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Protein

Protein phosphatase 1K, mitochondrial

Gene

PPM1K

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

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

Cofactori

Mg2+, Mn2+Note: Binds 1 Mg2+ or Mn2+ ion per subunit.

Kineticsi

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

  1. KM=10.7 mM for p-nitrophenylphosphate1 Publication
  1. Vmax=3.6 µmol/min/mg enzyme toward p-nitrophenylphosphate (at 30 degrees Celsius)1 Publication
  2. Vmax=4 nmol/min/mg enzyme toward branched-chain alpha-ketoacid dehydrogenase complex (at 37 degrees Celsius)1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi127Magnesium1
Metal bindingi128Magnesium; via carbonyl oxygen1
Metal bindingi337Magnesium1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Ligandi

Magnesium, Manganese, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS08904-MONOMER.
BRENDAi3.1.3.16. 2681.
ReactomeiR-HSA-70895. Branched-chain amino acid catabolism.
SIGNORiQ8N3J5.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:PPM1K
Synonyms:PP2CM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:25415. PPM1K.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Maple syrup urine disease, mild variant (MSUDMV)1 Publication
The gene represented in this entry is involved in disease pathogenesis.
Disease descriptionA 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.
See also OMIM:615135

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi298D → A: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi152926.
MalaCardsiPPM1K.
MIMi615135. phenotype.
OpenTargetsiENSG00000163644.
Orphaneti268162. Intermediate maple syrup urine disease.
PharmGKBiPA134912083.

Polymorphism and mutation databases

DMDMi74750962.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 29Mitochondrion1 PublicationAdd BLAST29
ChainiPRO_000027820830 – 372Protein phosphatase 1K, mitochondrialAdd BLAST343

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei248PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8N3J5.
PeptideAtlasiQ8N3J5.
PRIDEiQ8N3J5.

PTM databases

DEPODiQ8N3J5.
iPTMnetiQ8N3J5.
PhosphoSitePlusiQ8N3J5.

Expressioni

Gene expression databases

BgeeiENSG00000163644.
ExpressionAtlasiQ8N3J5. baseline and differential.
GenevisibleiQ8N3J5. HS.

Organism-specific databases

HPAiHPA020066.
HPA020862.
HPA023891.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
BIRC2Q134905EBI-3923368,EBI-514538

Protein-protein interaction databases

BioGridi127472. 18 interactors.
IntActiQ8N3J5. 6 interactors.
MINTiMINT-4725175.
STRINGi9606.ENSP00000295908.

Structurei

Secondary structure

1372
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi92 – 94Combined sources3
Beta strandi96 – 100Combined sources5
Beta strandi103 – 106Combined sources4
Beta strandi109 – 115Combined sources7
Beta strandi117 – 131Combined sources15
Helixi133 – 149Combined sources17
Turni150 – 152Combined sources3
Helixi156 – 176Combined sources21
Helixi183 – 185Combined sources3
Beta strandi190 – 196Combined sources7
Turni197 – 199Combined sources3
Beta strandi200 – 208Combined sources9
Beta strandi210 – 215Combined sources6
Beta strandi218 – 221Combined sources4
Helixi231 – 239Combined sources9
Beta strandi244 – 246Combined sources3
Beta strandi252 – 254Combined sources3
Turni255 – 257Combined sources3
Helixi267 – 269Combined sources3
Turni270 – 273Combined sources4
Beta strandi279 – 284Combined sources6
Turni287 – 289Combined sources3
Beta strandi290 – 296Combined sources7
Helixi298 – 301Combined sources4
Helixi306 – 314Combined sources9
Beta strandi316 – 318Combined sources3
Helixi319 – 332Combined sources14
Beta strandi339 – 345Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2IQ1X-ray2.25A89-351[»]
4DA1X-ray2.38A84-360[»]
ProteinModelPortaliQ8N3J5.
SMRiQ8N3J5.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8N3J5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini94 – 346PPM-type phosphatasePROSITE-ProRule annotationAdd BLAST253

Sequence similaritiesi

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

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0698. Eukaryota.
COG0631. LUCA.
GeneTreeiENSGT00840000129732.
HOVERGENiHBG096199.
InParanoidiQ8N3J5.
KOiK17505.
OMAiIKLYHAD.
OrthoDBiEOG091G0A0V.
PhylomeDBiQ8N3J5.
TreeFamiTF354344.

Family and domain databases

Gene3Di3.60.40.10. 1 hit.
InterProiIPR015655. PP2C.
IPR000222. PP2C_BS.
IPR001932. PPM-type_phosphatase_dom.
[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 (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N3J5-1) [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
MSTAALITLV RSGGNQVRRR VLLSSRLLQD DRRVTPTCHS STSEPRCSRF
60 70 80 90 100
DPDGSGSPAT WDNFGIWDNR IDEPILLPPS IKYGKPIPKI SLENVGCASQ
110 120 130 140 150
IGKRKENEDR FDFAQLTDEV LYFAVYDGHG GPAAADFCHT HMEKCIMDLL
160 170 180 190 200
PKEKNLETLL TLAFLEIDKA FSSHARLSAD ATLLTSGTTA TVALLRDGIE
210 220 230 240 250
LVVASVGDSR AILCRKGKPM KLTIDHTPER KDEKERIKKC GGFVAWNSLG
260 270 280 290 300
QPHVNGRLAM TRSIGDLDLK TSGVIAEPET KRIKLHHADD SFLVLTTDGI
310 320 330 340 350
NFMVNSQEIC DFVNQCHDPN EAAHAVTEQA IQYGTEDNST AVVVPFGAWG
360 370
KYKNSEINFS FSRSFASSGR WA
Length:372
Mass (Da):40,997
Last modified:October 1, 2002 - v1
Checksum:i9DD37EEC0EAD3313
GO
Isoform 2 (identifier: Q8N3J5-2) [UniParc]FASTAAdd to basket

