Q3U1V8 (M3K9_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase kinase kinase 9
EC=2.7.11.25

Gene names

Name:

Map3k9

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1077 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Homodimerization via the leucine zipper domains is required for autophosphorylation of multiple sites in the activation loop and subsequent activation By similarity. Autophosphorylation at Thr-305 is the key step in activation of MAP3K9/MLK1 and is required for full phosphorylation By similarity. Autophosphorylation at Thr-297 and Ser-301 have been shown to be of secondary importance in the activation of MAP3K9/MLK1 By similarity.
Subunit structure	Homodimer By similarity.
Tissue specificity	Expressed in cochlea and utricle. Ref.3
Post-translational modification	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.
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 protein kinase domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Apoptosis Stress response Transcription Transcription regulation
Domain	Repeat SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Inferred from electronic annotation. Source: EC protein tyrosine kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1077	1077	Mitogen-activated protein kinase kinase kinase 9		PRO_0000277825
Regions
	Domain	45 – 109	65	SH3
	Domain	137 – 405	269	Protein kinase
	Domain	423 – 444	22	Leucine-zipper 1
	Domain	458 – 479	22	Leucine-zipper 2
	Nucleotide binding	143 – 151	9	ATP By similarity
	Compositional bias	29 – 36	8	Poly-Glu
	Compositional bias	575 – 581	7	Poly-Glu
	Compositional bias	1011 – 1014	4	Poly-Ser
Sites
	Active site	261	1	Proton acceptor By similarity
	Binding site	164	1	ATP By similarity
Amino acid modifications
	Modified residue	297	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	301	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	305	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	522	1	Phosphothreonine By similarity
	Modified residue	526	1	Phosphoserine By similarity
	Modified residue	528	1	Phosphothreonine By similarity
	Modified residue	540	1	Phosphoserine By similarity
	Modified residue	545	1	Phosphoserine By similarity
	Modified residue	558	1	Phosphothreonine By similarity
	Modified residue	622	1	Phosphoserine By similarity
	Modified residue	663	1	Phosphoserine By similarity
	Modified residue	885	1	Phosphothreonine By similarity
	Modified residue	887	1	Phosphoserine By similarity
	Modified residue	902	1	Phosphoserine By similarity
	Modified residue	904	1	Phosphoserine By similarity
	Modified residue	907	1	Phosphoserine By similarity
	Modified residue	971	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	176	1	Q → K in BAC35552. Ref.1
	Sequence conflict	284	1	K → E in BAE33385. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q3U1V8 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 6D2060CEB04B97F8	FASTA	1,077	118,805
	10 20 30 40 50 60 MESSRSLLGC LASATAAPPG DDATGAGAEE EEDEEEAAAE LGSHAALPYW TAVFEYEAAG 70 80 90 100 110 120 EDELTLRLGD VVEVLSKDSQ VSGDEGWWTG QLNQRVGIFP SNYVTPRSAF SSRCQPGAED 130 140 150 160 170 180 PSCYPPIQLL EIDFAELTLE EIIGIGGFGK VYRAFWAGDE VAVKAARHDP DEDISQTIEN 190 200 210 220 230 240 VRQEAKLFAM LKHPNIIALR GVCLKEPNLC LVMEFARGGP LNRVLSGKRI PPDILVNWAV 250 260 270 280 290 300 QIARGMNYLH DEAIVPIIHR DLKSSNILIL QKVENGDLSN KILKITDFGL AREWHRTTKM 310 320 330 340 350 360 SAAGTYAWMA PEVIRASMFS KGSDVWSYGV LLWELLTGEV PFRGIDGLAV AYGVAMNKLA 370 380 390 400 410 420 LPIPSTCPEP FAKLMEDCWN PDPHSRPSFT SILDQLTTIE