MARK2_RAT
ID MARK2_RAT Reviewed; 722 AA.
AC O08679;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Serine/threonine-protein kinase MARK2;
DE EC=2.7.11.1;
DE EC=2.7.11.26;
DE AltName: Full=ELKL motif kinase 1;
DE Short=EMK-1;
DE AltName: Full=MAP/microtubule affinity-regulating kinase 2;
GN Name=Mark2 {ECO:0000312|RGD:708483};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAB06295.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:CAB06295.1};
RC TISSUE=Brain {ECO:0000312|EMBL:CAB06295.1};
RX PubMed=9108484; DOI=10.1016/s0092-8674(00)80208-1;
RA Drewes G., Ebneth A., Preuss U., Mandelkow E.-M., Mandelkow E.;
RT "MARK - a novel family of protein kinases that phosphorylate microtubule-
RT associated proteins and trigger microtubule disruption.";
RL Cell 89:297-308(1997).
RN [2]
RP FUNCTION, ACTIVITY REGULATION, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT
RP THR-58; THR-208; SER-212; SER-274 AND THR-275, AND MUTAGENESIS OF THR-208
RP AND SER-212.
RX PubMed=14517247; DOI=10.1093/emboj/cdg447;
RA Timm T., Li X.Y., Biernat J., Jiao J., Mandelkow E., Vandekerckhove J.,
RA Mandelkow E.M.;
RT "MARKK, a Ste20-like kinase, activates the polarity-inducing kinase
RT MARK/PAR-1.";
RL EMBO J. 22:5090-5101(2003).
RN [3]
RP FUNCTION.
RX PubMed=15466480; DOI=10.1083/jcb.200401085;
RA Mandelkow E.M., Thies E., Trinczek B., Biernat J., Mandelkow E.;
RT "MARK/PAR1 kinase is a regulator of microtubule-dependent transport in
RT axons.";
RL J. Cell Biol. 167:99-110(2004).
RN [4]
RP FUNCTION IN PHOSPHORYLATION OF DCX, AND SUBCELLULAR LOCATION.
RX PubMed=14741102; DOI=10.1016/s0896-6273(03)00843-2;
RA Schaar B.T., Kinoshita K., McConnell S.K.;
RT "Doublecortin microtubule affinity is regulated by a balance of kinase and
RT phosphatase activity at the leading edge of migrating neurons.";
RL Neuron 41:203-213(2004).
RN [5]
RP PHOSPHORYLATION AT SER-212, AND MUTAGENESIS OF THR-208 AND SER-212.
RX PubMed=16257959; DOI=10.1074/jbc.m507941200;
RA Kosuga S., Tashiro E., Kajioka T., Ueki M., Shimizu Y., Imoto M.;
RT "GSK-3beta directly phosphorylates and activates MARK2/PAR-1.";
RL J. Biol. Chem. 280:42715-42722(2005).
RN [6]
RP INTERACTION WITH PAK5.
RX PubMed=16014608; DOI=10.1091/mbc.e05-01-0081;
RA Matenia D., Griesshaber B., Li X.Y., Thiessen A., Johne C., Jiao J.,
RA Mandelkow E., Mandelkow E.M.;
RT "PAK5 kinase is an inhibitor of MARK/Par-1, which leads to stable
RT microtubules and dynamic actin.";
RL Mol. Biol. Cell 16:4410-4422(2005).
RN [7]
RP PHOSPHORYLATION AT THR-539, MUTAGENESIS OF THR-539, AND FUNCTION.
RX PubMed=16717194; DOI=10.1073/pnas.0509955103;
RA Chen Y.M., Wang Q.J., Hu H.S., Yu P.C., Zhu J., Drewes G.,
RA Piwnica-Worms H., Luo Z.G.;
RT "Microtubule affinity-regulating kinase 2 functions downstream of the PAR-
RT 3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:8534-8539(2006).
RN [8]
RP PHOSPHORYLATION AT SER-91; SER-92; SER-93 AND THR-294, AND MUTAGENESIS OF
RP LYS-82; 91-SER--SER-93 AND THR-294.
RX PubMed=17442826; DOI=10.1523/jneurosci.0725-07.2007;
RA Uboha N.V., Flajolet M., Nairn A.C., Picciotto M.R.;
RT "A calcium- and calmodulin-dependent kinase Ialpha/microtubule affinity
RT regulating kinase 2 signaling cascade mediates calcium-dependent neurite
RT outgrowth.";
RL J. Neurosci. 27:4413-4423(2007).
RN [9]
RP PHOSPHORYLATION AT SER-212, AND MUTAGENESIS OF THR-208 AND SER-212.
