MARCS_MOUSE
ID MARCS_MOUSE Reviewed; 309 AA.
AC P26645;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Myristoylated alanine-rich C-kinase substrate;
DE Short=MARCKS;
GN Name=Marcks; Synonyms=Macs;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Macrophage;
RX PubMed=2006186; DOI=10.1073/pnas.88.6.2505;
RA Seykora J.T., Ravetch J.V., Aderem A.;
RT "Cloning and molecular characterization of the murine macrophage '68-kDa'
RT protein kinase C substrate and its regulation by bacterial
RT lipopolysaccharide.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:2505-2509(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Fibroblast;
RX PubMed=1868832; DOI=10.1002/j.1460-2075.1991.tb07789.x;
RA Brooks S.F., Herget T., Erusalimsky J.D., Rozengurt E.;
RT "Protein kinase C activation potently down-regulates the expression of its
RT major substrate, 80K, in Swiss 3T3 cells.";
RL EMBO J. 10:2497-2505(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 131-145 AND 170-186, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP PARTIAL PROTEIN SEQUENCE.
RC STRAIN=SWR/J; TISSUE=Fibroblast;
RX PubMed=2384168; DOI=10.1016/0014-5793(90)81030-r;
RA Brooks S.F., Erusalimsky J.D., Totty N.F., Rozengurt E.;
RT "Purification and internal amino acid sequence of the 80 kDa protein kinase
RT C substrate from Swiss 3T3 fibroblasts. Homology with substrates from
RT brain.";
RL FEBS Lett. 268:291-295(1990).
RN [6]
RP PROTEIN SEQUENCE OF 102-130, PHOSPHORYLATION AT SER-113, AND MUTAGENESIS OF
RP SER-113.
RX PubMed=8849678; DOI=10.1016/0014-5793(96)00991-x;
RA Schoenwasser D.C., Palmer R.H., Herget T., Parker P.J.;
RT "p42 MAPK phosphorylates 80 kDa MARCKS at Ser-113.";
RL FEBS Lett. 395:1-5(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 182-301.
RX PubMed=1396720; DOI=10.1111/j.1432-1033.1992.tb17255.x;
RA Herget T., Brooks S.F., Broad S., Rozengurt E.;
RT "Relationship between the major protein kinase C substrates acidic 80-kDa
RT protein-kinase-C substrate (80K) and myristoylated alanine-rich C-kinase
RT substrate (MARCKS). Members of a gene family or equivalent genes in
RT different species.";
RL Eur. J. Biochem. 209:7-14(1992).
RN [8]
RP PHOSPHORYLATION AT SER-152; SER-156 AND SER-163.
RX PubMed=7588787; DOI=10.1111/j.1432-1033.1995.448_2.x;
RA Herget T., Oehrlein S.A., Pappin D.J.C., Rozengurt E., Parker P.J.;
RT "The myristoylated alanine-rich C-kinase substrate (MARCKS) is sequentially
RT phosphorylated by conventional, novel and atypical isotypes of protein
RT kinase C.";
RL Eur. J. Biochem. 233:448-457(1995).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46 AND SER-246, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-15; SER-27; SER-46; SER-138;
RP SER-140; SER-141; THR-143 AND SER-171, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 148-166 IN COMPLEX WITH
RP CALMODULIN.
RX PubMed=12577052; DOI=10.1038/nsb900;
RA Yamauchi E., Nakatsu T., Matsubara M., Kato H., Taniguchi H.;
RT "Crystal structure of a MARCKS peptide containing the calmodulin-binding
RT domain in complex with Ca2+-calmodulin.";
RL Nat. Struct. Biol. 10:226-231(2003).
CC -!- FUNCTION: MARCKS is the most prominent cellular substrate for protein
CC kinase C. This protein binds calmodulin, actin, and synapsin. MARCKS is
CC a filamentous (F) actin cross-linking protein.
CC -!- INTERACTION:
CC P26645; P62158: CALM3; Xeno; NbExp=2; IntAct=EBI-911805, EBI-397435;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000305}. Membrane
CC {ECO:0000250|UniProtKB:P29966}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P29966}.
CC -!- TISSUE SPECIFICITY: Brain, spleen, less in kidney and heart, and very
CC low levels in liver.
CC -!- INDUCTION: By lipopolysaccharides (LPS).
CC -!- PTM: Phosphorylation by PKC displaces MARCKS from the membrane. It also
CC inhibits the F-actin cross-linking activity.
CC {ECO:0000269|PubMed:7588787, ECO:0000269|PubMed:8849678}.
CC -!- SIMILARITY: Belongs to the MARCKS family. {ECO:0000305}.
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DR EMBL; M60474; AAA39491.1; -; mRNA.
DR EMBL; BC046601; AAH46601.1; -; mRNA.
DR CCDS; CCDS23784.1; -.
DR PIR; A39169; A39169.
DR RefSeq; NP_032564.1; NM_008538.2.
DR PDB; 1IWQ; X-ray; 2.00 A; B=148-166.
DR PDBsum; 1IWQ; -.
DR AlphaFoldDB; P26645; -.
DR BioGRID; 201268; 13.
DR IntAct; P26645; 4.
DR MINT; P26645; -.
DR STRING; 10090.ENSMUSP00000090245; -.
DR iPTMnet; P26645; -.
DR PhosphoSitePlus; P26645; -.
DR SwissPalm; P26645; -.
DR CPTAC; non-CPTAC-4045; -.
DR EPD; P26645; -.
DR jPOST; P26645; -.
DR MaxQB; P26645; -.
DR PaxDb; P26645; -.
DR PeptideAtlas; P26645; -.
DR PRIDE; P26645; -.
DR ProteomicsDB; 287311; -.
DR TopDownProteomics; P26645; -.
