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Protein

Mitogen-activated protein kinase kinase kinase 9

Gene

Map3k9

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Plays also a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Homodimerization via the leucine zipper domains is required for autophosphorylation of multiple sites in the activation loop and subsequent activation. Autophosphorylation at Thr-305 is the key step in activation of MAP3K9/MLK1 and is required for full phosphorylation. Autophosphorylation at Thr-297 and Ser-301 have been shown to be of secondary importance in the activation of MAP3K9/MLK1.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei164 – 1641ATPPROSITE-ProRule annotation
Active sitei261 – 2611Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi143 – 1519ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Stress response, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase 9 (EC:2.7.11.25)
Gene namesi
Name:Map3k9
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:2449952. Map3k9.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10771077Mitogen-activated protein kinase kinase kinase 9PRO_0000277825Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei297 – 2971Phosphothreonine; by autocatalysisBy similarity
Modified residuei298 – 2981Phosphothreonine; by autocatalysisBy similarity
Modified residuei301 – 3011Phosphoserine; by autocatalysisBy similarity
Modified residuei305 – 3051Phosphothreonine; by autocatalysisBy similarity
Modified residuei526 – 5261PhosphoserineBy similarity

Post-translational modificationi

Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation. Thr-305 is likely to be the main autophosphorylation site (By similarity). Autophosphorylation also occurs on Thr-297 and Ser-301 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ3U1V8.
PaxDbiQ3U1V8.
PeptideAtlasiQ3U1V8.
PRIDEiQ3U1V8.

PTM databases

iPTMnetiQ3U1V8.
PhosphoSiteiQ3U1V8.

Expressioni

Tissue specificityi

Expressed in cochlea and utricle.1 Publication

Gene expression databases

BgeeiENSMUSG00000042724.
CleanExiMM_MAP3K9.
GenevisibleiQ3U1V8. MM.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000041819.

Structurei

3D structure databases

ProteinModelPortaliQ3U1V8.
SMRiQ3U1V8. Positions 48-106, 129-398.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini45 – 10965SH3PROSITE-ProRule annotationAdd
BLAST
Domaini137 – 405269Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni423 – 44422Leucine-zipper 1Add
BLAST
Regioni458 – 47922Leucine-zipper 2Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi29 – 368Poly-Glu
Compositional biasi575 – 5817Poly-Glu
Compositional biasi1011 – 10144Poly-Ser

