O14733 (MP2K7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dual specificity mitogen-activated protein kinase kinase 7
Short name=MAP kinase kinase 7
Short name=MAPKK 7
EC=2.7.12.2

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 names

Name:	MAP2K7
Synonyms:	JNKK2, MEK7, MKK7, PRKMK7, SKK4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	419 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1 Ref.2 Ref.3 Ref.5
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Activated by phosphorylation by specific MAP kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 and MAP3K12/DLK. Ref.2 Ref.4
Subunit structure	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. Ref.10 Ref.12 Ref.14 Ref.17
Subcellular location	Nucleus. Cytoplasm By similarity.
Tissue specificity	Ubiquitous; with highest level of expression in skeletal muscle. Isoform 3 is found at low levels in placenta, fetal liver, and skeletal muscle. Ref.1 Ref.3 Ref.4
Domain	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. Ref.13 The D domain (residues 37-57) contains a conserved docking site and is required for the binding to MAPK substrates. Ref.13
Post-translational modification	Activated by phosphorylation on Ser-271 and Thr-275 by MAP kinase kinase kinases (MAP3Ks) By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence AAB97813.1 differs from that shown. Reason: Erroneous termination at position 420. Translated as stop. The sequence AAB97813.1 differs from that shown. Reason: Frameshift at positions 402 and 410.

Ontologies

Keywords
Biological process	Apoptosis Stress response
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome TRIF-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome Toll signaling pathway Traceable author statement. Source: Reactome activation of JUN kinase activity Inferred from sequence or structural similarity. Source: BHF-UCL apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome positive regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 3 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW JUN kinase kinase activity Inferred from electronic annotation. Source: Compara MAP kinase kinase activity Inferred from direct assay Ref.3. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.3. Source: UniProtKB protein phosphatase binding Inferred from sequence or structural similarity. Source: BHF-UCL protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LRRK2	Q5S007	3	EBI-492605,EBI-5323863
MAPK8	P45983	3	EBI-492627,EBI-286483

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O14733-1)

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.

Isoform 2 (identifier: O14733-2)

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.

Isoform 3 (identifier: O14733-3)

Also known as: gamma1;

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

Isoform 4 (identifier: O14733-4)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 419

419

Dual specificity mitogen-activated protein kinase kinase 7

PRO_0000086388

Regions

Domain

120 – 380

261

Protein kinase

Nucleotide binding

126 – 134

9

ATP By similarity

Region

37 – 57

21

D domain By similarity

Region

377 – 400

24

DVD domain

Coiled coil

2 – 30

29

Potential

Sites

Active site

243

1

Proton acceptor By similarity

Binding site

149

1

ATP By similarity

Site

44 – 45

2

Cleavage; by anthrax lethal factor

Site

76 – 77

2

Cleavage; by anthrax lethal factor

Amino acid modifications

Modified residue

271

1

Phosphoserine; by MAP3K By similarity

Modified residue

275

1

Phosphothreonine; by MAP3K By similarity

Natural variations

Alternative sequence

42

1

T → IIVITLSPAPAPSQRAA in isoform 3.

VSP_022309

Alternative sequence

111

1

Q → QVPPSLWRGEGGGPARLDPS WERQWGAGGGGRAPGTLQPS LSSQ in isoform 2.

VSP_004883

Alternative sequence

312

1

L → LPCPSPSQ in isoform 4.

VSP_022310

Natural variant

118

1

N → S. Ref.20
Corresponds to variant rs56316660 [ dbSNP | Ensembl ].

VAR_040825

Natural variant

138

1

R → C. Ref.20
Corresponds to variant rs56106612 [ dbSNP | Ensembl ].

VAR_040826

Natural variant

162

1

R → C in a colorectal adenocarcinoma sample; somatic mutation. Ref.20

VAR_040827

Natural variant

162

1

R → H in a colorectal adenocarcinoma sample; somatic mutation. Ref.20

VAR_040828

Natural variant

195

1

A → T. Ref.20
Corresponds to variant rs55800262 [ dbSNP | Ensembl ].

