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Protein

Mitogen-activated protein kinase kinase kinase 2

Gene

MAP3K2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics.By similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Activity regulationi

Activated by phosphorylation on Thr-524.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei385ATPPROSITE-ProRule annotation1
Active sitei483Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi362 – 371ATPPROSITE-ProRule annotation10

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase kinase kinase activity Source: UniProtKB-EC
  • metal ion binding Source: UniProtKB-KW
  • protein kinase activity Source: MGI
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2 2681
SignaLinkiQ9Y2U5
SIGNORiQ9Y2U5

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase 2 (EC:2.7.11.25)
Alternative name(s):
MAPK/ERK kinase kinase 2
Short name:
MEK kinase 2
Short name:
MEKK 2
Gene namesi
Name:MAP3K2
Synonyms:MAPKKK2, MEKK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000169967.16
HGNCiHGNC:6854 MAP3K2
MIMi609487 gene
neXtProtiNX_Q9Y2U5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi10746
OpenTargetsiENSG00000169967
PharmGKBiPA30598

Chemistry databases

ChEMBLiCHEMBL5914
DrugBankiDB06616 Bosutinib
GuidetoPHARMACOLOGYi2077

Polymorphism and mutation databases

BioMutaiMAP3K2
DMDMi97536681

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862431 – 619Mitogen-activated protein kinase kinase kinase 2Add BLAST619

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei26PhosphoserineCombined sources1
Modified residuei153PhosphoserineCombined sources1
Modified residuei159PhosphoserineCombined sources1
Modified residuei164PhosphoserineCombined sources1
Modified residuei239PhosphoserineCombined sources1
Modified residuei297PhosphoserineCombined sources1
Modified residuei311PhosphoserineCombined sources1
Modified residuei331PhosphoserineCombined sources1
Modified residuei344PhosphoserineCombined sources1
Modified residuei349PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated.By similarity
Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9Y2U5
MaxQBiQ9Y2U5
PaxDbiQ9Y2U5
PeptideAtlasiQ9Y2U5
PRIDEiQ9Y2U5
ProteomicsDBi85903

PTM databases

iPTMnetiQ9Y2U5
PhosphoSitePlusiQ9Y2U5

Expressioni

Gene expression databases

BgeeiENSG00000169967 Expressed in 218 organ(s), highest expression level in blood
CleanExiHS_MAP3K2
ExpressionAtlasiQ9Y2U5 baseline and differential
GenevisibleiQ9Y2U5 HS

Organism-specific databases

HPAiHPA021540

Interactioni

Subunit structurei

Interacts with PKN2; the interaction activates PKN2 kinase activity in a MAP3K2-independent kinase activity (By similarity). Self-associates. Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts (via the kinase catalytic domain) with STK38. Interacts with XIAP/BIRC4.By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115969, 39 interactors
CORUMiQ9Y2U5
DIPiDIP-39756N
IntActiQ9Y2U5, 18 interactors
MINTiQ9Y2U5
STRINGi9606.ENSP00000343463

Chemistry databases

BindingDBiQ9Y2U5

Structurei

Secondary structure

1619
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Y2U5
SMRiQ9Y2U5
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y2U5

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini43 – 122PB1PROSITE-ProRule annotationAdd BLAST80
Domaini357 – 617Protein kinasePROSITE-ProRule annotationAdd BLAST261

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0198 Eukaryota
ENOG410XQGS LUCA
GeneTreeiENSGT00800000124036
HOVERGENiHBG006303
InParanoidiQ9Y2U5
KOiK04420
OMAiRSVHMKS
OrthoDBiEOG091G038L
PhylomeDBiQ9Y2U5
TreeFamiTF105113

