P62714 (PP2AB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform
Short name=PP2A-beta
EC=3.1.3.16

Gene names

Name:

PPP2CB

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	309 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Ref.7
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	Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with TBCD By similarity. PP2A consists of a common heterodimeric core enzyme (composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65) (subunit A)) that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Binds PPME1. May indirectly interact with SGOL1, most probably through regulatory B56 subunits. Interacts with CTTNBP2NL. Ref.8 Ref.10 Ref.11 Ref.12
Subcellular location	Cytoplasm. Nucleus. Chromosome › centromere. Cytoplasm › cytoskeleton › spindle pole. Note: In prometaphase cells, but not in anaphase cells, localizes at centromeres. During mitosis, also found at spindle poles. Ref.11
Post-translational modification	Reversibly methyl esterified on Leu-309. Carboxyl methylation may play a role in holoenzyme assembly. It varies during the cell cycle. Demethylated by PME1 (in vitro). Ref.9 Ref.10 Phosphorylation of either threonine (by autophosphorylation-activated protein kinase) or tyrosine results in inactivation of the phosphatase. Auto-dephosphorylation has been suggested as a mechanism for reactivation.
Sequence similarities	Belongs to the PPP phosphatase family. PP-1 subfamily.

Ontologies

Keywords
Cellular component	Centromere Chromosome Cytoplasm Cytoskeleton Nucleus
Ligand	Iron Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Methylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome negative regulation of Ras protein signal transduction Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara proteasomal ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara protein dephosphorylation Traceable author statement Ref.1. Source: UniProtKB regulation of gene expression Inferred from electronic annotation. Source: Compara response to antibiotic Inferred from electronic annotation. Source: Compara response to hydrogen peroxide Inferred from electronic annotation. Source: Compara
Cellular_component	chromosome, centromeric region Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell protein phosphatase type 2A complex Traceable author statement Ref.9. Source: UniProtKB spindle pole Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine phosphatase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IGBP1	P78318	3	EBI-1044367,EBI-1055954

