Q8BHN0 (PPM1L_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Ppm1l
Synonyms:	Kiaa4175

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	360 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 2 magnesium or manganese ions per subunit By similarity.
Subunit structure	Interacts with MAP3K7/TAK1 and MAP3K5. Ref.1 Ref.6
Subcellular location	Membrane; Single-pass type I membrane protein Potential.
Tissue specificity	Expressed in brain, heart, testis, liver, lung and skeletal muscle. Ref.1
Disruption phenotype	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. Ref.7
Sequence similarities	Belongs to the PP2C family. Contains 1 PP2C-like domain.
Sequence caution	The sequence AAO43055.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	Magnesium Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from physical interaction PubMed 12823230. Source: MGI protein dephosphorylation Inferred from electronic annotation. Source: InterPro transmembrane receptor protein serine/threonine kinase signaling pathway Inferred from direct assay PubMed 12823230. Source: MGI
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine phosphatase activity Inferred from direct assay Ref.1. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8BHN0-1)

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.

Isoform 2 (identifier: Q8BHN0-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 360	360	Protein phosphatase 1L		PRO_0000057755
Regions
	Topological domain	1 – 25	25	Extracellular Potential
	Transmembrane	26 – 42	17	Helical; Potential
	Topological domain	43 – 360	318	Cytoplasmic Potential
	Domain	91 – 344	254	PP2C-like
Sites
	Metal binding	128	1	Manganese 1 By similarity
	Metal binding	128	1	Manganese 2 By similarity
	Metal binding	129	1	Manganese 1; via carbonyl oxygen By similarity
	Metal binding	302	1	Manganese 2 By similarity
	Metal binding	342	1	Manganese 2 By similarity
Natural variations
	Alternative sequence	1 – 105	105	Missing in isoform 2.		VSP_016928
	Alternative sequence	106 – 133	28	EDRFE…GHGGE → MPTEQPEVPSQSLEAVEKGS LSSEDAGL in isoform 2.		VSP_016929
Experimental info
	Mutagenesis	130	1	H → L: Abolishes phosphatase activity. Ref.1
	Mutagenesis	239	1	R → G: Slightly abolishes phosphatase activity. Ref.1
	Mutagenesis	241	1	R → G: Abolishes phosphatase activity. Ref.1
	Mutagenesis	265	1	R → A: Abolishes phosphatase activity. Ref.1
	Mutagenesis	302	1	D → 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. Ref.1
	Sequence conflict	5	1	T → I Ref.1
	Sequence conflict	51	1	S → Y in BAC27913. Ref.2
	Sequence conflict	89	1	K → E in AAO43055. Ref.1
	Sequence conflict	198	1	A → P in AAD17235. Ref.5
	Sequence conflict	236	1	L → P in AAD17235. Ref.5
	Sequence conflict	332	1	V → I in BAE28196. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 026CAC7687E5EA1E	FASTA	360	41,049
	10 20 30 40 50 60 MIEDTMTLLS LLGRIMRYFL LRPETLFLLC ISLALWSYFF HTDEVKTIVK SSRDAVKMVK 70 80 90 100 110 120 GKVAEIMQND RLGGLDVLEA EFSKTWEFKS HNVAVYSIQG RRDHMEDRFE VLTDLANKTH 130 140 150 160 170 180 PSIFGIFDGH GGETAAEYVK SRLPEALKQH LQDYEKDKEN SVLTYQTILE QQILSIDREM 190 200 210 220 230 240 LEKLTVSYDE AGTTCLIALL SDKDLTVANV GDSRGVLCDK DGNAIPLSHD HKPYQLKERK 250 260 270 280 290 300 RIKRAGGFIS FNGSWRVQGI LAMSRSLGDY PLKNLNVVIP DPDILTFDLD KLQPEFMILA 310 320 330 340 350 360 SDGLWDAFSN EEAVRFIKER LDEPHFGAKS IVLQSFYRGC PDNITVMVVK FRNSSKTEEH
	Isoform 2 [UniParc]. Checksum: 0D09778B248E52CC	FASTA	255	28,649
	10 20 30 40 50 60 MPTEQPEVPS QSLEAVEKGS LSSEDAGLTA AEYVKSRLPE ALKQHLQDYE KDKENSVLTY 70 80 90 100 110 120 QTILEQQILS IDREMLEKLT VSYDEAGTTC LIALLSDKDL TVANVGDSRG VLCDKDGNAI 130 140 150 160 170 180 PLSHDHKPYQ LKERKRIKRA GGFISFNGSW RVQGILAMSR SLGDYPLKNL NVVIPDPDIL 190 200 210 220 230 240 TFDLDKLQPE FMILASDGLW DAFSNEEAVR FIKERLDEPH FGAKSIVLQS FYRGCPDNIT 250 VMVVKFRNSS KTEEH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"Variations in DNA elucidate molecular networks that cause disease." Chen Y., Zhu J., Lum P.Y., Yang X., Pinto S., MacNeil D.J., Zhang C., Lamb J., Edwards S., Sieberts S.K., Leonardson A., Castellini L.W., Wang S., Champy M.-F., Zhang B., Emilsson V., Doss S., Ghazalpour A. , Horvath S., Drake T.A., Lusis A.J., Schadt E.E. Nature 452:429-435(2008) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00340241. IPI00404418.
RefSeq	NP_848841.2. NM_178726.3.
UniGene	Mm.40577.
3D structure databases
ProteinModelPortal	Q8BHN0.
SMR	Q8BHN0. Positions 97-352.
ModBase	Search...
PTM databases
PhosphoSite	Q8BHN0.
Proteomic databases
PaxDb	Q8BHN0.
PRIDE	Q8BHN0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000029355; ENSMUSP00000029355; ENSMUSG00000027784.
GeneID	242083.
KEGG	mmu:242083.
UCSC	uc008pmg.1. mouse. uc008pmh.1. mouse.
Organism-specific databases
CTD	151742.
MGI	MGI:2139740. Ppm1l.
Rouge	Search...
Phylogenomic databases
eggNOG	COG0631.
GeneTree	ENSGT00690000101775.
HOGENOM	HOG000233896.
HOVERGEN	HBG079483.
InParanoid	Q8BHN0.
OMA	TERIVAC.
OrthoDB	EOG466VM4.
Gene expression databases
ArrayExpress	Q8BHN0.
Bgee	Q8BHN0.
CleanEx	MM_PPM1L.
Genevestigator	Q8BHN0.
GermOnline	ENSMUSG00000027784. Mus musculus.
Family and domain databases
Gene3D	3.60.40.10. 1 hit.
InterPro	IPR001932. PP2C-like. IPR000222. PP2C_Mn2_Asp60_BS. IPR015655. Protein_Pase_2C. [Graphical view]
PANTHER	PTHR13832. PTHR13832. 1 hit.
Pfam	PF00481. PP2C. 1 hit. [Graphical view]
SMART	SM00331. PP2C_SIG. 1 hit. SM00332. PP2Cc. 1 hit. [Graphical view]
SUPFAM	SSF81606. PP2C-related. 1 hit.
PROSITE	PS01032. PP2C. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	385221.
SOURCE	Search...

Entry information

Entry name

PPM1L_MOUSE

Accession

Primary (citable) accession number: Q8BHN0
Secondary accession number(s): Q3UGL2 , Q810H0, Q8C021, Q8C1D5, Q9Z0T1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2006
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program