Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P45985 (MP2K4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dual specificity mitogen-activated protein kinase kinase 4

Short name=MAP kinase kinase 4
Short name=MAPKK 4
EC=2.7.12.2
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 names
Name:MAP2K4
Synonyms:JNKK1, MEK4, MKK4, PRKMK4, SEK1, SERK1, SKK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length399 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 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. Ref.2

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

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. Ref.11

Subunit structure

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. Ref.11 Ref.13 Ref.14 Ref.15 Ref.19

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Tissue specificity

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

Domain

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. Ref.15 Ref.16

The D domain (residues 34-52) contains a conserved docking site and is required for the binding to MAPK substrates. Ref.15 Ref.16

Post-translational modification

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

Sequence similarities

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

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Stress response
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
Tyrosine-protein kinase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

JNK cascade

Traceable author statement. Source: Reactome

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to mechanical stimulus

Inferred from expression pattern PubMed 19593445. Source: UniProtKB

cellular response to sorbitol

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

positive regulation of DNA replication

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.2. Source: ProtInc

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 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

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

dendrite cytoplasm

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perikaryon

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

JUN kinase kinase activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 9808624. Source: IntAct

protein kinase activity

Traceable author statement Ref.2. Source: ProtInc

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

MAP3K1Q132333EBI-447868,EBI-49776

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P45985-1)

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: P45985-2)

The sequence of this isoform differs from the canonical sequence as follows:
     39-39: G → GFQINFCEKAQS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.18
Chain2 – 399398Dual specificity mitogen-activated protein kinase kinase 4
PRO_0000086381

Regions

Domain102 – 367266Protein kinase
Nucleotide binding108 – 1169ATP By similarity
Region37 – 5216D domain
Region364 – 38724DVD domain
Compositional bias5 – 1915Gly/Ser-rich

Sites

Active site2291Proton acceptor By similarity
Binding site1311ATP By similarity
Site45 – 462Cleavage; by anthrax lethal factor
Site58 – 592Cleavage; by anthrax lethal factor

Amino acid modifications

Modified residue21N-acetylalanine Ref.18
Modified residue901Phosphoserine Ref.17
Modified residue2571Phosphoserine; by MAP3K Ref.21
Modified residue2611Phosphothreonine; by MAP3K Ref.11

Natural variations

Alternative sequence391G → GFQINFCEKAQS in isoform 2.
VSP_038838
Natural variant161S → R. Ref.10
Corresponds to variant rs17855590 [ dbSNP | Ensembl ].
VAR_062963
Natural variant1421Q → L in a lung squamous cell carcinoma sample; somatic mutation. Ref.27
VAR_040818
Natural variant1541R → W in a colorectal adenocarcinoma sample; somatic mutation. Ref.27
VAR_040819
Natural variant2341N → I in an ovarian serous carcinoma sample; somatic mutation. Ref.27
VAR_040820
Natural variant2511S → N in a metastatic melanoma sample; somatic mutation. Ref.27
VAR_040821
Natural variant2791A → T in a colorectal adenocarcinoma sample; somatic mutation. Ref.27
VAR_040822

Experimental info

Sequence conflict1181K → R in CAG38801. Ref.4
Sequence conflict1791E → G in BAG35884. Ref.6
Sequence conflict3561P → L in AAH60764. Ref.10

Secondary structure

.................................................... 399
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: A472537F2F26770B

FASTA39944,288
        10         20         30         40         50         60 
MAAPSPSGGG GSGGGSGSGT PGPVGSPAPG HPAVSSMQGK RKALKLNFAN PPFKSTARFT 

        70         80         90        100        110        120 
LNPNPTGVQN PHIERLRTHS IESSGKLKIS PEQHWDFTAE DLKDLGEIGR GAYGSVNKMV 

       130        140        150        160        170        180 
HKPSGQIMAV KRIRSTVDEK EQKQLLMDLD VVMRSSDCPY IVQFYGALFR EGDCWICMEL 

       190        200        210        220        230        240 
MSTSFDKFYK YVYSVLDDVI PEEILGKITL ATVKALNHLK ENLKIIHRDI KPSNILLDRS 

       250        260        270        280        290        300 
GNIKLCDFGI SGQLVDSIAK TRDAGCRPYM APERIDPSAS RQGYDVRSDV WSLGITLYEL 

       310        320        330        340        350        360 
ATGRFPYPKW NSVFDQLTQV VKGDPPQLSN SEEREFSPSF INFVNLCLTK DESKRPKYKE 

       370        380        390 
LLKHPFILMY EERAVEVACY VCKILDQMPA TPSSPMYVD 

« Hide

Isoform 2 [UniParc].

Checksum: 097F8966398DD6C0
Show »

FASTA41045,584

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]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. expand/collapse author list , 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].
[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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L36870 mRNA. Translation: AAC41719.1.
U17743 mRNA. Translation: AAC50127.1.
AF070090 expand/collapse EMBL AC list , 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.
CCDSCCDS11162.1. [P45985-1]
CCDS62095.1. [P45985-2]
PIRI38901.
RefSeqNP_001268364.1. NM_001281435.1. [P45985-2]
NP_003001.1. NM_003010.3. [P45985-1]
UniGeneHs.514681.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3ALNX-ray2.30A/B/C80-399[»]
3ALOX-ray2.60A80-399[»]
3VUTX-ray3.50A/B80-399[»]
ProteinModelPortalP45985.
SMRP45985. Positions 95-388.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112315. 37 interactions.
IntActP45985. 11 interactions.
MINTMINT-151438.
STRING9606.ENSP00000262445.

Chemistry

BindingDBP45985.
ChEMBLCHEMBL2897.
GuidetoPHARMACOLOGY2065.

PTM databases

PhosphoSiteP45985.

Polymorphism databases

DMDM1170596.

Proteomic databases

MaxQBP45985.
PaxDbP45985.
PRIDEP45985.

Protocols and materials databases

DNASU6416.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000353533; ENSP00000262445; ENSG00000065559. [P45985-1]
ENST00000415385; ENSP00000410402; ENSG00000065559. [P45985-2]
GeneID6416.
KEGGhsa:6416.
UCSCuc002gnj.3. human. [P45985-1]
uc002gnk.3. human. [P45985-2]

Organism-specific databases

CTD6416.
GeneCardsGC17P011864.
HGNCHGNC:6844. MAP2K4.
HPACAB007751.
MIM601335. gene.
neXtProtNX_P45985.
PharmGKBPA30589.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG108518.
InParanoidP45985.
KOK04430.
OMAVMKSNDC.
OrthoDBEOG7J9VPW.
PhylomeDBP45985.
TreeFamTF350701.

Enzyme and pathway databases

BRENDA2.7.12.2. 2681.
ReactomeREACT_120956. Cellular responses to stress.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkP45985.

Gene expression databases

ArrayExpressP45985.
BgeeP45985.
CleanExHS_MAP2K4.
GenevestigatorP45985.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMAP2K4. human.
EvolutionaryTraceP45985.
GeneWikiMAP2K4.
GenomeRNAi6416.
NextBio24922.
PMAP-CutDBP45985.
PROP45985.
SOURCESearch...

Entry information

Entry nameMP2K4_HUMAN
AccessionPrimary (citable) accession number: P45985
Secondary accession number(s): B2R7N7 expand/collapse secondary AC list , B3KYB2, D3DTS5, Q5U0B8, Q6FHX4, Q6P9H2, Q6PIE6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 148 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM