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   27-MAR-2024, entry version 159.
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,
RC   and 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; 4.
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; 10090-ENSMUSP00000029355; -.
DR   PeptideAtlas; Q8BHN0; -.
DR   ProteomicsDB; 289739; -. [Q8BHN0-1]
DR   ProteomicsDB; 289740; -. [Q8BHN0-2]
DR   Pumba; Q8BHN0; -.
DR   Antibodypedia; 18529; 168 antibodies from 28 providers.
DR   DNASU; 242083; -.
DR   Ensembl; ENSMUST00000029355.9; ENSMUSP00000029355.7; ENSMUSG00000027784.11. [Q8BHN0-1]
DR   GeneID; 242083; -.
DR   KEGG; mmu:242083; -.
DR   UCSC; uc008pmg.1; mouse. [Q8BHN0-1]
DR   UCSC; uc008pmh.1; mouse. [Q8BHN0-2]
DR   AGR; MGI:2139740; -.
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; IDDQEAC; -.
DR   OrthoDB; 11028at2759; -.
DR   PhylomeDB; Q8BHN0; -.
DR   TreeFam; TF332888; -.
DR   BioGRID-ORCS; 242083; 2 hits in 81 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 260 other cell types or tissues.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
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:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IDA:MGI.
DR   CDD; cd00143; PP2Cc; 1.
DR   Gene3D; 3.60.40.10; PPM-type phosphatase domain; 1.
DR   InterPro; IPR015655; PP2C.
DR   InterPro; IPR000222; PP2C_BS.
DR   InterPro; IPR036457; PPM-type-like_dom_sf.
DR   InterPro; IPR001932; PPM-type_phosphatase-like_dom.
DR   PANTHER; PTHR47992; PROTEIN PHOSPHATASE; 1.
DR   PANTHER; PTHR47992:SF105; PROTEIN PHOSPHATASE 1B; 1.
DR   Pfam; PF00481; PP2C; 1.
DR   SMART; SM00331; PP2C_SIG; 1.
DR   SMART; SM00332; PP2Cc; 1.
DR   SUPFAM; SSF81606; PP2C-like; 1.
DR   PROSITE; PS01032; PPM_1; 1.
DR   PROSITE; PS51746; PPM_2; 1.
DR   Genevisible; Q8BHN0; MM.
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
//