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Q8N3J5 (PPM1K_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein phosphatase 1K, mitochondrial

EC=3.1.3.16
Alternative name(s):
PP2C domain-containing protein phosphatase 1K
PP2C-like mitochondrial protein
PP2C-type mitochondrial phosphoprotein phosphatase
Short name=PTMP
Protein phosphatase 2C isoform kappa
Short name=PP2C-kappa
Gene names
Name:PPM1K
Synonyms:PP2CM
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length372 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Regulates the mitochondrial permeability transition pore and is essential for cellular survival and development. Ref.1

Catalytic activity

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

Cofactor

Binds 1 magnesium or manganese ion per subunit.

Subcellular location

Mitochondrion matrix Ref.1 Ref.3.

Involvement in disease

Maple syrup urine disease, mild variant (MSUDMV) [MIM:615135]: A mild form of maple syrup urine disease, a metabolic disorder due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine. Accumulation of these 3 amino acids and their corresponding keto acids leads to encephalopathy and progressive neurodegeneration. Clinical features include mental and physical retardation, feeding problems, and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine. If untreated, maple syrup urine disease can lead to seizures, coma, and death. The disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still involve developmental delay and other medical problems if not treated. MSUDMV is characterized by increased plasma levels of branched-chain amino acids (BCAA) apparent at birth. Treatment with a low-protein diet free of BCAA can result in normal psychomotor development and lack of metabolic episodes.
Note: The gene represented in this entry is involved in disease pathogenesis. Ref.10

Sequence similarities

Belongs to the PP2C family.

Contains 1 PP2C-like domain.

Caution

Ref.11 has crystallized PPM1K in the presence of magnesium ions. However, Ref.3 reported that no activity toward p-nitrophenylphosphate was seen in the absence of manganese ions and magnesium could not substitute for manganese.

Biophysicochemical properties

Kinetic parameters:

Half maximal activity toward p-nitrophenylphosphate achieved with 3.7 mM of manganese ions.

KM=10.7 mM for p-nitrophenylphosphate Ref.3

Vmax=3.6 µmol/min/mg enzyme toward p-nitrophenylphosphate (at 30 degrees Celsius)

Vmax=4 nmol/min/mg enzyme toward branched-chain alpha-ketoacid dehydrogenase complex (at 37 degrees Celsius)

Ontologies

Keywords
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransit peptide
   LigandMagnesium
Manganese
Metal-binding
   Molecular functionHydrolase
Protein phosphatase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processprotein dephosphorylation

Inferred from electronic annotation. Source: InterPro

   Cellular_componentmitochondrial matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from direct assay. Source: HPA

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein serine/threonine phosphatase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N3J5-1)

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: Q8N3J5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     181-233: ATLLTSGTTA...IDHTPERKDE → ENCAWSAALD...REGSHISLSH
     234-372: Missing.
Isoform 3 (identifier: Q8N3J5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     148-150: DLL → YVQ
     151-372: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2929Mitochondrion
Chain30 – 372343Protein phosphatase 1K, mitochondrial
PRO_0000278208

Regions

Domain93 – 346254PP2C-like

Sites

Metal binding1271Magnesium
Metal binding1281Magnesium; via carbonyl oxygen
Metal binding3371Magnesium

Amino acid modifications

Modified residue2481Phosphoserine By similarity

Natural variations

Alternative sequence148 – 1503DLL → YVQ in isoform 3.
VSP_023156
Alternative sequence151 – 372222Missing in isoform 3.
VSP_023157
Alternative sequence181 – 23353ATLLT…ERKDE → ENCAWSAALDLEPVDTICGA SVEREICLILSQVKESSGSY PGLREGSHISLSH in isoform 2.
VSP_023158
Alternative sequence234 – 372139Missing in isoform 2.
VSP_023159
Natural variant261R → H. Ref.12
VAR_069736
Natural variant941N → K. Ref.9
Corresponds to variant rs17853762 [ dbSNP | Ensembl ].
VAR_030691
Natural variant3211E → K.
Corresponds to variant rs35523553 [ dbSNP | Ensembl ].
VAR_050621

