Q8N3J5 (PPM1K_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	PPM1K
Synonyms:	PP2CM

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	372 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	Regulates the mitochondrial permeability transition pore and is essential for cellular survival and development. Ref.1
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 1 magnesium or manganese ion per subunit.
Subcellular location	Mitochondrion matrix Ref.1 Ref.3.
Sequence similarities	Belongs to the PP2C family. Contains 1 PP2C-like domain.
Caution	Ref.10 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 component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	Magnesium Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein dephosphorylation Inferred from electronic annotation. Source: InterPro
Cellular_component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from direct assay. Source: HPA
Molecular_function	metal 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 29

29

Mitochondrion

Chain

30 – 372

343

Protein phosphatase 1K, mitochondrial

PRO_0000278208

Regions

Domain

93 – 346

254

PP2C-like

Sites

Metal binding

127

1

Magnesium

Metal binding

128

1

Magnesium; via carbonyl oxygen

Metal binding

337

1

Magnesium

Natural variations

Alternative sequence

148 – 150

3

DLL → YVQ in isoform 3.

VSP_023156

Alternative sequence

151 – 372

222

Missing in isoform 3.

VSP_023157

Alternative sequence

181 – 233

53

ATLLT…ERKDE → ENCAWSAALDLEPVDTICGA SVEREICLILSQVKESSGSY PGLREGSHISLSH in isoform 2.

VSP_023158

Alternative sequence

234 – 372

139

Missing in isoform 2.

VSP_023159

Natural variant

94

1

N → K. Ref.9
Corresponds to variant rs17853762 [ dbSNP | Ensembl ].

VAR_030691

Natural variant

321

1

E → K.
Corresponds to variant rs35523553 [ dbSNP | Ensembl ].

VAR_050621

Experimental info

Mutagenesis

298

1

D → A: Loss of activity. Ref.1

Sequence conflict

17

1

V → A in AAX77016. Ref.3

Sequence conflict

194

1

L → I in AAX77016. Ref.3

Sequence conflict

211

1

A → V in AAH20850. Ref.9

Sequence conflict

264

1

I → V in BAB70790. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

372

Helix Strand Turn

Details...

Helix

92 – 94

3

Beta strand

96 – 100

5

Beta strand

103 – 106

4

Beta strand

109 – 115

7

Beta strand

117 – 131

15

Helix

133 – 149

17

Turn

150 – 152

3

Helix

156 – 176

21

Helix

183 – 185

3

Beta strand

190 – 196

7

Turn

197 – 199

3

Beta strand

200 – 208

9

Beta strand

210 – 215

6

Beta strand

218 – 221

4

Helix

231 – 239

9

Beta strand

244 – 246

3

Beta strand

252 – 254

3

Turn

255 – 257

3

Helix

267 – 269

3

Turn

270 – 273

4

Beta strand

279 – 284

6

Turn

287 – 289

3

Beta strand

290 – 296

7

Helix

298 – 301

4

Helix

306 – 314

9

Beta strand

316 – 318

3

Helix

319 – 332

14

Beta strand

339 – 345

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 9DD37EEC0EAD3313	FASTA	372	40,997
	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
	Isoform 2 [UniParc]. Checksum: EB90A7B3BC1BDD08	FASTA	233	25,692
	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 ENCAWSAALD LEPVDTICGA SVEREICLIL SQVKESSGSY PGLREGSHIS LSH
	Isoform 3 [UniParc]. Checksum: 5433CAA1302FC04E	FASTA	150	16,759
	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 LYFAVYDGHG GPAAADFCHT HMEKCIMYVQ

References

	« Hide 'large scale' referencesShow '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, IDENTIFICATION OF TRANSIT PEPTIDE, 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. , 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. , 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. , 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]	"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. , 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.
+	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.

IPI

IPI00217525.
IPI00292799.
IPI00827632.

RefSeq

NP_689755.3. NM_152542.4.

UniGene

Hs.291000.
Hs.709966.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2IQ1	X-ray	2.25	A	89-351	[»]
4DA1	X-ray	2.38	A	84-360	[»]

ProteinModelPortal

Q8N3J5.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8N3J5. 1 interaction.

PTM databases

PhosphoSite

Q8N3J5.

Polymorphism databases

DMDM

74750962.

Proteomic databases

PaxDb

Q8N3J5.

PRIDE

Q8N3J5.

Protocols and materials databases

DNASU

152926.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000295908; ENSP00000295908; ENSG00000163644.
ENST00000315194; ENSP00000324761; ENSG00000163644.
ENST00000506423; ENSP00000424155; ENSG00000163644.

GeneID

152926.

KEGG

hsa:152926.

UCSC

uc003hrm.4. human.
uc003hrn.3. human.

Organism-specific databases

CTD

152926.

GeneCards

GC04M089178.

HGNC

HGNC:25415. PPM1K.

HPA

HPA020066.
HPA020862.
HPA023891.

MIM

611065. gene.

neXtProt

NX_Q8N3J5.

PharmGKB

PA134912083.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0631.

HOVERGEN

HBG096199.

InParanoid

Q8N3J5.

OMA

GCASHIG.

OrthoDB

EOG4MCX0J.

PhylomeDB

Q8N3J5.

Enzyme and pathway databases

BRENDA

3.1.3.16. 2681.

Gene expression databases

Bgee

Q8N3J5.

Genevestigator

Q8N3J5.

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

EvolutionaryTrace

Q8N3J5.

GenomeRNAi

152926.

NextBio

87055.

SOURCE

Search...

Entry information

Entry name

PPM1K_HUMAN

Accession

Primary (citable) accession number: Q8N3J5
Secondary accession number(s): B2RAZ1 , 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:	May 1, 2013
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.