Family and domain databases

CDDicd06405 PB1_Mekk2_3, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000270 PB1_dom
IPR034879 PB1_MEKK2/3
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00564 PB1, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00666 PB1, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51745 PB1, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q9Y2U5-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDDQQALNSI MQDLAVLHKA SRPALSLQET RKAKSSSPKK QNDVRVKFEH
60 70 80 90 100
RGEKRILQFP RPVKLEDLRS KAKIAFGQSM DLHYTNNELV IPLTTQDDLD
110 120 130 140 150
KAVELLDRSI HMKSLKILLV INGSTQATNL EPLPSLEDLD NTVFGAERKK
160 170 180 190 200
RLSIIGPTSR DRSSPPPGYI PDELHQVARN GSFTSINSEG EFIPESMDQM
210 220 230 240 250
LDPLSLSSPE NSGSGSCPSL DSPLDGESYP KSRMPRAQSY PDNHQEFSDY
260 270 280 290 300
DNPIFEKFGK GGTYPRRYHV SYHHQEYNDG RKTFPRARRT QGTSLRSPVS
310 320 330 340 350
FSPTDHSLST SSGSSIFTPE YDDSRIRRRG SDIDNPTLTV MDISPPSRSP
360 370 380 390 400
RAPTNWRLGK LLGQGAFGRV YLCYDVDTGR ELAVKQVQFD PDSPETSKEV
410 420 430 440 450
NALECEIQLL KNLLHERIVQ YYGCLRDPQE KTLSIFMEYM PGGSIKDQLK
460 470 480 490 500
AYGALTENVT RKYTRQILEG VHYLHSNMIV HRDIKGANIL RDSTGNVKLG
510 520 530 540 550
DFGASKRLQT ICLSGTGMKS VTGTPYWMSP EVISGEGYGR KADIWSVACT
560 570 580 590 600
VVEMLTEKPP WAEFEAMAAI FKIATQPTNP KLPPHVSDYT RDFLKRIFVE
610
AKLRPSADEL LRHMFVHYH
Length:619
Mass (Da):69,741
Last modified:May 16, 2006 - v2
Checksum:iE034580D349F097F
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8W6K3F8W6K3_HUMAN
Mitogen-activated protein kinase ki...
MAP3K2
47Annotation score:

Sequence cautioni

The sequence BAC11348 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1M → GTR in BAD92200 (Ref. 3) Curated1
Sequence conflicti103V → L in AAD28547 (Ref. 1) Curated1
Sequence conflicti103V → L in AAF63496 (Ref. 2) Curated1
Sequence conflicti198D → E in AAD28547 (Ref. 1) Curated1
Sequence conflicti198D → E in AAF63496 (Ref. 2) Curated1
Sequence conflicti225D → G in AAD28547 (Ref. 1) Curated1
Sequence conflicti275 – 277QEY → KD in AAD28547 (Ref. 1) Curated3
Sequence conflicti293 – 296TSLR → NQLT in AAD28547 (Ref. 1) Curated4
Sequence conflicti293 – 296TSLR → NQLT in AAF63496 (Ref. 2) Curated4
Sequence conflicti413L → F in AAD28547 (Ref. 1) Curated1
Sequence conflicti459V → G in AAD28547 (Ref. 1) Curated1
Sequence conflicti480V → L in AAD28547 (Ref. 1) Curated1
Sequence conflicti536E → Q in AAD28547 (Ref. 1) Curated1
Sequence conflicti536E → Q in AAF63496 (Ref. 2) Curated1
Sequence conflicti579N → S in BAC11348 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040682110I → V1 PublicationCorresponds to variant dbSNP:rs55767983Ensembl.1
Natural variantiVAR_040683112M → I in a lung large cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040684140D → G1 PublicationCorresponds to variant dbSNP:rs56307783Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF111105 mRNA Translation: AAD28547.1
AF239798 mRNA Translation: AAF63496.1
AB208963 mRNA Translation: BAD92200.1
AC068282 Genomic DNA Translation: AAY15043.1
AC110926 Genomic DNA Translation: AAY15070.1
CH471103 Genomic DNA Translation: EAW95315.1
BC136293 mRNA Translation: AAI36294.1
AK075004 mRNA Translation: BAC11348.1 Different initiation.
CCDSiCCDS46404.1
RefSeqiNP_006600.3, NM_006609.4
UniGeneiHs.145605

