Q66GT5 (PTPM1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1
EC=3.1.3.27

Alternative name(s):
PTEN-like phosphatase
Phosphoinositide lipid phosphatase
Protein-tyrosine phosphatase mitochondrial 1
EC=3.1.3.16
EC=3.1.3.48

Gene names

Name:	Ptpmt1
Synonyms:	Plip

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	193 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Lipid phosphatase which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG). PGP is an essential intermediate in the biosynthetic pathway of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle. Has also been shown to display phosphatase activity toward phosphoprotein substrates, specifically mediates dephosphorylation of mitochondrial proteins, thereby playing an essential role in ATP production. Has probably a preference for proteins phosphorylated on Ser and/or Thr residues compared to proteins phosphorylated on Tyr residues. Probably involved in regulation of insulin secretion in pancreatic beta cells By similarity. Ref.4 Ref.5
Catalytic activity	Phosphatidylglycerophosphate + H2O = phosphatidylglycerol + phosphate. Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. A phosphoprotein + H2O = a protein + phosphate.
Pathway	Phospholipid metabolism; phosphatidylglycerol biosynthesis; phosphatidylglycerol from CDP-diacylglycerol: step 2/2.
Subcellular location	Mitochondrion inner membrane. Note: Associated with the inner membrane. Ref.4
Tissue specificity	Predominantly expressed in testis. Expressed at lower level in heart, brain, spleen, lung, liver, skeletal muscle, kidney, bone marrow, eye, lymph node, smooth muscle, prostate, thymus, stomach and uterus. Ref.3
Disruption phenotype	Mice die prior to E8.5. Ref.5
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily. Contains 1 tyrosine-protein phosphatase domain.
Caution	Was originally (Ref.3) thought to have phosphatidylinositol 5-phosphatase activity, however, it was later shown (Ref.4) that it is probably not the case in vivo.
Sequence caution	The sequence AAH26750.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence BAB28400.1 differs from that shown. Reason: Frameshift at position 36. The sequence BAB29504.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Lipid biosynthesis Lipid metabolism Phospholipid biosynthesis Phospholipid metabolism
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Domain	Transit peptide
Molecular function	Hydrolase Protein phosphatase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiolipin biosynthetic process Inferred from mutant phenotype Ref.5. Source: UniProtKB inositol phosphate dephosphorylation Inferred from Biological aspect of Ancestor. Source: RefGenome peptidyl-tyrosine dephosphorylation Inferred from electronic annotation. Source: GOC phosphatidylinositol metabolic process Inferred by curator Ref.3. Source: MGI
Cellular_component	mitochondrial inner membrane Inferred from sequence orthology PubMed 17376863. Source: MGI
Molecular_function	phosphatidylglycerophosphatase activity Inferred from mutant phenotype Ref.5. Source: UniProtKB phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity Inferred from direct assay Ref.3. Source: MGI protein tyrosine phosphatase activity Inferred from electronic annotation. Source: EC protein tyrosine/serine/threonine phosphatase activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 31

31

Mitochondrion Potential

Chain

32 – 193

162

Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1

PRO_0000025424

Regions

Domain

109 – 177

69

Tyrosine-protein phosphatase

Sites

Active site

132

1

Phosphocysteine intermediate By similarity

Experimental info

Mutagenesis

73

1

E → A: Fails to dephosphorylate PGP in vitro. Ref.6

Mutagenesis

76

1

E → A: Fails to dephosphorylate PGP in vitro. Ref.6

Mutagenesis

101

1

D → A: Fails to dephosphorylate PGP in vitro. Ref.6

Mutagenesis

132

1

C → S: Does not affect level of Akt phosphorylation; Fails to dephosphorylate PGP in vitro. Ref.3 Ref.6

Secondary structure

1

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193

Helix Strand Turn

Details...

