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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

Mg2+1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei49 – 491ATP1 PublicationPROSITE-ProRule annotation
Active sitei140 – 1401Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi26 – 349ATPPROSITE-ProRule annotation

GO - Molecular functioni

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

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)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Unplaced

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 5PRO_0000086282Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei335 – 3351PhosphoserineBy 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

BgeeiQ9Y4K4.
CleanExiHS_MAP4K5.
ExpressionAtlasiQ9Y4K4. baseline and differential.
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. 12 interactions.
IntActiQ9Y4K4. 9 interactions.
MINTiMINT-7241969.
STRINGi9606.ENSP00000414032.

Structurei

3D structure databases

ProteinModelPortaliQ9Y4K4.
SMRiQ9Y4K4. Positions 13-346.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 277258Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini506 – 819314CNHPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 CNH domain.CuratedPROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

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.
[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

        10         20         30         40         50
MEAPLRPAAD ILRRNPQQDY ELVQRVGSGT YGDVYKARNV HTGELAAVKI
60 70 80 90 100
IKLEPGDDFS LIQQEIFMVK ECKHCNIVAY FGSYLSREKL WICMEYCGGG
110 120 130 140 150
SLQDIYHVTG PLSELQIAYV CRETLQGLAY LHTKGKMHRD IKGANILLTD
160 170 180 190 200
HGDVKLADFG VAAKITATIA KRKSFIGTPY WMAPEVAAVE KNGGYNQLCD
210 220 230 240 250
IWAVGITAIE LGELQPPMFD LHPMRALFLM SKSNFQPPKL KDKTKWSSTF
260 270 280 290 300
HNFVKIALTK NPKKRPTAER LLTHTFVAQP GLSRALAVEL LDKVNNPDNH
310 320 330 340 350
AHYTEADDDD FEPHAIIRHT IRSTNRNARA ERTASEINFD KLQFEPPLRK
360 370 380 390 400
ETEARDEMGL SSDPNFMLQW NPFVDGANTG KSTSKRAIPP PLPPKPRISS
410 420 430 440 450
YPEDNFPDEE KASTIKHCPD SESRAPQILR RQSSPSCGPV AETSSIGNGD
460 470 480 490 500
GISKLMSENT EGSAQAPQLP RKNDKRDFPK PAINGLPPTP KVLMGACFSK
510 520 530 540 550
VFDGCPLKIN CATSWIHPDT KDQYIIFGTE DGIYTLNLNE LHEATMEQLF
560 570 580 590 600
PRKCTWLYVI NNTLMSLSEG KTFQLYSHNL IALFEHAKKP GLAAHIQTHR
610 620 630 640 650
FPDRILPRKF ALTTKIPDTK GCHKCCIVRN PYTGHKYLCG ALQSGIVLLQ
660 670 680 690 700
WYEPMQKFML IKHFDFPLPS PLNVFEMLVI PEQEYPMVCV AISKGTESNQ
710 720 730 740 750
VVQFETINLN SASSWFTEIG AGSQQLDSIH VTQLERDTVL VCLDKFVKIV
760 770 780 790 800
NLQGKLKSSK KLASELSFDF RIESVVCLQD SVLAFWKHGM QGKSFKSDEV
810 820 830 840
TQEISDETRV FRLLGSDRVV VLESRPTENP TAHSNLYILA GHENSY
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:
EMBLi
GenBanki
DDBJi
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

GeneIDi11183.
KEGGihsa:11183.
UCSCiuc001wya.3. human.

Polymorphism databases

DMDMi30316147.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 116353. 12 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

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

Bgeei Q9Y4K4.
CleanExi HS_MAP4K5.
ExpressionAtlasi Q9Y4K4. baseline and differential.
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.
[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: November 26, 2014
This is version 129 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