VAR_040829

Natural variant

259

1

L → F. Ref.3
Corresponds to variant rs1053566 [ dbSNP | Ensembl ].

VAR_029890

Experimental info

Sequence conflict

94

1

Q → H in AAB97813. Ref.2

Sequence conflict

106

1

L → P in ABE03013. Ref.4

Sequence conflict

133

1

Q → P in AAB97813. Ref.2

Sequence conflict

142

1

T → N in AAB88048. Ref.1

Sequence conflict

407

1

S → N in AAB97813. Ref.2

Sequence conflict

415

1

L → LG in AAB97813. Ref.2

Secondary structure

1

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419

Helix Strand Turn

Details...

Beta strand

105 – 114

10

Helix

117 – 119

3

Beta strand

120 – 125

6

Beta strand

134 – 139

6

Turn

140 – 142

3

Beta strand

145 – 152

8

Helix

157 – 172

16

Turn

173 – 175

3

Beta strand

182 – 187

6

Beta strand

189 – 196

8

Beta strand

200 – 202

3

Helix

203 – 210

8

Helix

216 – 237

22

Helix

246 – 248

3

Beta strand

249 – 251

3

Beta strand

257 – 259

3

Helix

286 – 289

4

Helix

302 – 317

16

Turn

321 – 324

4

Helix

328 – 337

10

Beta strand

345 – 347

3

Helix

351 – 360

10

Turn

365 – 367

3

Helix

371 – 374

4

Helix

378 – 385

8

Helix

390 – 399

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (A) [UniParc]. Last modified May 30, 2000. Version 2. Checksum: F1B22E050F54299A	FASTA	419	47,485
	10 20 30 40 50 60 MAASSLEQKL SRLEAKLKQE NREARRRIDL NLDISPQRPR PTLQLPLAND GGSRSPSSES 70 80 90 100 110 120 SPQHPTPPAR PRHMLGLPST LFTPRSMESI EIDQKLQEIM KQTGYLTIGG QRYQAEINDL 130 140 150 160 170 180 ENLGEMGSGT CGQVWKMRFR KTGHVIAVKQ MRRSGNKEEN KRILMDLDVV LKSHDCPYIV 190 200 210 220 230 240 QCFGTFITNT DVFIAMELMG TCAEKLKKRM QGPIPERILG KMTVAIVKAL YYLKEKHGVI 250 260 270 280 290 300 HRDVKPSNIL LDERGQIKLC DFGISGRLVD SKAKTRSAGC AAYMAPERID PPDPTKPDYD 310 320 330 340 350 360 IRADVWSLGI SLVELATGQF PYKNCKTDFE VLTKVLQEEP PLLPGHMGFS GDFQSFVKDC 370 380 390 400 410 LTKDHRKRPK YNKLLEHSFI KRYETLEVDV ASWFKDVMAK TESPRTSGVL SQPHLPFFR
	Isoform 2 (B) [UniParc]. Checksum: DF3496066961B0C7	FASTA	462	51,881
	10 20 30 40 50 60 MAASSLEQKL SRLEAKLKQE NREARRRIDL NLDISPQRPR PTLQLPLAND GGSRSPSSES 70 80 90 100 110 120 SPQHPTPPAR PRHMLGLPST LFTPRSMESI EIDQKLQEIM KQTGYLTIGG QVPPSLWRGE 130 140 150 160 170 180 GGGPARLDPS WERQWGAGGG GRAPGTLQPS LSSQRYQAEI NDLENLGEMG SGTCGQVWKM 190 200 210 220 230 240 RFRKTGHVIA VKQMRRSGNK EENKRILMDL DVVLKSHDCP YIVQCFGTFI TNTDVFIAME 250 260 270 280 290 300 LMGTCAEKLK KRMQGPIPER ILGKMTVAIV KALYYLKEKH GVIHRDVKPS NILLDERGQI 310 320 330 340 350 360 KLCDFGISGR LVDSKAKTRS AGCAAYMAPE RIDPPDPTKP DYDIRADVWS LGISLVELAT 370 380 390 400 410 420 GQFPYKNCKT DFEVLTKVLQ EEPPLLPGHM GFSGDFQSFV KDCLTKDHRK RPKYNKLLEH 430 440 450 460 SFIKRYETLE VDVASWFKDV MAKTESPRTS GVLSQPHLPF FR
	Isoform 3 (gamma1) [UniParc]. Checksum: 8812A87DB28F2C22	FASTA	435	49,071
	10 20 30 40 50 60 MAASSLEQKL SRLEAKLKQE NREARRRIDL NLDISPQRPR PIIVITLSPA PAPSQRAALQ 70 80 90 100 110 120 LPLANDGGSR SPSSESSPQH PTPPARPRHM LGLPSTLFTP RSMESIEIDQ KLQEIMKQTG 130 140 150 160 170 180 YLTIGGQRYQ AEINDLENLG EMGSGTCGQV WKMRFRKTGH VIAVKQMRRS GNKEENKRIL 190 200 210 220 230 240 MDLDVVLKSH DCPYIVQCFG TFITNTDVFI AMELMGTCAE KLKKRMQGPI PERILGKMTV 250 260 270 280 290 300 AIVKALYYLK EKHGVIHRDV KPSNILLDER GQIKLCDFGI SGRLVDSKAK TRSAGCAAYM 310 320 330 340 350 360 APERIDPPDP TKPDYDIRAD VWSLGISLVE LATGQFPYKN CKTDFEVLTK VLQEEPPLLP 370 380 390 400 410 420 GHMGFSGDFQ SFVKDCLTKD HRKRPKYNKL LEHSFIKRYE TLEVDVASWF KDVMAKTESP 430 RTSGVLSQPH LPFFR
	Isoform 4 [UniParc]. Checksum: 7934E29217D8A137	FASTA	426	48,182