Beta strand

38 – 40

3

Beta strand

42 – 49

8

Helix

53 – 55

3

Helix

56 – 62

7

Beta strand

65 – 72

8

Turn

75 – 79

5

Helix

84 – 89

6

Beta strand

93 – 97

5

Turn

101 – 103

3

Helix

108 – 124

17

Beta strand

127 – 137

11

Helix

138 – 151

14

Helix

155 – 165

11

Helix

173 – 190

18

Sequences

	Sequence		Length	Mass (Da)
	Q66GT5 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: 740D39798855D439	FASTA	193	21,943
	10 20 30 40 50 60 MAASAWLEAG LARVLFYPTL LYTVFRGRVR GPAHRDWYHR IDHTVLLGAL PLKNMTRRLV 70 80 90 100 110 120 LDENVRGVIT MNEEYETRFL CNTSKEWKKA GVEQLRLSTV DMTGVPTLAN LHKGVQFALK 130 140 150 160 170 180 YQALGQCVYV HCKAGRSRSA TMVAAYLIQV HNWSPEEAIE AIAKIRSHIS IRPSQLEVLK 190 EFHKEITARA AKN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Strain: C57BL/6J. Tissue: Head.
[2]	"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]. Strain: FVB/N. Tissue: Liver.
[3]	"A PTEN-like phosphatase with a novel substrate specificity." Pagliarini D.J., Worby C.A., Dixon J.E. J. Biol. Chem. 279:38590-38596(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-132.
[4]	"Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic beta cells." Pagliarini D.J., Wiley S.E., Kimple M.E., Dixon J.R., Kelly P., Worby C.A., Casey P.J., Dixon J.E. Mol. Cell 19:197-207(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS PROTEIN PHOSPHATASE, SUBCELLULAR LOCATION.
[5]	"Mitochondrial phosphatase PTPMT1 is essential for cardiolipin biosynthesis." Zhang J., Guan Z., Murphy A.N., Wiley S.E., Perkins G.A., Worby C.A., Engel J.L., Heacock P., Nguyen O.K., Wang J.H., Raetz C.R., Dowhan W., Dixon J.E. Cell Metab. 13:690-700(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS PHOSPHATIDYLGLYCEROPHOSPHATASE, DISRUPTION PHENOTYPE.
[6]	"Structural and functional analysis of PTPMT1, a phosphatase required for cardiolipin synthesis." Xiao J., Engel J.L., Zhang J., Chen M.J., Manning G., Dixon J.E. Proc. Natl. Acad. Sci. U.S.A. 108:11860-11865(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 37-193 IN COMPLEX WITH PHOSPHATIDYLINOSITOL 5-PHOSPHATE, MUTAGENESIS OF GLU-73; GLU-76; ASP-101 AND CYS-132.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK012674 mRNA. Translation: BAB28400.1. Frameshift.
AK014691 mRNA. Translation: BAB29504.1. Different initiation.
BC026750 mRNA. Translation: AAH26750.1. Different initiation.
BK005540 mRNA. Translation: DAA05585.1.

IPI

IPI00134918.

RefSeq

NP_079852.1. NM_025576.2.

UniGene

Mm.23926.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3RGO	X-ray	1.93	A	37-193	[»]
3RGQ	X-ray	2.05	A	36-191	[»]

ProteinModelPortal

Q66GT5.

SMR

Q66GT5. Positions 37-193.

ModBase

Search...

PTM databases

PhosphoSite

Q66GT5.

Proteomic databases

PaxDb

Q66GT5.

PRIDE

Q66GT5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

66461.

KEGG

mmu:66461.

Organism-specific databases

CTD

114971.

MGI

MGI:1913711. Ptpmt1.

Phylogenomic databases

eggNOG

NOG146651.

HOVERGEN

HBG079822.

InParanoid

Q66GT5.

KO

K14165.

Enzyme and pathway databases

UniPathway

UPA00084; UER00504.

Gene expression databases

CleanEx

MM_PTPMT1.

Genevestigator

Q66GT5.

GermOnline

ENSMUSG00000063235. Mus musculus.

Family and domain databases

InterPro

IPR000340. Dual-sp_phosphatase_cat-dom.
IPR024950. DUSP.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
[Graphical view]

PANTHER

PTHR10159. PTHR10159. 1 hit.

Pfam

PF00782. DSPc. 1 hit.
[Graphical view]

PROSITE

PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q66GT5.

NextBio

321760.

SOURCE

Search...

Entry information

Entry name

PTPM1_MOUSE

Accession

Primary (citable) accession number: Q66GT5
Secondary accession number(s): Q9CSJ8, Q9D622

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2005
Last sequence update:	October 11, 2004
Last modified:	April 3, 2013
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program