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Reviewed, UniProtKB/Swiss-Prot Q13163 (MP2K5_HUMAN)

Last modified November 25, 2008. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Dual specificity mitogen-activated protein kinase kinase 5
      Short name=MAP kinase kinase 5
      Short name=MAPKK 5
    EC=2.7.12.2
Alternative name(s):
    MAPK/ERK kinase 5
Gene names
Name: MAP2K5
Synonyms: MEK5, MKK5, PRKMK5
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length448 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appear to play a critical role in protecting cells from stress-induced apopotosis, neuronal survival and cardiac development and angiogenesis.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Subunit structure

Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex with SQSTM1 and PRKCZ or PRKCI By similarity. Interacts with Yersinia yopJ.

Tissue specificity

Expressed in many adult tissues. Abundant in heart and skeletal muscle.

Domain

Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the OPR domain. This domain also mediates interactions with SQSTM1 and PARD6A By similarity.

Post-translational modification

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

Yersinia yopJ may acetylate Ser/Thr residues, preventing phosphorylation and activation, thus blocking the MAPK signaling pathway.

Sequence similarities

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

Contains 1 OPR domain.

Contains 1 protein kinase domain.

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform B (identifier: Q13163-1)

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 A (identifier: Q13163-2)

The sequence of this isoform differs from the canonical sequence as follows:
     349-358: Missing.
Isoform C (identifier: Q13163-3)

The sequence of this isoform differs from the canonical sequence as follows:
     349-358: Missing.
     444-448: QQGPP → LASLPSPSPSV
Notes: Incomplete sequence.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 448448Dual specificity mitogen-activated protein kinase kinase 5
PRO_0000086383

Regions

Domain18 – 9780OPR
Domain166 – 409244Protein kinase
Nucleotide binding172 – 1809ATP By similarity
Region18 – 258Interaction with MAPK7 By similarity
Region64 – 685Interaction with MAP3K2/MAP3K3 By similarity
Region117 – 13115Interaction with MAPK7 By similarity

Sites

Active site2831Proton acceptor By similarity
Binding site1951ATP

Amino acid modifications

Modified residue3111Phosphoserine
Modified residue3151Phosphothreonine

Natural variations

Alternative sequence349 – 35810Missing in isoform A and isoform C.
VSP_021825
Alternative sequence444 – 4485QQGPP → LASLPSPSPSV in isoform C.
VSP_021826
Natural variant1181H → R: dbSNP rs56241934.
VAR_040823
Natural variant4271A → V
VAR_040824
Natural variant4281A → T: dbSNP rs55811347.
VAR_046070

Experimental info

Mutagenesis1951K → M: Inactivation
Mutagenesis3111S → A: Inactivation
Mutagenesis3151T → A: Inactivation

Secondary structure

................ 448
Helix Strand Turn

Details...

Sequences

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

Last modified November 28, 2006. Version 2.
Checksum: F23BB327E2A9C7DC

FASTA44850,112
        10         20         30         40         50         60 
MLWLALGPFP AMENQVLVIR IKIPNSGAVD WTVHSGPQLL FRDVLDVIGQ VLPEATTTAF 

        70         80         90        100        110        120 
EYEDEDGDRI TVRSDEEMKA MLSYYYSTVM EQQVNGQLIE PLQIFPRACK PPGERNIHGL 

       130        140        150        160        170        180 
KVNTRAGPSQ HSSPAVSDSL PSNSLKKSSA ELKKILANGQ MNEQDIRYRD TLGHGNGGTV 

       190        200        210        220        230        240 
YKAYHVPSGK ILAVKVILLD ITLELQKQIM SELEILYKCD SSYIIGFYGA FFVENRISIC 

       250        260        270        280        290        300 
TEFMDGGSLD VYRKMPEHVL GRIAVAVVKG LTYLWSLKIL HRDVKPSNML VNTRGQVKLC 

       310        320        330        340        350        360 
DFGVSTQLVN SIAKTYVGTN AYMAPERISG EQYGIHSDVW SLGISFMELA LGRFPYPQIQ 

       370        380        390        400        410        420 
KNQGSLMPLQ LLQCIVDEDS PVLPVGEFSE PFVHFITQCM RKQPKERPAP EELMGHPFIV 

       430        440 
QFNDGNAAVV SMWVCRALEE RRSQQGPP 

« Hide

Isoform A [UniParc].

