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Protein

Protein phosphatase 1L

Gene

Ppm1l

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a suppressor of the SAPK signaling pathways by associating with and dephosphorylating MAP3K7/TAK1 and MAP3K5, and by attenuating the association between MAP3K7/TAK1 and MAP2K4 or MAP2K6.1 Publication

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Cofactori

Mg2+By similarity, Mn2+By similarityNote: Binds 2 magnesium or manganese ions per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi128 – 1281Manganese 1By similarity
Metal bindingi128 – 1281Manganese 2By similarity
Metal bindingi129 – 1291Manganese 1; via carbonyl oxygenBy similarity
Metal bindingi302 – 3021Manganese 2By similarity
Metal bindingi342 – 3421Manganese 2By similarity

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. protein serine/threonine phosphatase activity Source: MGI

GO - Biological processi

  1. MAPK cascade Source: MGI
  2. protein dephosphorylation Source: InterPro
  3. transmembrane receptor protein serine/threonine kinase signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Ligandi

Magnesium, Manganese, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_198151. Sphingolipid de novo biosynthesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein phosphatase 1L (EC:3.1.3.16)
Alternative name(s):
Protein phosphatase 1-like
Protein phosphatase 2C isoform epsilon
Short name:
PP2C-epsilon
Gene namesi
Name:Ppm1l
Synonyms:Kiaa4175
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 3

Organism-specific databases

MGIiMGI:2139740. Ppm1l.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2525ExtracellularSequence AnalysisAdd
BLAST
Transmembranei26 – 4217HelicalSequence AnalysisAdd
BLAST
Topological domaini43 – 360318CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. extracellular vesicular exosome Source: MGI
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Disruption phenotypei

Mice exhibit increased fat mass and higher plasma glucose levels compared to wild type mice. Male mice also exhibit a decrease in free fatty acids and higher blood pressure.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi130 – 1301H → L: Abolishes phosphatase activity. 1 Publication
Mutagenesisi239 – 2391R → G: Slightly abolishes phosphatase activity. 1 Publication
Mutagenesisi241 – 2411R → G: Abolishes phosphatase activity. 1 Publication
Mutagenesisi265 – 2651R → A: Abolishes phosphatase activity. 1 Publication
Mutagenesisi302 – 3021D → A: Abolishes phosphatase activity, prevents MAP3K7/TAK1 phosphorylation in vitro, does not abolish interaction with MAP3K7/TAK1, found in a complex with MAP3K7/TAK1, MAP2K4 or MAP2K6 and enhances the association between MAP3K7/TAK1, MAP2K4 or MAP2K6. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 360360Protein phosphatase 1LPRO_0000057755Add
BLAST

Proteomic databases

MaxQBiQ8BHN0.
PaxDbiQ8BHN0.
PRIDEiQ8BHN0.

PTM databases

PhosphoSiteiQ8BHN0.

Expressioni

Tissue specificityi

Expressed in brain, heart, testis, liver, lung and skeletal muscle.1 Publication

Gene expression databases

BgeeiQ8BHN0.
CleanExiMM_PPM1L.
GenevestigatoriQ8BHN0.

Interactioni

Subunit structurei

Interacts with MAP3K7/TAK1 and MAP3K5.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ACBD3Q9H3P73EBI-7970002,EBI-1791792From a different organism.
MARK3P274483EBI-7970002,EBI-707595From a different organism.

Protein-protein interaction databases

IntActiQ8BHN0. 5 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ8BHN0.
SMRiQ8BHN0. Positions 97-352.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini91 – 344254PP2C-likeAdd
BLAST

Sequence similaritiesi

Belongs to the PP2C family.Curated
Contains 1 PP2C-like domain.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0631.
GeneTreeiENSGT00740000114971.
HOGENOMiHOG000233896.
HOVERGENiHBG079483.
InParanoidiQ8BHN0.
KOiK17506.
OMAiTERIVAC.
OrthoDBiEOG74J98W.
PhylomeDBiQ8BHN0.
TreeFamiTF332888.

