P62139 (PP1A_RABIT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein phosphatase PP1-alpha catalytic subunit
Short name=PP-1A
EC=3.1.3.16

Gene names

Name:	PPP1CA
Synonyms:	PPP1A

Organism

Oryctolagus cuniculus (Rabbit) [Reference proteome]

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	330 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	Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca2+/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development By similarity.
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 1 iron ion per subunit. Binds 1 manganese ion per subunit.
Subunit structure	PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts with PPP1R15A and PPP1R15B; the interactions mediate binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Component of the MLL5-L complex, at least composed of MLL5, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT. Interacts with PPP1R9A, PPP1R9B and PPP1R7. Interacts with YLPM1. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, RBMX and NCOA5. Interacts with NOM1 and PPP1R8. Interacts with PPP1R16B. Interacts with RPSA only in the presence of PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R10/PNUTS and PPP1R8. Interacts with WDR82 in the presence of PPP1R10/PNUTS. Interacts with TRIM28; the interaction dephosphorylates TRIM28 on 'Ser-824' and forms a complex at the p21 promoter site By similarity. Interacts with PPP1R39. Interacts with NEK2. Interacts with PHACTR4; which acts as an activator of PP1 activity. Interacts with FER; this promotes phosphorylation at Thr-320 By similarity. Ref.5
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Nucleus › nucleoplasm By similarity. Nucleus › nucleolus By similarity. Note: Primarily nuclear and largely excluded from the nucleolus. Highly mobile in cells and can be relocalized through interaction with targeting subunits. NOM1 plays a role in targeting this protein to the nucleolus. In the presence of PPP1R8 relocalizes from the nucleus to nuclear speckles By similarity.
Post-translational modification	Phosphorylated. Dephosphorylated at Thr-320 in the presence of ionizing radiation By similarity.
Sequence similarities	Belongs to the PPP phosphatase family. PP-1 subfamily.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Cell cycle Cell division Glycogen metabolism
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Iron Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW glycogen metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	PTW/PP1 phosphatase complex Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphoprotein phosphatase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 2 (identifier: P62139-1)

Also known as: 1-alpha-2;

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 1 (identifier: P62139-2)

Also known as: 1-alpha-1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: MSDSEKLNLDSIIGRLLEVQGSRPGKNVQLTEN → MVTIMTTSEYLSGY

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 330

329

Serine/threonine-protein phosphatase PP1-alpha catalytic subunit

PRO_0000058776

Sites

Active site

125

1

Proton donor By similarity

Metal binding

64

1

Iron

Metal binding

66

1

Iron

Metal binding

92

1

Iron

Metal binding

92

1

Manganese

Metal binding

124

1

Manganese

Metal binding

173

1

Manganese

Metal binding

248

1

Manganese

Amino acid modifications

Modified residue

2

1

N-acetylserine By similarity

Modified residue

306

1

Phosphotyrosine By similarity

Modified residue

320

1

Phosphothreonine By similarity

Natural variations

Alternative sequence

1 – 33

33

MSDSE…QLTEN → MVTIMTTSEYLSGY in isoform 1.

VSP_010642

Experimental info

Sequence conflict

309

1

F → L in CAA68693. Ref.1

Sequence conflict

309

1

F → L in CAA30645. Ref.3

Secondary structure

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330

Helix Strand Turn

Details...

