Reviewed, UniProtKB/Swiss-Prot P35813 (PPM1A_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein phosphatase 1A
    EC=3.1.3.16
Alternative name(s):
    Protein phosphatase 2C isoform alpha
      Short name=PP2C-alpha
    Protein phosphatase IA

Gene names

Name:	PPM1A
Synonyms:	PPPM1A

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	382 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Enzyme with a broad specificity.
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 2 magnesium or manganese ions per subunit.
Subunit structure	Monomer.
Sequence similarities	Belongs to the PP2C family.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Ligand	Magnesium Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from direct assay. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype. Source: UniProtKB positive regulation of Wnt receptor signaling pathway Inferred from direct assay. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay. Source: UniProtKB
Cellular component	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 serine/threonine phosphatase activity Ref.1 Inferred from direct assay. Source: UniProtKB signal transducer activity Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARRB1	P49407	1	EBI-989143,EBI-743313
ARRB2	P32121	1	EBI-989143,EBI-714559
LXN	Q9BS40	1	EBI-989143,EBI-1044504
SGOL1	Q5FBB7	1	EBI-989143,EBI-989069
SGOL2	Q562F6	1	EBI-989143,EBI-989213

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha-1 (identifier: P35813-1)

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 Alpha-2 (identifier: P35813-2)

The sequence of this isoform differs from the canonical sequence as follows:
     318-324: EIIKKQG → GGSFNKK
     325-382: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 382

382

Protein phosphatase 1A

PRO_0000057741

Sites

Metal binding

60

1

Manganese 1

Metal binding

60

1

Manganese 2

Metal binding

61

1

Manganese 1; via carbonyl oxygen

Metal binding

239

1

Manganese 2

Metal binding

282

1

Manganese 2

Amino acid modifications

Modified residue

375

1

Phosphoserine Ref.7

Modified residue

377

1

Phosphoserine By similarity

Natural variations

Alternative sequence

318 – 324

7

EIIKKQG → GGSFNKK in isoform Alpha-2.

VSP_005085

Alternative sequence

325 – 382

58

Missing in isoform Alpha-2.

VSP_005086

Secondary structure

1

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382

Helix Strand Turn

Details...

