PPM1B_MOUSE
ID PPM1B_MOUSE Reviewed; 390 AA.
AC P36993;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Protein phosphatase 1B;
DE EC=3.1.3.16;
DE AltName: Full=Protein phosphatase 2C isoform beta;
DE Short=PP2C-beta;
GN Name=Ppm1b; Synonyms=Pp2c2, Pppm1b;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=8274020; DOI=10.1006/abbi.1993.1598;
RA Terasawa T., Kobayashi T., Murakami T., Ohnishi M., Kato S., Tanaka O.,
RA Kondo H., Yamamoto H., Takeuchi T., Tamura S.;
RT "Molecular cloning of a novel isotype of Mg(2+)-dependent protein
RT phosphatase beta (type 2C beta) enriched in brain and heart.";
RL Arch. Biochem. Biophys. 307:342-349(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
RC TISSUE=Testis;
RX PubMed=7733667; DOI=10.1006/abbi.1995.1244;
RA Kato S., Terasawa T., Kobayashi T., Ohnishi M., Sasahara Y., Kusuda K.,
RA Yanagawa Y., Hiraga A., Matsui Y., Tamura S.;
RT "Molecular cloning and expression of mouse Mg(2+)-dependent protein
RT phosphatase beta-4 (type 2C beta-4).";
RL Arch. Biochem. Biophys. 318:387-393(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Testis;
RX PubMed=8038726;
RA Hou E.W., Kawai Y., Miyasaka H., Li S.S.;
RT "Molecular cloning and expression of cDNAs encoding two isoforms of protein
RT phosphatase 2C beta from mouse testis.";
RL Biochem. Mol. Biol. Int. 32:773-780(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=10469137; DOI=10.1046/j.1432-1327.1999.00580.x;
RA Ohnishi M., Chida N., Kobayashi T., Wang H., Ikeda S., Hanada M.,
RA Yanagawa Y., Katsura K., Hiraga A., Tamura S.;
RT "Alternative promoters direct tissue-specific expression of the mouse
RT protein phosphatase 2Cbeta gene.";
RL Eur. J. Biochem. 263:736-745(1999).
RN [5]
RP IDENTIFICATION BY MASS 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 [6]
RP SUBCELLULAR LOCATION.
RX PubMed=22781750; DOI=10.1016/j.cellsig.2012.07.003;
RA Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.;
RT "Protein phosphatase 5 modulates SMAD3 function in the transforming growth
RT factor-beta pathway.";
RL Cell. Signal. 24:1999-2006(2012).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND MYRISTOYLATION AT GLY-2.
RX PubMed=23088624; DOI=10.1042/bj20121201;
RA Chida T., Ando M., Matsuki T., Masu Y., Nagaura Y., Takano-Yamamoto T.,
RA Tamura S., Kobayashi T.;
RT "N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to
RT dephosphorylate their physiological substrates in cells.";
RL Biochem. J. 449:741-749(2013).
CC -!- FUNCTION: Enzyme with a broad specificity. Dephosphorylates PRKAA1 and
CC PRKAA2. Inhibits TBK1-mediated antiviral signaling by dephosphorylating
CC it at 'Ser-172'. Plays an important role in the termination of TNF-
CC alpha-mediated NF-kappa-B activation through dephosphorylating and
CC inactivating IKBKB/IKKB. {ECO:0000269|PubMed:23088624}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:83421; EC=3.1.3.16;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61977; EC=3.1.3.16;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 2 magnesium or manganese ions per subunit. {ECO:0000250};
CC -!- SUBUNIT: Monomer. Interacts with PAK6 (By similarity). Interacts with
CC the phosphorylated form of IKBKB/IKKB (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:22781750,
CC ECO:0000269|PubMed:23088624}. Membrane {ECO:0000269|PubMed:23088624};
CC Lipid-anchor {ECO:0000269|PubMed:23088624}. Note=Weakly associates at
CC the membrane and N-myristoylation mediates the membrane localization.