	10 20 30 40 50 60 MAASSLEQKL SRLEAKLKQE NREARRRIDL NLDISPQRPR PTLQLPLAND GGSRSPSSES 70 80 90 100 110 120 SPQHPTPPAR PRHMLGLPST LFTPRSMESI EIDQKLQEIM KQTGYLTIGG QRYQAEINDL 130 140 150 160 170 180 ENLGEMGSGT CGQVWKMRFR KTGHVIAVKQ MRRSGNKEEN KRILMDLDVV LKSHDCPYIV 190 200 210 220 230 240 QCFGTFITNT DVFIAMELMG TCAEKLKKRM QGPIPERILG KMTVAIVKAL YYLKEKHGVI 250 260 270 280 290 300 HRDVKPSNIL LDERGQIKLC DFGISGRLVD SKAKTRSAGC AAYMAPERID PPDPTKPDYD 310 320 330 340 350 360 IRADVWSLGI SLPCPSPSQV ELATGQFPYK NCKTDFEVLT KVLQEEPPLL PGHMGFSGDF 370 380 390 400 410 420 QSFVKDCLTK DHRKRPKYNK LLEHSFIKRY ETLEVDVASW FKDVMAKTES PRTSGVLSQP HLPFFR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of human JNKK2, a novel jun NH2-terminal kinase-specific kinase." Wu Z., Wu J., Jacinto E., Karin M. Mol. Cell. Biol. 17:7407-7416(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY. Tissue: Heart and Skeletal muscle.
[2]	"Identification of c-Jun NH2-terminal protein kinase (JNK)-activating kinase 2 as an activator of JNK but not p38." Lu X., Nemoto S., Lin A. J. Biol. Chem. 272:24751-24754(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION.
[3]	"Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly conserved c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activated by environmental stresses and physiological stimuli." Foltz I.N., Gerl R.E., Wieler J.S., Luckach M., Salmon R.A., Schrader J.W. J. Biol. Chem. 273:9344-9351(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY, VARIANT PHE-259. Tissue: Fetal kidney.
[4]	"Cloning and expression of human mitogen-activated protein kinase kinase 7gamma1." Michael L., Swantek J., Robinson M.J. Biochem. Biophys. Res. Commun. 341:679-683(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ENZYME REGULATION, TISSUE SPECIFICITY.
[5]	"Molecular cloning of human JNKK2 reveals a novel kinase module for c-Jun N-terminal kinase activation." Yang J., New L., Yong J., Han J., Su B. Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN PHOSPHORYLATION OF MAPK8/JNK1 AND MAPK9/JNK2.
[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 1). Tissue: Brain.
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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 4). Tissue: Testis.
[9]	"Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase." Tournier C., Whitmarsh A.J., Cavanagh J., Barrett T., Davis R.J. Proc. Natl. Acad. Sci. U.S.A. 94:7337-7342(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-260 (ISOFORMS 1/4).
[10]	"The JIP group of mitogen-activated protein kinase scaffold proteins." Yasuda J., Whitmarsh A.J., Cavanagh J., Sharma M., Davis R.J. Mol. Cell. Biol. 19:7245-7254(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAPK8IP1/JIP1 AND MAPK8IP2/JIP2.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"Modulation of interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein." Blanco S., Sanz-Garcia M., Santos C.R., Lazo P.A. PLoS ONE 3:E1660-E1660(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VRK2.
[15]	"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.
[16]	"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.
[17]	"RASSF7 negatively regulates pro-apoptotic JNK signaling by inhibiting the activity of phosphorylated-MKK7." Takahashi S., Ebihara A., Kajiho H., Kontani K., Nishina H., Katada T. Cell Death Differ. 18:645-655(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RASSF7.
[18]	"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.
[19]	"Crystal structure of human mitogen-activated protein kinase kinase 7 activated mutant (s287d, t291d)." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 101-405.
[20]	"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] SER-118; CYS-138; CYS-162; HIS-162 AND THR-195.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00023636.
IPI00302112.
IPI00745806.
IPI00794495.

