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UniProtKB - O14733 (MP2K7_HUMAN)

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Protein

Dual specificity mitogen-activated protein kinase kinase 7

Gene

MAP2K7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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 MAP2K4/MKK4, 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/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+

Enzyme regulationi

Activated by phosphorylation by specific MAP kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 and MAP3K12/DLK.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei149ATPPROSITE-ProRule annotation1
Active sitei243Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi126 – 134ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • enzyme binding Source: BHF-UCL
  • magnesium ion binding Source: UniProtKB
  • MAP kinase kinase activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein phosphatase binding Source: BHF-UCL
  • protein serine/threonine kinase activity Source: GO_Central
  • protein tyrosine kinase activity Source: UniProtKB-KW
Complete GO annotation...

GO - Biological processi

  • activation of JUN kinase activity Source: BHF-UCL
  • apoptotic process Source: UniProtKB-KW
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • JNK cascade Source: Reactome
  • positive regulation of telomerase activity Source: BHF-UCL
  • positive regulation of telomere capping Source: BHF-UCL
  • positive regulation of telomere maintenance via telomerase Source: BHF-UCL
  • proteolysis in other organism Source: Reactome
  • regulation of apoptotic process Source: GO_Central
  • regulation of mitotic cell cycle Source: GO_Central
  • response to heat Source: UniProtKB
  • response to osmotic stress Source: UniProtKB
  • response to tumor necrosis factor Source: UniProtKB
  • response to UV Source: UniProtKB
  • signal transduction Source: ProtInc
  • stress-activated MAPK cascade Source: UniProtKB
Complete GO annotation...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase
Biological processApoptosis, Stress response
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 2681.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2871796. FCERI mediated MAPK activation.
R-HSA-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-HSA-5210891. Uptake and function of anthrax toxins.
SignaLinkiO14733.
SIGNORiO14733.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 7 (EC:2.7.12.2)
Short name:
MAP kinase kinase 7
Short name:
MAPKK 7
Alternative name(s):
JNK-activating kinase 2
MAPK/ERK kinase 7
Short name:
MEK 7
Stress-activated protein kinase kinase 4
Short name:
SAPK kinase 4
Short name:
SAPKK-4
Short name:
SAPKK4
c-Jun N-terminal kinase kinase 2
Short name:
JNK kinase 2
Short name:
JNKK 2
Gene namesi
Name:MAP2K7
Synonyms:JNKK2, MEK7, MKK7, PRKMK7, SKK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:6847. MAP2K7.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi5609.
OpenTargetsiENSG00000076984.
PharmGKBiPA284.

Chemistry databases

ChEMBLiCHEMBL3530.
GuidetoPHARMACOLOGYi2068.

Polymorphism and mutation databases

BioMutaiMAP2K7.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000863882 – 419Dual specificity mitogen-activated protein kinase kinase 7Add BLAST418

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei271Phosphoserine; by MAP3KBy similarity1
Modified residuei275Phosphothreonine; by MAP3KBy similarity1
Modified residuei411PhosphoserineCombined sources1

Post-translational modificationi

Activated by phosphorylation on Ser-271 and Thr-275 by MAP kinase kinase kinases (MAP3Ks).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei44 – 45Cleavage; by anthrax lethal factor2
Sitei76 – 77Cleavage; by anthrax lethal factor2

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO14733.
MaxQBiO14733.
PaxDbiO14733.
PeptideAtlasiO14733.
PRIDEiO14733.

PTM databases

iPTMnetiO14733.
PhosphoSitePlusiO14733.

Miscellaneous databases

PMAP-CutDBiO14733.

Expressioni

Tissue specificityi

Ubiquitous; with highest level of expression in skeletal muscle. Isoform 3 is found at low levels in placenta, fetal liver, and skeletal muscle.3 Publications

Gene expression databases

BgeeiENSG00000076984.
CleanExiHS_MAP2K7.
GenevisibleiO14733. HS.

Organism-specific databases

HPAiCAB004262.
HPA001633.
HPA064711.

Interactioni

Subunit structurei

Interacts with isoform 1 of VRK2. Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3 (By similarity). Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1 and MAP3K1/MEKK1 (By similarity). Interacts with MAPK8IP1/JIP1, MAPK8IP2/JIP2 and MAPK8IP3/JIP3 scaffold proteins. Interacts with RASSF7, the interaction promotes phosphorylation.By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • protein kinase binding Source: UniProtKB
  • protein phosphatase binding Source: BHF-UCL
Complete GO annotation...

