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

Q9Y4K4 (M4K5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase kinase kinase kinase 5

EC=2.7.11.1
Alternative name(s):
Kinase homologous to SPS1/STE20
Short name=KHS
MAPK/ERK kinase kinase kinase 5
Short name=MEK kinase kinase 5
Short name=MEKKK 5
Gene names
Name:MAP4K5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length846 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. Ref.1

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.1

Cofactor

Magnesium. Ref.1

Subunit structure

Interacts with both SH3 domains of the adapter proteins CRK and CRKL. Ref.3

Subcellular location

Cytoplasm Ref.1.

Tissue specificity

Ubiquitously expressed in all tissues examined, with high levels in the ovary, testis and prostate. Ref.1

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Contains 1 CNH domain.

Contains 1 protein kinase domain.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 846846Mitogen-activated protein kinase kinase kinase kinase 5
PRO_0000086282

Regions

Domain20 – 277258Protein kinase
Domain506 – 819314CNH
Nucleotide binding26 – 349ATP By similarity UniProtKB O00506

Sites

Active site1401Proton acceptor By similarity UniProtKB O00506
Binding site491ATP Ref.1

Amino acid modifications

Modified residue3351Phosphoserine By similarity

Natural variations

Natural variant411H → Y.
Corresponds to variant rs34726242 [ dbSNP | Ensembl ].
VAR_057102
Natural variant3341A → T. Ref.5
Corresponds to variant rs12881869 [ dbSNP | Ensembl ].
VAR_040747
Natural variant4071P → L. Ref.5
Corresponds to variant rs34818002 [ dbSNP | Ensembl ].
VAR_040748
Natural variant4461I → V. Ref.5
Corresponds to variant rs55815015 [ dbSNP | Ensembl ].
VAR_040749
Natural variant4731N → K. Ref.2 Ref.5
Corresponds to variant rs35768475 [ dbSNP | Ensembl ].
VAR_040750
Natural variant5521R → Q. Ref.5
Corresponds to variant rs55997280 [ dbSNP | Ensembl ].
VAR_040751
Natural variant6331T → M. Ref.5
Corresponds to variant rs17780143 [ dbSNP | Ensembl ].
VAR_040752

Experimental info

Mutagenesis491K → R: Loss of kinase activity and ability to activate JNK family. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9Y4K4 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: B17F95196AA14E08

FASTA84695,040
        10         20         30         40         50         60 
MEAPLRPAAD ILRRNPQQDY ELVQRVGSGT YGDVYKARNV HTGELAAVKI IKLEPGDDFS 

        70         80         90        100        110        120 
LIQQEIFMVK ECKHCNIVAY FGSYLSREKL WICMEYCGGG SLQDIYHVTG PLSELQIAYV 

       130        140        150        160        170        180 
CRETLQGLAY LHTKGKMHRD IKGANILLTD HGDVKLADFG VAAKITATIA KRKSFIGTPY 

       190        200        210        220        230        240 
WMAPEVAAVE KNGGYNQLCD IWAVGITAIE LGELQPPMFD LHPMRALFLM SKSNFQPPKL 

       250        260        270        280        290        300 
KDKTKWSSTF HNFVKIALTK NPKKRPTAER LLTHTFVAQP GLSRALAVEL LDKVNNPDNH 

       310        320        330        340        350        360 
AHYTEADDDD FEPHAIIRHT IRSTNRNARA ERTASEINFD KLQFEPPLRK ETEARDEMGL 

       370        380        390        400        410        420 
SSDPNFMLQW NPFVDGANTG KSTSKRAIPP PLPPKPRISS YPEDNFPDEE KASTIKHCPD 

       430        440        450        460        470        480 
SESRAPQILR RQSSPSCGPV AETSSIGNGD GISKLMSENT EGSAQAPQLP RKNDKRDFPK 

       490        500        510        520        530        540 
PAINGLPPTP KVLMGACFSK VFDGCPLKIN CATSWIHPDT KDQYIIFGTE DGIYTLNLNE 