RefSeq

NP_660186.1. NM_145185.2.

UniGene

Hs.531754.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DYL	X-ray	2.45	A	101-405	[»]

ProteinModelPortal

O14733.

ModBase

Search...

Protein-protein interaction databases

IntAct

O14733. 11 interactions.

MINT

MINT-1378223.

STRING

9606.ENSP00000381066.

PTM databases

PhosphoSite

O14733.

Proteomic databases

PaxDb

O14733.

PRIDE

O14733.

Protocols and materials databases

DNASU

5609.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000397979; ENSP00000381066; ENSG00000076984.
ENST00000397981; ENSP00000381068; ENSG00000076984.
ENST00000397983; ENSP00000381070; ENSG00000076984.

GeneID

5609.

KEGG

hsa:5609.

UCSC

uc002mit.3. human.
uc002miv.2. human.

Organism-specific databases

CTD

5609.

GeneCards

GC19P007968.

HGNC

HGNC:6847. MAP2K7.

HPA

CAB004262.
HPA001633.

MIM

603014. gene.

neXtProt

NX_O14733.

PharmGKB

PA284.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG108518.

KO

K04431.

Enzyme and pathway databases

BRENDA

2.7.12.2. 2681.

Pathway_Interaction_DB

anthraxpathway. Cellular roles of Anthrax toxin.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
reelinpathway. Reelin signaling pathway.
tnfpathway. TNF receptor signaling pathway.

Reactome

REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

O14733.

Bgee

O14733.

CleanEx

HS_MAP2K7.

Genevestigator

O14733.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O14733.

ChEMBL

CHEMBL3530.

DrugBank

DB00773. Etoposide.

EvolutionaryTrace

O14733.

GenomeRNAi

5609.

NextBio

21802.

PMAP-CutDB

O14733.

SOURCE

Search...

Entry information

Entry name

MP2K7_HUMAN

Accession

Primary (citable) accession number: O14733
Secondary accession number(s): B2R9S5 , D6W659, O14648, O14816, O60452, O60453, Q1PG43, Q8IY10

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 30, 2000
Last modified:	May 1, 2013
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.