Protein-protein interaction databases

BioGridi111595. 57 interactors.
IntActiO14733. 25 interactors.
MINTiMINT-1378223.
STRINGi9606.ENSP00000381066.

Chemistry databases

BindingDBiO14733.

Structurei

Secondary structure

1419
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi105 – 108Combined sources4
Beta strandi111 – 114Combined sources4
Helixi117 – 119Combined sources3
Beta strandi120 – 127Combined sources8
Beta strandi129 – 131Combined sources3
Beta strandi134 – 139Combined sources6
Turni140 – 142Combined sources3
Beta strandi145 – 152Combined sources8
Helixi157 – 172Combined sources16
Turni173 – 175Combined sources3
Beta strandi182 – 187Combined sources6
Beta strandi189 – 196Combined sources8
Beta strandi200 – 202Combined sources3
Helixi203 – 210Combined sources8
Helixi216 – 237Combined sources22
Helixi246 – 248Combined sources3
Beta strandi249 – 251Combined sources3
Beta strandi257 – 259Combined sources3
Turni262 – 265Combined sources4
Helixi281 – 283Combined sources3
Helixi286 – 289Combined sources4
Beta strandi292 – 297Combined sources6
Helixi302 – 317Combined sources16
Turni321 – 324Combined sources4
Helixi328 – 337Combined sources10
Beta strandi345 – 347Combined sources3
Helixi351 – 360Combined sources10
Helixi365 – 367Combined sources3
Helixi371 – 374Combined sources4
Helixi378 – 385Combined sources8
Helixi390 – 400Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DYLX-ray2.45A101-405[»]
3WZUX-ray3.01A103-419[»]
4UX9X-ray2.34F/G/H/I37-48[»]
5B2KX-ray2.75A103-419[»]
5B2LX-ray2.10A103-419[»]
5B2MX-ray3.06A103-419[»]
DisProtiDP00841.
ProteinModelPortaliO14733.
SMRiO14733.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14733.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini120 – 380Protein kinasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni37 – 57D domainBy similarityAdd BLAST21
Regioni377 – 400DVD domainAdd BLAST24

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili2 – 30Sequence analysisAdd BLAST29

Domaini

The DVD domain (residues 377-400) 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.1 Publication
The D domain (residues 37-57) contains a conserved docking site and is required for the binding to MAPK substrates.1 Publication

Sequence similaritiesi

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0983. Eukaryota.
ENOG410XTNQ. LUCA.
GeneTreeiENSGT00760000119199.
HOVERGENiHBG108518.
InParanoidiO14733.
KOiK04431.
OMAiHPVIVIT.
OrthoDBiEOG091G0A9H.
PhylomeDBiO14733.
TreeFamiTF350701.

Family and domain databases

InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O14733-1) [UniParc]FASTAAdd to basket
Also known as: A

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

        10         20         30         40         50
MAASSLEQKL SRLEAKLKQE NREARRRIDL NLDISPQRPR PTLQLPLAND 
        60         70         80         90        100
GGSRSPSSES SPQHPTPPAR PRHMLGLPST LFTPRSMESI EIDQKLQEIM 
       110        120        130        140        150
KQTGYLTIGG QRYQAEINDL ENLGEMGSGT CGQVWKMRFR KTGHVIAVKQ 
       160        170        180        190        200
MRRSGNKEEN KRILMDLDVV LKSHDCPYIV QCFGTFITNT DVFIAMELMG 
       210        220        230        240        250
TCAEKLKKRM QGPIPERILG KMTVAIVKAL YYLKEKHGVI HRDVKPSNIL 
       260        270        280        290        300
LDERGQIKLC DFGISGRLVD SKAKTRSAGC AAYMAPERID PPDPTKPDYD 
       310        320        330        340        350
IRADVWSLGI SLVELATGQF PYKNCKTDFE VLTKVLQEEP PLLPGHMGFS 
       360        370        380        390        400
GDFQSFVKDC LTKDHRKRPK YNKLLEHSFI KRYETLEVDV ASWFKDVMAK 
       410 
TESPRTSGVL SQPHLPFFR
Length:419
Mass (Da):47,485
Last modified:May 30, 2000 - v2
Checksum:iF1B22E050F54299A
GO
Isoform 2 (identifier: O14733-2) [UniParc]FASTAAdd to basket
Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
     111-111: Q → QVPPSLWRGEGGGPARLDPSWERQWGAGGGGRAPGTLQPSLSSQ

