Mitogen-activated protein kinase kinase kinase kinase 5

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Q9Y4K4 (M4K5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 114. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	846 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of JUN kinase activity Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cytoplasm Inferred from direct assay Ref.1. Source: UniProtKB plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	ATP binding Inferred from direct assay Ref.1. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.1. Source: UniProtKB small GTPase regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct
CRK	P46108	5	EBI-1279,EBI-886
GRB2	P62993	4	EBI-1279,EBI-401755
NCK1	P16333	2	EBI-1279,EBI-389883

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 846

846

Mitogen-activated protein kinase kinase kinase kinase 5

PRO_0000086282

Regions

Domain

20 – 277

258

Protein kinase

Domain

506 – 819

314

CNH

Nucleotide binding

26 – 34

ATP By similarity UniProtKB O00506

Sites

Active site

140

Proton acceptor By similarity UniProtKB O00506

Binding site

ATP Ref.1

Natural variations

Natural variant

H → Y.
Corresponds to variant rs34726242 [ dbSNP | Ensembl ].

VAR_057102

Natural variant

334

A → T. Ref.5
Corresponds to variant rs12881869 [ dbSNP | Ensembl ].

VAR_040747

Natural variant

407

P → L. Ref.5
Corresponds to variant rs34818002 [ dbSNP | Ensembl ].

VAR_040748

Natural variant

446

I → V. Ref.5
Corresponds to variant rs55815015 [ dbSNP | Ensembl ].

VAR_040749

Natural variant

473

N → K. Ref.2 Ref.5
Corresponds to variant rs35768475 [ dbSNP | Ensembl ].

VAR_040750

Natural variant

552

R → Q. Ref.5
Corresponds to variant rs55997280 [ dbSNP | Ensembl ].

VAR_040751

Natural variant

633

T → M. Ref.5
Corresponds to variant rs17780143 [ dbSNP | Ensembl ].

VAR_040752

Experimental info

Mutagenesis

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

Sequences

Sequence

Length

Mass (Da)

Tools

Q9Y4K4 [UniParc].

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

FASTA

846

95,040

        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' referencesShow '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. 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.
IPI	IPI00294842.
RefSeq	NP_006566.2. NM_006575.4. NP_942089.1. NM_198794.2.
UniGene	Hs.130491.
3D structure databases
ProteinModelPortal	Q9Y4K4.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y4K4. 8 interactions.
MINT	MINT-7241969.
STRING	9606.ENSP00000414032.
PTM databases
PhosphoSite	Q9Y4K4.
Polymorphism databases
DMDM	30316147.
Proteomic databases
PaxDb	Q9Y4K4.
PRIDE	Q9Y4K4.
Protocols and materials databases
DNASU	11183.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000013125; ENSP00000013125; ENSG00000012983.
GeneID	11183.
KEGG	hsa:11183.
UCSC	uc001wya.3. human.
Organism-specific databases
CTD	11183.
GeneCards	GC14M050885.
HGNC	HGNC:6867. MAP4K5.
HPA	HPA036696.
MIM	604923. gene.
neXtProt	NX_Q9Y4K4.
PharmGKB	PA30613.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000230824.
HOVERGEN	HBG036702.
InParanoid	Q9Y4K4.
KO	K08833.
OrthoDB	EOG483D3W.
Enzyme and pathway databases
Pathway_Interaction_DB	tnfpathway. TNF receptor signaling pathway.
Gene expression databases
ArrayExpress	Q9Y4K4.
Bgee	Q9Y4K4.
CleanEx	HS_MAP4K5.
Genevestigator	Q9Y4K4.
GermOnline	ENSG00000012983. Homo sapiens.
Family and domain databases
InterPro	IPR001180. Citron. IPR011009. Kinase-like_dom. IPR021160. MAPKKKK. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. [Graphical view]
Pfam	PF00780. CNH. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF038172. MAPKKKK. 1 hit.
SMART	SM00036. CNH. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50219. CNH. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9Y4K4.
ChEMBL	CHEMBL4852.
ChiTaRS	MAP4K5. human.
GenomeRNAi	11183.
NextBio	42555.
SOURCE	Search...

Entry information

Entry name

M4K5_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 114 of the entry and version 1 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.

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Human and mouse protein kinases: classification and index

Human chromosome 14

Human chromosome 14: 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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents