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   14-OCT-2015, entry version 141.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; 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-
RT   kDa' 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;
RA   Brooks S.F., Herget T., Erusalimsky J.D., Rozengurt E.;
RT   "Protein kinase C activation potently down-regulates the expression of
RT   its 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
RT   project: 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/6; TISSUE=Brain;
RA   Lubec G., Kang S.U.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [5]
RP   PARTIAL PROTEIN SEQUENCE.
RC   STRAIN=Swiss; 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
RT   kinase C substrate from Swiss 3T3 fibroblasts. Homology with
RT   substrates from brain.";
RL   FEBS Lett. 268:291-295(1990).
RN   [6]
RP   PROTEIN SEQUENCE OF 102-130, PHOSPHORYLATION AT SER-113, AND
RP   MUTAGENESIS OF 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-
RT   kDa protein-kinase-C substrate (80K) and myristoylated alanine-rich C-
RT   kinase substrate (MARCKS). Members of a gene family or equivalent
RT   genes in 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
RT   sequentially phosphorylated by conventional, novel and atypical
RT   isotypes of protein 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
RP   BY 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
RT   electron 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;
RP   SER-138; SER-140; SER-141; THR-143 AND SER-171, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, 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
RT   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-
RT   binding domain in complex with Ca2+-calmodulin.";
RL   Nat. Struct. Biol. 10:226-231(2003).
CC   -!- FUNCTION: MARCKS is the most prominent cellular substrate for
CC       protein kinase C. This protein binds calmodulin, actin, and
CC       synapsin. MARCKS is a filamentous (F) actin cross-linking protein.
CC   -!- INTERACTION:
CC       P62158:CALM3 (xeno); NbExp=2; IntAct=EBI-911805, EBI-397435;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000305}.
CC       Membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Brain, spleen, less in kidney and heart, and
CC       very low levels in liver.
CC   -!- INDUCTION: By lipopolysaccharides (LPS).
CC   -!- PTM: Phosphorylation by PKC displaces MARCKS from the membrane. It
CC       also 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   UniGene; Mm.30059; -.
DR   PDB; 1IWQ; X-ray; 2.00 A; B=148-166.
DR   PDBsum; 1IWQ; -.
DR   DisProt; DP00253; -.
DR   ProteinModelPortal; P26645; -.
DR   BioGrid; 201268; 8.
DR   IntAct; P26645; 2.
DR   MINT; MINT-4101028; -.
DR   STRING; 10090.ENSMUSP00000090245; -.
DR   PhosphoSite; P26645; -.
DR   MaxQB; P26645; -.
DR   PaxDb; P26645; -.
DR   PRIDE; P26645; -.
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   eggNOG; NOG44640; -.
DR   GeneTree; ENSGT00730000111419; -.
DR   HOGENOM; HOG000113482; -.
DR   InParanoid; P26645; -.
DR   KO; K12561; -.
DR   OMA; DSAAFRI; -.
DR   OrthoDB; EOG7P2XW3; -.
DR   TreeFam; TF332815; -.
DR   Reactome; R-MMU-399997; Acetylcholine regulates insulin secretion.
DR   ChiTaRS; Marcks; mouse.
DR   EvolutionaryTrace; P26645; -.
DR   NextBio; 291280; -.
DR   PRO; PR:P26645; -.
DR   Proteomes; UP000000589; Chromosome 10.
DR   Bgee; P26645; -.
DR   Genevisible; P26645; MM.
DR   GO; GO:0005938; C:cell cortex; IDA:MGI.
DR   GO; GO:0005813; C:centrosome; IDA:MGI.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0070062; C:extracellular exosome; IEA:Ensembl.
DR   GO; GO:0005925; C:focal adhesion; IEA:Ensembl.
DR   GO; GO:0042585; C:germinal vesicle; IDA:MGI.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0005080; F:protein kinase C binding; IPI:BHF-UCL.
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; Complete proteome;
KW   Cytoplasm; Cytoskeleton; Direct protein sequencing; Lipoprotein;
KW   Membrane; Myristate; Phosphoprotein; Reference proteome.
FT   INIT_MET      1      1       Removed. {ECO:0000250|UniProtKB:P12624}.
FT   CHAIN         2    309       Myristoylated alanine-rich C-kinase
FT                                substrate.
FT                                /FTId=PRO_0000157149.
FT   REGION      145    169       Calmodulin-binding (PSD).
FT   MOD_RES      15     15       Phosphothreonine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES      26     26       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P29966}.
FT   MOD_RES      27     27       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES      29     29       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P29966}.
FT   MOD_RES      46     46       Phosphoserine.
FT                                {ECO:0000244|PubMed:15345747,
FT                                ECO:0000244|PubMed:21183079}.
FT   MOD_RES      63     63       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P29966}.
FT   MOD_RES      74     74       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P30009}.
FT   MOD_RES      79     79       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:P30009}.
FT   MOD_RES     113    113       Phosphoserine; by MAPK.
FT                                {ECO:0000269|PubMed:8849678}.
FT   MOD_RES     122    122       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P30009}.
FT   MOD_RES     128    128       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P12624}.
FT   MOD_RES     138    138       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES     140    140       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES     141    141       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES     143    143       Phosphothreonine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES     152    152       Phosphoserine; by PKC.
FT                                {ECO:0000269|PubMed:7588787}.
FT   MOD_RES     156    156       Phosphoserine; by PKC.
FT                                {ECO:0000269|PubMed:7588787}.
FT   MOD_RES     160    160       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P12624}.
FT   MOD_RES     163    163       Phosphoserine; by PKC.
FT                                {ECO:0000244|PubMed:19131326,
FT                                ECO:0000269|PubMed:7588787}.
FT   MOD_RES     171    171       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES     246    246       Phosphoserine.
FT                                {ECO:0000244|PubMed:15345747}.
FT   MOD_RES     291    291       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P29966}.
FT   LIPID         2      2       N-myristoyl glycine. {ECO:0000250}.
FT   MUTAGEN     113    113       S->A: Poorly phosphorylated.
FT                                {ECO:0000269|PubMed:8849678}.
FT   CONFLICT     96     98       AGA -> TGT (in Ref. 2; AA sequence).
FT                                {ECO:0000305}.
FT   HELIX       157    162       {ECO:0000244|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
//