovers association sites within the JNK/beta arrestin signalling complex."
    Li X., MacLeod R., Dunlop A.J., Edwards H.V., Advant N., Gibson L.C., Devine N.M., Brown K.M., Adams D.R., Houslay M.D., Baillie G.S.
    FEBS Lett. 583:3310-3316(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ARRB1 AND ARRB2.
  20. "Differential regulation and properties of MAPKs."
    Raman M., Chen W., Cobb M.H.
    Oncogene 26:3100-3112(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON ENZYME REGULATION.
  21. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  22. "Diverse physiological functions of MKK4 and MKK7 during early embryogenesis."
    Asaoka Y., Nishina H.
    J. Biochem. 148:393-401(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  23. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  24. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  25. "The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7."
    Haeusgen W., Herdegen T., Waetzig V.
    Eur. J. Cell Biol. 90:536-544(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON REGULATION, REVIEW ON FUNCTION.
  26. "Crystal structures of MKK4 kinase domain reveal that substrate peptide binds to an allosteric site and induces an auto-inhibition state."
    Matsumoto T., Kinoshita T., Kirii Y., Yokota K., Hamada K., Tada T.
    Biochem. Biophys. Res. Commun. 400:369-373(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 80-399.
  27. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-142; TRP-154; ILE-234; ASN-251 AND THR-279.

Entry informationi

Entry nameiMP2K4_HUMAN
AccessioniPrimary (citable) accession number: P45985
Secondary accession number(s): B2R7N7
, B3KYB2, D3DTS5, Q5U0B8, Q6FHX4, Q6P9H2, Q6PIE6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: September 3, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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