PPM1L_HUMAN
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 03-AUG-2022, entry version 143.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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; 24.
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; Q5SGD2; -.
DR PeptideAtlas; Q5SGD2; -.
DR PRIDE; Q5SGD2; -.
DR ProteomicsDB; 63756; -. [Q5SGD2-1]
DR ProteomicsDB; 63757; -. [Q5SGD2-2]
DR ProteomicsDB; 63758; -. [Q5SGD2-3]
DR ProteomicsDB; 63759; -. [Q5SGD2-4]
DR TopDownProteomics; Q5SGD2-1; -. [Q5SGD2-1]
DR Antibodypedia; 18529; 150 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 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; ASKWCGS; -.
DR OrthoDB; 1044139at2759; -.
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 1065 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 190 other tissues.
DR Genevisible; Q5SGD2; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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; TAS:Reactome.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; IBA:GO_Central.
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; -; 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_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
