ID   PPM1L_HUMAN             Reviewed;         360 AA.
AC   Q5SGD2; Q2M3J2; Q96NM7;
DT   10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   27-MAR-2024, entry version 152.
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=PP2CE;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC   TISSUE=Fetal brain;
RX   PubMed=15560375; DOI=10.1023/b:mole.0000043624.96006.eb;
RA   Jin F., Ji C., Liu L., Dai J., Gu S., Sun X., Xie Y., Mao Y.;
RT   "Molecular cloning and characterization of a novel human protein
RT   phosphatase 2C cDNA (PP2C epsilon).";
RL   Mol. Biol. Rep. 31:197-202(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC   TISSUE=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   [4]
RP   FUNCTION, AND 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).
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:17456047}.
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 (By similarity). Interacts with
CC       MAP3K5. {ECO:0000250, ECO:0000269|PubMed:17456047}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC       membrane protein {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1;
CC         IsoId=Q5SGD2-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q5SGD2-2; Sequence=VSP_016927;
CC       Name=3;
CC         IsoId=Q5SGD2-3; Sequence=VSP_037552, VSP_037553;
CC       Name=4;
CC         IsoId=Q5SGD2-4; Sequence=VSP_037554, VSP_037555;
CC   -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in heart, placenta,
CC       lung, liver, kidney and pancreas. {ECO:0000269|PubMed:15560375}.
CC   -!- SIMILARITY: Belongs to the PP2C family. {ECO:0000305}.
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DR   EMBL; AY337264; AAR00269.1; -; mRNA.
DR   EMBL; AK055115; BAB70856.1; -; mRNA.
DR   EMBL; BC104885; AAI04886.1; -; mRNA.
DR   EMBL; BC104887; AAI04888.1; -; mRNA.
DR   EMBL; BC110801; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS33886.1; -. [Q5SGD2-1]
DR   CCDS; CCDS82868.1; -. [Q5SGD2-3]
DR   CCDS; CCDS82869.1; -. [Q5SGD2-2]
DR   RefSeq; NP_001304840.1; NM_001317911.1. [Q5SGD2-3]
DR   RefSeq; NP_001304841.1; NM_001317912.1. [Q5SGD2-2]
DR   RefSeq; NP_640338.2; NM_139245.3. [Q5SGD2-1]
DR   AlphaFoldDB; Q5SGD2; -.
DR   SMR; Q5SGD2; -.
DR   BioGRID; 127400; 25.
DR   IntAct; Q5SGD2; 5.
DR   MINT; Q5SGD2; -.
DR   STRING; 9606.ENSP00000417659; -.
DR   DEPOD; PPM1L; -.
DR   GlyGen; Q5SGD2; 1 site.
DR   iPTMnet; Q5SGD2; -.
DR   PhosphoSitePlus; Q5SGD2; -.
DR   BioMuta; PPM1L; -.
DR   DMDM; 74743437; -.
DR   EPD; Q5SGD2; -.
DR   jPOST; Q5SGD2; -.
DR   MassIVE; Q5SGD2; -.
DR   MaxQB; Q5SGD2; -.
DR   PaxDb; 9606-ENSP00000417659; -.
DR   PeptideAtlas; Q5SGD2; -.
DR   ProteomicsDB; 63756; -. [Q5SGD2-1]
DR   ProteomicsDB; 63757; -. [Q5SGD2-2]
DR   ProteomicsDB; 63758; -. [Q5SGD2-3]
DR   ProteomicsDB; 63759; -. [Q5SGD2-4]
DR   Pumba; Q5SGD2; -.
DR   TopDownProteomics; Q5SGD2-1; -. [Q5SGD2-1]
DR   Antibodypedia; 18529; 168 antibodies from 28 providers.
DR   DNASU; 151742; -.