ESGFFEMPKD SFHCLQDDWK 430 440 450 460 470 480 HEIQEMFDQL RAKEKELRTW EEELTRAALQ QKNQEELLRR REQELAEREI DILERELNII 490 500 510 520 530 540 IHQLCQEKPR VKKRKGKFRK SRLKLKDGNR ISLPSDFQHK FTVQASPTMD KRKSLISNRS 550 560 570 580 590 600 SPPASPTIIP RLRAIQLTPG ESSKTWGRSS VVPKEEGEEE EKRAPKKKGR TWGPGTLGQK 610 620 630 640 650 660 ELTSGDEGLK SLVDGYKQWS SSAPNLGKGP RSSPALPGFT SLMEIEDEDS EGPGSGENHQ 670 680 690 700 710 720 QHSPNQSYLC IPFPRGEDGD GPSSDGVHEE PTPVNSATST PQLTPTNSLK RGGTHHRRCE 730 740 750 760 770 780 VALLGCGAVL AATGLGFDLL EAGKCQLLPP EEPEPPAREE KKRREGLFQR ASRPRRSTSP 790 800 810 820 830 840 PSRKLFKKEE PMTLLGDPSA SLTLLSLSSI SECNSTRSLL RSDSDEIVVY EMPVSPVEAP 850 860 870 880 890 900 PLTQCTHNPL VNVRVERFKR DPNQSLTPTH VTLTAPTQPS GHRRTPSDGA LKPTAAPAVL 910 920 930 940 950 960 GSRSPSSNGM SPSPGTGMLK TPSPSRDPGE FPRLPDPNVV FPPTPRRWNT QRDSTLERPK 970 980 990 1000 1010 1020 TLEFLPRPRP SANRQRLDPW WFVSPSHARS ASPANSSSTE TPSNLDSCFA SSSSTVEERP 1030 1040 1050 1060 1070 GLPALLPLQA GPLLPAERTL LDLDAEGQSQ DSTVPLCRAE LNAHGPSPYE IQQEFWS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Eye.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[3]	"Ablation of mixed lineage kinase 3 (Mlk3) does not inhibit ototoxicity induced by acoustic trauma or aminoglycoside exposure." Polesskaya O., Cunningham L.L., Francis S.P., Luebke A.E., Zhu X., Collins D., Vasilyeva O.N., Sahler J., Desmet E.A., Gelbard H.A., Maggirwar S.B., Walton J.P., Frisina R.D. Jr., Dewhurst S. Hear. Res. 270:21-27(2010) [PubMed: 20971179] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK053843 mRNA. Translation: BAC35552.1. AK155677 mRNA. Translation: BAE33385.1. AC124595 Genomic DNA. No translation available. AC125351 Genomic DNA. No translation available.
IPI	IPI00465709.
RefSeq	NP_001167578.1. NM_001174107.1. NP_796369.2. NM_177395.5.
UniGene	Mm.35284.
3D structure databases
HSSP	HSSP built from PDB template 2FRW based on UniProtKB O43639.
ProteinModelPortal	Q3U1V8.
SMR	Q3U1V8. Positions 39-400.
ModBase	Search...
Protein-protein interaction databases
STRING	Q3U1V8.
PTM databases
PhosphoSite	Q3U1V8.
Proteomic databases
PRIDE	Q3U1V8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000035987; ENSMUSP00000041819; ENSMUSG00000042724.
GeneID	338372.
KEGG	mmu:338372.
UCSC	uc007oco.2. mouse.
Organism-specific databases
CTD	4293.
MGI	MGI:2449952. Map3k9.
Phylogenomic databases
eggNOG	roNOG12191.
HOGENOM	HBG716519.
HOVERGEN	HBG067662.
InParanoid	Q3U1V8.
OrthoDB	EOG4SN1MZ.
Gene expression databases
ArrayExpress	Q3U1V8.
Bgee	Q3U1V8.
CleanEx	MM_MAP3K9.
Genevestigator	Q3U1V8.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR016231. MAPKKK9/10/11. IPR015785. MAPKKK9/10/11-like. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase. IPR008271. Ser/Thr_kinase_AS. IPR011511. SH3_2. IPR001452. SH3_domain. IPR020635. Tyr_kinase_cat_dom. [Graphical view]
KO	K04417.
PANTHER	PTHR23257:SF87. MAPKKK-like. 1 hit.
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF07653. SH3_2. 1 hit. [Graphical view]
PIRSF	PIRSF000556. MAPKKK9_11. 1 hit.
PRINTS	PR00452. SH3DOMAIN. PR00109. TYRKINASE.
SMART	SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50044. SH3. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

M3K9_MOUSE

Accession

Primary (citable) accession number: Q3U1V8
Secondary accession number(s): E9QLZ4, Q8BIG8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 20, 2007
Last sequence update:	July 27, 2011
Last modified:	December 14, 2011
This is version 70 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program