MARK1_RAT
ID MARK1_RAT Reviewed; 793 AA.
AC O08678;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Serine/threonine-protein kinase MARK1;
DE EC=2.7.11.1;
DE EC=2.7.11.26;
DE AltName: Full=MAP/microtubule affinity-regulating kinase 1;
GN Name=Mark1 {ECO:0000312|RGD:619882};
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:CAB06294.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, PHOSPHORYLATION AT THR-215 AND SER-219, AND MUTAGENESIS OF
RP LYS-89; THR-215 AND SER-219.
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:CAB06294.1};
RC TISSUE=Brain {ECO:0000312|EMBL:CAB06294.1};
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, PHOSPHORYLATION AT THR-215 AND SER-219, AND
RP MUTAGENESIS OF THR-215 AND SER-219.
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 IN PHOSPHORYLATION OF DCX.
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-444, AND IDENTIFICATION BY
RP 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).
CC -!- FUNCTION: Serine/threonine-protein kinase (By similarity). Involved in
CC cell polarity and microtubule dynamics regulation. Phosphorylates DCX,
CC MAP2 and MAP4. Phosphorylates the microtubule-associated protein
CC MAPT/TAU (By similarity). Involved in cell polarity by phosphorylating
CC the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS
CC motifs, causing detachment from microtubules, and their disassembly.
CC Involved in the regulation of neuronal migration through its dual
CC activities in regulating cellular polarity and microtubule dynamics,
CC possibly by phosphorylating and regulating DCX. Also acts as a positive
CC regulator of the Wnt signaling pathway, probably by mediating
CC phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3)
CC (PubMed:14517247, PubMed:14741102, PubMed:9108484).
CC {ECO:0000250|UniProtKB:Q9P0L2, ECO:0000269|PubMed:14517247,
CC ECO:0000269|PubMed:14741102, ECO:0000269|PubMed:9108484}.
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:0000269|PubMed:9108484};
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:0000269|PubMed:9108484};
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; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-215. Inhibited
CC by phosphorylation at Ser-219. {ECO:0000269|PubMed:14517247}.
CC -!- SUBUNIT: Interacts with MAPT/TAU. {ECO:0000250|UniProtKB:Q9P0L2}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:9108484}. Cytoplasm {ECO:0000250|UniProtKB:Q9P0L2}.
CC Cell projection, dendrite {ECO:0000250|UniProtKB:Q9P0L2}. Note=Appears
CC to localize to an intracellular network.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and spleen and at lower
CC levels in kidney and skeletal muscle. {ECO:0000269|PubMed:9108484}.
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 -!- DOMAIN: The KA1 domain mediates binding to phospholipids and targeting
CC to membranes. Binds phosphatidic acid (PA), phosphatidylserine (PtdSer)
CC and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation at Thr-613 by PRKCZ/aPKC in polarized epithelial
CC cells inhibits the kinase activity (By similarity). Phosphorylated at
CC Thr-215 by STK11/LKB1 in complex with STE20-related adapter-alpha
CC (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-215 by TAOK1
CC activates the kinase activity, leading to phosphorylation and
CC detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-219 by
CC GSK3-beta (GSK3B) inhibits the kinase activity. {ECO:0000250,
CC ECO:0000269|PubMed:14517247, ECO:0000269|PubMed:9108484}.
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; Z83868; CAB06294.1; -; mRNA.
DR RefSeq; NP_446399.1; NM_053947.1.
DR AlphaFoldDB; O08678; -.
DR SMR; O08678; -.
DR BioGRID; 250617; 1.
DR STRING; 10116.ENSRNOP00000003198; -.
DR iPTMnet; O08678; -.
DR PhosphoSitePlus; O08678; -.
DR PaxDb; O08678; -.
DR PRIDE; O08678; -.
DR GeneID; 117016; -.
DR KEGG; rno:117016; -.
DR UCSC; RGD:619882; rat.
DR CTD; 4139; -.
DR RGD; 619882; Mark1.
DR VEuPathDB; HostDB:ENSRNOG00000002339; -.
DR eggNOG; KOG0586; Eukaryota.
DR HOGENOM; CLU_000288_157_5_1; -.
DR InParanoid; O08678; -.
DR OMA; DWVIFED; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; O08678; -.
DR PRO; PR:O08678; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000002339; Expressed in frontal cortex and 20 other tissues.
DR ExpressionAtlas; O08678; baseline and differential.
