Reviewed, UniProtKB/Swiss-Prot P29678 (MP2K1_RABIT)

Names and origin

Protein names

Recommended name:
    Dual specificity mitogen-activated protein kinase kinase 1
      Short name=MAP kinase kinase 1
      Short name=MAPKK 1
    EC=2.7.12.2
Alternative name(s):
    ERK activator kinase 1
    MAPK/ERK kinase 1
      Short name=MEK 1

Gene names

Name:	MAP2K1
Synonyms:	MEK1, PRKMK1

Organism

Oryctolagus cuniculus (Rabbit)

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	393 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	Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates ERK1 and ERK2 MAP kinases.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with MORG1. Interacts with ARRB2 By similarity.
Post-translational modification	MAPKK is itself dependent on Ser/Thr phosphorylation for activity catalyzed by MAP kinase kinase kinases (RAF or MEKK1).
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAP3K8	P41279	1	EBI-1631983,EBI-354900	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.3
	Chain	2 – 393	392	Dual specificity mitogen-activated protein kinase kinase 1		PRO_0000086368
Regions
	Domain	68 – 361	294	Protein kinase
	Nucleotide binding	74 – 82	9	ATP By similarity
	Compositional bias	262 – 307	46	Pro-rich
Sites
	Active site	190	1	Proton acceptor By similarity
	Binding site	97	1	ATP By similarity
	Site	8 – 9	2	Cleavage; by anthrax lethal factor By similarity
Amino acid modifications
	Modified residue	218	1	Phosphoserine; by RAF Ref.1
	Modified residue	222	1	Phosphoserine; by RAF Ref.1
	Modified residue	231	1	Phosphoserine By similarity
	Modified residue	286	1	Phosphothreonine By similarity
	Modified residue	385	1	Phosphoserine By similarity
	Modified residue	386	1	Phosphothreonine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P29678-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 0341B42FF9218D51	FASTA	393	43,453
	10 20 30 40 50 60 MPKKKPTPIQ LNPAPDGSAV NGTSSAETNL EALQKKLEEL ELDEQQRKRL EAFLTQKQKV 70 80 90 100 110 120 GELKDDDFEK ISELGAGNGG VVFKVSHKPS GLVMARKLIH LEIKPAIRNQ IIRELQVLHE 130 140 150 160 170 180 CNSPYIVGFY GAFYSDGEIS ICMEHMDGGS LDQVLKKAGR IPEQILGKVS IAVIKGLTYL 190 200 210 220 230 240 REKHKIMHRD VKPSNILVNS RGEIKLCDFG VSGQLIDSMA NSFVGTRSYM SPERLQGTHY 250 260 270 280 290 300 SVQSDIWSMG LSLVEMAVGR YPIPPPDAKE LELMFGCQVE GDAAETPPRP RTPGRPLSSY 310 320 330 340 350 360 GMDSRPPMAI FELLDYIVNE PPPKLPSAVF SLEFQDFVNK CLIKNPAERA DLKQLMVHAF 370 380 390 IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA AGV

References

[1]	"Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1." Alessi D.R., Saito Y., Campbell D.G., Cohen P., Sithanadam G., Rapp U., Ashworth A., Marshall C.J., Cowley S. EMBO J. 13:1610-1619(1994) [PubMed: 8157000] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT SER-218 AND SER-222 BY RAF.
[2]	"The amino acid sequence of a mammalian MAP kinase kinase." Ashworth A., Nakielny S., Cohen P., Marshall C. Oncogene 7:2555-2556(1992) [PubMed: 1461659] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 16-393, PARTIAL PROTEIN SEQUENCE. Tissue: Brain and Skeletal muscle.
[3]	"MAP kinase kinase from rabbit skeletal muscle. A novel dual specificity enzyme showing homology to yeast protein kinases involved in pheromone-dependent signal transduction." Nakielny S., Campbell D.G., Cohen P. FEBS Lett. 308:183-189(1992) [PubMed: 1499729] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 2-16; 85-96 AND 190-201. Tissue: Skeletal muscle.
[4]	"Renaturation and partial peptide sequencing of mitogen-activated protein kinase (MAP kinase) activator from rabbit skeletal muscle." Wu J., Michel H., Rossomando A., Haystead T., Shabanowitz J., Hunt D.F., Sturgill T.W. Biochem. J. 285:701-705(1992) [PubMed: 1379797] [Abstract] Cited for: PROTEIN SEQUENCE OF 85-96 AND 190-201. Tissue: Skeletal muscle.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z30163 mRNA. Translation: CAA82912.1.
PIR	S42068.
RefSeq	NP_001076098.1.
UniGene	Ocu.3187
3D structure databases
SMR	P29678. Positions 13-214, 62-382.
ModBase	Search...
Protein-protein interaction databases
IntAct	P29678. 1 interaction.
Genome annotation databases
GeneID	100009316.
Phylogenomic databases
eggNOG	maNOG09203.
HOVERGEN	P29678.
Enzyme and pathway databases
BRENDA	2.7.12.2. 255.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. 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. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	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. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

MP2K1_RABIT

Accession

Primary (citable) accession number: P29678

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 76 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)