Reviewed, UniProtKB/Swiss-Prot Q62925 (M3K1_RAT)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase kinase kinase 1
    EC=2.7.11.25
Alternative name(s):
    MAPK/ERK kinase kinase 1
      Short name=MEK kinase 1
      Short name=MEKK 1

Gene names

Name:	Map3k1
Synonyms:	Mekk, Mekk1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1493 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Component of a protein kinase signal transduction cascade. Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway. Ref.2
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Activated by autophosphorylation on Thr-1381 and Thr-1393 following oligomerization. Ref.2
Subunit structure	Binds both upstream activators and downstream substrates in multimolecular complexes through its N-terminus. Oligomerizes after binding MAP4K2 or TRAF2. Ref.2
Subcellular location	Membrane; Peripheral membrane protein Ref.1.
Tissue specificity	Most highly expressed in spleen, kidney and lung.
Post-translational modification	Autophosphorylated. Ref.2
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 RING-type zinc finger. Contains 1 SWIM-type zinc finger.

Ontologies

Keywords
Cellular component	Membrane
Domain	Zinc-finger
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Gene Ontology (GO)
Biological process	activation of JNKK activity Inferred from direct assay. Source: RGD negative regulation of actin filament bundle assembly Inferred from direct assay. Source: RGD peptidyl-serine phosphorylation Inferred from direct assay. Source: RGD positive regulation of apoptosis Inferred from mutant phenotype. Source: RGD positive regulation of gene-specific transcription from RNA polymerase II promoter Inferred from direct assay. Source: RGD positive regulation of viral transcription Inferred from direct assay. Source: RGD protein amino acid autophosphorylation Ref.2 Inferred from direct assay. Source: RGD protein oligomerization Ref.2 Inferred from direct assay. Source: RGD protein polyubiquitination Inferred from mutant phenotype. Source: RGD protein ubiquitination during ubiquitin-dependent protein catabolic process Inferred from genetic interaction. Source: RGD response to osmotic stress Inferred from mutant phenotype. Source: RGD
Cellular component	cytoplasm Inferred from direct assay. Source: RGD extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Ref.1 Inferred from direct assay. Source: RGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW JUN kinase binding Inferred from physical interaction. Source: RGD JUN kinase kinase kinase activity Inferred from direct assay. Source: RGD MAP/ERK kinase kinase activity Inferred from direct assay. Source: RGD identical protein binding Ref.2 Inferred from physical interaction. Source: IntAct magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW mitogen-activated protein kinase binding Inferred from physical interaction. Source: RGD mitogen-activated protein kinase kinase binding Inferred from physical interaction. Source: RGD sphingolipid binding Inferred from physical interaction. Source: RGD ubiquitin-protein ligase activity Inferred from mutant phenotype. Source: RGD zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-636664,EBI-636664
MAP4K2	Q12851	1	EBI-636664,EBI-49783	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 1493	1492	Mitogen-activated protein kinase kinase kinase 1		PRO_0000086242
Regions
	Domain	1224 – 1489	266	Protein kinase
	Zinc finger	328 – 356	29	SWIM-type
	Zinc finger	433 – 482	50	RING-type
	Nucleotide binding	1230 – 1238	9	ATP By similarity
	Compositional bias	25 – 29	5	Poly-Gly
	Compositional bias	74 – 149	76	Pro-rich
	Compositional bias	233 – 291	59	Pro-rich
	Compositional bias	412 – 421	10	Poly-Ser
	Compositional bias	1163 – 1168	6	Poly-Glu
Sites
	Active site	1350	1	Proton acceptor