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH3 domain

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000060081.
HOVERGENiHBG067662.
InParanoidiQ3U1V8.
KOiK04417.
OMAiHHRRCEV.
OrthoDBiEOG091G0JNI.
TreeFamiTF105118.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR016231. MLK1/MLK2/MLK4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PIRSFiPIRSF000556. MAPKKK9_11. 1 hit.
PRINTSiPR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q3U1V8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MESSRSLLGC LASATAAPPG DDATGAGAEE EEDEEEAAAE LGSHAALPYW
60 70 80 90 100
TAVFEYEAAG EDELTLRLGD VVEVLSKDSQ VSGDEGWWTG QLNQRVGIFP
110 120 130 140 150
SNYVTPRSAF SSRCQPGAED PSCYPPIQLL EIDFAELTLE EIIGIGGFGK
160 170 180 190 200
VYRAFWAGDE VAVKAARHDP DEDISQTIEN VRQEAKLFAM LKHPNIIALR
210 220 230 240 250
GVCLKEPNLC LVMEFARGGP LNRVLSGKRI PPDILVNWAV QIARGMNYLH
260 270 280 290 300
DEAIVPIIHR DLKSSNILIL QKVENGDLSN KILKITDFGL AREWHRTTKM
310 320 330 340 350
SAAGTYAWMA PEVIRASMFS KGSDVWSYGV LLWELLTGEV PFRGIDGLAV
360 370 380 390 400
AYGVAMNKLA LPIPSTCPEP FAKLMEDCWN PDPHSRPSFT SILDQLTTIE
410 420 430 440 450
ESGFFEMPKD SFHCLQDDWK HEIQEMFDQL RAKEKELRTW EEELTRAALQ
460 470 480 490 500
QKNQEELLRR REQELAEREI DILERELNII IHQLCQEKPR VKKRKGKFRK
510 520 530 540 550
SRLKLKDGNR ISLPSDFQHK FTVQASPTMD KRKSLISNRS SPPASPTIIP
560 570 580 590 600
RLRAIQLTPG ESSKTWGRSS VVPKEEGEEE EKRAPKKKGR TWGPGTLGQK
610 620 630 640 650
ELTSGDEGLK SLVDGYKQWS SSAPNLGKGP RSSPALPGFT SLMEIEDEDS
660 670 680 690 700
EGPGSGENHQ QHSPNQSYLC IPFPRGEDGD GPSSDGVHEE PTPVNSATST
710 720 730 740 750
PQLTPTNSLK RGGTHHRRCE VALLGCGAVL AATGLGFDLL EAGKCQLLPP
760 770 780 790 800
EEPEPPAREE KKRREGLFQR ASRPRRSTSP PSRKLFKKEE PMTLLGDPSA
810 820 830 840 850
SLTLLSLSSI SECNSTRSLL RSDSDEIVVY EMPVSPVEAP PLTQCTHNPL
860 870 880 890 900
VNVRVERFKR DPNQSLTPTH VTLTAPTQPS GHRRTPSDGA LKPTAAPAVL
910 920 930 940 950
GSRSPSSNGM SPSPGTGMLK TPSPSRDPGE FPRLPDPNVV FPPTPRRWNT
960 970 980 990 1000
QRDSTLERPK TLEFLPRPRP SANRQRLDPW WFVSPSHARS ASPANSSSTE
1010 1020 1030 1040 1050
TPSNLDSCFA SSSSTVEERP GLPALLPLQA GPLLPAERTL LDLDAEGQSQ
1060 1070
DSTVPLCRAE LNAHGPSPYE IQQEFWS
Length:1,077
Mass (Da):118,805
Last modified:July 27, 2011 - v2
Checksum:i6D2060CEB04B97F8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti176 – 1761Q → K in BAC35552 (PubMed:16141072).Curated
Sequence conflicti284 – 2841K → E in BAE33385 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK053843 mRNA. Translation: BAC35552.1.
AK155677 mRNA. Translation: BAE33385.1.
AC124595 Genomic DNA. No translation available.
AC125351 Genomic DNA. No translation available.
CCDSiCCDS49104.1.
RefSeqiNP_001167578.1. NM_001174107.1.
NP_796369.2. NM_177395.5.
UniGeneiMm.35284.

Genome annotation databases

EnsembliENSMUST00000035987; ENSMUSP00000041819; ENSMUSG00000042724.
GeneIDi338372.
KEGGimmu:338372.
UCSCiuc007oco.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK053843 mRNA. Translation: BAC35552.1.
AK155677 mRNA. Translation: BAE33385.1.
AC124595 Genomic DNA. No translation available.
AC125351 Genomic DNA. No translation available.
CCDSiCCDS49104.1.
RefSeqiNP_001167578.1. NM_001174107.1.
NP_796369.2. NM_177395.5.
UniGeneiMm.35284.

3D structure databases

ProteinModelPortaliQ3U1V8.
SMRiQ3U1V8. Positions 48-106, 129-398.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000041819.

PTM databases

iPTMnetiQ3U1V8.
PhosphoSiteiQ3U1V8.

Proteomic databases

MaxQBiQ3U1V8.
PaxDbiQ3U1V8.
PeptideAtlasiQ3U1V8.
PRIDEiQ3U1V8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000035987; ENSMUSP00000041819; ENSMUSG00000042724.
GeneIDi338372.
KEGGimmu:338372.
UCSCiuc007oco.2. mouse.

Organism-specific databases

CTDi4293.
MGIiMGI:2449952. Map3k9.

Phylogenomic databases

eggNOGiKOG0192. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000060081.
HOVERGENiHBG067662.
InParanoidiQ3U1V8.
KOiK04417.
OMAiHHRRCEV.
OrthoDBiEOG091G0JNI.
TreeFamiTF105118.

Miscellaneous databases

PROiQ3U1V8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000042724.
CleanExiMM_MAP3K9.
GenevisibleiQ3U1V8. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR016231. MLK1/MLK2/MLK4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PIRSFiPIRSF000556. MAPKKK9_11. 1 hit.
PRINTSiPR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiM3K9_MOUSE
AccessioniPrimary (citable) accession number: Q3U1V8
Secondary accession number(s): E9QLZ4, Q8BIG8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: July 27, 2011
Last modified: September 7, 2016
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.