MYLKA_DICDI
ID MYLKA_DICDI Reviewed; 295 AA.
AC P25323; Q54W26;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Myosin light chain kinase A;
DE Short=MLCK-A {ECO:0000303|PubMed:16546177};
DE EC=2.7.11.18 {ECO:0000305|PubMed:16546177};
GN Name=mlkA; ORFNames=DDB_G0279925;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=AX3;
RX PubMed=1651931; DOI=10.1016/s0021-9258(18)98513-3;
RA Tan J.L., Spudich J.A.;
RT "Characterization and bacterial expression of the Dictyostelium myosin
RT light chain kinase cDNA. Identification of an autoinhibitory domain.";
RL J. Biol. Chem. 266:16044-16049(1991).
RN [2]
RP SEQUENCE REVISION.
RA Spudich J.A.;
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [4]
RP PARTIAL PROTEIN SEQUENCE, AND AUTOPHOSPHORYLATION.
RC STRAIN=AX3;
RX PubMed=2380188; DOI=10.1016/s0021-9258(18)77421-8;
RA Tan J.L., Spudich J.A.;
RT "Dictyostelium myosin light chain kinase. Purification and
RT characterization.";
RL J. Biol. Chem. 265:13818-13824(1990).
RN [5]
RP PHOSPHORYLATION AT THR-166 AND THR-289, MUTAGENESIS OF THR-166 AND THR-289,
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16546177; DOI=10.1016/j.febslet.2006.03.008;
RA Goldberg J.M., Wolpin E.S., Bosgraaf L., Clarkson B.K.,
RA Van Haastert P.J.M., Smith J.L.;
RT "Myosin light chain kinase A is activated by cGMP-dependent and cGMP-
RT independent pathways.";
RL FEBS Lett. 580:2059-2064(2006).
CC -!- FUNCTION: Phosphorylates a specific serine in the N-terminus of a
CC myosin light chain (By similarity). Phosphorylates regulatory myosin
CC light chain (mlcR) during chemotaxis (PubMed:16546177). mlcR
CC phosphorylation increases the motility and actin-activated ATPase
CC activity of myosin, contributing to chemotaxis (PubMed:16546177).
CC {ECO:0000250, ECO:0000269|PubMed:16546177,
CC ECO:0000303|PubMed:16546177}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[myosin light chain] = ADP + H(+) + O-phospho-L-
CC seryl-[myosin light chain]; Xref=Rhea:RHEA:22004, Rhea:RHEA-
CC COMP:13684, Rhea:RHEA-COMP:13685, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
CC ChEBI:CHEBI:456216; EC=2.7.11.18;
CC Evidence={ECO:0000305|PubMed:16546177};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22005;
CC Evidence={ECO:0000305|PubMed:16546177};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[myosin light chain] = ADP + H(+) + O-
CC phospho-L-threonyl-[myosin light chain]; Xref=Rhea:RHEA:53900,
CC Rhea:RHEA-COMP:13686, Rhea:RHEA-COMP:13687, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977,
CC ChEBI:CHEBI:456216; EC=2.7.11.18;
CC Evidence={ECO:0000305|PubMed:16546177};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53901;
CC Evidence={ECO:0000305|PubMed:16546177};
CC -!- ACTIVITY REGULATION: Possesses an autoinhibitory domain.
CC Autophosphorylation appears to increase the enzymatic activity.
CC Activation is gbdC-dependent. Does not have a calmodulin-binding
CC domain.
CC -!- PTM: Autophosphorylated. Transiently phosphorylated on Thr-166 and Thr-
CC 289. This phosphorylation is gbpC-dependent.
CC {ECO:0000269|PubMed:16546177}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
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DR EMBL; M64176; AAB06337.1; -; mRNA.
DR EMBL; AAFI02000035; EAL67434.1; -; Genomic_DNA.
DR PIR; A40811; A40811.
DR RefSeq; XP_641424.1; XM_636332.1.
DR AlphaFoldDB; P25323; -.
DR SMR; P25323; -.
DR DIP; DIP-153N; -.
DR STRING; 44689.DDB0214815; -.
DR iPTMnet; P25323; -.
DR PaxDb; P25323; -.
DR EnsemblProtists; EAL67434; EAL67434; DDB_G0279925.
DR GeneID; 8622308; -.
DR KEGG; ddi:DDB_G0279925; -.
DR dictyBase; DDB_G0279925; mlkA.
DR eggNOG; KOG0032; Eukaryota.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; P25323; -.
DR OMA; WKAADPP; -.
DR PhylomeDB; P25323; -.
DR BRENDA; 2.7.11.18; 1939.
DR Reactome; R-DDI-9619229; Activation of RAC1 downstream of NMDARs.
DR PRO; PR:P25323; -.
DR Proteomes; UP000002195; Chromosome 3.
DR GO; GO:0005737; C:cytoplasm; IDA:dictyBase.
DR GO; GO:0005524; F:ATP binding; IC:dictyBase.
DR GO; GO:0000146; F:microfilament motor activity; IDA:dictyBase.
DR GO; GO:0004687; F:myosin light chain kinase activity; IDA:dictyBase.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:dictyBase.
DR GO; GO:0140582; P:adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway; IDA:dictyBase.
DR GO; GO:0019934; P:cGMP-mediated signaling; IDA:dictyBase.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:dictyBase.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:dictyBase.
DR GO; GO:0050920; P:regulation of chemotaxis; IMP:dictyBase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Direct protein sequencing; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..295
FT /note="Myosin light chain kinase A"
FT /id="PRO_0000086412"
FT DOMAIN 8..265
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 264..295
FT /note="Autoinhibitory domain"
FT ACT_SITE 130
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 14..22
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 37
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 166
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16546177"
FT MOD_RES 289
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16546177"
FT MUTAGEN 166
FT /note="T->A: Slight increase in phosphorylation and loss of
FT mlcR phosphorylation."
FT /evidence="ECO:0000269|PubMed:16546177"
FT MUTAGEN 289
FT /note="T->A: Great increase in phosphorylation."
FT /evidence="ECO:0000269|PubMed:16546177"
SQ SEQUENCE 295 AA; 33407 MW; 546CAEED8F6ECD0B CRC64;
MTEVEKIYEF KEELGRGAFS IVYLGENKQT KQRYAIKVIN KSELGKDYEK NLKMEVDILK
KVNHPNIIAL KELFDTPEKL YLVMELVTGG ELFDKIVEKG SYSEADAANL VKKIVSAVGY
LHGLNIVHRD LKPENLLLKS KENHLEVAIA DFGLSKIIGQ TLVMQTACGT PSYVAPEVLN
ATGYDKEVDM WSIGVITYIL LCGFPPFYGD TVPEIFEQIM EANYEFPEEY WGGISKEAKD
FIGKLLVVDV SKRLNATNAL NHPWLKSNNS NNTIDTVKMK EYIVERQKTQ TKLVN
