P62137 (PP1A_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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. Ref.8 Ref.11
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 1 iron ion per subunit By similarity. Binds 1 manganese ion per subunit By similarity.
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. 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 PPP1R15A; the interaction mediates binding to EIF2S1. 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 PPP1R39. Interacts with TRIM28; the interaction dephosphorylates TRIM28 on 'Ser-824' and forms a complex at the p21 promoter site By similarity. Interacts with PPP1R15B; the interaction mediates binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with NEK2. Interacts with FER; this promotes phosphorylation at Thr-320 By similarity. Interacts with PHACTR4; which acts as an activator of PP1 activity. Ref.6 Ref.7 Ref.8
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
Ligand	Iron Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	branching morphogenesis of an epithelial tube Inferred from mutant phenotype PubMed 15042703. Source: MGI cell division Inferred from electronic annotation. Source: UniProtKB-KW female meiosis Traceable author statement PubMed 9882488. Source: MGI glycogen metabolic process Traceable author statement PubMed 7736790. Source: MGI lung development Inferred from mutant phenotype PubMed 15042703. Source: MGI protein dephosphorylation Inferred from direct assay PubMed 14580336PubMed 14640981. Source: MGI regulation of glycogen biosynthetic process Inferred from electronic annotation. Source: Compara regulation of glycogen catabolic process Inferred from electronic annotation. Source: Compara regulation of translation Traceable author statement PubMed 7736790. Source: MGI
Cellular_component	MLL5-L complex Inferred from electronic annotation. Source: Compara PTW/PP1 phosphatase complex Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from direct assay PubMed 15042703PubMed 21471512PubMed 9882488. Source: MGI dendritic spine Inferred from electronic annotation. Source: Compara glycogen granule Inferred from electronic annotation. Source: Compara nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Inferred from direct assay PubMed 15042703PubMed 9882488. Source: MGI perikaryon Inferred from electronic annotation. Source: Compara protein phosphatase type 1 complex Inferred from electronic annotation. Source: Compara
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine phosphatase activity Inferred from direct assay PubMed 12115603PubMed 14640981. Source: MGI ribonucleoprotein complex binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Arntl	Q9WTL8	2	EBI-357187,EBI-644534
Id2	P41136	2	EBI-357187,EBI-309167
Pcna	P17918	2	EBI-357187,EBI-1173716
Skp1	Q9WTX5	2	EBI-357187,EBI-1202363

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_0000058775
Sites
	Active site	125	1	Proton donor By similarity
	Metal binding	64	1	Iron By similarity
	Metal binding	66	1	Iron By similarity
	Metal binding	92	1	Iron By similarity
	Metal binding	92	1	Manganese By similarity
	Metal binding	124	1	Manganese By similarity
	Metal binding	173	1	Manganese By similarity
	Metal binding	248	1	Manganese By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylserine By similarity
	Modified residue	306	1	Phosphotyrosine Ref.10
	Modified residue	320	1	Phosphothreonine Ref.9

Sequences

	Sequence		Length	Mass (Da)
	P62137 [UniParc]. Last modified June 21, 2004. Version 1. Checksum: 8FBFD158A52282E0	FASTA	330	37,540
	10 20 30 40 50 60 MSDSEKLNLD SIIGRLLEVQ GSRPGKNVQL TENEIRGLCL KSREIFLSQP ILLELEAPLK 70 80 90 100 110 120 ICGDIHGQYY DLLRLFEYGG FPPESNYLFL GDYVDRGKQS LETICLLLAY KIRYPENFFL 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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Ortiz J.M., Lorenzo M.L., Eguiraun A., Andres I., Sangrador A., Allshire R., Hastie N.D. Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and DBA/2. Tissue: Extraembryonic tissue, Liver, Pancreas and Placenta.
[3]	"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]. Tissue: Kidney.
[4]	Lubec G., Klug S. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 44-74; 114-122 AND 247-260, MASS SPECTROMETRY. Tissue: Hippocampus.
[5]	"Molecular cloning of a protein serine/threonine phosphatase containing a putative regulatory tetratricopeptide repeat domain." Becker W., Kentrup H., Klumpp S., Schultz J.E., Joost H.G. J. Biol. Chem. 269:22586-22592(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 69-90.
[6]	"Inhibition of a constitutive translation initiation factor 2alpha phosphatase, CReP, promotes survival of stressed cells." Jousse C., Oyadomari S., Novoa I., Lu P., Zhang Y., Harding H.P., Ron D. J. Cell Biol. 163:767-775(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PPP1R15B.
[7]	"Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress." Latreille M., Larose L. J. Biol. Chem. 281:26633-26644(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN COMPLEX WITH PPP1R15B AND NCK1.
[8]	"Phactr4 regulates neural tube and optic fissure closure by controlling PP1-, Rb-, and E2F1-regulated cell-cycle progression." Kim T.H., Goodman J., Anderson K.V., Niswander L. Dev. Cell 13:87-102(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PHACTR4.
[9]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-320, MASS SPECTROMETRY. Tissue: Melanoma.
[10]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-306, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[11]	"Phactr4 regulates directional migration of enteric neural crest through PP1, integrin signaling, and cofilin activity." Zhang Y., Kim T.H., Niswander L. Genes Dev. 26:69-81(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

The things we forget - Issue 32 of March 2003

Cross-references

Sequence databases
EMBL GenBank DDBJ	U25809 mRNA. Translation: AAC99814.1. AK007932 mRNA. Translation: BAB25358.1. AK028392 mRNA. Translation: BAC25928.1. AK090070 mRNA. Translation: BAC41078.1. AK151582 mRNA. Translation: BAE30522.1. AK152667 mRNA. Translation: BAE31402.1. AK153517 mRNA. Translation: BAE32060.1. AK159575 mRNA. Translation: BAE35196.1. AK167244 mRNA. Translation: BAE39365.1. AK167538 mRNA. Translation: BAE39605.1. AK167880 mRNA. Translation: BAE39893.1. AK167981 mRNA. Translation: BAE39973.1. BC014828 mRNA. Translation: AAH14828.1.
IPI	IPI00130185.
RefSeq	NP_114074.1. NM_031868.2.
UniGene	Mm.1970.
3D structure databases
ProteinModelPortal	P62137.
SMR	P62137. Positions 7-299.
ModBase	Search...
Protein-protein interaction databases
IntAct	P62137. 22 interactions.
PTM databases
PhosphoSite	P62137.
Proteomic databases
PaxDb	P62137.
PRIDE	P62137.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000046094; ENSMUSP00000039109; ENSMUSG00000040385. ENSMUST00000180575; ENSMUSP00000137997; ENSMUSG00000096994.
GeneID	19045.
KEGG	mmu:19045.
Organism-specific databases
CTD	5499.
MGI	MGI:103016. Ppp1ca.
Phylogenomic databases
eggNOG	COG0639.
GeneTree	ENSGT00530000062911.
HOGENOM	HOG000172697.
HOVERGEN	HBG000216.
InParanoid	P62137.
KO	K06269.
OMA	APNYCNE.
OrthoDB	EOG49GKGT.
Gene expression databases
Bgee	P62137.
Genevestigator	P62137.
GermOnline	ENSMUSG00000040385. Mus musculus.
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
ChEMBL	CHEMBL2187.
ChiTaRS	PPP1CA. mouse.
NextBio	21272.
SOURCE	Search...

Entry information

Entry name

PP1A_MOUSE

Accession

Primary (citable) accession number: P62137
Secondary accession number(s): P08129 , P20653, P22802, Q3U7G7, Q9Z1G2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	June 21, 2004
Last modified:	May 1, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program