Family and domain databases

Gene3Di3.60.40.10. 1 hit.
InterProiIPR001932. PP2C-like_dom.
IPR000222. PP2C_Mn2_Asp60_BS.
IPR015655. Protein_Pase_2C.
[Graphical view]
PANTHERiPTHR13832. PTHR13832. 1 hit.
PfamiPF00481. PP2C. 1 hit.
[Graphical view]
SMARTiSM00331. PP2C_SIG. 1 hit.
SM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF81606. SSF81606. 1 hit.
PROSITEiPS01032. PP2C. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8BHN0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MIEDTMTLLS LLGRIMRYFL LRPETLFLLC ISLALWSYFF HTDEVKTIVK
60 70 80 90 100
SSRDAVKMVK GKVAEIMQND RLGGLDVLEA EFSKTWEFKS HNVAVYSIQG
110 120 130 140 150
RRDHMEDRFE VLTDLANKTH PSIFGIFDGH GGETAAEYVK SRLPEALKQH
160 170 180 190 200
LQDYEKDKEN SVLTYQTILE QQILSIDREM LEKLTVSYDE AGTTCLIALL
210 220 230 240 250
SDKDLTVANV GDSRGVLCDK DGNAIPLSHD HKPYQLKERK RIKRAGGFIS
260 270 280 290 300
FNGSWRVQGI LAMSRSLGDY PLKNLNVVIP DPDILTFDLD KLQPEFMILA
310 320 330 340 350
SDGLWDAFSN EEAVRFIKER LDEPHFGAKS IVLQSFYRGC PDNITVMVVK
360
FRNSSKTEEH
Length:360
Mass (Da):41,049
Last modified:March 1, 2003 - v1
Checksum:i026CAC7687E5EA1E
GO
Isoform 2 (identifier: Q8BHN0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: Missing.
     106-133: EDRFEVLTDLANKTHPSIFGIFDGHGGE → MPTEQPEVPSQSLEAVEKGSLSSEDAGL

Show »
Length:255
Mass (Da):28,649
Checksum:i0D09778B248E52CC
GO

Sequence cautioni

The sequence AAO43055.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti5 – 51T → I (PubMed:12556533).Curated
Sequence conflicti51 – 511S → Y in BAC27913 (PubMed:16141072).Curated
Sequence conflicti89 – 891K → E in AAO43055 (PubMed:12556533).Curated
Sequence conflicti198 – 1981A → P in AAD17235 (Ref. 5) Curated
Sequence conflicti236 – 2361L → P in AAD17235 (Ref. 5) Curated
Sequence conflicti332 – 3321V → I in BAE28196 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 105105Missing in isoform 2. 1 PublicationVSP_016928Add
BLAST
Alternative sequencei106 – 13328EDRFE…GHGGE → MPTEQPEVPSQSLEAVEKGS LSSEDAGL in isoform 2. 1 PublicationVSP_016929Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY184801 mRNA. Translation: AAO43055.1. Different initiation.
AK028275 mRNA. Translation: BAC25853.1.
AK032529 mRNA. Translation: BAC27913.1.
AK035912 mRNA. Translation: BAC29241.1.
AK045724 mRNA. Translation: BAC32472.1.
AK131646 mRNA. Translation: BAE20738.1.
AK147876 mRNA. Translation: BAE28196.1.
AK220523 mRNA. Translation: BAD90308.1.
BC096031 mRNA. Translation: AAH96031.1.
AF117832 mRNA. Translation: AAD17235.1.
CCDSiCCDS17405.1. [Q8BHN0-1]
RefSeqiNP_848841.2. NM_178726.3. [Q8BHN0-1]
UniGeneiMm.40577.

Genome annotation databases

EnsembliENSMUST00000029355; ENSMUSP00000029355; ENSMUSG00000027784. [Q8BHN0-1]
GeneIDi242083.
KEGGimmu:242083.
UCSCiuc008pmg.1. mouse. [Q8BHN0-1]
uc008pmh.1. mouse. [Q8BHN0-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY184801 mRNA. Translation: AAO43055.1. Different initiation.
AK028275 mRNA. Translation: BAC25853.1.
AK032529 mRNA. Translation: BAC27913.1.
AK035912 mRNA. Translation: BAC29241.1.
AK045724 mRNA. Translation: BAC32472.1.
AK131646 mRNA. Translation: BAE20738.1.
AK147876 mRNA. Translation: BAE28196.1.
AK220523 mRNA. Translation: BAD90308.1.
BC096031 mRNA. Translation: AAH96031.1.
AF117832 mRNA. Translation: AAD17235.1.
CCDSiCCDS17405.1. [Q8BHN0-1]
RefSeqiNP_848841.2. NM_178726.3. [Q8BHN0-1]
UniGeneiMm.40577.