RX PubMed=18424437; DOI=10.1074/jbc.m706596200;
RA Timm T., Balusamy K., Li X., Biernat J., Mandelkow E., Mandelkow E.M.;
RT "Glycogen synthase kinase (GSK) 3beta directly phosphorylates Serine 212 in
RT the regulatory loop and inhibits microtubule affinity-regulating kinase
RT (MARK) 2.";
RL J. Biol. Chem. 283:18873-18882(2008).
RN [10]
RP FUNCTION.
RX PubMed=18509032; DOI=10.1523/jneurosci.0911-08.2008;
RA Sapir T., Sapoznik S., Levy T., Finkelshtein D., Shmueli A., Timm T.,
RA Mandelkow E.M., Reiner O.;
RT "Accurate balance of the polarity kinase MARK2/Par-1 is required for proper
RT cortical neuronal migration.";
RL J. Neurosci. 28:5710-5720(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-408; SER-409; SER-453 AND
RP SER-483, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 39-364 OF WILD-TYPE AND MUTANT
RP THR-208 AND SER-212, AND SUBUNIT.
RX PubMed=16472737; DOI=10.1016/j.str.2005.09.022;
RA Panneerselvam S., Marx A., Mandelkow E.M., Mandelkow E.;
RT "Structure of the catalytic and ubiquitin-associated domains of the protein
RT kinase MARK/Par-1.";
RL Structure 14:173-183(2006).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) OF 39-364.
RX PubMed=20071654; DOI=10.1096/fj.09-148064;
RA Marx A., Nugoor C., Panneerselvam S., Mandelkow E.;
RT "Structure and function of polarity-inducing kinase family MARK/Par-1
RT within the branch of AMPK/Snf1-related kinases.";
RL FASEB J. 24:1637-1648(2010).
CC -!- FUNCTION: Serine/threonine-protein kinase. Involved in cell polarity
CC and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX,
CC HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the
CC microtubule-associated protein MAPT/TAU. Plays a key role in cell
CC polarity by phosphorylating the microtubule-associated proteins MAP2,
CC MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules,
CC and their disassembly. Regulates epithelial cell polarity by
CC phosphorylating RAB11FIP2. Involved in the regulation of neuronal
CC migration through its dual activities in regulating cellular polarity
CC and microtubule dynamics, possibly by phosphorylating and regulating
CC DCX. Regulates axogenesis by phosphorylating KIF13B, promoting
CC interaction between KIF13B and 14-3-3 and inhibiting microtubule-
CC dependent accumulation of KIF13B. Also required for neurite outgrowth
CC and establishment of neuronal polarity. Regulates localization and
CC activity of some histone deacetylases by mediating phosphorylation of
CC HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and
CC export from the nucleus. Also acts as a positive regulator of the Wnt
CC signaling pathway, probably by mediating phosphorylation of dishevelled
CC proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision
CC to build a columnar versus a hepatic epithelial cell apparently by
CC promoting a switch from a direct to a transcytotic mode of apical
CC protein delivery. Essential for the asymmetric development of membrane
CC domains of polarized epithelial cells. {ECO:0000250|UniProtKB:Q7KZI7,
CC ECO:0000269|PubMed:14517247, ECO:0000269|PubMed:14741102,
CC ECO:0000269|PubMed:15466480, ECO:0000269|PubMed:16717194,
CC ECO:0000269|PubMed:18509032}.
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:Q7KZI7};
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:Q7KZI7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-
CC [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-
CC COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703,
CC Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.26;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q7KZI7};
CC -!- ACTIVITY REGULATION: Inhibited by hymenialdisine (By similarity).
CC Activated by phosphorylation on Thr-208 by STK11/LKB1 and TAOK1.
CC Inhibited by phosphorylation at Ser-212 or Thr-539. Inhibited by PAK5;
CC inhibition is independent of the kinase activity of PAK5. {ECO:0000250,
CC ECO:0000269|PubMed:14517247}.
CC -!- SUBUNIT: Homodimer (PubMed:16472737). Interacts (when phosphorylated at
CC Thr-539) with YWHAZ (By similarity). Interacts with MTCL1; the
CC interaction is direct and increases MARK2 microtubule-binding ability
CC (By similarity). Interacts with PAK5; leading to inhibit the protein
CC kinase activity (PubMed:16014608). Interacts with MAPT/TAU (By
CC similarity). Interacts with YWHAB, YWHAG and YWHAQ (By similarity).
CC {ECO:0000250|UniProtKB:Q7KZI7, ECO:0000269|PubMed:16014608,
CC ECO:0000269|PubMed:16472737}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14741102};
CC Peripheral membrane protein {ECO:0000269|PubMed:14741102}. Lateral cell
CC membrane {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q7KZI7}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q7KZI7}. Note=Phosphorylation at Thr-539 by
CC PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ
CC promotes relocation from the cell membrane to the cytoplasm.
CC {ECO:0000250}.
