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Reviewed, UniProtKB/Swiss-Prot P45985 (MP2K4_HUMAN)

Last modified June 16, 2009. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Dual specificity mitogen-activated protein kinase kinase 4
      Short name=MAP kinase kinase 4
    EC=2.7.12.2
Alternative name(s):
    JNK-activating kinase 1
    c-Jun N-terminal kinase kinase 1
      Short name=JNKK
    SAPK/ERK kinase 1
      Short name=SEK1
Gene names
Name: MAP2K4
Synonyms: JNKK1, MKK4, PRKMK4, SERK1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length399 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Dual specificity kinase that activates the JUN kinases MAPK8 (JNK1) and MAPK9 (JNK2) as well as MAPK14 (p38) but not MAPK1 (ERK2) or MAPK3 (ERK1).

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

Interacts with SPAG9 By similarity.

Tissue specificity

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

Post-translational modification

Activated by phosphorylation on Ser/Thr by MAP kinase kinase kinases 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.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 399399Dual specificity mitogen-activated protein kinase kinase 4
PRO_0000086381

Regions

Domain102 – 367266Protein kinase
Nucleotide binding108 – 1169ATP By similarity
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 residue901Phosphoserine Ref.7

Natural variations

Natural variant1421Q → L in a lung squamous cell carcinoma sample; somatic mutation. Ref.9
VAR_040818
Natural variant1541R → W in a colorectal adenocarcinoma sample; somatic mutation. Ref.9
VAR_040819
Natural variant2341N → I in an ovarian serous carcinoma sample; somatic mutation. Ref.9
VAR_040820
Natural variant2511S → N in a metastatic melanoma sample; somatic mutation. Ref.9
VAR_040821
Natural variant2791A → T in a colorectal adenocarcinoma sample; somatic mutation. Ref.9
VAR_040822

Sequences

Sequence LengthMass (Da)Tools
P45985-1 [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

References

« Hide 'large scale' references
[1]"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: 7716521] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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: 7839144] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[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: 9622070] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"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].
[5]NIEHS SNPs program
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"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: 11104681] [Abstract]
Cited for: CLEAVAGE BY ANTHRAX LETHAL FACTOR.
[7]"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: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90, MASS SPECTROMETRY.
[8]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]"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: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-142; TRP-154; ILE-234; ASN-251 AND THR-279.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

U17743 mRNA. Translation: AAC50127.1.
L36870 mRNA. Translation: AAC41719.1.
AF070090 expand/collapse EMBL AC list , AF070080, AF070081, AF070082, AF070083, AF070084, AF070085, AF070086, AF070087, AF070088, AF070089 Genomic DNA. Translation: AAC24130.1.
BT019676 mRNA. Translation: AAV38482.1.
DQ015703 Genomic DNA. Translation: AAY22176.1.
IPIIPI00024674.
PIRI38901.
RefSeqNP_003001.1.
UniGeneHs.514681

3D structure databases

HSSPHSSP built from PDB template 1F3M based on UniProtKB Q13153.
ModBaseSearch...

Protein-protein interaction databases

IntActP45985. 5 interactions.

PTM databases

PhosphoSiteP45985.

Proteomic databases

PRIDEP45985.

Genome annotation databases

EnsemblENSG00000065559. Homo sapiens. [Contig view]
GeneID6416.
KEGGhsa:6416.
NMPDRfig|9606.3.peg.13149.

Organism-specific databases

GeneCardsGC17P011864.
H-InvDBHIX0027148.
HGNCHGNC:6844. MAP2K4.
HPACAB007751.
MIM601335. gene.
PharmGKBPA30589.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP45985.
HOVERGENP45985.
OMAP45985. NILMDRR.

Enzyme and pathway databases

BRENDA2.7.12.2. 247.
Pathway_Interaction_DBanthraxpathway. Cellular roles of Anthrax toxin.
ceramidepathway. Ceramide signaling pathway.
ephrinbrevpathway. Ephrin B reverse signaling.
faspathway. FAS signaling pathway (CD95).
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
il6_7pathway. IL6-mediated signaling events.
tcrjnkpathway. JNK signaling in the CD4+ TCR pathway.
ar_tf_pathway. Regulation of Androgen receptor activity.
p38alphabetapathway. Regulation of p38-alpha and p38-beta.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
trail_pathway. TRAIL signaling pathway.
lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.

Gene expression databases

ArrayExpressP45985.
BgeeP45985.
CleanExHS_MAP2K4.

Family and domain databases

InterProIPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio24922.
PMAP-CutDBP45985.
SOURCESearch...

Entry information

Entry nameMP2K4_HUMAN
AccessionPrimary (citable) accession number: P45985
Secondary accession number(s): Q5U0B8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: June 16, 2009
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 17

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents