MAK2_CAEEL
ID MAK2_CAEEL Reviewed; 366 AA.
AC Q965G5;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=MAP kinase-activated protein kinase mak-2 {ECO:0000305};
DE Short=MAPK-activated protein kinase mak-2 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q21360};
GN Name=mak-2 {ECO:0000312|WormBase:C44C8.6};
GN ORFNames=C44C8.6 {ECO:0000312|WormBase:C44C8.6};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, INTERACTION WITH PMK-3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP MOTIF, PHOSPHORYLATION AT THR-173 AND THR-285, AND MUTAGENESIS OF LYS-26;
RP LEU-142; THR-173; THR-285; 301-THR--GLY-317 AND 330-ASN--LYS-353.
RX PubMed=19737525; DOI=10.1016/j.cell.2009.06.023;
RA Yan D., Wu Z., Chisholm A.D., Jin Y.;
RT "The DLK-1 kinase promotes mRNA stability and local translation in C.
RT elegans synapses and axon regeneration.";
RL Cell 138:1005-1018(2009).
RN [3] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25851606; DOI=10.1091/mbc.e14-05-1009;
RA Matsunaga Y., Qadota H., Furukawa M., Choe H.H., Benian G.M.;
RT "Twitchin kinase interacts with MAPKAP kinase 2 in Caenorhabditis elegans
RT striated muscle.";
RL Mol. Biol. Cell 26:2096-2111(2015).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27123983; DOI=10.1371/journal.pgen.1006010;
RA D'Souza S.A., Rajendran L., Bagg R., Barbier L., van Pel D.M., Moshiri H.,
RA Roy P.J.;
RT "The MADD-3 LAMMER kinase interacts with a p38 MAP kinase pathway to
RT regulate the display of the EVA-1 guidance receptor in Caenorhabditis
RT elegans.";
RL PLoS Genet. 12:E1006010-E1006010(2016).
CC -!- FUNCTION: Serine/threonine-protein kinase which is involved in
CC maintaining synapse and axon morphology as well as touch neuron axon
CC regeneration after injury by regulating cebp-1 mRNA stability
CC downstream of the dlk-1, mkk-4 and pmk-3 signaling cascade
CC (PubMed:19737525). May play a role in body wall muscle contraction
CC (PubMed:19737525). Plays a role in the formation of muscle connections,
CC also called muscle arm extensions, between the body wall and the motor
CC axons in the dorsal and ventral cord (PubMed:27123983).
CC {ECO:0000269|PubMed:19737525, ECO:0000269|PubMed:25851606,
CC ECO:0000269|PubMed:27123983}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q21360};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q21360};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q21360};
CC -!- SUBUNIT: Interacts with pmk-3. {ECO:0000269|PubMed:19737525}.
CC -!- SUBCELLULAR LOCATION: Perikaryon {ECO:0000269|PubMed:19737525}. Nucleus
CC {ECO:0000269|PubMed:19737525}. Synapse {ECO:0000269|PubMed:19737525}.
CC Note=Colocalizes with snb-1 and partially with cebp-1 at synapses.
CC {ECO:0000269|PubMed:19737525}.
CC -!- TISSUE SPECIFICITY: Expressed in pharynx, intestine and body wall
CC muscles (PubMed:25851606). Expressed in the nervous system
CC (PubMed:19737525). {ECO:0000269|PubMed:19737525,
CC ECO:0000269|PubMed:25851606}.
CC -!- PTM: May be phosphorylated at Thr-173 and Thr-285 by pmk-3.
CC {ECO:0000269|PubMed:19737525}.
CC -!- DISRUPTION PHENOTYPE: Weak defect in the extension of body wall muscle
CC connections or arms towards the ventral nerve cord. Double knockout
CC with madd-3 suppresses the muscle arm extension defects, eva-1
CC expression defects and restores the defect in the recruitment of madd-4
CC to the muscle membrane in the madd-3 single knockout. Triple knockout
CC with madd-3 and unc-54 results in paralysis (as in the unc-54 single
CC knockout), and suppresses the lethality phenotype in the double madd-3
CC and unc-54 mutant. {ECO:0000269|PubMed:27123983}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; BX284604; CCD67275.1; -; Genomic_DNA.
DR RefSeq; NP_500006.2; NM_067605.4.
DR AlphaFoldDB; Q965G5; -.
DR SMR; Q965G5; -.
DR STRING; 6239.C44C8.6.1; -.
DR iPTMnet; Q965G5; -.
DR EPD; Q965G5; -.
DR PaxDb; Q965G5; -.
DR PeptideAtlas; Q965G5; -.
DR EnsemblMetazoa; C44C8.6.1; C44C8.6.1; WBGene00007007.
DR EnsemblMetazoa; C44C8.6.2; C44C8.6.2; WBGene00007007.
DR UCSC; C44C8.6a; c. elegans.
DR WormBase; C44C8.6; CE33566; WBGene00007007; mak-2.
DR eggNOG; KOG0604; Eukaryota.
DR GeneTree; ENSGT00940000169538; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR OMA; MSHPWIS; -.