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

Show »
Length:233
Mass (Da):25,692
Checksum:iEB90A7B3BC1BDD08
GO
Isoform 3 (identifier: Q8N3J5-3) [UniParc]FASTAAdd to basket

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

Show »
Length:150
Mass (Da):16,759
Checksum:i5433CAA1302FC04E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti17V → A in AAX77016 (PubMed:17336929).Curated1
Sequence conflicti194L → I in AAX77016 (PubMed:17336929).Curated1
Sequence conflicti211A → V in AAH20850 (PubMed:15489334).Curated1
Sequence conflicti264I → V in BAB70790 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06973626R → H.1 PublicationCorresponds to variant rs369916009dbSNPEnsembl.1
Natural variantiVAR_03069194N → K.1 PublicationCorresponds to variant rs17853762dbSNPEnsembl.1
Natural variantiVAR_050621321E → K.Corresponds to variant rs35523553dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023156148 – 150DLL → YVQ in isoform 3. 1 Publication3
Alternative sequenceiVSP_023157151 – 372Missing in isoform 3. 1 PublicationAdd BLAST222
Alternative sequenceiVSP_023158181 – 233ATLLT…ERKDE → ENCAWSAALDLEPVDTICGA SVEREICLILSQVKESSGSY PGLREGSHISLSH in isoform 2. 1 PublicationAdd BLAST53
Alternative sequenceiVSP_023159234 – 372Missing in isoform 2. 1 PublicationAdd BLAST139

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3629.1. [Q8N3J5-1]
RefSeqiNP_689755.3. NM_152542.4. [Q8N3J5-1]
XP_006714174.1. XM_006714111.3. [Q8N3J5-1]
XP_016863292.1. XM_017007803.1. [Q8N3J5-1]
UniGeneiHs.43744.

Genome annotation databases

EnsembliENST00000608933; ENSP00000477341; ENSG00000163644. [Q8N3J5-1]
GeneIDi152926.
KEGGihsa:152926.
UCSCiuc003hrm.6. human. [Q8N3J5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3629.1. [Q8N3J5-1]
RefSeqiNP_689755.3. NM_152542.4. [Q8N3J5-1]
XP_006714174.1. XM_006714111.3. [Q8N3J5-1]
XP_016863292.1. XM_017007803.1. [Q8N3J5-1]
UniGeneiHs.43744.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2IQ1X-ray2.25A89-351[»]
4DA1X-ray2.38A84-360[»]
ProteinModelPortaliQ8N3J5.
SMRiQ8N3J5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127472. 18 interactors.
IntActiQ8N3J5. 6 interactors.
MINTiMINT-4725175.
STRINGi9606.ENSP00000295908.

PTM databases

DEPODiQ8N3J5.
iPTMnetiQ8N3J5.
PhosphoSitePlusiQ8N3J5.

Polymorphism and mutation databases

DMDMi74750962.

Proteomic databases

PaxDbiQ8N3J5.
PeptideAtlasiQ8N3J5.
PRIDEiQ8N3J5.

Protocols and materials databases

DNASUi152926.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000608933; ENSP00000477341; ENSG00000163644. [Q8N3J5-1]
GeneIDi152926.
KEGGihsa:152926.
UCSCiuc003hrm.6. human. [Q8N3J5-1]

Organism-specific databases

CTDi152926.
DisGeNETi152926.
GeneCardsiPPM1K.
HGNCiHGNC:25415. PPM1K.
HPAiHPA020066.
HPA020862.
HPA023891.
MalaCardsiPPM1K.
MIMi611065. gene.
615135. phenotype.
neXtProtiNX_Q8N3J5.
OpenTargetsiENSG00000163644.
Orphaneti268162. Intermediate maple syrup urine disease.
PharmGKBiPA134912083.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0698. Eukaryota.
COG0631. LUCA.
GeneTreeiENSGT00840000129732.
HOVERGENiHBG096199.
InParanoidiQ8N3J5.
KOiK17505.
OMAiIKLYHAD.
OrthoDBiEOG091G0A0V.
PhylomeDBiQ8N3J5.
TreeFamiTF354344.

Enzyme and pathway databases

BioCyciZFISH:HS08904-MONOMER.
BRENDAi3.1.3.16. 2681.
ReactomeiR-HSA-70895. Branched-chain amino acid catabolism.
SIGNORiQ8N3J5.

Miscellaneous databases

ChiTaRSiPPM1K. human.
EvolutionaryTraceiQ8N3J5.
GeneWikiiPPM1K.
GenomeRNAii152926.
PROiQ8N3J5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163644.
ExpressionAtlasiQ8N3J5. baseline and differential.
GenevisibleiQ8N3J5. HS.

Family and domain databases

Gene3Di3.60.40.10. 1 hit.
InterProiIPR015655. PP2C.
IPR000222. PP2C_BS.
IPR001932. PPM-type_phosphatase_dom.
[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...

Entry informationi

Entry nameiPPM1K_HUMAN
AccessioniPrimary (citable) accession number: Q8N3J5
Secondary accession number(s): B2RAZ1
, Q05CT5, Q49AB5, Q4W5E6, Q56AN8, Q8IUZ7, Q8IXG7, Q8ND70, Q96NT4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: October 1, 2002
Last modified: November 30, 2016
This is version 124 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

Caution

PubMed:18058037 has crystallized PPM1K in the presence of magnesium ions. However, PubMed:17336929 reported that no activity toward p-nitrophenylphosphate was seen in the absence of manganese ions and magnesium could not substitute for manganese.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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 one 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.