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Protein

Protein phosphatase 1L

Gene

PPM1L

Organism
Homo sapiens (Human)
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: Reactome

GO - Biological processi

  1. MAPK cascade Source: Ensembl
  2. protein dephosphorylation Source: InterPro
  3. small molecule metabolic process Source: Reactome
  4. sphingolipid biosynthetic process Source: Reactome
  5. sphingolipid metabolic process Source: Reactome
  6. transmembrane receptor protein serine/threonine kinase signaling pathway Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Ligandi

Magnesium, Manganese, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.3.16. 2681.
ReactomeiREACT_115810. 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:PP2CE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:16381. 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. endoplasmic reticulum membrane Source: Reactome
  2. extracellular vesicular exosome Source: UniProtKB
  3. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134871016.

Polymorphism and mutation databases

BioMutaiPPM1L.
DMDMi74743437.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 360360Protein phosphatase 1LPRO_0000057754Add
BLAST

Proteomic databases

MaxQBiQ5SGD2.
PaxDbiQ5SGD2.
PRIDEiQ5SGD2.

PTM databases

DEPODiQ5SGD2.
PhosphoSiteiQ5SGD2.

Expressioni

Tissue specificityi

Ubiquitous. Highly expressed in heart, placenta, lung, liver, kidney and pancreas.1 Publication

Gene expression databases

BgeeiQ5SGD2.
CleanExiHS_PPM1L.
GenevestigatoriQ5SGD2.

Organism-specific databases

HPAiHPA019891.
HPA019953.

Interactioni

Subunit structurei

Interacts with MAP3K7/TAK1 (By similarity). Interacts with MAP3K5.By similarity1 Publication

Protein-protein interaction databases

BioGridi127400. 2 interactions.
STRINGi9606.ENSP00000417659.

Structurei

3D structure databases

ProteinModelPortaliQ5SGD2.
SMRiQ5SGD2. Positions 93-352.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini92 – 351260PPM-type phosphatasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the PP2C family.Curated
Contains 1 PPM-type phosphatase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0631.
GeneTreeiENSGT00740000114971.
HOGENOMiHOG000233896.
HOVERGENiHBG079483.
InParanoidiQ5SGD2.
KOiK17506.
OMAiTERIVAC.
OrthoDBiEOG74J98W.
PhylomeDBiQ5SGD2.
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. PPM_1. 1 hit.
PS51746. PPM_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5SGD2-1) [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 EFSKTWEFKN HNVAVYSIQG
110 120 130 140 150
RRDHMEDRFE VLTDLANKTH PSIFGIFDGH GGETAAEYVK SRLPEALKQH
160 170 180 190 200
LQDYEKDKEN SVLSYQTILE 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
FRNSSKTEEQ
Length:360
Mass (Da):41,053
Last modified:December 21, 2004 - v1
Checksum:i08212E7BA32AFE2B
GO
Isoform 2 (identifier: Q5SGD2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-179: Missing.

Show »
Length:181
Mass (Da):20,324
Checksum:i74F07366F3C3FB4B
GO
Isoform 3 (identifier: Q5SGD2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: Missing.
     128-133: DGHGGE → MPAFST

Show »
Length:233
Mass (Da):26,363
Checksum:i5522C3B41C506168
GO
Isoform 4 (identifier: Q5SGD2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     192-194: GTT → VTF
     195-360: Missing.

Show »
Length:194
Mass (Da):22,475
Checksum:iBD4465CB810BCBB9
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti262 – 2621A → S.
Corresponds to variant rs13326359 [ dbSNP | Ensembl ].
VAR_050622

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 179179Missing in isoform 2. 1 PublicationVSP_016927Add
BLAST
Alternative sequencei1 – 127127Missing in isoform 3. 1 PublicationVSP_037552Add
BLAST
Alternative sequencei128 – 1336DGHGGE → MPAFST in isoform 3. 1 PublicationVSP_037553
Alternative sequencei192 – 1943GTT → VTF in isoform 4. 1 PublicationVSP_037554
Alternative sequencei195 – 360166Missing in isoform 4. 1 PublicationVSP_037555Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY337264 mRNA. Translation: AAR00269.1.
AK055115 mRNA. Translation: BAB70856.1.
BC104885 mRNA. Translation: AAI04886.1.
BC104887 mRNA. Translation: AAI04888.1.
BC110801 mRNA. No translation available.
CCDSiCCDS33886.1. [Q5SGD2-1]
RefSeqiNP_640338.2. NM_139245.2. [Q5SGD2-1]
UniGeneiHs.389027.