	Binding site	1253	1	ATP By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	21	1	Phosphoserine By similarity
	Modified residue	133	1	Phosphoserine By similarity
	Modified residue	242	1	Phosphoserine By similarity
	Modified residue	265	1	Phosphoserine By similarity
	Modified residue	282	1	Phosphoserine By similarity
	Modified residue	287	1	Phosphoserine By similarity
	Modified residue	290	1	Phosphoserine By similarity
	Modified residue	497	1	Phosphoserine By similarity
	Modified residue	501	1	Phosphoserine By similarity
	Modified residue	648	1	Phosphothreonine By similarity
	Modified residue	656	1	Phosphothreonine By similarity
	Modified residue	910	1	Phosphoserine By similarity
	Modified residue	997	1	Phosphoserine By similarity
	Modified residue	999	1	Phosphoserine By similarity
	Modified residue	1024	1	Phosphoserine By similarity
	Modified residue	1138	1	Phosphoserine By similarity
	Modified residue	1381	1	Phosphothreonine; by autocatalysis Ref.2
	Modified residue	1393	1	Phosphothreonine; by autocatalysis Ref.2
Experimental info
	Mutagenesis	1350	1	D → N: Loss of kinase activity and of autophosphorylation activity. Ref.2
	Mutagenesis	1369	1	D → A: Inactivation. Ref.1
	Mutagenesis	1381	1	T → A: Loss of kinase activity and activation by autophosphorylation; when associated with T-1393. Ref.2
	Mutagenesis	1393	1	T → A: Loss of kinase activity and activation by autophosphorylation; when associated with T-1381. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q62925-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 8C5F29F866898524	FASTA	1,493	161,315
	10 20 30 40 50 60 MAAAAGDRAS SSGFPGAAAA SPEAGGGGGA LQGSGAPAAG AGLLRETGSA GRERADWRRQ 70 80 90 100 110 120 QLRKVRSVEL DQLPEQPLFL TASPPCPSTS PSPEPADAAA GASGFQPAAG PPPPGAASRC 130 140 150 160 170 180 GSHSAELAAA RDSGARSPAG AEPPSAAAPS GREMENKETL KGLHKMDDRP EERMIREKLK 190 200 210 220 230 240 ATCMPAWKHE WLERRNRRGP VVVKPIPIKG DGSEMSNLAA ELQGEGQAGS AAPAPKGRRS 250 260 270 280 290 300 PSPGSSPSGR SGKPESPGVR RKRVSPVPFQ SGRITPPRRA PSPDGFSPYS PEETSRRVNK 310 320 330 340 350 360 VMRARLYLLQ QIGPNSFLIG GDSPDNKYRV FIGPQNCSCG RGTFCIHLLF VMLRVFQLEP 370 380 390 400 410 420 SDPMLWRKTL KNFEVESLFQ KYHSRRSSRI KAPSRNTIQK FVSRMSNCHT LSSSSTSTSS 430 440 450 460 470 480 SENSIKDEEE QMCPICLLGM LDEESLTVCE DGCRNKLHHH CMSIWAEECR RNREPLICPL 490 500 510 520 530 540 CRSKWRSHDF YSHELSSPVD SPTSLRGVQQ PSSPQQPVAG SQRRNQESNF NLTHYGTQQI 550 560 570 580 590 600 PPAYKDLAEP WIQAFGMELV GCLFSRNWNV REMALRRLSH DVSGALLLAN GESTGTSGGG 610 620 630 640 650 660 SGGSLSAGAA SGSSQPSISG DVVEAFCSVL SIVCADPVYK VYVAALKTLR AMLVYTPCHS 670 680 690 700 710 720 LAERIKLQRL LRPVVDTILV KCADANSRTS QLSISTLLEL CKGQAGELAV GREILKAGSI 730 740 750 760 770 780 GVGGVDYVLS CILGNQAESN NWQELLGRLC LIDRLLLEIS AEFYPHIVST DVSQAEPVEI 790 800 810 820 830 840 RYKKLLSLLA FALQSIDNSH SMVGKLSRRI YLSSARMVTT VPPLFSKLVT MLSASGSSHF 850 860 870 880 890 900 ARMRRRLMAI ADEVEIAEVI QLGSEDTLDG QQDSSQALAP PRYPESSSLE HTAHVEKTGK 910 920 930 940 950 960 GLKATRLSAS SEDISDRLAG VSVGLPSSAT TEQPKPTVQT KGRPHSQCLN SSPLSPPQLM 970 980 990 1000 1010 1020 FPAISAPCSS APSVPAGSVT DASKHRPRAF VPCKIPSASP QTQRKFSLQF QRTCSENRDS 1030 1040 1050 1060 1070 1080 EKLSPVFTQS RPPPSSNIHR AKASRPVPGS TSKLGDASKN SMTLDLNSAS QCDDSFGSGS 1090 1100 1110 1120 1130 1140 NSGSAVIPSE ETAFTPAEDK CRLDVNPELN SSIEDLLEAS MPSSDTTVTF KSEVAVLSPE 1150 1160 1170 1180 1190 1200 KAESDDTYKD DVNHNQKCKE KMEAEEEEAL AIAMAMSASQ DALPIVPQLQ VENGEDIIII 1210 1220 1230 1240 1250 1260 QQDTPETLPG HTKANEPYRE DTEWLKGQQI GLGAFSSCYQ AQDVGTGTLM AVKQVTYVRN 1270 1280 1290 1300 1310 1320 TSSEQEEVVE ALREEIRMMS HLNHPNIIRM LGATCEKSNY NLFIEWMAGA SVAHLLSKYG 1330 1340 1350 1360 1370 1380 AFKESVVINY TEQLLRGLSY LHENQIIHRD VKGANLLIDS TGQRLRIADF GAAARLASKG 1390 1400 1410 1420 1430 1440 TGAGEFQGQL LGTIAFMAPE VLRGQQYGRS CDVWSVGCAI IEMACAKPPW NAEKHSNHLA 1450 1460 1470 1480 1490 LIFKIASATT APSIPSHLSP GLRDVALRCL ELQPQDRPPS RELLKHPVFR TTW