CC {ECO:0000269|PubMed:23088624}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Beta-1 {ECO:0000303|PubMed:8274020};
CC IsoId=P36993-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta-3 {ECO:0000303|PubMed:7733667};
CC IsoId=P36993-3; Sequence=VSP_005090;
CC Name=3; Synonyms=Beta-4 {ECO:0000303|PubMed:7733667};
CC IsoId=P36993-4; Sequence=VSP_005091;
CC Name=4; Synonyms=Beta-5 {ECO:0000303|PubMed:7733667};
CC IsoId=P36993-5; Sequence=VSP_005092;
CC -!- TISSUE SPECIFICITY: Isoform 1: Expressed ubiquitously. Isoform 2:
CC Expressed exclusively in testis and intestine. Isoform 3: Expressed
CC exclusively in brain and intestine. Isoform 4: Expressed exclusively in
CC testis and intestine.
CC -!- PTM: Isgylation negatively regulates its activity. {ECO:0000250}.
CC -!- PTM: N-myristoylation is essential for the recognition of its
CC substrates for dephosphorylation. {ECO:0000269|PubMed:23088624}.
CC -!- SIMILARITY: Belongs to the PP2C family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA04234.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; D17411; BAA04233.1; -; mRNA.
DR EMBL; D17412; BAA04234.1; ALT_SEQ; mRNA.
DR EMBL; D45859; BAA08293.1; -; mRNA.
DR EMBL; D45860; BAA08294.1; -; mRNA.
DR EMBL; D45861; BAA08295.1; -; mRNA.
DR EMBL; U09218; AAB60442.1; -; mRNA.
DR EMBL; AB007798; BAA84471.1; -; Genomic_DNA.
DR CCDS; CCDS37710.1; -. [P36993-1]
DR CCDS; CCDS50200.1; -. [P36993-3]
DR CCDS; CCDS50201.1; -. [P36993-4]
DR PIR; I49016; I49016.
DR PIR; S65672; S65672.
DR RefSeq; NP_001152969.1; NM_001159497.1. [P36993-4]
DR RefSeq; NP_001152970.1; NM_001159498.1. [P36993-3]
DR RefSeq; NP_035281.1; NM_011151.2. [P36993-1]
DR RefSeq; XP_006523924.1; XM_006523861.3. [P36993-3]
DR RefSeq; XP_006523925.1; XM_006523862.3. [P36993-4]
DR RefSeq; XP_011244625.1; XM_011246323.1.
DR AlphaFoldDB; P36993; -.
DR SMR; P36993; -.
DR BioGRID; 202333; 9.
DR STRING; 10090.ENSMUSP00000079107; -.
DR iPTMnet; P36993; -.
DR PhosphoSitePlus; P36993; -.
DR EPD; P36993; -.
DR jPOST; P36993; -.
DR MaxQB; P36993; -.
DR PaxDb; P36993; -.
DR PeptideAtlas; P36993; -.
DR PRIDE; P36993; -.
DR ProteomicsDB; 289810; -. [P36993-1]
DR ProteomicsDB; 289812; -. [P36993-3]
DR ProteomicsDB; 289813; -. [P36993-4]
DR ProteomicsDB; 289814; -. [P36993-5]
DR DNASU; 19043; -.
DR Ensembl; ENSMUST00000112304; ENSMUSP00000107923; ENSMUSG00000061130. [P36993-1]
DR Ensembl; ENSMUST00000112305; ENSMUSP00000107924; ENSMUSG00000061130. [P36993-4]
DR Ensembl; ENSMUST00000112307; ENSMUSP00000107926; ENSMUSG00000061130. [P36993-3]
DR Ensembl; ENSMUST00000234332; ENSMUSP00000157013; ENSMUSG00000061130. [P36993-4]
DR Ensembl; ENSMUST00000234540; ENSMUSP00000157282; ENSMUSG00000061130. [P36993-3]
DR Ensembl; ENSMUST00000234851; ENSMUSP00000157058; ENSMUSG00000061130. [P36993-5]
DR GeneID; 19043; -.
DR KEGG; mmu:19043; -.
DR UCSC; uc008dth.2; mouse. [P36993-1]
DR UCSC; uc008dti.2; mouse. [P36993-4]
DR UCSC; uc008dtj.2; mouse. [P36993-3]
DR UCSC; uc008dtk.2; mouse. [P36993-5]
DR CTD; 5495; -.