CC -!- DOMAIN: The KA1 domain mediates binding to phospholipids and targeting
CC to membranes. {ECO:0000250}.
CC -!- DOMAIN: The UBA domain does not seem to bind ubiquitin and ubiquitin-
CC like and might play a role in regulating the enzyme conformation and
CC localization. Activation of the kinase activity following
CC phosphorylation at Thr-208 is accompanied by a conformational change
CC that alters the orientation of the UBA domain with respect to the
CC catalytic domain (By similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylated. Phosphorylated at Thr-208 by STK11/LKB1 in
CC complex with STE20-related adapter-alpha (STRADA) pseudo kinase and
CC CAB39. Phosphorylation at Thr-208 by TAOK1 activates the kinase
CC activity, leading to phosphorylation and detachment of MAPT/TAU from
CC microtubules. Phosphorylation at Ser-212 by GSK3-beta (GSK3B) inhibits
CC the kinase activity. Phosphorylation by CaMK1 promotes activity and is
CC required to promote neurite outgrowth. Phosphorylation at Thr-539 by
CC PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity
CC and promotes binding to 14-3-3 protein YWHAZ, leading to relocation
CC from cell membrane to cytoplasm. {ECO:0000269|PubMed:14517247,
CC ECO:0000269|PubMed:16257959, ECO:0000269|PubMed:16717194,
CC ECO:0000269|PubMed:17442826, ECO:0000269|PubMed:18424437}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
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DR EMBL; Z83869; CAB06295.1; -; mRNA.
DR RefSeq; NP_067731.1; NM_021699.1.
DR PDB; 1Y8G; X-ray; 2.50 A; A/B=39-364.
DR PDB; 1ZMU; X-ray; 2.90 A; A/B=39-364.
DR PDB; 1ZMV; X-ray; 3.10 A; A/B=39-364.
DR PDB; 1ZMW; X-ray; 2.80 A; A/B=39-364.
DR PDB; 2R0I; X-ray; 2.20 A; A/B=39-364.
DR PDB; 2WZJ; X-ray; 2.79 A; A/B/C/D/E/F=39-364.
DR PDBsum; 1Y8G; -.
DR PDBsum; 1ZMU; -.
DR PDBsum; 1ZMV; -.
DR PDBsum; 1ZMW; -.
DR PDBsum; 2R0I; -.
DR PDBsum; 2WZJ; -.
DR AlphaFoldDB; O08679; -.
DR SMR; O08679; -.
DR BioGRID; 248778; 1.
DR DIP; DIP-29029N; -.
DR IntAct; O08679; 1.
DR MINT; O08679; -.
DR STRING; 10116.ENSRNOP00000028763; -.
DR iPTMnet; O08679; -.
DR PhosphoSitePlus; O08679; -.
DR PaxDb; O08679; -.
DR PRIDE; O08679; -.
DR GeneID; 60328; -.
DR KEGG; rno:60328; -.
DR UCSC; RGD:708483; rat.
DR CTD; 2011; -.
DR RGD; 708483; Mark2.
DR VEuPathDB; HostDB:ENSRNOG00000021184; -.
DR eggNOG; KOG0586; Eukaryota.
DR InParanoid; O08679; -.
DR OrthoDB; 1127668at2759; -.
DR EvolutionaryTrace; O08679; -.
DR PRO; PR:O08679; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000021184; Expressed in jejunum and 19 other tissues.
DR ExpressionAtlas; O08679; baseline and differential.
DR Genevisible; O08679; RN.
DR GO; GO:0005884; C:actin filament; ISS:UniProtKB.
DR GO; GO:0045180; C:basal cortex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0016328; C:lateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0097427; C:microtubule bundle; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:ARUK-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0048156; F:tau protein binding; IPI:ARUK-UCL.
DR GO; GO:0050321; F:tau-protein kinase activity; IDA:UniProtKB.
DR GO; GO:0061564; P:axon development; IMP:ARUK-UCL.
DR GO; GO:0030010; P:establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:0071963; P:establishment or maintenance of cell polarity regulating cell shape; IMP:ARUK-UCL.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0001764; P:neuron migration; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:ARUK-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:RGD.
DR GO; GO:0050770; P:regulation of axonogenesis; ISS:UniProtKB.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:1904526; P:regulation of microtubule binding; IMP:ARUK-UCL.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IDA:ARUK-UCL.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR001772; KA1_dom.
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 InterPro; IPR015940; UBA.
DR Pfam; PF02149; KA1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00627; UBA; 1.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00165; UBA; 1.
DR SUPFAM; SSF103243; SSF103243; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50032; KA1; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50030; UBA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; Developmental protein; Differentiation; Kinase;
KW Lipid-binding; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Wnt signaling pathway.