Experimental info

Mutagenesis2981D → A: Loss of activity. Ref.1
Sequence conflict171V → A in AAX77016. Ref.3
Sequence conflict1941L → I in AAX77016. Ref.3
Sequence conflict2111A → V in AAH20850. Ref.9
Sequence conflict2641I → V in BAB70790. Ref.5

Secondary structure

.................................................. 372
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 9DD37EEC0EAD3313

FASTA37240,997
        10         20         30         40         50         60 
MSTAALITLV RSGGNQVRRR VLLSSRLLQD DRRVTPTCHS STSEPRCSRF DPDGSGSPAT 

        70         80         90        100        110        120 
WDNFGIWDNR IDEPILLPPS IKYGKPIPKI SLENVGCASQ IGKRKENEDR FDFAQLTDEV 

       130        140        150        160        170        180 
LYFAVYDGHG GPAAADFCHT HMEKCIMDLL PKEKNLETLL TLAFLEIDKA FSSHARLSAD 

       190        200        210        220        230        240 
ATLLTSGTTA TVALLRDGIE LVVASVGDSR AILCRKGKPM KLTIDHTPER KDEKERIKKC 

       250        260        270        280        290        300 
GGFVAWNSLG QPHVNGRLAM TRSIGDLDLK TSGVIAEPET KRIKLHHADD SFLVLTTDGI 

       310        320        330        340        350        360 
NFMVNSQEIC DFVNQCHDPN EAAHAVTEQA IQYGTEDNST AVVVPFGAWG KYKNSEINFS 

       370 
FSRSFASSGR WA 

« Hide

Isoform 2 [UniParc].

Checksum: EB90A7B3BC1BDD08
Show »

FASTA23325,692
Isoform 3 [UniParc].

Checksum: 5433CAA1302FC04E
Show »

FASTA15016,759

References

« Hide 'large scale' references
[1]"A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development."
Lu G., Ren S., Korge P., Choi J., Dong Y., Weiss J., Koehler C., Chen J.-N., Wang Y.
Genes Dev. 21:784-796(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TRANSIT PEPTIDE CLEAVAGE SITE, MUTAGENESIS OF ASP-298.
[2]"Cloning and characterization of a novel human PP2C gene from fetal brain."
Mao Y., Xie Y., Dai J.
Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[3]"Identification of a novel PP2C-type mitochondrial phosphatase."
Joshi M.A., Jeoung N.H., Popov K.M., Harris R.A.
Biochem. Biophys. Res. Commun. 356:38-44(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES.
[4]"Protein phosphatase 2C kappa is upregulated in heart failure and attenuates agonist-induced cardiomyocyte hypertrophy."
Xu J., Stagliano N., Deponte J. III, Rodrigue-Way A., Golden S., Katz S., Jeyaseelan R., Donoghue M., Meyers R., Gottfried S., Wysong D., McGovern K., Pollman M., Breitbart R.E., Acton S.
Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]"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. expand/collapse author list , 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 1).
Tissue: Cerebellum and Testis.
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Amygdala and Lymph node.
[7]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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 1 AND 3), VARIANT LYS-94.
Tissue: Pancreas and Testis.
[10]"A novel regulatory defect in the branched-chain alpha-keto acid dehydrogenase complex due to a mutation in the PPM1K gene causes a mild variant phenotype of maple syrup urine disease."
Oyarzabal A., Martinez-Pardo M., Merinero B., Navarrete R., Desviat L.R., Ugarte M., Rodriguez-Pombo P.
Hum. Mutat. 34:355-362(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MSUDMV.
[11]"Structural genomics of protein phosphatases."
Almo S.C., Bonanno J.B., Sauder J.M., Emtage S., Dilorenzo T.P., Malashkevich V., Wasserman S.R., Swaminathan S., Eswaramoorthy S., Agarwal R., Kumaran D., Madegowda M., Ragumani S., Patskovsky Y., Alvarado J., Ramagopal U.A., Faber-Barata J., Chance M.R. expand/collapse author list , Sali A., Fiser A., Zhang Z.Y., Lawrence D.S., Burley S.K.
J. Struct. Funct. Genomics 8:121-140(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 89-351, MAGNESIUM-BINDING.
[12]"Mutations in ANO3 cause dominant craniocervical dystonia: ion channel implicated in pathogenesis."
Charlesworth G., Plagnol V., Holmstroem K.M., Bras J., Sheerin U.M., Preza E., Rubio-Agusti I., Ryten M., Schneider S.A., Stamelou M., Trabzuni D., Abramov A.Y., Bhatia K.P., Wood N.W.
Am. J. Hum. Genet. 91:1041-1050(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HIS-26.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY157615 mRNA. Translation: AAO17296.1.
AF351614 mRNA. Translation: AAN76514.1.
AY994097 mRNA. Translation: AAX77016.1.
AY435431 mRNA. Translation: AAR06213.1.
AK054678 mRNA. Translation: BAB70790.1.
AK314417 mRNA. Translation: BAG37038.1.
AL834167 mRNA. Translation: CAD38869.2.
AL834271 mRNA. Translation: CAD38946.1.
AC107067 Genomic DNA. Translation: AAY41021.1.
AC108213 Genomic DNA. No translation available.
CH471057 Genomic DNA. Translation: EAX06016.1.
BC020850 mRNA. Translation: AAH20850.1. Different termination.
BC037552 mRNA. Translation: AAH37552.1.
BC041350 mRNA. Translation: AAH41350.1.
RefSeqNP_689755.3. NM_152542.4.
UniGeneHs.43744.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2IQ1X-ray2.25A89-351[»]
4DA1X-ray2.38A84-360[»]
ProteinModelPortalQ8N3J5.
SMRQ8N3J5. Positions 90-349.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid127472. 2 interactions.
IntActQ8N3J5. 1 interaction.
MINTMINT-4725175.