DR Antibodypedia; 72851; 915 antibodies from 43 providers.
DR DNASU; 17118; -.
DR Ensembl; ENSMUST00000092584; ENSMUSP00000090245; ENSMUSG00000069662.
DR GeneID; 17118; -.
DR KEGG; mmu:17118; -.
DR UCSC; uc007evg.1; mouse.
DR CTD; 4082; -.
DR MGI; MGI:96907; Marcks.
DR VEuPathDB; HostDB:ENSMUSG00000069662; -.
DR eggNOG; ENOG502RB4V; Eukaryota.
DR GeneTree; ENSGT00730000111419; -.
DR HOGENOM; CLU_073091_0_1_1; -.
DR InParanoid; P26645; -.
DR OMA; HAHQPAK; -.
DR OrthoDB; 1636177at2759; -.
DR TreeFam; TF332815; -.
DR Reactome; R-MMU-399997; Acetylcholine regulates insulin secretion.
DR BioGRID-ORCS; 17118; 6 hits in 73 CRISPR screens.
DR ChiTaRS; Marcks; mouse.
DR EvolutionaryTrace; P26645; -.
DR PRO; PR:P26645; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P26645; protein.
DR Bgee; ENSMUSG00000069662; Expressed in rostral migratory stream and 259 other tissues.
DR Genevisible; P26645; MM.
DR GO; GO:0032432; C:actin filament bundle; IDA:CAFA.
DR GO; GO:0099025; C:anchored component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0099026; C:anchored component of presynaptic membrane; ISO:MGI.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0032059; C:bleb; ISO:MGI.
DR GO; GO:0005938; C:cell cortex; IDA:MGI.
DR GO; GO:0005813; C:centrosome; IDA:MGI.
DR GO; GO:0033391; C:chromatoid body; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0044307; C:dendritic branch; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0042585; C:germinal vesicle; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0043226; C:organelle; IDA:MGI.
DR GO; GO:0001520; C:outer dense fiber; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0099571; C:postsynaptic cytoskeleton; ISO:MGI.
DR GO; GO:0099523; C:presynaptic cytosol; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0051015; F:actin filament binding; IPI:CAFA.
DR GO; GO:0005516; F:calmodulin binding; IPI:CAFA.
DR GO; GO:0042802; F:identical protein binding; IDA:CAFA.
DR GO; GO:0001786; F:phosphatidylserine binding; ISO:MGI.
DR GO; GO:0005543; F:phospholipid binding; ISO:MGI.
DR GO; GO:0005080; F:protein kinase C binding; IPI:BHF-UCL.
DR GO; GO:0051764; P:actin crosslink formation; IDA:CAFA.
DR GO; GO:0051017; P:actin filament bundle assembly; IDA:CAFA.
DR GO; GO:0007015; P:actin filament organization; ISO:MGI.
DR GO; GO:0031584; P:activation of phospholipase D activity; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0031589; P:cell-substrate adhesion; ISO:MGI.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; ISO:MGI.
DR GO; GO:0007005; P:mitochondrion organization; IDA:MGI.
DR GO; GO:0021915; P:neural tube development; IMP:MGI.
DR GO; GO:0022008; P:neurogenesis; IMP:MGI.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; ISO:MGI.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:1900020; P:positive regulation of protein kinase C activity; ISO:MGI.
DR GO; GO:1905274; P:regulation of modification of postsynaptic actin cytoskeleton; ISO:MGI.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:MGI.
DR DisProt; DP00253; -.
DR InterPro; IPR002101; MARCKS.
DR PANTHER; PTHR14353; PTHR14353; 1.
DR Pfam; PF02063; MARCKS; 1.
DR PRINTS; PR00963; MARCKS.
DR PROSITE; PS00826; MARCKS_1; 1.
DR PROSITE; PS00827; MARCKS_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Calmodulin-binding; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Lipoprotein; Membrane; Myristate;
KW Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P12624"
FT CHAIN 2..309
FT /note="Myristoylated alanine-rich C-kinase substrate"
FT /id="PRO_0000157149"
FT REGION 1..309
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 145..169
FT /note="Calmodulin-binding (PSD)"
FT COMPBIAS 118..134
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 163..183
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..309
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 15
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29966"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29966"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29966"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30009"
FT MOD_RES 79
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P30009"
FT MOD_RES 113
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000269|PubMed:8849678"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30009"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12624"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 143
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 152
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:7588787"
FT MOD_RES 156
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:7588787"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12624"
FT MOD_RES 163
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:7588787,
FT ECO:0007744|PubMed:19131326"
FT MOD_RES 171
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29966"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P29966"
FT MUTAGEN 113
FT /note="S->A: Poorly phosphorylated."
FT /evidence="ECO:0000269|PubMed:8849678"
FT CONFLICT 96..98
FT /note="AGA -> TGT (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 157..162
FT /evidence="ECO:0007829|PDB:1IWQ"
SQ SEQUENCE 309 AA; 29661 MW; 3BB1E392D74B5A98 CRC64;
MGAQFSKTAA KGEATAERPG EAAVASSPSK ANGQENGHVK VNGDASPAAA EPGAKEELQA
NGSAPAADKE EPASGSAATP AAAEKDEAAA ATEPGAGAAD KEAAEAEPAE PSSPAAEAEG
ASASSTSSPK AEDGAAPSPS SETPKKKKKR FSFKKSFKLS GFSFKKSKKE SGEGAEAEGA
TAEGAKDEAA AAAGGEGAAA PGEQAGGAGA EGAAGGEPRE AEAAEPEQPE QPEQPAAEEP
QAEEQSEAAG EKAEEPAPGA TAGDASSAAG PEQEAPAATD EAAASAAPAA SPEPQPECSP
EAPPAPTAE
