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Protein

Mitogen-activated protein kinase kinase kinase 3

Gene

MAP3K3

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. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators.4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

Activated by phosphorylation on Thr-530.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei391ATPPROSITE-ProRule annotation1
Active sitei489Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi368 – 376ATPPROSITE-ProRule annotation9

GO - Molecular functioni

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

GO - Biological processi

  • blood vessel development Source: Ensembl
  • intracellular signal transduction Source: MGI
  • MAPK cascade Source: ProtInc
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of p38MAPK cascade Source: Ensembl
  • protein autophosphorylation Source: MGI
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

BioCyciZFISH:HS01586-MONOMER.
BRENDAi2.7.11.25. 2681.
2.7.12.2. 2681.
ReactomeiR-HSA-446652. Interleukin-1 signaling.
SignaLinkiQ99759.
SIGNORiQ99759.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase 3 (EC:2.7.11.25)
Alternative name(s):
MAPK/ERK kinase kinase 3
Short name:
MEK kinase 3
Short name:
MEKK 3
Gene namesi
Name:MAP3K3
Synonyms:MAPKKK3, MEKK3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:6855. MAP3K3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi4215.
OpenTargetsiENSG00000198909.
PharmGKBiPA30599.

Chemistry databases

ChEMBLiCHEMBL5970.
GuidetoPHARMACOLOGYi2078.

Polymorphism and mutation databases

BioMutaiMAP3K3.
DMDMi160332306.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862451 – 626Mitogen-activated protein kinase kinase kinase 3Add BLAST626

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei147PhosphoserineBy similarity1
Modified residuei166Phosphoserine; by SGK1Combined sources1 Publication1
Modified residuei250PhosphoserineCombined sources1
Modified residuei312PhosphoserineCombined sources1
Modified residuei337Phosphoserine; by SGK1Combined sources1 Publication1
Modified residuei340PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Ser-166 and Ser-337 by SGK1 inhibits its activity.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ99759.
MaxQBiQ99759.
PaxDbiQ99759.
PeptideAtlasiQ99759.
PRIDEiQ99759.

PTM databases

iPTMnetiQ99759.
PhosphoSitePlusiQ99759.

Expressioni

Gene expression databases

BgeeiENSG00000198909.
CleanExiHS_MAP3K3.
ExpressionAtlasiQ99759. baseline and differential.
GenevisibleiQ99759. HS.

Organism-specific databases

HPAiCAB007764.
HPA035410.
HPA035411.

Interactioni

Subunit structurei

Binds both upstream activators and downstream substrates in multimolecular complexes. Part of a complex with MAP2K3, RAC1 and CCM2. Interacts with MAP2K5 and SPAG9.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAP2K5Q131632EBI-307281,EBI-307294
TRAF7Q6Q0C02EBI-307281,EBI-307556
YWHABP319462EBI-307281,EBI-359815
YWHAEP622583EBI-307281,EBI-356498

Protein-protein interaction databases

BioGridi110379. 50 interactors.
DIPiDIP-27521N.
IntActiQ99759. 33 interactors.
MINTiMINT-272157.
STRINGi9606.ENSP00000354927.

Chemistry databases

BindingDBiQ99759.

Structurei

Secondary structure

1626
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 18Combined sources16
Beta strandi45 – 51Combined sources7
Beta strandi54 – 60Combined sources7
Helixi66 – 77Combined sources12
Beta strandi82 – 86Combined sources5
Helixi88 – 90Combined sources3
Beta strandi91 – 93Combined sources3
Helixi97 – 109Combined sources13
Turni111 – 114Combined sources4
Beta strandi115 – 121Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2C60X-ray1.25A37-124[»]
2JRHNMR-A42-126[»]
2O2VX-ray1.83B37-124[»]
2PPHNMR-A42-126[»]
4Y5OX-ray2.35B1-124[»]
4YL6X-ray2.10B1-22[»]
ProteinModelPortaliQ99759.
SMRiQ99759.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99759.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 123PB1PROSITE-ProRule annotationAdd BLAST80
Domaini362 – 622Protein kinasePROSITE-ProRule annotationAdd BLAST261

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0198. Eukaryota.
ENOG410XQGS. LUCA.
GeneTreeiENSGT00800000124036.
HOGENOMiHOG000049130.
HOVERGENiHBG006303.
InParanoidiQ99759.
KOiK04421.
OMAiHPNRQSD.
OrthoDBiEOG091G038L.
PhylomeDBiQ99759.
TreeFamiTF105113.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
[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.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99759-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDEQEALNSI MNDLVALQMN RRHRMPGYET MKNKDTGHSN RQSDVRIKFE
60 70 80 90 100
HNGERRIIAF SRPVKYEDVE HKVTTVFGQP LDLHYMNNEL SILLKNQDDL
110 120 130 140 150
DKAIDILDRS SSMKSLRILL LSQDRNHNSS SPHSGVSRQV RIKASQSAGD
160 170 180 190 200
INTIYQPPEP RSRHLSVSSQ NPGRSSPPPG YVPERQQHIA RQGSYTSINS
210 220 230 240 250
EGEFIPETSE QCMLDPLSSA ENSLSGSCQS LDRSADSPSF RKSRMSRAQS
260 270 280 290 300
FPDNRQEYSD RETQLYDKGV KGGTYPRRYH VSVHHKDYSD GRRTFPRIRR
310 320 330 340 350
HQGNLFTLVP SSRSLSTNGE NMGLAVQYLD PRGRLRSADS ENALSVQERN
360 370 380 390 400
VPTKSPSAPI NWRRGKLLGQ GAFGRVYLCY DVDTGRELAS KQVQFDPDSP
410 420 430 440 450
ETSKEVSALE CEIQLLKNLQ HERIVQYYGC LRDRAEKTLT IFMEYMPGGS
460 470 480 490 500
VKDQLKAYGA LTESVTRKYT RQILEGMSYL HSNMIVHRDI KGANILRDSA
510 520 530 540 550
GNVKLGDFGA SKRLQTICMS GTGMRSVTGT PYWMSPEVIS GEGYGRKADV
560 570 580 590 600
WSLGCTVVEM LTEKPPWAEY EAMAAIFKIA TQPTNPQLPS HISEHGRDFL
610 620
RRIFVEARQR PSAEELLTHH FAQLMY
Length:626
Mass (Da):70,898
Last modified:November 13, 2007 - v2
Checksum:i28129168A57571DD
GO
Isoform 2 (identifier: Q99759-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     42-42: Q → QKKHNSSSSALLNSPTVTTSSCAGASEKKKFL

Show »
Length:657
Mass (Da):74,089
Checksum:iDF37E5E568FE937E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti135G → E in AAB41729 (PubMed:9006902).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040685281V → M.1 PublicationCorresponds to variant rs36109904dbSNPEnsembl.1
Natural variantiVAR_037275325A → G.Corresponds to variant rs34042309dbSNPEnsembl.1
Natural variantiVAR_037276435A → G.Corresponds to variant rs9910858dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03596742Q → QKKHNSSSSALLNSPTVTTS SCAGASEKKKFL in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78876 mRNA. Translation: AAB41729.1.
AK315305 mRNA. Translation: BAG37709.1.
AL834303 mRNA. Translation: CAD38973.1.
AC046185 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94297.1.
CH471109 Genomic DNA. Translation: EAW94298.1.
CH471109 Genomic DNA. Translation: EAW94299.1.
BC090859 mRNA. Translation: AAH90859.1.
BC093672 mRNA. Translation: AAH93672.1.
BC093674 mRNA. Translation: AAH93674.1.
CCDSiCCDS32701.1. [Q99759-2]
CCDS32702.1. [Q99759-1]
RefSeqiNP_002392.2. NM_002401.3. [Q99759-1]
NP_976226.1. NM_203351.1. [Q99759-2]
UniGeneiHs.29282.