PTM databases

PhosphoSiteQ8N3J5.

Polymorphism databases

DMDM74750962.

Proteomic databases

PaxDbQ8N3J5.
PRIDEQ8N3J5.

Protocols and materials databases

DNASU152926.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000315194; ENSP00000324761; ENSG00000163644. [Q8N3J5-2]
ENST00000608933; ENSP00000477341; ENSG00000163644. [Q8N3J5-1]
GeneID152926.
KEGGhsa:152926.
UCSCuc003hrm.5. human. [Q8N3J5-1]
uc003hrn.4. human. [Q8N3J5-2]

Organism-specific databases

CTD152926.
GeneCardsGC04M089178.
HGNCHGNC:25415. PPM1K.
HPAHPA020066.
HPA020862.
HPA023891.
MIM611065. gene.
615135. phenotype.
neXtProtNX_Q8N3J5.
Orphanet268162. Intermediate maple syrup urine disease.
PharmGKBPA134912083.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0631.
HOVERGENHBG096199.
InParanoidQ8N3J5.
KOK17505.
OMADTFGIWD.
OrthoDBEOG7992QN.
PhylomeDBQ8N3J5.
TreeFamTF354344.

Enzyme and pathway databases

BRENDA3.1.3.16. 2681.

Gene expression databases

BgeeQ8N3J5.
GenevestigatorQ8N3J5.

Family and domain databases

Gene3D3.60.40.10. 1 hit.
InterProIPR001932. PP2C-like_dom.
IPR000222. PP2C_Mn2_Asp60_BS.
IPR015655. Protein_Pase_2C.
[Graphical view]
PANTHERPTHR13832. PTHR13832. 1 hit.
PfamPF00481. PP2C. 1 hit.
[Graphical view]
SMARTSM00331. PP2C_SIG. 1 hit.
SM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMSSF81606. SSF81606. 1 hit.
PROSITEPS01032. PP2C. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ8N3J5.
GeneWikiPPM1K.
GenomeRNAi152926.
NextBio87055.
PROQ8N3J5.
SOURCESearch...

Entry information

Entry namePPM1K_HUMAN
AccessionPrimary (citable) accession number: Q8N3J5
Secondary accession number(s): B2RAZ1 expand/collapse secondary AC list , Q05CT5, Q49AB5, Q4W5E6, Q56AN8, Q8IUZ7, Q8IXG7, Q8ND70, Q96NT4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM