MARK3_RAT
ID MARK3_RAT Reviewed; 797 AA.
AC Q8VHF0;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=MAP/microtubule affinity-regulating kinase 3;
DE EC=2.7.11.1;
GN Name=Mark3;
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]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Drewes G.;
RT "Characterization of a third microtubule affinity-regulating kinase from
RT rat brain.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-374 AND SER-469, AND
RP 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).
CC -!- FUNCTION: Serine/threonine-protein kinase. Involved in the specific
CC phosphorylation of microtubule-associated proteins for MAPT/TAU, MAP2
CC and MAP4. Phosphorylates CDC25C. Regulates localization and activity of
CC some histone deacetylases by mediating phosphorylation of HDAC7,
CC promoting subsequent interaction between HDAC7 and 14-3-3 and export
CC from the nucleus. Negatively regulates the Hippo signaling pathway and
CC antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to
CC inhibit the kinase activity of STK3/MST2 toward LATS1.
CC {ECO:0000250|UniProtKB:P27448}.
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 -!- 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;
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-211. Inhibited
CC by phosphorylation on Thr-617 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with MAPT/TAU. Interacts with DLG5 (via coiled-coil
CC domain). Interacts with STK3/MST2 and STK4/MST1 in the presence of
CC DLG5. Interacts with YWHAB, YWHAG, YWHAQ and YWHAZ (By similarity).
CC {ECO:0000250|UniProtKB:P27448}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P27448};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P27448}. Cell
CC projection, dendrite {ECO:0000250|UniProtKB:P27448}. Cytoplasm
CC {ECO:0000250|UniProtKB:P27448}.
CC -!- PTM: Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-
CC related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation
CC at Thr-617 by PRKCZ/aPKC inhibits the kinase activity (By similarity).
CC {ECO:0000250}.
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; AF465412; AAL69981.1; -; mRNA.
DR RefSeq; NP_570105.1; NM_130749.1.
DR AlphaFoldDB; Q8VHF0; -.
DR SMR; Q8VHF0; -.
DR BioGRID; 250933; 1.
DR IntAct; Q8VHF0; 2.
DR STRING; 10116.ENSRNOP00000014395; -.
DR iPTMnet; Q8VHF0; -.
DR PhosphoSitePlus; Q8VHF0; -.
DR PaxDb; Q8VHF0; -.
DR PRIDE; Q8VHF0; -.
DR GeneID; 170577; -.
DR KEGG; rno:170577; -.
DR UCSC; RGD:619883; rat.
DR CTD; 4140; -.
DR RGD; 619883; Mark3.
DR eggNOG; KOG0586; Eukaryota.
DR InParanoid; Q8VHF0; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q8VHF0; -.
DR Reactome; R-RNO-5673000; RAF activation.
DR Reactome; R-RNO-5674135; MAP2K and MAPK activation.
DR Reactome; R-RNO-5675221; Negative regulation of MAPK pathway.
DR PRO; PR:Q8VHF0; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0050321; F:tau-protein kinase activity; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0035331; P:negative regulation of hippo signaling; ISS:UniProtKB.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; ISS:ARUK-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:ARUK-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; ISS:ARUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR001772; KA1_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR033628; MARK3.
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:SF1; PTHR24346:SF1; 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; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..797
FT /note="MAP/microtubule affinity-regulating kinase 3"
FT /id="PRO_0000086306"
FT DOMAIN 56..307
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 326..365
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 748..797
FT /note="KA1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00565"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 372..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 585..701
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..28
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 372..418
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 585..605
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 631..666
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 667..701
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 178
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 62..70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 85
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 211
FT /note="Phosphothreonine; by LKB1"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03141"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 400
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 593
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 596
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03141"
FT MOD_RES 602
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 617
FT /note="Phosphothreonine; by PKC/PRKCZ"
FT /evidence="ECO:0000250"
FT MOD_RES 636
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 654
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
FT MOD_RES 687
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27448"
SQ SEQUENCE 797 AA; 88751 MW; E9834D5DB613ED37 CRC64;
MSTRTPLPTV NERDTENHIS HGDGRQEVTS RTGRSGARCR NSIASCADEQ PHIGNYRLLK
TIGKGNFAKV KLARHILTGR EVAIKIIDKT QLNPTSLQKL FREVRIMKIL NHPNIVKLFE
VIETEKTLYL IMEYASGGEV FDYLVAHGRM KEKEARAKFR QIVSAVQYCH QKRIVHRDLK
AENLLLDADM NIKITDFGFS NEFTVGSKLD TFCGSPPYAA PELFQGKKYD GPEVDVWSLG
VILYTLVSGS LPFDGQNLKE LRERVLRGKY RIPFYMSTDC ENLLKRFLVL NPVKRGTLEQ
IMKDRWINAG HEEEELKPFV EPELDISDQK RIDIMVGMGY SQEEIQESLS KMKYDEITAT
YLLLGRKSAE LDASDSSSSS NLSLAKVRPS SDLSNSTGQS PHHKGQRSVS SSQKQRRYSD
HAGPAIPSVV AYPKRSQTST ADSDLKEDGV PSRKSGSSAV GGKGIAPASP MLGNASNPNK
ADIPERKKSP AVPSSNAASG GMTRRNTYVC SERCAADRHS VIQNGKESSL TEVFAYAASP
ASLCATSTCR LRHQRSMSVS ASGHPKMVLP PIDSEGDTFK AITTPDQRTP VASTHSISSA
TTPDRIRFPR GTASRSTFHG QPRERRTATY NGPPASPSLS HEATPLSQTR SRGSTNLFSK
LTSKLTRRLP TEYERNGRYE GSSRNVSSEQ KDENREAKPR SLRFTWSMKT TSSMDPSDMM
REIRKVLDAN TCDYEQRERF LLFCVHGDGH AESLVQWEME VCKLPRLSLN GVRFKRISGT
SIAFKNIASK IANELKL