Genome annotation databases

EnsembliENST00000361357; ENSP00000354927; ENSG00000198909. [Q99759-2]
ENST00000361733; ENSP00000354485; ENSG00000198909. [Q99759-1]
ENST00000579585; ENSP00000461988; ENSG00000198909. [Q99759-2]
GeneIDi4215.
KEGGihsa:4215.
UCSCiuc002jbe.4. human. [Q99759-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78876 mRNA. Translation: AAB41729.1.
AK315305 mRNA. Translation: BAG37709.1.
AL834303 mRNA. Translation: CAD38973.1.
AC046185 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94297.1.
CH471109 Genomic DNA. Translation: EAW94298.1.
CH471109 Genomic DNA. Translation: EAW94299.1.
BC090859 mRNA. Translation: AAH90859.1.
BC093672 mRNA. Translation: AAH93672.1.
BC093674 mRNA. Translation: AAH93674.1.
CCDSiCCDS32701.1. [Q99759-2]
CCDS32702.1. [Q99759-1]
RefSeqiNP_002392.2. NM_002401.3. [Q99759-1]
NP_976226.1. NM_203351.1. [Q99759-2]
UniGeneiHs.29282.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2C60X-ray1.25A37-124[»]
2JRHNMR-A42-126[»]
2O2VX-ray1.83B37-124[»]
2PPHNMR-A42-126[»]
4Y5OX-ray2.35B1-124[»]
4YL6X-ray2.10B1-22[»]
ProteinModelPortaliQ99759.
SMRiQ99759.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110379. 50 interactors.
DIPiDIP-27521N.
IntActiQ99759. 33 interactors.
MINTiMINT-272157.
STRINGi9606.ENSP00000354927.

Chemistry databases

BindingDBiQ99759.
ChEMBLiCHEMBL5970.
GuidetoPHARMACOLOGYi2078.

PTM databases

iPTMnetiQ99759.
PhosphoSitePlusiQ99759.

Polymorphism and mutation databases

BioMutaiMAP3K3.
DMDMi160332306.

Proteomic databases

EPDiQ99759.
MaxQBiQ99759.
PaxDbiQ99759.
PeptideAtlasiQ99759.
PRIDEiQ99759.

Protocols and materials databases

DNASUi4215.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361357; ENSP00000354927; ENSG00000198909. [Q99759-2]
ENST00000361733; ENSP00000354485; ENSG00000198909. [Q99759-1]
ENST00000579585; ENSP00000461988; ENSG00000198909. [Q99759-2]
GeneIDi4215.
KEGGihsa:4215.
UCSCiuc002jbe.4. human. [Q99759-1]

Organism-specific databases

CTDi4215.
DisGeNETi4215.
GeneCardsiMAP3K3.
HGNCiHGNC:6855. MAP3K3.
HPAiCAB007764.
HPA035410.
HPA035411.
MIMi602539. gene.
neXtProtiNX_Q99759.
OpenTargetsiENSG00000198909.
PharmGKBiPA30599.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0198. Eukaryota.
ENOG410XQGS. LUCA.
GeneTreeiENSGT00800000124036.
HOGENOMiHOG000049130.
HOVERGENiHBG006303.
InParanoidiQ99759.
KOiK04421.
OMAiHPNRQSD.
OrthoDBiEOG091G038L.
PhylomeDBiQ99759.
TreeFamiTF105113.

Enzyme and pathway databases

BioCyciZFISH:HS01586-MONOMER.
BRENDAi2.7.11.25. 2681.
2.7.12.2. 2681.
ReactomeiR-HSA-446652. Interleukin-1 signaling.
SignaLinkiQ99759.
SIGNORiQ99759.

Miscellaneous databases

ChiTaRSiMAP3K3. human.
EvolutionaryTraceiQ99759.
GeneWikiiMAP3K3.
GenomeRNAii4215.
PROiQ99759.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198909.
CleanExiHS_MAP3K3.
ExpressionAtlasiQ99759. baseline and differential.
GenevisibleiQ99759. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
[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.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiM3K3_HUMAN
AccessioniPrimary (citable) accession number: Q99759
Secondary accession number(s): B2RCW2
, D3DU15, Q5BKZ6, Q8N3I9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 13, 2007
Last modified: November 2, 2016
This is version 179 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 17
    Human chromosome 17: 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.