3D structure databases

ProteinModelPortaliQ8BHN0.
SMRiQ8BHN0. Positions 97-352.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8BHN0. 5 interactions.

PTM databases

PhosphoSiteiQ8BHN0.

Proteomic databases

MaxQBiQ8BHN0.
PaxDbiQ8BHN0.
PRIDEiQ8BHN0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029355; ENSMUSP00000029355; ENSMUSG00000027784. [Q8BHN0-1]
GeneIDi242083.
KEGGimmu:242083.
UCSCiuc008pmg.1. mouse. [Q8BHN0-1]
uc008pmh.1. mouse. [Q8BHN0-2]

Organism-specific databases

CTDi151742.
MGIiMGI:2139740. Ppm1l.
RougeiSearch...

Phylogenomic databases

eggNOGiCOG0631.
GeneTreeiENSGT00740000114971.
HOGENOMiHOG000233896.
HOVERGENiHBG079483.
InParanoidiQ8BHN0.
KOiK17506.
OMAiTERIVAC.
OrthoDBiEOG74J98W.
PhylomeDBiQ8BHN0.
TreeFamiTF332888.

Enzyme and pathway databases

ReactomeiREACT_198151. Sphingolipid de novo biosynthesis.

Miscellaneous databases

ChiTaRSiPpm1l. mouse.
NextBioi385221.
PROiQ8BHN0.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BHN0.
CleanExiMM_PPM1L.
GenevestigatoriQ8BHN0.

Family and domain databases

Gene3Di3.60.40.10. 1 hit.
InterProiIPR001932. PP2C-like_dom.
IPR000222. PP2C_Mn2_Asp60_BS.
IPR015655. Protein_Pase_2C.
[Graphical view]
PANTHERiPTHR13832. PTHR13832. 1 hit.
PfamiPF00481. PP2C. 1 hit.
[Graphical view]
SMARTiSM00331. PP2C_SIG. 1 hit.
SM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF81606. SSF81606. 1 hit.
PROSITEiPS01032. PP2C. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Regulation of the interleukin-1-induced signaling pathways by a novel member of the protein phosphatase 2C family (PP2Cepsilon)."
    Li M.G., Katsura K., Nomiyama H., Komaki K., Ninomiya-Tsuji J., Matsumoto K., Kobayashi T., Tamura S.
    J. Biol. Chem. 278:12013-12021(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH MAP3K7, MUTAGENESIS OF HIS-130; ARG-239; ARG-241; ARG-265 AND ASP-302, TISSUE SPECIFICITY.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J.
    Tissue: Cerebellum, Corpora quadrigemina, Embryonic head, Melanocyte and Olfactory bulb.
  3. "Prediction of the coding sequences of mouse homologues of KIAA gene. The complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O., Koga H.
    Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Fetal brain.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: C57BL/6.
    Tissue: Embryonic brain.
  5. "Isolation of PP2C sequences using degenerate-oligo PCR."
    Stothard P.M., Pilgrim D.
    Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 133-299 (ISOFORMS 1/2).
    Tissue: Lung.
  6. "Regulation of apoptosis signal-regulating kinase 1 by protein phosphatase 2Cepsilon."
    Saito J., Toriumi S., Awano K., Ichijo H., Sasaki K., Kobayashi T., Tamura S.
    Biochem. J. 405:591-596(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAP3K5.
  7. Cited for: DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiPPM1L_MOUSE
AccessioniPrimary (citable) accession number: Q8BHN0
Secondary accession number(s): Q3UGL2
, Q810H0, Q8C021, Q8C1D5, Q9Z0T1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: March 1, 2003
Last modified: March 4, 2015
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.