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Protein

Mitogen-activated protein kinase kinase kinase kinase 5

Gene

MAP4K5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Binding sitei49ATPPROSITE-ProRule annotation1 Publication1
Active sitei140Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi26 – 34ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • MAP kinase kinase kinase kinase activity Source: InterPro
  • protein kinase activity Source: ProtInc
  • protein serine/threonine kinase activity Source: UniProtKB
  • receptor signaling protein serine/threonine kinase activity Source: GO_Central

GO - Biological processi

  • activation of JUN kinase activity Source: ProtInc
  • intracellular signal transduction Source: UniProtKB
  • 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

BioCyciZFISH:HS00338-MONOMER.
SignaLinkiQ9Y4K4.
SIGNORiQ9Y4K4.

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
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:6867. MAP4K5.

Subcellular locationi

  • Cytoplasm 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi49K → R: Loss of kinase activity and ability to activate JNK family. 1 Publication1

Organism-specific databases

DisGeNETi11183.
PharmGKBiPA30613.

Chemistry databases

ChEMBLiCHEMBL4852.
GuidetoPHARMACOLOGYi2089.

Polymorphism and mutation databases

BioMutaiMAP4K5.
DMDMi30316147.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862821 – 846Mitogen-activated protein kinase kinase kinase kinase 5Add BLAST846

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei335PhosphoserineCombined sources1
Modified residuei433PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9Y4K4.
MaxQBiQ9Y4K4.
PaxDbiQ9Y4K4.
PeptideAtlasiQ9Y4K4.
PRIDEiQ9Y4K4.

PTM databases

iPTMnetiQ9Y4K4.
PhosphoSitePlusiQ9Y4K4.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000012983.
CleanExiHS_MAP4K5.

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. 15 interactors.
IntActiQ9Y4K4. 9 interactors.
MINTiMINT-7241969.
STRINGi9606.ENSP00000013125.

Chemistry databases

BindingDBiQ9Y4K4.

Structurei

3D structure databases

ProteinModelPortaliQ9Y4K4.
SMRiQ9Y4K4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 277Protein kinasePROSITE-ProRule annotationAdd BLAST258
Domaini506 – 819CNHPROSITE-ProRule annotationAdd BLAST314

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0576. Eukaryota.
ENOG410XP9G. LUCA.
HOGENOMiHOG000230824.
HOVERGENiHBG036702.
InParanoidiQ9Y4K4.
KOiK08833.
PhylomeDBiQ9Y4K4.
TreeFamiTF105121.

Family and domain databases

InterProiIPR001180. CNH_dom.
IPR011009. Kinase-like_dom.
IPR021160. MAPKKKK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[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)DescriptionActionsGraphical viewLength
Natural variantiVAR_05710241H → Y.Corresponds to variant rs34726242dbSNPEnsembl.1
Natural variantiVAR_040747334A → T.1 PublicationCorresponds to variant rs12881869dbSNPEnsembl.1
Natural variantiVAR_040748407P → L.1 PublicationCorresponds to variant rs34818002dbSNPEnsembl.1
Natural variantiVAR_040749446I → V.1 PublicationCorresponds to variant rs55815015dbSNPEnsembl.1
Natural variantiVAR_040750473N → K.2 PublicationsCorresponds to variant rs35768475dbSNPEnsembl.1
Natural variantiVAR_040751552R → Q.1 PublicationCorresponds to variant rs55997280dbSNPEnsembl.1
Natural variantiVAR_040752633T → M.1 PublicationCorresponds to variant rs17780143dbSNPEnsembl.1

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_006720013.3.
UniGeneiHs.130491.

Genome annotation databases

GeneIDi11183.
KEGGihsa:11183.

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.
RefSeqiNP_006566.2. NM_006575.4.
NP_942089.1. NM_198794.2.
XP_006720076.1. XM_006720013.3.
UniGeneiHs.130491.

3D structure databases

ProteinModelPortaliQ9Y4K4.
SMRiQ9Y4K4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116353. 15 interactors.
IntActiQ9Y4K4. 9 interactors.
MINTiMINT-7241969.
STRINGi9606.ENSP00000013125.

Chemistry databases

BindingDBiQ9Y4K4.
ChEMBLiCHEMBL4852.
GuidetoPHARMACOLOGYi2089.

PTM databases

iPTMnetiQ9Y4K4.
PhosphoSitePlusiQ9Y4K4.

Polymorphism and mutation databases

BioMutaiMAP4K5.
DMDMi30316147.

Proteomic databases

EPDiQ9Y4K4.
MaxQBiQ9Y4K4.
PaxDbiQ9Y4K4.
PeptideAtlasiQ9Y4K4.
PRIDEiQ9Y4K4.

Protocols and materials databases

DNASUi11183.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi11183.
KEGGihsa:11183.

Organism-specific databases

CTDi11183.
DisGeNETi11183.
GeneCardsiMAP4K5.
HGNCiHGNC:6867. MAP4K5.
HPAiHPA036696.
MIMi604923. gene.
neXtProtiNX_Q9Y4K4.
PharmGKBiPA30613.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0576. Eukaryota.
ENOG410XP9G. LUCA.
HOGENOMiHOG000230824.
HOVERGENiHBG036702.
InParanoidiQ9Y4K4.
KOiK08833.
PhylomeDBiQ9Y4K4.
TreeFamiTF105121.

Enzyme and pathway databases

BioCyciZFISH:HS00338-MONOMER.
SignaLinkiQ9Y4K4.
SIGNORiQ9Y4K4.

Miscellaneous databases

ChiTaRSiMAP4K5. human.
GeneWikiiMAP4K5.
GenomeRNAii11183.
PROiQ9Y4K4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000012983.
CleanExiHS_MAP4K5.

Family and domain databases

InterProiIPR001180. CNH_dom.
IPR011009. Kinase-like_dom.
IPR021160. MAPKKKK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[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]
ProtoNetiSearch...

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 2, 2016
This is version 149 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.