Genome annotation databases

EnsembliENST00000344908; ENSP00000343463; ENSG00000169967
ENST00000409947; ENSP00000387246; ENSG00000169967
GeneIDi10746
KEGGihsa:10746
UCSCiuc002toj.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF111105 mRNA Translation: AAD28547.1
AF239798 mRNA Translation: AAF63496.1
AB208963 mRNA Translation: BAD92200.1
AC068282 Genomic DNA Translation: AAY15043.1
AC110926 Genomic DNA Translation: AAY15070.1
CH471103 Genomic DNA Translation: EAW95315.1
BC136293 mRNA Translation: AAI36294.1
AK075004 mRNA Translation: BAC11348.1 Different initiation.
CCDSiCCDS46404.1
RefSeqiNP_006600.3, NM_006609.4
UniGeneiHs.145605

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CU1NMR-A43-132[»]
2NPTX-ray1.75B/D26-123[»]
5EX0X-ray2.70D256-265[»]
5HQ8X-ray1.72I/J250-264[»]
ProteinModelPortaliQ9Y2U5
SMRiQ9Y2U5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115969, 39 interactors
CORUMiQ9Y2U5
DIPiDIP-39756N
IntActiQ9Y2U5, 18 interactors
MINTiQ9Y2U5
STRINGi9606.ENSP00000343463

Chemistry databases

BindingDBiQ9Y2U5
ChEMBLiCHEMBL5914
DrugBankiDB06616 Bosutinib
GuidetoPHARMACOLOGYi2077

PTM databases

iPTMnetiQ9Y2U5
PhosphoSitePlusiQ9Y2U5

Polymorphism and mutation databases

BioMutaiMAP3K2
DMDMi97536681

Proteomic databases

EPDiQ9Y2U5
MaxQBiQ9Y2U5
PaxDbiQ9Y2U5
PeptideAtlasiQ9Y2U5
PRIDEiQ9Y2U5
ProteomicsDBi85903

Protocols and materials databases

DNASUi10746
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344908; ENSP00000343463; ENSG00000169967
ENST00000409947; ENSP00000387246; ENSG00000169967
GeneIDi10746
KEGGihsa:10746
UCSCiuc002toj.3 human

Organism-specific databases

CTDi10746
DisGeNETi10746
EuPathDBiHostDB:ENSG00000169967.16
GeneCardsiMAP3K2
H-InvDBiHIX0002433
HGNCiHGNC:6854 MAP3K2
HPAiHPA021540
MIMi609487 gene
neXtProtiNX_Q9Y2U5
OpenTargetsiENSG00000169967
PharmGKBiPA30598
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0198 Eukaryota
ENOG410XQGS LUCA
GeneTreeiENSGT00800000124036
HOVERGENiHBG006303
InParanoidiQ9Y2U5
KOiK04420
OMAiRSVHMKS
OrthoDBiEOG091G038L
PhylomeDBiQ9Y2U5
TreeFamiTF105113

Enzyme and pathway databases

BRENDAi2.7.12.2 2681
SignaLinkiQ9Y2U5
SIGNORiQ9Y2U5

Miscellaneous databases

ChiTaRSiMAP3K2 human
EvolutionaryTraceiQ9Y2U5
GeneWikiiMAP3K2
GenomeRNAii10746
PROiPR:Q9Y2U5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169967 Expressed in 218 organ(s), highest expression level in blood
CleanExiHS_MAP3K2
ExpressionAtlasiQ9Y2U5 baseline and differential
GenevisibleiQ9Y2U5 HS

Family and domain databases

CDDicd06405 PB1_Mekk2_3, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000270 PB1_dom
IPR034879 PB1_MEKK2/3
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00564 PB1, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00666 PB1, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51745 PB1, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiM3K2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2U5
Secondary accession number(s): B9EG87
, Q53QL9, Q53S75, Q59GZ6, Q8NC32, Q9NYK3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 16, 2006
Last modified: September 12, 2018
This is version 191 of the entry and version 2 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

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

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