PPM1L_MOUSE
ID PPM1L_MOUSE Reviewed; 360 AA.
AC Q8BHN0; Q3UGL2; Q810H0; Q8C021; Q8C1D5; Q9Z0T1;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Protein phosphatase 1L;
DE EC=3.1.3.16;
DE AltName: Full=Protein phosphatase 1-like;
DE AltName: Full=Protein phosphatase 2C isoform epsilon;
DE Short=PP2C-epsilon;
GN Name=Ppm1l; Synonyms=Kiaa4175;
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), FUNCTION, INTERACTION WITH MAP3K7,
RP MUTAGENESIS OF HIS-130; ARG-239; ARG-241; ARG-265 AND ASP-302, AND TISSUE
RP SPECIFICITY.
RX PubMed=12556533; DOI=10.1074/jbc.m211474200;
RA Li M.G., Katsura K., Nomiyama H., Komaki K., Ninomiya-Tsuji J.,
RA Matsumoto K., Kobayashi T., Tamura S.;
RT "Regulation of the interleukin-1-induced signaling pathways by a novel
RT member of the protein phosphatase 2C family (PP2Cepsilon).";
RL J. Biol. Chem. 278:12013-12021(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RC TISSUE=Cerebellum, Corpora quadrigemina, Embryonic head, Melanocyte, and
RC Olfactory bulb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryonic brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 133-299 (ISOFORMS 1/2).
RC TISSUE=Lung;
RA Stothard P.M., Pilgrim D.;
RT "Isolation of PP2C sequences using degenerate-oligo PCR.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH MAP3K5.
RX PubMed=17456047; DOI=10.1042/bj20070231;
RA Saito J., Toriumi S., Awano K., Ichijo H., Sasaki K., Kobayashi T.,
RA Tamura S.;
RT "Regulation of apoptosis signal-regulating kinase 1 by protein phosphatase
RT 2Cepsilon.";
RL Biochem. J. 405:591-596(2007).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=18344982; DOI=10.1038/nature06757;
RA Chen Y., Zhu J., Lum P.Y., Yang X., Pinto S., MacNeil D.J., Zhang C.,
RA Lamb J., Edwards S., Sieberts S.K., Leonardson A., Castellini L.W.,
RA Wang S., Champy M.-F., Zhang B., Emilsson V., Doss S., Ghazalpour A.,
RA Horvath S., Drake T.A., Lusis A.J., Schadt E.E.;
RT "Variations in DNA elucidate molecular networks that cause disease.";
RL Nature 452:429-435(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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).
CC -!- FUNCTION: Acts as a suppressor of the SAPK signaling pathways by
CC associating with and dephosphorylating MAP3K7/TAK1 and MAP3K5, and by
CC attenuating the association between MAP3K7/TAK1 and MAP2K4 or MAP2K6.
CC {ECO:0000269|PubMed:12556533}.
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: Interacts with MAP3K7/TAK1 and MAP3K5.
CC {ECO:0000269|PubMed:12556533, ECO:0000269|PubMed:17456047}.
CC -!- INTERACTION:
CC Q8BHN0; Q9H3P7: ACBD3; Xeno; NbExp=3; IntAct=EBI-7970002, EBI-1791792;
CC Q8BHN0; P27448: MARK3; Xeno; NbExp=3; IntAct=EBI-7970002, EBI-707595;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BHN0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BHN0-2; Sequence=VSP_016928, VSP_016929;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, testis, liver, lung and
CC skeletal muscle. {ECO:0000269|PubMed:12556533}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit increased fat mass and higher plasma
CC glucose levels compared to wild type mice. Male mice also exhibit a
CC decrease in free fatty acids and higher blood pressure.
CC {ECO:0000269|PubMed:18344982}.
CC -!- SIMILARITY: Belongs to the PP2C family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO43055.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY184801; AAO43055.1; ALT_INIT; mRNA.
DR EMBL; AK028275; BAC25853.1; -; mRNA.
DR EMBL; AK032529; BAC27913.1; -; mRNA.
DR EMBL; AK035912; BAC29241.1; -; mRNA.
DR EMBL; AK045724; BAC32472.1; -; mRNA.
DR EMBL; AK131646; BAE20738.1; -; mRNA.
DR EMBL; AK147876; BAE28196.1; -; mRNA.
DR EMBL; AK220523; BAD90308.1; -; mRNA.
DR EMBL; BC096031; AAH96031.1; -; mRNA.
DR EMBL; AF117832; AAD17235.1; -; mRNA.
DR CCDS; CCDS17405.1; -. [Q8BHN0-1]
DR RefSeq; NP_848841.2; NM_178726.3. [Q8BHN0-1]
DR AlphaFoldDB; Q8BHN0; -.
DR SMR; Q8BHN0; -.
DR BioGRID; 232372; 2.
DR IntAct; Q8BHN0; 5.
DR MINT; Q8BHN0; -.
DR STRING; 10090.ENSMUSP00000029355; -.
DR iPTMnet; Q8BHN0; -.
DR PhosphoSitePlus; Q8BHN0; -.
DR EPD; Q8BHN0; -.
DR MaxQB; Q8BHN0; -.
DR PaxDb; Q8BHN0; -.
