Reviewed, UniProtKB/Swiss-Prot Q55CL6 (MP2K1_DICDI)

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=MEK1
      Short name=DdMEK1
    MAPK/ERK kinase A
      Short name=MEKA

Gene names

Name:	mekA
Synonyms:	MEK1
ORF Names:	DDB_G0269152

Organism

Dictyostelium discoideum (Slime mold) [Complete proteome]

Taxonomic identifier

44689 [NCBI]

Taxonomic lineage

Eukaryota › Amoebozoa › Mycetozoa › Dictyosteliida › Dictyostelium

Protein attributes

Sequence length	660 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for cAMP-mediated activation of guanylyl cyclase activity and plays an essential role in aggregation, morphogenesis, and chemotaxis. Appears to act upstream of erk1 but not erk2. Ref.1 Ref.3
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB Q869N2
Cofactor	Magnesium By similarity. UniProtKB Q869N2
Subunit structure	Interacts with mip1. Ref.3
Subcellular location	Cytoplasm. Nucleus. Note: Predominantly nuclear in vegetatively growing cells. Translocates to the cell cortex in response to chemoattractant stimulation and is present at the leading edge of chemotaxing cells. Ref.3
Post-translational modification	Sumoylated and ubiquitinated in response to chemoattractant stimulation. Sumoylation is linked to kinase activation and results in translocation. Ref.3
Disruption phenotype	Cells are unable to undergo chemotaxis properly during aggregation in response to the chemoattractant cAMP or activate guanylyl cyclase. Form extremely small aggregates resulting in the development of slugs and terminal fruiting bodies that are significantly smaller than those of wild-type cells. Transfer of the temperature-sensitive mutants from a temperature of 18 degrees Celsius to 27 degrees Celsius causes forming aggregates to split into multiple small aggregates. Ref.1
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. UniProtKB Q869N2 Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Chemotaxis
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	chemotaxis Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 660	660	Dual specificity mitogen-activated protein kinase kinase 1		PRO_0000371251
Regions
	Domain	292 – 641	350	Protein kinase
	Nucleotide binding	298 – 306	9	ATP By similarity UniProtKB P28523
	Compositional bias	25 – 47	23	Poly-Asn
	Compositional bias	50 – 57	8	Poly-Asn
	Compositional bias	149 – 168	20	Poly-Asn
	Compositional bias	202 – 238	37	Poly-Asn
	Compositional bias	241 – 249	9	Poly-Asn
Sites
	Active site	414	1	Proton acceptor By similarity UniProtKB P28523
	Binding site	321	1	ATP By similarity UniProtKB P28523
Amino acid modifications
	Cross-link	105		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.3
Experimental info
	Mutagenesis	105	1	K → R: Loss of sumoylation, and translocation ability. Ref.3
	Mutagenesis	321	1	K → A: Loss of aggregation ability. Ref.1
	Mutagenesis	444	1	S → A: Loss of aggregation ability, sumoylation and translocation; when associated with A-448. Ref.1 Ref.3
	Mutagenesis	444	1	S → D: Loss of aggregation ability and defects in cAMP-mediated signaling pathways; when associated with D-448. Ref.1 Ref.3
	Mutagenesis	444	1	S → E: Constitutively sumoylated and cytosolic; when associated with E-448. Ref.1 Ref.3
	Mutagenesis	448	1	T → A: Loss of aggregation ability, sumoylation and translocation; when associated with A-444. Ref.1 Ref.3
	Mutagenesis	448	1	T → D: Loss of aggregation ability and defects in cAMP-mediated signaling pathways; when associated with D-444. Ref.1 Ref.3
	Mutagenesis	448	1	T → E: Constitutively sumoylated and cytosolic; when associated with E-444. Ref.1 Ref.3
	Mutagenesis	458	1	P → S: Temperature-sensitive mutant. Ref.1
	Sequence conflict	471	1	E → D in AAB58577. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q55CL6-1 [UniParc]. Last modified May 24, 2005. Version 1. Checksum: 3B66637C4BA520FF	FASTA	660	74,138