DR   Ensembl; ENST00000295839.9; ENSP00000295839.9; ENSG00000163590.14. [Q5SGD2-3]
DR   Ensembl; ENST00000464260.5; ENSP00000420746.1; ENSG00000163590.14. [Q5SGD2-2]
DR   Ensembl; ENST00000497343.5; ENSP00000420354.1; ENSG00000163590.14. [Q5SGD2-4]
DR   Ensembl; ENST00000498165.6; ENSP00000417659.1; ENSG00000163590.14. [Q5SGD2-1]
DR   GeneID; 151742; -.
DR   KEGG; hsa:151742; -.
DR   MANE-Select; ENST00000498165.6; ENSP00000417659.1; NM_139245.4; NP_640338.2.
DR   UCSC; uc003fds.4; human. [Q5SGD2-1]
DR   AGR; HGNC:16381; -.
DR   CTD; 151742; -.
DR   DisGeNET; 151742; -.
DR   GeneCards; PPM1L; -.
DR   HGNC; HGNC:16381; PPM1L.
DR   HPA; ENSG00000163590; Low tissue specificity.
DR   MIM; 611931; gene.
DR   neXtProt; NX_Q5SGD2; -.
DR   OpenTargets; ENSG00000163590; -.
DR   PharmGKB; PA134871016; -.
DR   VEuPathDB; HostDB:ENSG00000163590; -.
DR   eggNOG; KOG0698; Eukaryota.
DR   GeneTree; ENSGT00940000157030; -.
DR   HOGENOM; CLU_013173_11_1_1; -.
DR   InParanoid; Q5SGD2; -.
DR   OMA; IDDQEAC; -.
DR   OrthoDB; 11028at2759; -.
DR   PhylomeDB; Q5SGD2; -.
DR   TreeFam; TF332888; -.
DR   BRENDA; 3.1.3.16; 2681.
DR   PathwayCommons; Q5SGD2; -.
DR   Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR   SignaLink; Q5SGD2; -.
DR   SIGNOR; Q5SGD2; -.
DR   BioGRID-ORCS; 151742; 5 hits in 1159 CRISPR screens.
DR   ChiTaRS; PPM1L; human.
DR   GenomeRNAi; 151742; -.
DR   Pharos; Q5SGD2; Tbio.
DR   PRO; PR:Q5SGD2; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q5SGD2; Protein.
DR   Bgee; ENSG00000163590; Expressed in Brodmann (1909) area 23 and 192 other cell types or tissues.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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; TAS:Reactome.
DR   GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR   GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR   GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IEA:Ensembl.
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; Q5SGD2; HS.
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_0000057754"
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..179
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_016927"
FT   VAR_SEQ         1..127
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_037552"
FT   VAR_SEQ         128..133
FT                   /note="DGHGGE -> MPAFST (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_037553"
FT   VAR_SEQ         192..194
FT                   /note="GTT -> VTF (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_037554"
FT   VAR_SEQ         195..360
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_037555"
FT   VARIANT         262
FT                   /note="A -> S (in dbSNP:rs13326359)"
FT                   /id="VAR_050622"
SQ   SEQUENCE   360 AA;  41053 MW;  08212E7BA32AFE2B CRC64;
     MIEDTMTLLS LLGRIMRYFL LRPETLFLLC ISLALWSYFF HTDEVKTIVK SSRDAVKMVK
     GKVAEIMQND RLGGLDVLEA EFSKTWEFKN HNVAVYSIQG RRDHMEDRFE VLTDLANKTH
     PSIFGIFDGH GGETAAEYVK SRLPEALKQH LQDYEKDKEN SVLSYQTILE QQILSIDREM
     LEKLTVSYDE AGTTCLIALL SDKDLTVANV GDSRGVLCDK DGNAIPLSHD HKPYQLKERK
     RIKRAGGFIS FNGSWRVQGI LAMSRSLGDY PLKNLNVVIP DPDILTFDLD KLQPEFMILA
     SDGLWDAFSN EEAVRFIKER LDEPHFGAKS IVLQSFYRGC PDNITVMVVK FRNSSKTEEQ
//