DR PeptideAtlas; Q8BHN0; -.
DR PRIDE; Q8BHN0; -.
DR ProteomicsDB; 289739; -. [Q8BHN0-1]
DR ProteomicsDB; 289740; -. [Q8BHN0-2]
DR Antibodypedia; 18529; 150 antibodies from 28 providers.
DR DNASU; 242083; -.
DR Ensembl; ENSMUST00000029355; ENSMUSP00000029355; ENSMUSG00000027784. [Q8BHN0-1]
DR GeneID; 242083; -.
DR KEGG; mmu:242083; -.
DR UCSC; uc008pmg.1; mouse. [Q8BHN0-1]
DR UCSC; uc008pmh.1; mouse. [Q8BHN0-2]
DR CTD; 151742; -.
DR MGI; MGI:2139740; Ppm1l.
DR VEuPathDB; HostDB:ENSMUSG00000027784; -.
DR eggNOG; KOG0698; Eukaryota.
DR GeneTree; ENSGT00940000157030; -.
DR HOGENOM; CLU_013173_11_0_1; -.
DR InParanoid; Q8BHN0; -.
DR OMA; ASKWCGS; -.
DR OrthoDB; 1044139at2759; -.
DR PhylomeDB; Q8BHN0; -.
DR TreeFam; TF332888; -.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR BioGRID-ORCS; 242083; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Ppm1l; mouse.
DR PRO; PR:Q8BHN0; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8BHN0; protein.
DR Bgee; ENSMUSG00000027784; Expressed in otolith organ and 258 other tissues.
DR Genevisible; Q8BHN0; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:MGI.
DR GO; GO:0000165; P:MAPK cascade; IPI:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; IBA:GO_Central.
DR GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IDA:MGI.
DR CDD; cd00143; PP2Cc; 1.
DR Gene3D; 3.60.40.10; -; 1.
DR InterPro; IPR015655; PP2C.
DR InterPro; IPR000222; PP2C_BS.
DR InterPro; IPR036457; PPM-type_dom_sf.
DR InterPro; IPR001932; PPM-type_phosphatase_dom.
DR PANTHER; PTHR13832; PTHR13832; 1.
DR Pfam; PF00481; PP2C; 1.
DR SMART; SM00331; PP2C_SIG; 1.
DR SMART; SM00332; PP2Cc; 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; Hydrolase; Magnesium; Manganese; Membrane;
KW Metal-binding; Protein phosphatase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..360
FT /note="Protein phosphatase 1L"
FT /id="PRO_0000057755"
FT TOPO_DOM 1..25
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 26..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 43..360
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 92..351
FT /note="PPM-type phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01082"
FT BINDING 128
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 128
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 129
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 302
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 342
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..105
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016928"
FT VAR_SEQ 106..133
FT /note="EDRFEVLTDLANKTHPSIFGIFDGHGGE -> MPTEQPEVPSQSLEAVEKGS
FT LSSEDAGL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016929"
FT MUTAGEN 130
FT /note="H->L: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12556533"
FT MUTAGEN 239
FT /note="R->G: Slightly abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12556533"
FT MUTAGEN 241
FT /note="R->G: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12556533"
FT MUTAGEN 265
FT /note="R->A: Abolishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12556533"
FT MUTAGEN 302
FT /note="D->A: Abolishes phosphatase activity, prevents
FT MAP3K7/TAK1 phosphorylation in vitro, does not abolish
FT interaction with MAP3K7/TAK1, found in a complex with
FT MAP3K7/TAK1, MAP2K4 or MAP2K6 and enhances the association
FT between MAP3K7/TAK1, MAP2K4 or MAP2K6."
FT /evidence="ECO:0000269|PubMed:12556533"
FT CONFLICT 5
FT /note="T -> I (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="S -> Y (in Ref. 2; BAC27913)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="K -> E (in Ref. 1; AAO43055)"
FT /evidence="ECO:0000305"
FT CONFLICT 198
FT /note="A -> P (in Ref. 5; AAD17235)"
FT /evidence="ECO:0000305"
FT CONFLICT 236
FT /note="L -> P (in Ref. 5; AAD17235)"
FT /evidence="ECO:0000305"
FT CONFLICT 332
FT /note="V -> I (in Ref. 2; BAE28196)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 360 AA; 41049 MW; 026CAC7687E5EA1E CRC64;
MIEDTMTLLS LLGRIMRYFL LRPETLFLLC ISLALWSYFF HTDEVKTIVK SSRDAVKMVK
GKVAEIMQND RLGGLDVLEA EFSKTWEFKS HNVAVYSIQG RRDHMEDRFE VLTDLANKTH
PSIFGIFDGH GGETAAEYVK SRLPEALKQH LQDYEKDKEN SVLTYQTILE QQILSIDREM
LEKLTVSYDE AGTTCLIALL SDKDLTVANV GDSRGVLCDK DGNAIPLSHD HKPYQLKERK
RIKRAGGFIS FNGSWRVQGI LAMSRSLGDY PLKNLNVVIP DPDILTFDLD KLQPEFMILA
SDGLWDAFSN EEAVRFIKER LDEPHFGAKS IVLQSFYRGC PDNITVMVVK FRNSSKTEEH
