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Q9Y4K4

- M4K5_HUMAN

UniProt

Q9Y4K4 - M4K5_HUMAN

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Protein
Mitogen-activated protein kinase kinase kinase kinase 5
Gene
MAP4K5
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

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

Cofactori

Magnesium.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei49 – 491ATP1 Publication
Active sitei140 – 1401Proton acceptor By similarityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi26 – 349ATP By similarityBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. protein binding Source: IntAct
  3. protein kinase activity Source: ProtInc
  4. protein serine/threonine kinase activity Source: UniProtKB
  5. small GTPase regulator activity Source: InterPro
Complete GO annotation...

GO - Biological processi

  1. activation of JUN kinase activity Source: ProtInc
  2. intracellular signal transduction Source: UniProtKB
  3. protein phosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ9Y4K4.

Names & Taxonomyi

Protein namesi
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 namesi
Name:MAP4K5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:6867. MAP4K5.

Subcellular locationi

Cytoplasm 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. plasma membrane Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi49 – 491K → R: Loss of kinase activity and ability to activate JNK family. 1 Publication

Organism-specific databases

PharmGKBiPA30613.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 846846Mitogen-activated protein kinase kinase kinase kinase 5
PRO_0000086282Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei335 – 3351Phosphoserine By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9Y4K4.
PaxDbiQ9Y4K4.
PRIDEiQ9Y4K4.

PTM databases

PhosphoSiteiQ9Y4K4.

Expressioni

Tissue specificityi

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

Gene expression databases

ArrayExpressiQ9Y4K4.
BgeeiQ9Y4K4.
CleanExiHS_MAP4K5.
GenevestigatoriQ9Y4K4.

Organism-specific databases

HPAiHPA036696.

Interactioni

Subunit structurei

Interacts with both SH3 domains of the adapter proteins CRK and CRKL.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CRKP461085EBI-1279,EBI-886
GRB2P629934EBI-1279,EBI-401755
NCK1P163332EBI-1279,EBI-389883

Protein-protein interaction databases

BioGridi116353. 11 interactions.
IntActiQ9Y4K4. 9 interactions.
MINTiMINT-7241969.
STRINGi9606.ENSP00000414032.

Structurei

3D structure databases

ProteinModelPortaliQ9Y4K4.
SMRiQ9Y4K4. Positions 13-346.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 277258Protein kinase
Add
BLAST
Domaini506 – 819314CNH
Add
BLAST

Sequence similaritiesi

Contains 1 CNH domain.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000230824.
HOVERGENiHBG036702.
InParanoidiQ9Y4K4.
KOiK08833.
OrthoDBiEOG7WX07M.
PhylomeDBiQ9Y4K4.
TreeFamiTF105121.

Family and domain databases

InterProiIPR001180. 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]
PfamiPF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF038172. MAPKKKK. 1 hit.
SMARTiSM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Y4K4-1 [UniParc]FASTAAdd to Basket

« Hide

MEAPLRPAAD ILRRNPQQDY ELVQRVGSGT YGDVYKARNV HTGELAAVKI    50
IKLEPGDDFS LIQQEIFMVK ECKHCNIVAY FGSYLSREKL WICMEYCGGG 100
SLQDIYHVTG PLSELQIAYV CRETLQGLAY LHTKGKMHRD IKGANILLTD 150
HGDVKLADFG VAAKITATIA KRKSFIGTPY WMAPEVAAVE KNGGYNQLCD 200
IWAVGITAIE LGELQPPMFD LHPMRALFLM SKSNFQPPKL KDKTKWSSTF 250
HNFVKIALTK NPKKRPTAER LLTHTFVAQP GLSRALAVEL LDKVNNPDNH 300
AHYTEADDDD FEPHAIIRHT IRSTNRNARA ERTASEINFD KLQFEPPLRK 350
ETEARDEMGL SSDPNFMLQW NPFVDGANTG KSTSKRAIPP PLPPKPRISS 400
YPEDNFPDEE KASTIKHCPD SESRAPQILR RQSSPSCGPV AETSSIGNGD 450
GISKLMSENT EGSAQAPQLP RKNDKRDFPK PAINGLPPTP KVLMGACFSK 500
VFDGCPLKIN CATSWIHPDT KDQYIIFGTE DGIYTLNLNE LHEATMEQLF 550
PRKCTWLYVI NNTLMSLSEG KTFQLYSHNL IALFEHAKKP GLAAHIQTHR 600
FPDRILPRKF ALTTKIPDTK GCHKCCIVRN PYTGHKYLCG ALQSGIVLLQ 650
WYEPMQKFML IKHFDFPLPS PLNVFEMLVI PEQEYPMVCV AISKGTESNQ 700
VVQFETINLN SASSWFTEIG AGSQQLDSIH VTQLERDTVL VCLDKFVKIV 750
NLQGKLKSSK KLASELSFDF RIESVVCLQD SVLAFWKHGM QGKSFKSDEV 800
TQEISDETRV FRLLGSDRVV VLESRPTENP TAHSNLYILA GHENSY 846
Length:846
Mass (Da):95,040
Last modified:November 1, 1999 - v1
Checksum:iB17F95196AA14E08
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti41 – 411H → Y.
Corresponds to variant rs34726242 [ dbSNP | Ensembl ].
VAR_057102
Natural varianti334 – 3341A → T.1 Publication
Corresponds to variant rs12881869 [ dbSNP | Ensembl ].
VAR_040747
Natural varianti407 – 4071P → L.1 Publication
Corresponds to variant rs34818002 [ dbSNP | Ensembl ].
VAR_040748
Natural varianti446 – 4461I → V.1 Publication
Corresponds to variant rs55815015 [ dbSNP | Ensembl ].
VAR_040749
Natural varianti473 – 4731N → K.2 Publications
Corresponds to variant rs35768475 [ dbSNP | Ensembl ].
VAR_040750
Natural varianti552 – 5521R → Q.1 Publication
Corresponds to variant rs55997280 [ dbSNP | Ensembl ].
VAR_040751
Natural varianti633 – 6331T → M.1 Publication
Corresponds to variant rs17780143 [ dbSNP | Ensembl ].
VAR_040752

