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Protein

Mitogen-activated protein kinase kinase kinase 2

Gene

MAP3K2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme regulationi

Activated by phosphorylation on Thr-524.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei385 – 3851ATPPROSITE-ProRule annotation
Active sitei483 – 4831Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi362 – 37110ATPPROSITE-ProRule annotation

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
  • receptor signaling protein serine/threonine kinase activity Source: GO_Central

GO - Biological processi

  • activation of JUN kinase activity Source: ProtInc
  • activation of MAPK activity Source: ProtInc
  • cellular response to mechanical stimulus Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • protein phosphorylation Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-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

HGNCiHGNC:6854. MAP3K2.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: Upon EGF stimulation, translocates into the nucleus.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30598.

Chemistry

ChEMBLiCHEMBL5914.
DrugBankiDB06616. Bosutinib.
GuidetoPHARMACOLOGYi2077.

Polymorphism and mutation databases

BioMutaiMAP3K2.
DMDMi97536681.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 619619Mitogen-activated protein kinase kinase kinase 2PRO_0000086243Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei26 – 261PhosphoserineCombined sources
Modified residuei153 – 1531PhosphoserineCombined sources
Modified residuei159 – 1591PhosphoserineCombined sources
Modified residuei164 – 1641PhosphoserineCombined sources
Modified residuei239 – 2391PhosphoserineCombined sources
Modified residuei297 – 2971PhosphoserineCombined sources
Modified residuei311 – 3111PhosphoserineCombined sources
Modified residuei331 – 3311PhosphoserineCombined sources
Modified residuei344 – 3441PhosphoserineCombined sources
Modified residuei349 – 3491PhosphoserineBy similarity

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.

PTM databases

iPTMnetiQ9Y2U5.
PhosphoSiteiQ9Y2U5.

Expressioni

Gene expression databases

BgeeiENSG00000169967.
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

WithEntry#Exp.IntActNotes
SFNP319472EBI-357393,EBI-476295
STUB1Q9UNE79EBI-357393,EBI-357085

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115969. 31 interactions.
IntActiQ9Y2U5. 17 interactions.
MINTiMINT-272127.
STRINGi9606.ENSP00000343463.

Chemistry

BindingDBiQ9Y2U5.

Structurei

Secondary structure

1
619
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi44 – 507Combined sources
Beta strandi53 – 597Combined sources
Helixi65 – 7612Combined sources
Beta strandi80 – 867Combined sources
Beta strandi89 – 924Combined sources
Helixi96 – 10813Combined sources
Beta strandi114 – 1218Combined sources
Beta strandi260 – 2623Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CU1NMR-A43-132[»]
2NPTX-ray1.75B/D26-123[»]
5EX0X-ray2.70D256-265[»]
5HQ8X-ray1.72I/J250-264[»]
ProteinModelPortaliQ9Y2U5.
SMRiQ9Y2U5. Positions 1-122, 328-616.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y2U5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini43 – 12280PB1PROSITE-ProRule annotationAdd
BLAST
Domaini357 – 617261Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 PB1 domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1 – 11M → GTR in BAD92200 (Ref. 3) Curated
Sequence conflicti103 – 1031V → L in AAD28547 (Ref. 1) Curated
Sequence conflicti103 – 1031V → L in AAF63496 (Ref. 2) Curated
Sequence conflicti198 – 1981D → E in AAD28547 (Ref. 1) Curated
Sequence conflicti198 – 1981D → E in AAF63496 (Ref. 2) Curated
Sequence conflicti225 – 2251D → G in AAD28547 (Ref. 1) Curated
Sequence conflicti275 – 2773QEY → KD in AAD28547 (Ref. 1) Curated
Sequence conflicti293 – 2964TSLR → NQLT in AAD28547 (Ref. 1) Curated
Sequence conflicti293 – 2964TSLR → NQLT in AAF63496 (Ref. 2) Curated
Sequence conflicti413 – 4131L → F in AAD28547 (Ref. 1) Curated
Sequence conflicti459 – 4591V → G in AAD28547 (Ref. 1) Curated
Sequence conflicti480 – 4801V → L in AAD28547 (Ref. 1) Curated
Sequence conflicti536 – 5361E → Q in AAD28547 (Ref. 1) Curated
Sequence conflicti536 – 5361E → Q in AAF63496 (Ref. 2) Curated
Sequence conflicti579 – 5791N → S in BAC11348 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti110 – 1101I → V.1 Publication
Corresponds to variant rs55767983 [ dbSNP | Ensembl ].
VAR_040682
Natural varianti112 – 1121M → I in a lung large cell carcinoma sample; somatic mutation. 1 Publication
VAR_040683
Natural varianti140 – 1401D → G.1 Publication
Corresponds to variant rs56307783 [ dbSNP | Ensembl ].
VAR_040684

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

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
EntryMethodResolution (Å)ChainPositionsPDBsum
2CU1NMR-A43-132[»]
2NPTX-ray1.75B/D26-123[»]
5EX0X-ray2.70D256-265[»]
5HQ8X-ray1.72I/J250-264[»]
ProteinModelPortaliQ9Y2U5.
SMRiQ9Y2U5. Positions 1-122, 328-616.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115969. 31 interactions.
IntActiQ9Y2U5. 17 interactions.
MINTiMINT-272127.
STRINGi9606.ENSP00000343463.

Chemistry

BindingDBiQ9Y2U5.
ChEMBLiCHEMBL5914.
DrugBankiDB06616. Bosutinib.
GuidetoPHARMACOLOGYi2077.

PTM databases

iPTMnetiQ9Y2U5.
PhosphoSiteiQ9Y2U5.

Polymorphism and mutation databases

BioMutaiMAP3K2.
DMDMi97536681.

Proteomic databases

EPDiQ9Y2U5.
MaxQBiQ9Y2U5.
PaxDbiQ9Y2U5.
PeptideAtlasiQ9Y2U5.
PRIDEiQ9Y2U5.

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.
GeneCardsiMAP3K2.
H-InvDBHIX0002433.
HGNCiHGNC:6854. MAP3K2.
HPAiHPA021540.
MIMi609487. gene.
neXtProtiNX_Q9Y2U5.
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.
PROiQ9Y2U5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169967.
CleanExiHS_MAP3K2.
ExpressionAtlasiQ9Y2U5. baseline and differential.
GenevisibleiQ9Y2U5. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiM3K2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2U5
Secondary accession number(s): B9EG87
, Q53QL9, Q53S75, Q59GZ6, Q8NC32, Q9NYK3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 16, 2006
Last modified: September 7, 2016
This is version 175 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.