FT CHAIN 1..722
FT /note="Serine/threonine-protein kinase MARK2"
FT /id="PRO_0000086303"
FT DOMAIN 53..304
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 323..362
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 673..722
FT /note="KA1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00565"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 373..576
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..429
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 430..444
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 462..576
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 175
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 59..67
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 82
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O08678,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 58
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:14517247"
FT MOD_RES 91
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000269|PubMed:17442826"
FT MOD_RES 92
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000269|PubMed:17442826"
FT MOD_RES 93
FT /note="Phosphoserine; by CaMK1"
FT /evidence="ECO:0000269|PubMed:17442826"
FT MOD_RES 208
FT /note="Phosphothreonine; by LKB1 and TAOK1"
FT /evidence="ECO:0000269|PubMed:14517247"
FT MOD_RES 212
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:14517247,
FT ECO:0000269|PubMed:16257959, ECO:0000269|PubMed:18424437"
FT MOD_RES 274
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:14517247"
FT MOD_RES 275
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:14517247"
FT MOD_RES 294
FT /note="Phosphothreonine; by CaMK1"
FT /evidence="ECO:0000269|PubMed:17442826"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 464
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 514
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 539
FT /note="Phosphothreonine; by PKC/PRKCZ"
FT /evidence="ECO:0000269|PubMed:16717194"
FT MOD_RES 562
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MOD_RES 656
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7KZI7"
FT MUTAGEN 82
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:17442826"
FT MUTAGEN 91..93
FT /note="SSS->AAA: Loss of phosphorylation by CaMK1, decrease
FT in kinase activity and ability to promote neurite
FT outgrowth; when associated with A-294."
FT /evidence="ECO:0000269|PubMed:17442826"
FT MUTAGEN 208
FT /note="T->A: Abolishes activation of serine/threonine-
FT protein kinase activity and only basal activity remains."
FT /evidence="ECO:0000269|PubMed:14517247,
FT ECO:0000269|PubMed:16257959, ECO:0000269|PubMed:18424437"
FT MUTAGEN 208
FT /note="T->E: Phosphomimetic mutant that leads to activation
FT but not in presence of GSK3-beta."
FT /evidence="ECO:0000269|PubMed:14517247,
FT ECO:0000269|PubMed:16257959, ECO:0000269|PubMed:18424437"
FT MUTAGEN 212
FT /note="S->A: Loss of activity; neither activated by TAOK1
FT nor by STK11/LKB1."
FT /evidence="ECO:0000269|PubMed:14517247,
FT ECO:0000269|PubMed:16257959, ECO:0000269|PubMed:18424437"
FT MUTAGEN 294
FT /note="T->A: Loss of phosphorylation by CaMK1, decrease in
FT kinase activity and ability to promote neurite outgrowth;
FT when associated with 91-A--A-93."
FT /evidence="ECO:0000269|PubMed:17442826"
FT MUTAGEN 539
FT /note="T->A: Abolishes phosphorylation by PKC/PRKCZ."
FT /evidence="ECO:0000269|PubMed:16717194"
FT STRAND 53..61
FT /evidence="ECO:0007829|PDB:2R0I"
FT STRAND 63..72
FT /evidence="ECO:0007829|PDB:2R0I"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:2R0I"
FT STRAND 78..85
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 91..106
FT /evidence="ECO:0007829|PDB:2R0I"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:2R0I"
FT STRAND 122..130
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 137..144
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 149..168
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:2R0I"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:2R0I"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:2R0I"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:2WZJ"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:2WZJ"
FT TURN 208..211
FT /evidence="ECO:0007829|PDB:1Y8G"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 229..245
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 255..264
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 275..284
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 295..298
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 302..305
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 326..334
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 339..347
FT /evidence="ECO:0007829|PDB:2R0I"
FT HELIX 353..361
FT /evidence="ECO:0007829|PDB:2R0I"
SQ SEQUENCE 722 AA; 80872 MW; 2CBAFD1C38007ECC CRC64;
MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMLRGRNS ATSADEQPHI GNYRLLKTIG
KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE
TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN
LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL
YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK
DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL
LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRSSD QAVPAIPTSN
SYSKKTQSNN AENKRPEEET GRKASSTAKV PASPLPGLDR KKTTPTPSTN SVLSTSTNRS
RNSPLLDRAS LGQASIQNGK DSTAPQRVPV ASPSAHNISS SSGAPDRTNF PRGVSSRSTF
HAGQLRQVRD QQNLPFGVTP ASPSGHSQGR RGASGSIFSK FTSKFVRRNL NEPESKDRVE
TLRPHVVGGG GTDKEKEEFR EAKPRSLRFT WSMKTTSSME PNEMMREIRK VLDANSCQSE
LHERYMLLCV HGTPGHENFV QWEMEVCKLP RLSLNGVRFK RISGTSMAFK NIASKIANEL
KL