DR Genevisible; O08678; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; NAS:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; ISS:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:RGD.
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:0050321; F:tau-protein kinase activity; IDA:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0051654; P:establishment of mitochondrion localization; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IDA:RGD.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0001764; P:neuron migration; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050773; P:regulation of dendrite development; ISO:RGD.
DR GO; GO:0010975; P:regulation of neuron projection development; ISO:RGD.
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; IPR033627; MARK1.
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 PANTHER; PTHR24346:SF21; PTHR24346:SF21; 1.
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 ATP-binding; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton;
KW Kinase; Lipid-binding; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Wnt signaling pathway.
FT CHAIN 1..793
FT /note="Serine/threonine-protein kinase MARK1"
FT /id="PRO_0000086300"
FT DOMAIN 60..311
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 329..370
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 744..793
FT /note="KA1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00565"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 377..499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 517..697
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 22..40
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 381..423
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..459
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 485..499
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 517..563
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 586..614
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 679..697
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 182
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 66..74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H0K1,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:9108484"
FT MOD_RES 5
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9P0L2"
FT MOD_RES 208
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9P0L2"
FT MOD_RES 215
FT /note="Phosphothreonine; by LKB1 and TAOK1"
FT /evidence="ECO:0000269|PubMed:14517247,
FT ECO:0000269|PubMed:9108484"
FT MOD_RES 219
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:14517247,
FT ECO:0000269|PubMed:9108484"
FT MOD_RES 382
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT MOD_RES 390
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P0L2"
FT MOD_RES 423
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 475
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT MOD_RES 588
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9P0L2"
FT MOD_RES 613
FT /note="Phosphothreonine; by PKC/PRKCZ"
FT /evidence="ECO:0000250"
FT MOD_RES 666
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHJ5"
FT MUTAGEN 89
FT /note="K->R: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:9108484"
FT MUTAGEN 215
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:9108484"
FT MUTAGEN 215
FT /note="T->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:14517247,
FT ECO:0000269|PubMed:9108484"
FT MUTAGEN 215
FT /note="T->E: Induces an increase of the basal
FT serine/threonine-protein kinase activity."
FT /evidence="ECO:0000269|PubMed:14517247,
FT ECO:0000269|PubMed:9108484"
FT MUTAGEN 219
FT /note="S->A,E: Loss of activity."
FT /evidence="ECO:0000269|PubMed:14517247,
FT ECO:0000269|PubMed:9108484"
FT MUTAGEN 219
FT /note="S->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:14517247,
FT ECO:0000269|PubMed:9108484"
SQ SEQUENCE 793 AA; 88235 MW; C5BCCACE0BB9A0A3 CRC64;
MSARTPLPTV NERDTENHTS VDGYTETHIP PTKSSSRQNI PRCRNSITSA TDEQPHIGNY
RLQKTIGKGN FAKVKLARHV LTGREVAVKI IDKTQLNPTS LQKLFREVRI MKILNHPNIV
KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR AKFRQIVSAV QYCHQKCIVH
RDLKAENLLL DADMNIKIAD FGFSNEFTVG NKLDTFCGSP PYAAPELFQG KKYDGPEVDV
WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRVPFYM STDCENLLKK LLVLNPIKRG
SLEQIMKDRW MNVGHEEEEL KPYSEPELDL NDAKRIDIMV TMGFARDEIN DALVSQKYDE
VMATYILLGR KPPEFEGGES LSSGNLCQRS RPSSDLNNST LQSPAHLKVQ RSISANQKQR
RFSDHAGPSI PPAVSYTKRP QANSVESEQK EEWDKDTARR LGSTTVGSKS EVTASPLVGP
DRKKSSAGPS NNVYSGGSMT RRNTYVCERS TDRYAALQNG RDSSLTEMSA SSMSSTGSTV
ASAGPSARPR HQKSMSTSGH PIKVTLPTIK DGSEAYRPGT AQRVPAASPS AHSISASTPD
RTRFPRGSSS RSTFHGEQLR ERRSAAYSGP PASPSHDTAA LAHARRGTST GIISKITSKF
VRRDPSEGEA SGRTDTARGS SGEPKDKEEG KEAKPRSLRF TWSMKTTSSM DPNDMVREIR
KVLDANTCDY EQRERFLLFC VHGDARQDSL VQWEMEVCKL PRLSLNGVRF KRISGTSIAF
KNIASKIANE LKL
