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Protein

Mitogen-activated protein kinase kinase kinase 3

Gene

MAP3K3

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

Activity 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
  • protein serine/threonine kinase activity Source: GO_Central

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.7.11.25 2681
2.7.12.2 2681
ReactomeiR-HSA-9020702 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

EuPathDBiHostDB:ENSG00000198909.7
HGNCiHGNC:6855 MAP3K3
MIMi602539 gene
neXtProtiNX_Q99759

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi4215
OpenTargetsiENSG00000198909
PharmGKBiPA30599

Chemistry databases

ChEMBLiCHEMBL5970

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
ProteomicsDBi78464
78465 [Q99759-2]

PTM databases

iPTMnetiQ99759
PhosphoSitePlusiQ99759

Expressioni

Gene expression databases

BgeeiENSG00000198909 Expressed in 212 organ(s), highest expression level in blood
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

Protein-protein interaction databases

BioGridi110379, 51 interactors
CORUMiQ99759
DIPiDIP-27521N
IntActiQ99759, 34 interactors
MINTiQ99759
STRINGi9606.ENSP00000354927

Chemistry databases

BindingDBiQ99759

Structurei

Secondary structure

1626
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

eggNOGiKOG0198 Eukaryota
ENOG410XQGS LUCA
GeneTreeiENSGT00800000124036
HOGENOMiHOG000049130
HOVERGENiHBG006303
InParanoidiQ99759
KOiK04421
OMAiRIRRPQG
OrthoDBiEOG091G038L
PhylomeDBiQ99759
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
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
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3QRB6J3QRB6_HUMAN
Mitogen-activated protein kinase ki...
MAP3K3
653Annotation score:
J3KRN4J3KRN4_HUMAN
Mitogen-activated protein kinase ki...
MAP3K3
622Annotation score:
J3QS19J3QS19_HUMAN
Mitogen-activated protein kinase ki...
MAP3K3
42Annotation score:
J3KTC4J3KTC4_HUMAN
Mitogen-activated protein kinase ki...
MAP3K3
56Annotation score:
J3QS54J3QS54_HUMAN
Mitogen-activated protein kinase ki...
MAP3K3
31Annotation score:

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 → M1 PublicationCorresponds to variant dbSNP:rs36109904Ensembl.1
Natural variantiVAR_037275325A → G. Corresponds to variant dbSNP:rs34042309Ensembl.1
Natural variantiVAR_037276435A → G. Corresponds to variant dbSNP:rs9910858Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiM3K3_HUMAN
AccessioniPrimary (citable) accession number: Q99759
Secondary accession number(s): B2RCW2
, D3DU15, Q5BKZ6, Q8N3I9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 13, 2007
Last modified: September 12, 2018
This is version 193 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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