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U77129 mRNA. Translation: AAB48435.1.
BC036013 mRNA. Translation: AAH36013.1.
RefSeqiNP_006566.2. NM_006575.4.
NP_942089.1. NM_198794.2.
XP_006720076.1. XM_006720013.1.
UniGeneiHs.130491.

Genome annotation databases

EnsembliENST00000013125; ENSP00000013125; ENSG00000012983.
GeneIDi11183.
KEGGihsa:11183.
UCSCiuc001wya.3. human.

Polymorphism databases

DMDMi30316147.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U77129 mRNA. Translation: AAB48435.1 .
BC036013 mRNA. Translation: AAH36013.1 .
RefSeqi NP_006566.2. NM_006575.4.
NP_942089.1. NM_198794.2.
XP_006720076.1. XM_006720013.1.
UniGenei Hs.130491.

3D structure databases

ProteinModelPortali Q9Y4K4.
SMRi Q9Y4K4. Positions 13-346.
ModBasei Search...

Protein-protein interaction databases

BioGridi 116353. 11 interactions.
IntActi Q9Y4K4. 9 interactions.
MINTi MINT-7241969.
STRINGi 9606.ENSP00000414032.

Chemistry

BindingDBi Q9Y4K4.
ChEMBLi CHEMBL4852.
GuidetoPHARMACOLOGYi 2089.

PTM databases

PhosphoSitei Q9Y4K4.

Polymorphism databases

DMDMi 30316147.

Proteomic databases

MaxQBi Q9Y4K4.
PaxDbi Q9Y4K4.
PRIDEi Q9Y4K4.

Protocols and materials databases

DNASUi 11183.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000013125 ; ENSP00000013125 ; ENSG00000012983 .
GeneIDi 11183.
KEGGi hsa:11183.
UCSCi uc001wya.3. human.

Organism-specific databases

CTDi 11183.
GeneCardsi GC14M050885.
HGNCi HGNC:6867. MAP4K5.
HPAi HPA036696.
MIMi 604923. gene.
neXtProti NX_Q9Y4K4.
PharmGKBi PA30613.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000230824.
HOVERGENi HBG036702.
InParanoidi Q9Y4K4.
KOi K08833.
OrthoDBi EOG7WX07M.
PhylomeDBi Q9Y4K4.
TreeFami TF105121.

Enzyme and pathway databases

SignaLinki Q9Y4K4.

Miscellaneous databases

ChiTaRSi MAP4K5. human.
GeneWikii MAP4K5.
GenomeRNAii 11183.
NextBioi 42555.
PROi Q9Y4K4.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9Y4K4.
Bgeei Q9Y4K4.
CleanExi HS_MAP4K5.
Genevestigatori Q9Y4K4.

Family and domain databases

InterProi IPR001180. 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 ]
Pfami PF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
PIRSFi PIRSF038172. MAPKKKK. 1 hit.
SMARTi SM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiM4K5_HUMAN
AccessioniPrimary (citable) accession number: Q9Y4K4
Secondary accession number(s): Q8IYF6
Entry historyi
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 statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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