Helix

9 – 18

10

Turn

19 – 22

4

Helix

32 – 48

17

Beta strand

51 – 55

5

Beta strand

57 – 62

6

Helix

69 – 79

11

Beta strand

87 – 89

3

Beta strand

94 – 98

5

Helix

100 – 113

14

Turn

115 – 117

3

Beta strand

118 – 120

3

Helix

128 – 134

7

Helix

136 – 143

8

Helix

146 – 156

11

Beta strand

162 – 165

4

Turn

166 – 168

3

Beta strand

169 – 174

6

Helix

183 – 188

6

Beta strand

197 – 199

3

Helix

200 – 206

7

Beta strand

214 – 218

5

Beta strand

222 – 227

6

Helix

229 – 239

11

Beta strand

242 – 246

5

Beta strand

254 – 258

5

Turn

259 – 262

4

Beta strand

263 – 267

5

Beta strand

274 – 276

3

Beta strand

280 – 285

6

Beta strand

291 – 296

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (1-alpha-2) [UniParc]. Last modified June 21, 2004. Version 1. Checksum: 60C37E1AD9831DAC	FASTA	330	37,512
	10 20 30 40 50 60 MSDSEKLNLD SIIGRLLEVQ GSRPGKNVQL TENEIRGLCL KSREIFLSQP ILLELEAPLK 70 80 90 100 110 120 ICGDIHGQYY DLLRLFEYGG FPPESNYLFL GDYVDRGKQS LETICLLLAY KIKYPENFFL 130 140 150 160 170 180 LRGNHECASI NRIYGFYDEC KRRYNIKLWK TFTDCFNCLP IAAIVDEKIF CCHGGLSPDL 190 200 210 220 230 240 QSMEQIRRIM RPTDVPDQGL LCDLLWSDPD KDVQGWGEND RGVSFTFGAE VVAKFLHKHD 250 260 270 280 290 300 LDLICRAHQV VEDGYEFFAK RQLVTLFSAP NYCGEFDNAG AMMSVDETLM CSFQILKPAD 310 320 330 KNKGKYGQFS GLNPGGRPIT PPRNSAKAKK
	Isoform 1 (1-alpha-1) [UniParc] [UniParc]. Checksum: DACB568733E12EC3	FASTA	311	35,466
	10 20 30 40 50 60 MVTIMTTSEY LSGYEIRGLC LKSREIFLSQ PILLELEAPL KICGDIHGQY YDLLRLFEYG 70 80 90 100 110 120 GFPPESNYLF LGDYVDRGKQ SLETICLLLA YKIKYPENFF LLRGNHECAS INRIYGFYDE 130 140 150 160 170 180 CKRRYNIKLW KTFTDCFNCL PIAAIVDEKI FCCHGGLSPD LQSMEQIRRI MRPTDVPDQG 190 200 210 220 230 240 LLCDLLWSDP DKDVQGWGEN DRGVSFTFGA EVVAKFLHKH DLDLICRAHQ VVEDGYEFFA 250 260 270 280 290 300 KRQLVTLFSA PNYCGEFDNA GAMMSVDETL MCSFQILKPA DKNKGKYGQF SGLNPGGRPI 310 TPPRNSAKAK K

References

[1]	"Isolation and sequence analysis of a cDNA clone encoding a type-1 protein phosphatase catalytic subunit: homology with protein phosphatase 2A." Berndt N., Campbell D.G., Caudwell F.B., Cohen P., da Cruz e Silva E.F., da Cruz e Silva O.B., Cohen P.T.W. FEBS Lett. 223:340-346(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: New Zealand white. Tissue: Skeletal muscle.
[2]	"Molecular cloning of a cDNA for the catalytic subunit of rabbit muscle phosphorylase phosphatase." Bai G., Zhang Z., Amin J., Deans-Zirattu S.A., Lee E.Y.C. FASEB J. 2:3010-3016(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Muscle.
[3]	"Two isoforms of protein phosphatase 1 may be produced from the same gene." Cohen P.T.W. FEBS Lett. 232:17-23(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: New Zealand white. Tissue: Skeletal muscle.
[4]	"The major type-1 protein phosphatase catalytic subunits are the same gene products in rabbit skeletal muscle and rabbit liver." Cohen P.T.W., Schelling D.L., da Cruz e Silva O.B., Barker H.M., Cohen P. Biochim. Biophys. Acta 1008:125-128(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: New Zealand white. Tissue: Liver.
[5]	"FLJ23654 encodes a heart protein phosphatase 1-binding protein (Hepp1)." Chen C.Y., Lai N.S., Yang J.J., Huang H.L., Hung W.C., Li C., Lin T.H., Huang H.B. Biochem. Biophys. Res. Commun. 391:698-702(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PPP1R39.
[6]	"Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1." Goldberg J., Huang H.B., Kwon Y.G., Greengard P., Nairn A.C., Kuriyan J. Nature 376:745-753(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).

Web resources

Protein Spotlight

The things we forget - Issue 32 of March 2003

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00701 mRNA. Translation: CAA68693.1.
X07798 mRNA. Translation: CAA30645.1.
X14832 mRNA. Translation: CAA32941.1.

PIR

PARB11. S04335.

RefSeq

NP_001095176.1. NM_001101706.1.

UniGene

Ocu.2075.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FJM	X-ray	2.10	A/B	1-330	[»]

ProteinModelPortal

P62139.

ModBase

Search...

Protein-protein interaction databases

IntAct

P62139. 1 interaction.

Proteomic databases

PRIDE

P62139.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

100009298.

Organism-specific databases

CTD

5499.

Phylogenomic databases

eggNOG

COG0639.

HOVERGEN

HBG000216.

Family and domain databases

InterPro

IPR004843. Metallo_PEstase_dom.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view]

Pfam

PF00149. Metallophos. 1 hit.
[Graphical view]

PRINTS

PR00114. STPHPHTASE.

SMART

SM00156. PP2Ac. 1 hit.
[Graphical view]

PROSITE

PS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P62139.

ChEMBL

CHEMBL5458.

EvolutionaryTrace

P62139.

Entry information

Entry name

PP1A_RABIT

Accession

Primary (citable) accession number: P62139
Secondary accession number(s): P08128 , P08129, P20653, P22802

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	June 21, 2004
Last modified:	May 1, 2013
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program