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Protein

Protein phosphatase 1K, mitochondrial

Gene

PPM1K

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

Functioni

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

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

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

Keywordsi

Molecular functionHydrolase, Protein phosphatase
LigandMagnesium, Manganese, Metal-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000163644.14
HGNCiHGNC:25415 PPM1K
MIMi611065 gene
neXtProtiNX_Q8N3J5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 – 29MitochondrionSequence analysisAdd BLAST29
ChainiPRO_000027820830 – 372Protein phosphatase 1K, mitochondrialAdd BLAST343

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei248PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8N3J5
PaxDbiQ8N3J5
PeptideAtlasiQ8N3J5
PRIDEiQ8N3J5
ProteomicsDBi71811
71812 [Q8N3J5-2]
71813 [Q8N3J5-3]

PTM databases

DEPODiQ8N3J5
iPTMnetiQ8N3J5
PhosphoSitePlusiQ8N3J5

Expressioni

Gene expression databases

BgeeiENSG00000163644 Expressed in 206 organ(s), highest expression level in left ventricle myocardium
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, 25 interactors
IntActiQ8N3J5, 24 interactors
STRINGi9606.ENSP00000295908

Structurei

Secondary structure

1372
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0698 Eukaryota
COG0631 LUCA
GeneTreeiENSGT00900000140907
HOVERGENiHBG096199
InParanoidiQ8N3J5
KOiK17505
OMAiNVGCASH
OrthoDBiEOG091G0A0V
PhylomeDBiQ8N3J5
TreeFamiTF354344

Family and domain databases

CDDicd00143 PP2Cc, 1 hit
Gene3Di3.60.40.10, 1 hit
InterProiView protein in InterPro
IPR015655 PP2C
IPR000222 PP2C_BS
IPR036457 PPM-type_dom_sf
IPR001932 PPM-type_phosphatase_dom
PANTHERiPTHR13832 PTHR13832, 1 hit
PfamiView protein in Pfam
PF00481 PP2C, 1 hit
SMARTiView protein in SMART
SM00331 PP2C_SIG, 1 hit
SM00332 PP2Cc, 1 hit
SUPFAMiSSF81606 SSF81606, 1 hit
PROSITEiView protein in PROSITE
PS01032 PPM_1, 1 hit
PS51746 PPM_2, 1 hit

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

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MQZ4A0A0A0MQZ4_HUMAN
Protein phosphatase 1K, mitochondri...
PPM1K
327Annotation score:
V9GY69V9GY69_HUMAN
Protein phosphatase 1K, mitochondri...
PPM1K
153Annotation score:
V9GYZ5V9GYZ5_HUMAN
Protein phosphatase 1K (PP2C domain...
PPM1K hCG_39060
182Annotation score:
V9GYS8V9GYS8_HUMAN
Protein phosphatase 1K, mitochondri...
PPM1K
130Annotation score:
V9GYI6V9GYI6_HUMAN
Protein phosphatase 1K, mitochondri...
PPM1K
21Annotation score:

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 → H1 PublicationCorresponds to variant dbSNP:rs369916009Ensembl.1
Natural variantiVAR_03069194N → K1 PublicationCorresponds to variant dbSNP:rs17853762Ensembl.1
Natural variantiVAR_050621321E → K. Corresponds to variant dbSNP:rs35523553Ensembl.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

Similar proteinsi

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, 25 interactors
IntActiQ8N3J5, 24 interactors
STRINGi9606.ENSP00000295908

PTM databases

DEPODiQ8N3J5
iPTMnetiQ8N3J5
PhosphoSitePlusiQ8N3J5

Polymorphism and mutation databases

DMDMi74750962

Proteomic databases

EPDiQ8N3J5
PaxDbiQ8N3J5
PeptideAtlasiQ8N3J5
PRIDEiQ8N3J5
ProteomicsDBi71811
71812 [Q8N3J5-2]
71813 [Q8N3J5-3]

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
EuPathDBiHostDB:ENSG00000163644.14
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
GeneTreeiENSGT00900000140907
HOVERGENiHBG096199
InParanoidiQ8N3J5
KOiK17505
OMAiNVGCASH
OrthoDBiEOG091G0A0V
PhylomeDBiQ8N3J5
TreeFamiTF354344

Enzyme and pathway databases

BRENDAi3.1.3.16 2681
ReactomeiR-HSA-70895 Branched-chain amino acid catabolism
SIGNORiQ8N3J5

Miscellaneous databases

ChiTaRSiPPM1K human
EvolutionaryTraceiQ8N3J5
GeneWikiiPPM1K
GenomeRNAii152926
PROiPR:Q8N3J5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163644 Expressed in 206 organ(s), highest expression level in left ventricle myocardium
ExpressionAtlasiQ8N3J5 baseline and differential
GenevisibleiQ8N3J5 HS

Family and domain databases

CDDicd00143 PP2Cc, 1 hit
Gene3Di3.60.40.10, 1 hit
InterProiView protein in InterPro
IPR015655 PP2C
IPR000222 PP2C_BS
IPR036457 PPM-type_dom_sf
IPR001932 PPM-type_phosphatase_dom
PANTHERiPTHR13832 PTHR13832, 1 hit
PfamiView protein in Pfam
PF00481 PP2C, 1 hit
SMARTiView protein in SMART
SM00331 PP2C_SIG, 1 hit
SM00332 PP2Cc, 1 hit
SUPFAMiSSF81606 SSF81606, 1 hit
PROSITEiView protein in PROSITE
PS01032 PPM_1, 1 hit
PS51746 PPM_2, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: October 1, 2002
Last modified: October 10, 2018
This is version 135 of the entry and version 1 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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