DR MGI; MGI:101841; Ppm1b.
DR VEuPathDB; HostDB:ENSMUSG00000061130; -.
DR eggNOG; KOG0697; Eukaryota.
DR GeneTree; ENSGT00940000156070; -.
DR HOGENOM; CLU_013173_4_0_1; -.
DR InParanoid; P36993; -.
DR OMA; IYDVMEN; -.
DR PhylomeDB; P36993; -.
DR Reactome; R-MMU-1169408; ISG15 antiviral mechanism.
DR BioGRID-ORCS; 19043; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Ppm1b; mouse.
DR PRO; PR:P36993; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P36993; protein.
DR Bgee; ENSMUSG00000061130; Expressed in retinal neural layer and 249 other tissues.
DR ExpressionAtlas; P36993; baseline and differential.
DR Genevisible; P36993; MM.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISO:MGI.
DR GO; GO:0006499; P:N-terminal protein myristoylation; IDA:UniProtKB.
DR GO; GO:0050687; P:negative regulation of defense response to virus; ISS:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0032688; P:negative regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; ISO:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; IMP:UniProtKB.
DR CDD; cd00143; PP2Cc; 1.
DR Gene3D; 1.10.10.430; -; 1.
DR Gene3D; 3.60.40.10; -; 1.
DR InterPro; IPR000222; PP2C_BS.
DR InterPro; IPR012911; PP2C_C.
DR InterPro; IPR036580; PP2C_C_sf.
DR InterPro; IPR036457; PPM-type_dom_sf.
DR InterPro; IPR001932; PPM-type_phosphatase_dom.
DR Pfam; PF00481; PP2C; 1.
DR Pfam; PF07830; PP2C_C; 1.
DR SMART; SM00332; PP2Cc; 1.
DR SUPFAM; SSF81601; SSF81601; 1.
DR SUPFAM; SSF81606; SSF81606; 1.
DR PROSITE; PS01032; PPM_1; 1.
DR PROSITE; PS51746; PPM_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Hydrolase; Isopeptide bond; Lipoprotein;
KW Magnesium; Manganese; Membrane; Metal-binding; Myristate; Phosphoprotein;
KW Protein phosphatase; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:23088624"
FT CHAIN 2..390
FT /note="Protein phosphatase 1B"
FT /id="PRO_0000057747"
FT DOMAIN 23..295
FT /note="PPM-type phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01082"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 371..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..16
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 60
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 60
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O75688"
FT BINDING 61
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 243
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O75688"
FT BINDING 286
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O75688"
FT MOD_RES 386
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75688"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:23088624"
FT CROSSLNK 12
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ISG15)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 379..390
FT /note="GAGDLEDSLVAL -> FYQPSIAYSDNVFLL (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_005090"
FT VAR_SEQ 379..390
FT /note="GAGDLEDSLVAL -> MADLSTSICKPS (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_005091"
FT VAR_SEQ 388..390
FT /note="VAL -> FYQPSIAYSDNVFLL (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_005092"
SQ SEQUENCE 390 AA; 42795 MW; 255C97B4276189FD CRC64;
MGAFLDKPKT EKHNAHGAGN GLRYGLSSMQ GWRVEMEDAH TAVVGIPHGL DNWSFFAVYD
GHAGSRVANY CSTHLLEHIT TNEDFRAADK SGSALEPSVE SVKTGIRTGF LKIDEYMRNF
SDLRNGMDRS GSTAVGVMVS PTHMYFINCG DSRAVLCRNG QVCFSTQDHK PCNPVEKERI
QNAGGSVMIQ RVNGSLAVSR ALGDYDYKCV DGKGPTEQLV SPEPEVYEIV RAEEDEFVVL
ACDGIWDVMS NEELCEFVKS RLEVSDDLEN VCNWVVDTCL HKGSRDNMSV VLVCFSNAPK
VSEEAVKRDS ELDKHLESRV EEIMQKSGEE GMPDLAHVMR ILSAENIPNL PPGGGLAGKR
HVIEAVYSRL NPHKDNDGGA GDLEDSLVAL