DR OrthoDB; 843707at2759; -.
DR Reactome; R-CEL-171007; p38MAPK events.
DR Reactome; R-CEL-199920; CREB phosphorylation.
DR Reactome; R-CEL-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-CEL-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-CEL-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-CEL-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-CEL-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
DR Reactome; R-CEL-5687128; MAPK6/MAPK4 signaling.
DR SignaLink; Q965G5; -.
DR PRO; PR:Q965G5; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00007007; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0035095; P:behavioral response to nicotine; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:1905870; P:positive regulation of 3'-UTR-mediated mRNA stabilization; IMP:UniProtKB.
DR GO; GO:0048691; P:positive regulation of axon extension involved in regeneration; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR GO; GO:1905868; P:regulation of 3'-UTR-mediated mRNA stabilization; IGI:UniProtKB.
DR GO; GO:0048841; P:regulation of axon extension involved in axon guidance; IGI:UniProtKB.
DR GO; GO:1905606; P:regulation of presynapse assembly; IMP:UniProtKB.
DR Gene3D; 4.10.1170.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR027442; MAPKAPK_C.
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; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Synapse; Transferase.
FT CHAIN 1..366
FT /note="MAP kinase-activated protein kinase mak-2"
FT /evidence="ECO:0000305"
FT /id="PRO_0000438708"
FT DOMAIN 13..276
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 324..366
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 301..317
FT /note="Nuclear export signal"
FT /evidence="ECO:0000269|PubMed:19737525"
FT MOTIF 330..353
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:19737525"
FT COMPBIAS 331..351
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 135
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 19..27
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 42
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 173
FT /note="Phosphothreonine"
FT /evidence="ECO:0000303|PubMed:19737525"
FT MOD_RES 285
FT /note="Phosphothreonine"
FT /evidence="ECO:0000303|PubMed:19737525"
FT MUTAGEN 26
FT /note="K->R: Probable loss of kinase activity. PML axon
FT regeneration after injury is partially impaired. Partially
FT rescues PLM and ALM axon termination defects in a rpm-1
FT mutant background."
FT /evidence="ECO:0000269|PubMed:19737525"
FT MUTAGEN 142
FT /note="L->P: In ju637; partially rescues motor neuron
FT presynaptic and PLM and ALM axon termination defects in a
FT rpm-1 mutant background."
FT /evidence="ECO:0000269|PubMed:19737525"
FT MUTAGEN 173
FT /note="T->A: Abolishes phosphorylation. Partially rescues
FT motor neuron presynaptic and PLM and ALM axon termination
FT defects in a rpm-1 mutant background. Stronger rescue of
FT neuronal defects; when associated with A-285."
FT /evidence="ECO:0000269|PubMed:19737525"
FT MUTAGEN 173
FT /note="T->E: Phosphomimetic mutant. Defects in motor neuron
FT presynaptic and PLM and ALM axon termination and increased
FT cebp-1 mRNA levels; when associated with E-285. Localized
FT exclusively to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:19737525"
FT MUTAGEN 285
FT /note="T->A: Abolishes phosphorylation. Partially rescues
FT motor neuron presynaptic and PLM and ALM axon termination
FT defects in a rpm-1 mutant background. Stronger rescue of
FT neuronal defects; when associated with A-173."
FT /evidence="ECO:0000269|PubMed:19737525"
FT MUTAGEN 285
FT /note="T->E: Phosphomimetic mutant. Defects in motor neuron
FT presynaptic and PLM and ALM axon termination and increased
FT cebp-1 mRNA levels; when associated with E-173. Localized
FT exclusively to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:19737525"
FT MUTAGEN 301..317
FT /note="Missing: Only localized to the nucleus. Unable to
FT rescue PLM and ALM axon termination defects in a rpm-1
FT mutant background."
FT /evidence="ECO:0000269|PubMed:19737525"
FT MUTAGEN 330..353
FT /note="Missing: Only localized to the cytoplasm. Unable to
FT rescue PLM and ALM axon termination defects in a rpm-1
FT mutant background."
FT /evidence="ECO:0000269|PubMed:19737525"
SQ SEQUENCE 366 AA; 41541 MW; F406C2B2EA0E8CCF CRC64;
MAFHEYPVTQ DYRISRKVLG VGINGKVVEC EHRQSGDKFA LKVLRDTQKA RREVELHVMA
SGHGHVVSVH DVYKNSYNGV DCLLVVMENM KGGELFNRIQ ERGQKAFTER EAAGIVNEIC
SAVAHLHRMS IAHRDLKPEN LLYVTTASNA ALKLTDFGFA KKTDESEPQG LKTACFTPYY
CAPEVLGTEK YDKSCDLWSI GVIMYILLCG YPPFYSQHGQ PMSPGMKAKI KSGQYTFPSP
EWDCVSEAAK DLIRKLLRTE PTERITIEQT MEHKWISHYR RVPDTPLFTS SNLNDQREQW
TDMQDEMEAT LASMRVGPEN IQIKSLGDSN NKLLAKRRKG GASPKDDPMD DIKEEEKDDE
EEKMIS