       550        560        570        580        590        600 
LHEATMEQLF PRKCTWLYVI NNTLMSLSEG KTFQLYSHNL IALFEHAKKP GLAAHIQTHR 

       610        620        630        640        650        660 
FPDRILPRKF ALTTKIPDTK GCHKCCIVRN PYTGHKYLCG ALQSGIVLLQ WYEPMQKFML 

       670        680        690        700        710        720 
IKHFDFPLPS PLNVFEMLVI PEQEYPMVCV AISKGTESNQ VVQFETINLN SASSWFTEIG 

       730        740        750        760        770        780 
AGSQQLDSIH VTQLERDTVL VCLDKFVKIV NLQGKLKSSK KLASELSFDF RIESVVCLQD 

       790        800        810        820        830        840 
SVLAFWKHGM QGKSFKSDEV TQEISDETRV FRLLGSDRVV VLESRPTENP TAHSNLYILA 


GHENSY 

« Hide

References

« Hide 'large scale' references
[1]"A novel human SPS1/STE20 homologue, KHS, activates jun N-terminal kinase."
Tung R.M., Blenis J.
Oncogene 14:653-659(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-49.
Tissue: T-cell.
[2]"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], VARIANT LYS-473.
Tissue: Testis.
[3]"The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins."
Oehrl W., Kardinal C., Ruf S., Adermann K., Groffen J., Feng G.-S., Blenis J., Tan T.-H., Feller S.M.
Oncogene 17:1893-1901(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CRK AND CRKL.
[4]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[5]"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] THR-334; LEU-407; VAL-446; LYS-473; GLN-552 AND MET-633.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U77129 mRNA. Translation: AAB48435.1.
BC036013 mRNA. Translation: AAH36013.1.
RefSeqNP_006566.2. NM_006575.4.
NP_942089.1. NM_198794.2.
XP_006720076.1. XM_006720013.1.
UniGeneHs.130491.

3D structure databases

ProteinModelPortalQ9Y4K4.
SMRQ9Y4K4. Positions 13-346.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116353. 11 interactions.
IntActQ9Y4K4. 9 interactions.
MINTMINT-7241969.
STRING9606.ENSP00000414032.

Chemistry

BindingDBQ9Y4K4.
ChEMBLCHEMBL4852.
GuidetoPHARMACOLOGY2089.

PTM databases

PhosphoSiteQ9Y4K4.

Polymorphism databases

DMDM30316147.

Proteomic databases

MaxQBQ9Y4K4.
PaxDbQ9Y4K4.
PRIDEQ9Y4K4.

Protocols and materials databases

DNASU11183.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000013125; ENSP00000013125; ENSG00000012983.
GeneID11183.
KEGGhsa:11183.
UCSCuc001wya.3. human.

Organism-specific databases

CTD11183.
GeneCardsGC14M050885.
HGNCHGNC:6867. MAP4K5.
HPAHPA036696.
MIM604923. gene.
neXtProtNX_Q9Y4K4.
PharmGKBPA30613.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000230824.
HOVERGENHBG036702.
InParanoidQ9Y4K4.
KOK08833.
OrthoDBEOG7WX07M.
PhylomeDBQ9Y4K4.
TreeFamTF105121.

Enzyme and pathway databases

SignaLinkQ9Y4K4.

Gene expression databases

ArrayExpressQ9Y4K4.
BgeeQ9Y4K4.
CleanExHS_MAP4K5.
GenevestigatorQ9Y4K4.

Family and domain databases

InterProIPR001180. Citron.
IPR011009. Kinase-like_dom.
IPR021160. MAPKKKK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]
PfamPF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF038172. MAPKKKK. 1 hit.
SMARTSM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMAP4K5. human.
GeneWikiMAP4K5.
GenomeRNAi11183.
NextBio42555.
PROQ9Y4K4.
SOURCESearch...

Entry information

Entry nameM4K5_HUMAN
AccessionPrimary (citable) accession number: Q9Y4K4
Secondary accession number(s): Q8IYF6
Entry history
Integrated into UniProtKB/Swiss-Prot: April 30, 2003
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 126 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

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 14

Human chromosome 14: entries, gene names and cross-references to MIM