Reviewed, UniProtKB/Swiss-Prot O15297 (PPM1D_HUMAN)

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
    p53-induced protein phosphatase 1
    Protein phosphatase magnesium-dependent 1 delta

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.
Sequence processing	The displayed sequence is not processed.
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.3
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 2 magnesium or manganese ions per subunit By similarity.
Subunit structure	Interacts with CHEK1. Ref.3
Induction	By p53. Ref.3 Ref.1
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
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell proliferation Ref.1 Traceable author statement. Source: ProtInc protein amino acid dephosphorylation Ref.1 Traceable author statement. Source: ProtInc response to radiation Ref.1 Traceable author statement. Source: ProtInc
Cellular component	nucleus Ref.1 Traceable author statement. Source: ProtInc protein serine/threonine phosphatase complex Inferred from electronic annotation. Source: InterPro
Molecular function	magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW manganese ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine phosphatase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDM2	Q00987	2	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
Experimental info
	Mutagenesis	314	1	D → A: Abrogates phosphatase activity. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O15297-1 [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]	"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.
[3]	"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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	U78305 mRNA. Translation: AAB61637.1. BC016480 mRNA. Translation: AAH16480.1.
IPI	IPI00005782.
RefSeq	NP_003611.1.
UniGene	Hs.591184
3D structure databases
HSSP	HSSP built from PDB template 1A6Q based on UniProtKB P35813.
ModBase	Search...
Protein-protein interaction databases
IntAct	O15297. 1 interaction.
PTM databases
PhosphoSite	O15297.
Proteomic databases
PRIDE	O15297.
Genome annotation databases
Ensembl	ENSG00000170836. Homo sapiens. [Contig view]
GeneID	8493.
KEGG	hsa:8493.
Organism-specific databases
GeneCards	GC17P056032.
H-InvDB	HIX0014055.
HGNC	HGNC:9277. PPM1D.
HPA	CAB009474.
MIM	605100. gene.
PharmGKB	PA33605.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O15297.
HOVERGEN	O15297.
OMA	O15297. NTIMDQK.
Enzyme and pathway databases
BRENDA	3.1.3.16. 247.
Gene expression databases
ArrayExpress	O15297.
Bgee	O15297.
CleanEx	HS_PPM1D.
Family and domain databases
InterPro	IPR015655. PP2C. IPR001932. PP2C-related. IPR000222. PP2C_Mn2_Asp60_BS. IPR014045. PP2C_N. [Graphical view]
Gene3D	G3DSA:3.60.40.10. PP2C-related. 1 hit.
PANTHER	PTHR13832. PP2C. 1 hit.
Pfam	PF00481. PP2C. 1 hit. [Graphical view]
SMART	SM00332. PP2Cc. 1 hit. [Graphical view]
PROSITE	PS01032. PP2C. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	31775.
SOURCE	Search...

Entry information

Entry name

PPM1D_HUMAN

Accession

Primary (citable) accession number: O15297

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	January 1, 1998
Last modified:	June 16, 2009
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)