References

[1]	"Cloning of rat MEK kinase 1 cDNA reveals an endogenous membrane-associated 195-kDa protein with a large regulatory domain." Xu S., Robbins D.J., Christerson L.B., English J.M., Vanderbilt C.A., Cobb M.H. Proc. Natl. Acad. Sci. U.S.A. 93:5291-5295(1996) [PubMed: 8643568] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-1369. Tissue: Brain.
[2]	"Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2." Chadee D.N., Yuasa T., Kyriakis J.M. Mol. Cell. Biol. 22:737-749(2002) [PubMed: 11784851] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, OLIGOMERIZATION, PHOSPHORYLATION AT THR-1381 AND THR-1393, MUTAGENESIS OF ASP-1350; THR-1381 AND THR-1393.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U48596 mRNA. Translation: AAC52596.1.
IPI	IPI00210195.
PIR	T10757.
RefSeq	NP_446339.1.
UniGene	Rn.11081
3D structure databases
SMR	Q62925. Positions 421-492, 1228-1492.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q62925. 2 interactions.
STRING	Q62925.
PTM databases
PhosphoSite	Q62925.
Proteomic databases
PRIDE	Q62925.
Genome annotation databases
Ensembl	ENSRNOT00000017968; ENSRNOP00000017968; ENSRNOG00000013177; Rattus norvegicus. [Genome view]
GeneID	116667.
KEGG	rno:116667.
UCSC	NM_053887. rat.
Organism-specific databases
CTD	116667.
RGD	620966. Map3k1.
Phylogenomic databases
eggNOG	roNOG06081.
HOVERGEN	Q62925.
InParanoid	Q62925.
Enzyme and pathway databases
BRENDA	2.7.11.25. 248. 2.7.12.2. 248.
Gene expression databases
ArrayExpress	Q62925.
Genevestigator	Q62925.
GermOnline	ENSRNOG00000013177. Rattus norvegicus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR015749. MAPKKK1. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. IPR001841. Znf_RING. IPR007527. Znf_SWIM. [Graphical view]
PANTHER	PTHR22986:SF65. MAPKKK1. 1 hit.
Pfam	PF00069. Pkinase. 1 hit. PF04434. SWIM. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. PS50966. ZF_SWIM. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	619471.

Entry information

Entry name

M3K1_RAT

Accession

Primary (citable) accession number: Q62925

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	February 9, 2010
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)