Checksum: 21246312F1640EE2
Show »

43848,968
Isoform C [UniParc].

Checksum: 574D15B06FD49134
Show »

44449,497

References

« Hide 'large scale' references
[1]"Components of a new human protein kinase signal transduction pathway."
Zhou G., Bao Z.Q., Dixon J.E.
J. Biol. Chem. 270:12665-12669(1995) [PubMed: 7759517] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, INTERACTION WITH ERK5 AND MAPK7, MUTAGENESIS OF LYS-195; SER-311 AND THR-315, PHOSPHORYLATION AT SER-311 AND THR-315.
Tissue: Fetal brain.
[2]"BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C."
Kato Y., Kravchenko V.V., Tapping R.I., Han J., Ulevitch R.J., Lee J.-D.
EMBO J. 16:7054-7066(1997) [PubMed: 9384584] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C), FUNCTION.
Tissue: Placenta.
[3]Lee J.D.
Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO C-TERMINUS OF ISOFORM C.
[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 (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
[6]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
Tissue: Brain.
[7]"Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation."
Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J., Orth K.
Science 312:1211-1214(2006) [PubMed: 16728640] [Abstract]
Cited for: INTERACTION WITH YOPJ, ACETYLATION.
[8]"Crystal structure of the complex of human mitogen activated protein kinase kinase 5 phox domain (MAP2K5-Phox) with human mitogen activated protein kinase kinase kinase 3 (MAP3K2B-Phox)."
Structural genomics consortium (SGC)
Submitted (NOV-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 4-108 IN COMPLEX WITH MAP3K2.
[9]"Crystal structure of the complex of human mitogen activated protein kinase kinase 5 phox domain (MAP2K5-Phox) with human mitogen activated protein kinase kinase kinase 3 (MAP3K3B-Phox)."
Structural genomics consortium (SGC)
Submitted (NOV-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 4-108 IN COMPLEX WITH MAP3K3.
[10]"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] ARG-118; VAL-427 AND THR-428.
+Additional computationally mapped references.

Cross-references

Sequence databases

U25265 mRNA. Translation: AAA96146.1.
U71087 mRNA. Translation: AAB16851.1.
U71088 mRNA. Translation: AAB16852.2.
BT006780 mRNA. Translation: AAP35426.1.
CR542229 mRNA. Translation: CAG47025.1.
BC008838 mRNA. Translation: AAH08838.1.
RefSeqNP_002748.1.
NP_660143.1.
UniGeneHs.114198
Hs.646519

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2NPTX-ray1.75A/C4-108[»]
2O2VX-ray1.83A4-108[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:27558N.
IntActQ13163.

PTM databases

PhosphoSiteQ13163.

Genome annotation databases

EnsemblENSG00000137764. Homo sapiens. [Contig view]
GeneID5607.
KEGGhsa:5607.

Organism-specific databases

HGNCHGNC:6845. MAP2K5.
MIM602520. gene.
PharmGKBPA30590.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMQ13163.
HOVERGENQ13163.

Gene expression databases

ArrayExpressQ13163.
CleanExHS_MAP2K5.
GermOnlineENSG00000137764. Homo sapiens.

Family and domain databases

InterProIPR000270. OPR_PB1.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]
PfamPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00666. PB1. 1 hit.
SM00220. 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

NextBio21792.
SOURCESearch...

Entry information

Entry nameMP2K5_HUMAN
AccessionPrimary (citable) accession number: Q13163
Secondary accession number(s): Q92961, Q92962
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 28, 2006
Last modified: November 25, 2008
This is version 87 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 15

Human chromosome 15: 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents