O15297 (PPM1D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein phosphatase 1D
EC=3.1.3.16

Alternative name(s):
Protein phosphatase 2C isoform delta
Short name=PP2C-delta
Protein phosphatase magnesium-dependent 1 delta
p53-induced protein phosphatase 1

Gene names

Name:	PPM1D
Synonyms:	WIP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	605 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins. Ref.5 Ref.6
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 2 magnesium or manganese ions per subunit By similarity.
Subunit structure	Interacts with CHEK1 and CHEK2; dephosphorylates them. Ref.5 Ref.6
Induction	By p53/TP53. Ref.1 Ref.5
Sequence similarities	Belongs to the PP2C family. Contains 1 PP2C-like domain.

Ontologies

Keywords
Biological process	Cell cycle
Ligand	Magnesium Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of cell proliferation Traceable author statement. Source: ProtInc protein dephosphorylation Traceable author statement. Source: ProtInc response to radiation Traceable author statement. Source: ProtInc
Cellular component	nucleus Traceable author statement. Source: ProtInc protein serine/threonine phosphatase complex Inferred from electronic annotation. Source: InterPro
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine phosphatase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDM2	Q00987	4	EBI-1551512,EBI-389668

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 605	605	Protein phosphatase 1D		PRO_0000057752
Regions
	Domain	61 – 378	318	PP2C-like
	Region	1 – 101	101	Interaction with CHEK1
Sites
	Metal binding	105	1	Manganese 1 By similarity
	Metal binding	105	1	Manganese 2 By similarity
	Metal binding	106	1	Manganese 1; via carbonyl oxygen By similarity
	Metal binding	314	1	Manganese 2 By similarity
	Metal binding	366	1	Manganese 2 By similarity
Amino acid modifications
	Modified residue	40	1	Phosphoserine Ref.8
	Modified residue	85	1	Phosphoserine Ref.7
Experimental info
	Mutagenesis	314	1	D → A: Abrogates phosphatase activity. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	O15297 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: E6C5884CF04008B7	FASTA	605	66,675
	10 20 30 40 50 60 MAGLYSLGVS VFSDQGGRKY MEDVTQIVVE PEPTAEEKPS PRRSLSQPLP PRPSPAALPG 70 80 90 100 110 120 GEVSGKGPAV AAREARDPLP DAGASPAPSR CCRRRSSVAF FAVCDGHGGR EAAQFAREHL 130 140 150 160 170 180 WGFIKKQKGF TSSEPAKVCA AIRKGFLACH LAMWKKLAEW PKTMTGLPST SGTTASVVII 190 200 210 220 230 240 RGMKMYVAHV GDSGVVLGIQ DDPKDDFVRA VEVTQDHKPE LPKERERIEG LGGSVMNKSG 250 260 270 280 290 300 VNRVVWKRPR LTHNGPVRRS TVIDQIPFLA VARALGDLWS YDFFSGEFVV SPEPDTSVHT 310 320 330 340 350 360 LDPQKHKYII LGSDGLWNMI PPQDAISMCQ DQEEKKYLMG EHGQSCAKML VNRALGRWRQ 370 380 390 400 410 420 RMLRADNTSA IVICISPEVD NQGNFTNEDE LYLNLTDSPS YNSQETCVMT PSPCSTPPVK 430 440 450 460 470 480 SLEEDPWPRV NSKDHIPALV RSNAFSENFL EVSAEIAREN VQGVVIPSKD PEPLEENCAK 490 500 510 520 530 540 ALTLRIHDSL NNSLPIGLVP TNSTNTVMDQ KNLKMSTPGQ MKAQEIERTP PTNFKRTLEE 550 560 570 580 590 600 SNSGPLMKKH RRNGLSRSSG AQPASLPTTS QRKNSVKLTM RRRLRGQKKI GNPLLHQHRK TVCVC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner." Fiscella M., Zhang H., Fan S., Sakaguchi K., Shen S., Mercer W.E., Vande Woude G.F., O'Connor P.M., Appella E. Proc. Natl. Acad. Sci. U.S.A. 94:6048-6053(1997) [PubMed: 9177166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	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].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[5]	"PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints." Lu X., Nannenga B., Donehower L.A. Genes Dev. 19:1162-1174(2005) [PubMed: 15870257] [Abstract] Cited for: FUNCTION, INTERACTION WITH CHEK1, INDUCTION, MUTAGENESIS OF ASP-314.
[6]	"Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase." Fujimoto H., Onishi N., Kato N., Takekawa M., Xu X.Z., Kosugi A., Kondo T., Imamura M., Oishi I., Yoda A., Minami Y. Cell Death Differ. 13:1170-1180(2006) [PubMed: 16311512] [Abstract] Cited for: FUNCTION IN APOPTOSIS, FUNCTION IN DEPHOSPHORYLATION OF CHEK2, INTERACTION WITH CHEK2.
[7]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	U78305 mRNA. Translation: AAB61637.1. BT009780 mRNA. Translation: AAP88782.1. CH471179 Genomic DNA. Translation: EAW51408.1. BC016480 mRNA. Translation: AAH16480.1.
IPI	IPI00005782.
RefSeq	NP_003611.1. NM_003620.3.
UniGene	Hs.286073.
3D structure databases
ProteinModelPortal	O15297.
SMR	O15297. Positions 6-377.
ModBase	Search...
Protein-protein interaction databases
IntAct	O15297. 1 interaction.
STRING	O15297.
PTM databases
PhosphoSite	O15297.
Proteomic databases
PRIDE	O15297.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000305921; ENSP00000306682; ENSG00000170836.
GeneID	8493.
KEGG	hsa:8493.
UCSC	uc002iyt.1. human.
Organism-specific databases
CTD	8493.
GeneCards	GC17P058677.
H-InvDB	HIX0014055.
HGNC	HGNC:9277. PPM1D.
HPA	CAB009474. HPA022277.
MIM	605100. gene.
neXtProt	NX_O15297.
PharmGKB	PA33605.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG714124.
HOVERGEN	HBG058897.
InParanoid	O15297.
OMA	NTIMDQK.
OrthoDB	EOG41JZCG.
PhylomeDB	O15297.
Gene expression databases
ArrayExpress	O15297.
Bgee	O15297.
CleanEx	HS_PPM1D.
Genevestigator	O15297.
Family and domain databases
InterPro	IPR001932. PP2C-like. IPR000222. PP2C_Mn2_Asp60_BS. IPR015655. Protein_Pase_2C. [Graphical view]
Gene3D	G3DSA:3.60.40.10. PP2C-related. 2 hits.
KO	K10147.
PANTHER	PTHR13832. PP2C. 1 hit.
Pfam	PF00481. PP2C. 1 hit. [Graphical view]
SMART	SM00332. PP2Cc. 1 hit. [Graphical view]
SUPFAM	SSF81606. PP2C-related. 1 hit.
PROSITE	PS01032. PP2C. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	31775.
SOURCE	Search...

Entry information

Entry name

PPM1D_HUMAN

Accession

Primary (citable) accession number: O15297
Secondary accession number(s): Q53XP4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	January 1, 1998
Last modified:	January 25, 2012
This is version 106 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.