Genome annotation databases

EnsembliENST00000295839; ENSP00000295839; ENSG00000163590. [Q5SGD2-3]
ENST00000464260; ENSP00000420746; ENSG00000163590. [Q5SGD2-2]
ENST00000497343; ENSP00000420354; ENSG00000163590. [Q5SGD2-4]
ENST00000498165; ENSP00000417659; ENSG00000163590. [Q5SGD2-1]
GeneIDi151742.
KEGGihsa:151742.
UCSCiuc003fdr.3. human. [Q5SGD2-1]
uc003fdt.3. human. [Q5SGD2-3]

Polymorphism and mutation databases

BioMutaiPPM1L.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY337264 mRNA. Translation: AAR00269.1.
AK055115 mRNA. Translation: BAB70856.1.
BC104885 mRNA. Translation: AAI04886.1.
BC104887 mRNA. Translation: AAI04888.1.
BC110801 mRNA. No translation available.
CCDSiCCDS33886.1. [Q5SGD2-1]
RefSeqiNP_640338.2. NM_139245.2. [Q5SGD2-1]
UniGeneiHs.389027.

3D structure databases

ProteinModelPortaliQ5SGD2.
SMRiQ5SGD2. Positions 93-352.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127400. 2 interactions.
STRINGi9606.ENSP00000417659.

PTM databases

DEPODiQ5SGD2.
PhosphoSiteiQ5SGD2.

Polymorphism and mutation databases

BioMutaiPPM1L.
DMDMi74743437.

Proteomic databases

MaxQBiQ5SGD2.
PaxDbiQ5SGD2.
PRIDEiQ5SGD2.

Protocols and materials databases

DNASUi151742.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000295839; ENSP00000295839; ENSG00000163590. [Q5SGD2-3]
ENST00000464260; ENSP00000420746; ENSG00000163590. [Q5SGD2-2]
ENST00000497343; ENSP00000420354; ENSG00000163590. [Q5SGD2-4]
ENST00000498165; ENSP00000417659; ENSG00000163590. [Q5SGD2-1]
GeneIDi151742.
KEGGihsa:151742.
UCSCiuc003fdr.3. human. [Q5SGD2-1]
uc003fdt.3. human. [Q5SGD2-3]

Organism-specific databases

CTDi151742.
GeneCardsiGC03P160473.
HGNCiHGNC:16381. PPM1L.
HPAiHPA019891.
HPA019953.
MIMi611931. gene.
neXtProtiNX_Q5SGD2.
PharmGKBiPA134871016.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0631.
GeneTreeiENSGT00740000114971.
HOGENOMiHOG000233896.
HOVERGENiHBG079483.
InParanoidiQ5SGD2.
KOiK17506.
OMAiTERIVAC.
OrthoDBiEOG74J98W.
PhylomeDBiQ5SGD2.
TreeFamiTF332888.

Enzyme and pathway databases

BRENDAi3.1.3.16. 2681.
ReactomeiREACT_115810. Sphingolipid de novo biosynthesis.

Miscellaneous databases

ChiTaRSiPPM1L. human.
GenomeRNAii151742.
NextBioi86779.
PROiQ5SGD2.
SOURCEiSearch...

Gene expression databases

BgeeiQ5SGD2.
CleanExiHS_PPM1L.
GenevestigatoriQ5SGD2.

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. PPM_1. 1 hit.
PS51746. PPM_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and characterization of a novel human protein phosphatase 2C cDNA (PP2C epsilon)."
    Jin F., Ji C., Liu L., Dai J., Gu S., Sun X., Xie Y., Mao Y.
    Mol. Biol. Rep. 31:197-202(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Fetal brain.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Brain.
  3. "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] (ISOFORMS 3 AND 4).
    Tissue: Brain.
  4. "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: FUNCTION, INTERACTION WITH MAP3K5.

Entry informationi

Entry nameiPPM1L_HUMAN
AccessioniPrimary (citable) accession number: Q5SGD2
Secondary accession number(s): Q2M3J2, Q96NM7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: December 21, 2004
Last modified: April 29, 2015
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.