Note: May be due to intron retention.
Show »
Length:462
Mass (Da):51,881
Checksum:iDF3496066961B0C7
GO
Isoform 3 (identifier: O14733-3) [UniParc]FASTAAdd to basket
Also known as: gamma1

The sequence of this isoform differs from the canonical sequence as follows:
     42-42: T → IIVITLSPAPAPSQRAA

Show »
Length:435
Mass (Da):49,071
Checksum:i8812A87DB28F2C22
GO
Isoform 4 (identifier: O14733-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     312-312: L → LPCPSPSQ

Note: No experimental confirmation available.
Show »
Length:426
Mass (Da):48,182
Checksum:i7934E29217D8A137
GO

Sequence cautioni

The sequence AAB97813 differs from that shown. Reason: Frameshift at positions 402 and 410.Curated
The sequence AAB97813 differs from that shown. Reason: Erroneous termination at position 420. Translated as stop.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti94Q → H in AAB97813 (PubMed:9312068).Curated1
Sequence conflicti106L → P in ABE03013 (PubMed:16442502).Curated1
Sequence conflicti133Q → P in AAB97813 (PubMed:9312068).Curated1
Sequence conflicti142T → N in AAB88048 (PubMed:9372971).Curated1
Sequence conflicti407S → N in AAB97813 (PubMed:9312068).Curated1
Sequence conflicti415L → LG in AAB97813 (PubMed:9312068).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040825118N → S1 PublicationCorresponds to variant dbSNP:rs56316660Ensembl.1
Natural variantiVAR_040826138R → C1 PublicationCorresponds to variant dbSNP:rs56106612Ensembl.1
Natural variantiVAR_040827162R → C in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040828162R → H in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040829195A → T1 PublicationCorresponds to variant dbSNP:rs55800262Ensembl.1
Natural variantiVAR_029890259L → F1 PublicationCorresponds to variant dbSNP:rs1053566Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02230942T → IIVITLSPAPAPSQRAA in isoform 3. 1 Publication1
Alternative sequenceiVSP_004883111Q → QVPPSLWRGEGGGPARLDPS WERQWGAGGGGRAPGTLQPS LSSQ in isoform 2. 1 Publication1
Alternative sequenceiVSP_022310312L → LPCPSPSQ in isoform 4. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF014401 mRNA. Translation: AAB88048.1.
AF006689 mRNA. Translation: AAB97813.1. Sequence problems.
AF013588 mRNA. Translation: AAC16272.1.
AF013589 mRNA. Translation: AAC16273.1.
DQ445915 mRNA. Translation: ABE03013.1.
AF022805 mRNA. Translation: AAC26142.1.
AK313899 mRNA. Translation: BAG36622.1.
CH471139 Genomic DNA. Translation: EAW68964.1.
CH471139 Genomic DNA. Translation: EAW68968.1.
BC038295 mRNA. Translation: AAH38295.1.
AF003199 mRNA. Translation: AAB63374.1.
CCDSiCCDS42491.1. [O14733-1]
CCDS74277.1. [O14733-3]
CCDS74278.1. [O14733-4]
RefSeqiNP_001284484.1. NM_001297555.1. [O14733-3]
NP_001284485.1. NM_001297556.1. [O14733-4]
NP_660186.1. NM_145185.3. [O14733-1]
UniGeneiHs.531754.

Genome annotation databases

EnsembliENST00000397979; ENSP00000381066; ENSG00000076984. [O14733-1]
ENST00000397981; ENSP00000381068; ENSG00000076984. [O14733-4]
ENST00000397983; ENSP00000381070; ENSG00000076984. [O14733-3]
GeneIDi5609.
KEGGihsa:5609.
UCSCiuc002mit.4. human. [O14733-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiMP2K7_HUMAN
AccessioniPrimary (citable) accession number: O14733
Secondary accession number(s): B2R9S5
, D6W659, O14648, O14816, O60452, O60453, Q1PG43, Q8IY10
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2000
Last modified: July 5, 2017
This is version 172 of the entry and version 2 of the sequence. See 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 19
    Human chromosome 19: 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