Beta strand

9 – 19

11

Beta strand

22 – 31

10

Beta strand

33 – 35

3

Beta strand

38 – 46

9

Turn

47 – 49

3

Beta strand

50 – 63

14

Helix

66 – 80

15

Helix

83 – 86

4

Beta strand

88 – 91

4

Helix

94 – 118

25

Beta strand

129 – 134

6

Beta strand

136 – 146

11

Beta strand

148 – 153

6

Beta strand

156 – 160

5

Helix

169 – 177

9

Turn

188 – 190

3

Helix

200 – 202

3

Helix

210 – 212

3

Beta strand

213 – 216

4

Beta strand

220 – 225

6

Turn

228 – 230

3

Beta strand

231 – 237

7

Helix

239 – 242

4

Helix

247 – 258

12

Helix

264 – 277

14

Beta strand

284 – 290

7

Helix

299 – 319

21

Helix

330 – 339

10

Turn

347 – 349

3

Helix

350 – 354

5

Helix

355 – 365

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha-1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: D48EF508B4A76687	FASTA	382	42,448
	10 20 30 40 50 60 MGAFLDKPKM EKHNAQGQGN GLRYGLSSMQ GWRVEMEDAH TAVIGLPSGL ESWSFFAVYD 70 80 90 100 110 120 GHAGSQVAKY CCEHLLDHIT NNQDFKGSAG APSVENVKNG IRTGFLEIDE HMRVMSEKKH 130 140 150 160 170 180 GADRSGSTAV GVLISPQHTY FINCGDSRGL LCRNRKVHFF TQDHKPSNPL EKERIQNAGG 190 200 210 220 230 240 SVMIQRVNGS LAVSRALGDF DYKCVHGKGP TEQLVSPEPE VHDIERSEED DQFIILACDG 250 260 270 280 290 300 IWDVMGNEEL CDFVRSRLEV TDDLEKVCNE VVDTCLYKGS RDNMSVILIC FPNAPKVSPE 310 320 330 340 350 360 AVKKEAELDK YLECRVEEII KKQGEGVPDL VHVMRTLASE NIPSLPPGGE LASKRNVIEA 370 380 VYNRLNPYKN DDTDSTSTDD MW
	Isoform Alpha-2. Checksum: ED58E203BB26CE00	FASTA	324	35,958
	10 20 30 40 50 60 MGAFLDKPKM EKHNAQGQGN GLRYGLSSMQ GWRVEMEDAH TAVIGLPSGL ESWSFFAVYD 70 80 90 100 110 120 GHAGSQVAKY CCEHLLDHIT NNQDFKGSAG APSVENVKNG IRTGFLEIDE HMRVMSEKKH 130 140 150 160 170 180 GADRSGSTAV GVLISPQHTY FINCGDSRGL LCRNRKVHFF TQDHKPSNPL EKERIQNAGG 190 200 210 220 230 240 SVMIQRVNGS LAVSRALGDF DYKCVHGKGP TEQLVSPEPE VHDIERSEED DQFIILACDG 250 260 270 280 290 300 IWDVMGNEEL CDFVRSRLEV TDDLEKVCNE VVDTCLYKGS RDNMSVILIC FPNAPKVSPE 310 320 AVKKEAELDK YLECRVEGGS FNKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences." Mann D.J., Campbell D.G., McGowan C.H., Cohen P.T.W. Biochim. Biophys. Acta 1130:100-104(1992) [PubMed: 1311954] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
[2]	"Protein phosphatase 2Calpha inhibits the human stress-responsive p38 and JNK MAPK pathways." Takekawa M., Maeda T., Saito H. EMBO J. 17:4744-4752(1998) [PubMed: 9707433] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2).
[3]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed: 19054851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-1).
[4]	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].
[5]	"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] (ISOFORM ALPHA-1). Tissue: Colon and Lung.
[6]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[7]	"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-375, MASS SPECTROMETRY. Tissue: T-cell.
[8]	"Crystal structure of the protein serine/threonine phosphatase 2C at 2.0-A resolution." Das A.K., Helps N.R., Cohen P.T.W., Barford D. EMBO J. 15:6798-6809(1996) [PubMed: 9003755] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S87759 mRNA. Translation: AAB21784.1.
AF070670 mRNA. Translation: AAC28354.1.
AB451247 mRNA. Translation: BAG70061.1.
CH471061 Genomic DNA. Translation: EAW80774.1.
BC026691 mRNA. Translation: AAH26691.1.
BC063243 mRNA. Translation: AAH63243.1.

IPI

IPI00020950.
IPI00216196.

PIR

S22423.

RefSeq

NP_066283.1.
NP_808820.1.
NP_808821.2.

UniGene

Hs.130036

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A6Q	X-ray	2.00	A	1-382	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P35813. 5 interactions.

STRING

P35813.

PTM databases

PhosphoSite

P35813.

Proteomic databases

PeptideAtlas

P35813.

PRIDE

P35813.

Genome annotation databases

Ensembl

ENST00000325642; ENSP00000327255; ENSG00000100614; Homo sapiens. [Genome view]
ENST00000395076; ENSP00000378514; ENSG00000100614; Homo sapiens. [Genome view]

GeneID

5494.

KEGG

hsa:5494.

UCSC

uc001xew.2. human.
uc001xex.2. human.

Organism-specific databases

CTD

5494.

GeneCards

GC14P059782.

H-InvDB

HIX0011710.

HGNC

HGNC:9275. PPM1A.

MIM

606108. gene.

PharmGKB

PA33603.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG747569.

HOVERGEN

P35813.

InParanoid

P35813.

OrthoDB

EOG9TQPW2.

PhylomeDB

P35813.

Enzyme and pathway databases

BRENDA

3.1.3.16. 247.

Pathway_Interaction_DB

bmppathway. BMP receptor signaling.
smad2_3pathway. Regulation of cytoplasmic and nuclear SMAD2/3 signaling.

Gene expression databases

ArrayExpress

P35813.

Bgee

P35813.

CleanEx

HS_PPM1A.

Genevestigator

P35813.

GermOnline

ENSG00000100614. Homo sapiens.

Family and domain databases

InterPro

IPR015655. PP2C.
IPR001932. PP2C-related.
IPR012911. PP2C_C.
IPR000222. PP2C_Mn2_Asp60_BS.
IPR014045. PP2C_N.
[Graphical view]

Gene3D

G3DSA:3.60.40.10. PP2C-related. 1 hit.
G3DSA:1.10.10.430. PP2C_C. 1 hit.

PANTHER

PTHR13832. PP2C. 1 hit.

Pfam

PF00481. PP2C. 1 hit.
PF07830. PP2C_C. 1 hit.
[Graphical view]

SMART

SM00331. PP2C_SIG. 1 hit.
SM00332. PP2Cc. 1 hit.
[Graphical view]

PROSITE

PS01032. PP2C. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

21242.

SOURCE

Search...

Entry information

Entry name

PPM1A_HUMAN

Accession

Primary (citable) accession number: P35813
Secondary accession number(s): B5BU11, O75551

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	February 9, 2010
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.