	10 20 30 40 50 60 MNTNTNTNTN ISSSGNNIIN TPTTNNNNKN NNNNNNNNNN SNNSNNNSSN NNNNNNNAVG 70 80 90 100 110 120 VKTGKKVNLK VETPVQNNEN SYSLTTSGTF KEGDLLINKK GLLIKGESPK NSSVNDRNKN 130 140 150 160 170 180 KSLHSNLNPQ LLASPTSSES MDFNQGFYNN NNNNNNNNNN NNLNNFNNLM NNGIDSPQLS 190 200 210 220 230 240 GISISTPTSS HSFNNTFTNY YNNNNNYNNY NNNNNSNNNN NNYNNSNNNF NNFNNYNNYG 250 260 270 280 290 300 NNNNFNNFNA LQSSSNSSFD ISSSGSSNNY LNNSANNHPH YDTNLSYDLK DLKIIRVLGR 310 320 330 340 350 360 GAGGVVKLAY HETSGTYIAL KVITLDIQEN IRKQIILELK TLHKTSYPYI VSFYDAFYTE 370 380 390 400 410 420 GSIFIALEFM ELGSLSDIMK KTSTIPEPVL GKIAFQVLQG LVYLHRKLHL IHRDIKPSNI 430 440 450 460 470 480 LVNNKGEAKI ADFGVSGQLQ HTLSKAVTWV GTVTYMSPER ISGRSYSFDS EIWSLGLTIL 490 500 510 520 530 540 ECAIGKFPYG SNLPHQQQQP LQQQQQQQQQ QQQPLQQQQQ QQQQQQQPLQ LQLQNLDINN 550 560 570 580 590 600 SNNNIRNSNN NNNNNNNNNN NNNNNNNNNV LDISNGGLVD SGSSVPEGMG FWVLLDCIVK 610 620 630 640 650 660 EEVPILPSTF SKEFRSFISE CLQKEPTERP TASNLLNHEF VKKYQNFNVE KWTANLKQQQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Dictyostelium MAP kinase kinase DdMEK1 regulates chemotaxis and is essential for chemoattractant-mediated activation of guanylyl cyclase." Ma H., Gamper M., Parent C., Firtel R.A. EMBO J. 16:4317-4332(1997) [PubMed: 9250676] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE, MUTAGENESIS OF LYS-321; SER-444; THR-448 AND PRO-458. Strain: AX3-1.
[2]	"The genome of the social amoeba Dictyostelium discoideum." Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R., Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B., Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T., Lehmann R., Hamlin N. , Davies R., Gaudet P., Fey P., Pilcher K., Chen G., Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N., Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E., Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N., Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D., Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T., Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D., Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A., Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M., Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A., Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y., Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C., Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R., Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A. Nature 435:43-57(2005) [PubMed: 15875012] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: AX4.
[3]	"Regulated SUMOylation and ubiquitination of DdMEK1 is required for proper chemotaxis." Sobko A., Ma H., Firtel R.A. Dev. Cell 2:745-756(2002) [PubMed: 12062087] [Abstract] Cited for: FUNCTION, INTERACTION WITH MIP1, SUBCELLULAR LOCATION, SUMOYLATION AT LYS-105, UBIQUITINATION, MUTAGENESIS OF LYS-105; SER-444 AND THR-448.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U87912 mRNA. Translation: AAB58577.1. AAFI02000005 Genomic DNA. Translation: EAL71926.1.
RefSeq	XP_646465.1.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q55CL6.
Genome annotation databases
GeneID	3397732.
GenomeReviews	Gene locus mekA in contig CM000150_GR.
KEGG	ddi:DDB_0191164.
Organism-specific databases
dictyBase	DDB_G0269152. mekA.
Phylogenomic databases
OMA	TILECAI.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 2 hits. [Graphical view] [Entries sharing at least one domain]
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_DICDI

Accession

Primary (citable) accession number: Q55CL6
Secondary accession number(s): O00885

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 5, 2009
Last sequence update:	May 24, 2005
Last modified:	November 3, 2009
This is version 40 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)