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 309	309	Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform		PRO_0000058845
Sites
	Active site	118	1	Proton donor By similarity
	Metal binding	57	1	Iron By similarity
	Metal binding	59	1	Iron By similarity
	Metal binding	85	1	Iron By similarity
	Metal binding	85	1	Manganese By similarity
	Metal binding	117	1	Manganese By similarity
	Metal binding	167	1	Manganese By similarity
	Metal binding	241	1	Manganese By similarity
Amino acid modifications
	Modified residue	307	1	Phosphotyrosine By similarity
	Modified residue	309	1	Leucine methyl ester Ref.9
Experimental info
	Sequence conflict	19	1	E → D in AAB38020. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P62714 [UniParc]. Last modified July 19, 2004. Version 1. Checksum: 51DA9EB0633FC191	FASTA	309	35,575
	10 20 30 40 50 60 MDDKAFTKEL DQWVEQLNEC KQLNENQVRT LCEKAKEILT KESNVQEVRC PVTVCGDVHG 70 80 90 100 110 120 QFHDLMELFR IGGKSPDTNY LFMGDYVDRG YYSVETVTLL VALKVRYPER ITILRGNHES 130 140 150 160 170 180 RQITQVYGFY DECLRKYGNA NVWKYFTDLF DYLPLTALVD GQIFCLHGGL SPSIDTLDHI 190 200 210 220 230 240 RALDRLQEVP HEGPMCDLLW SDPDDRGGWG ISPRGAGYTF GQDISETFNH ANGLTLVSRA 250 260 270 280 290 300 HQLVMEGYNW CHDRNVVTIF SAPNYCYRCG NQAAIMELDD TLKYSFLQFD PAPRRGEPHV TRRTPDYFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of the cDNA encoding the human lung protein phosphatase 2A beta catalytic subunit." Hemmings B.A., Wernet W., Mayer R., Maurer F., Hofsteenge J., Stone S.R. Nucleic Acids Res. 16:11366-11366(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fibroblast.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Human liver phosphatase 2A: cDNA and amino acid sequence of two catalytic subunit isotypes." Arino J., Woon C.W., Brautigan D.L., Miller T.B. Jr., Johnson G.L. Proc. Natl. Acad. Sci. U.S.A. 85:4252-4256(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-309. Tissue: Liver.
[5]	"Structure and transcriptional regulation of protein phosphatase 2A catalytic subunit genes." Khew-Goodall Y., Mayer R.E., Maurer F., Stone S.R., Hemmings B.A. Biochemistry 30:89-97(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"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.
[7]	"Activation of SV40 DNA replication in vitro by cellular protein phosphatase 2A." Virshup D.M., Kauffman M.G., Kelly T.J. EMBO J. 8:3891-3898(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 91-97; 111-114; 122-127; 137-144 AND 207-238, FUNCTION.
[8]	"Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A." Pallas D.C., Shahrik L.K., Martin B.L., Jaspers S., Miller T.B. Jr., Brautigan D.L., Roberts T.M. Cell 60:167-176(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 75-89; 215-234; 270-294 AND 303-309, INTERACTION WITH VIRAL PROTEINS.
[9]	"The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo." Favre B., Zolnierowicz S., Turowski P., Hemmings B.A. J. Biol. Chem. 269:16311-16317(1994) [PubMed] [Europe PMC] [Abstract] Cited for: METHYLATION AT LEU-309.
[10]	"A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A." Ogris E., Du X., Nelson K.C., Mak E.K., Yu X.X., Lane W.S., Pallas D.C. J. Biol. Chem. 274:14382-14391(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PME1, DEMETHYLATION.
[11]	"Shugoshin collaborates with protein phosphatase 2A to protect cohesin." Kitajima T.S., Sakuno T., Ishiguro K., Iemura S., Natsume T., Kawashima S.A., Watanabe Y. Nature 441:46-52(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH SGOL1.
[12]	"A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein." Goudreault M., D'Ambrosio L.M., Kean M.J., Mullin M.J., Larsen B.G., Sanchez A., Chaudhry S., Chen G.I., Sicheri F., Nesvizhskii A.I., Aebersold R., Raught B., Gingras A.C. Mol. Cell. Proteomics 8:157-171(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CTTNBP2NL.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X12656 mRNA. Translation: CAA31183.1. CR541747 mRNA. Translation: CAG46547.1. J03805 mRNA. Translation: AAB38020.1. CH471080 Genomic DNA. Translation: EAW63434.1. CH471080 Genomic DNA. Translation: EAW63435.1. CH471080 Genomic DNA. Translation: EAW63436.1. BC012022 mRNA. Translation: AAH12022.1. M60484 Genomic DNA. Translation: AAA36467.1.
IPI	IPI00429689.
PIR	PAHU2B. B37135.
RefSeq	NP_001009552.1. NM_001009552.1.
UniGene	Hs.491440.
3D structure databases
ProteinModelPortal	P62714.
ModBase	Search...
Protein-protein interaction databases
IntAct	P62714. 58 interactions.
MINT	MINT-1348293.
STRING	9606.ENSP00000221138.
PTM databases
PhosphoSite	P62714.
Polymorphism databases
DMDM	50402236.
2D gel databases
OGP	P62714.
REPRODUCTION-2DPAGE	IPI00429689.
Proteomic databases
PaxDb	P62714.
PRIDE	P62714.
Protocols and materials databases
DNASU	5516.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000221138; ENSP00000221138; ENSG00000104695. ENST00000406655; ENSP00000384493; ENSG00000104695.
GeneID	5516.
KEGG	hsa:5516.
UCSC	uc003xik.3. human.
Organism-specific databases
CTD	5516.
GeneCards	GC08M030631.
HGNC	HGNC:9300. PPP2CB.
HPA	CAB018600.
MIM	176916. gene.
neXtProt	NX_P62714.
PharmGKB	PA33664.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0639.
HOGENOM	HOG000172696.
HOVERGEN	HBG000216.
InParanoid	P62714.
KO	K04382.
OMA	QVRFQER.
OrthoDB	EOG4Q58PR.
PhylomeDB	P62714.
Enzyme and pathway databases
Pathway_Interaction_DB	tgfbrpathway. TGF-beta receptor signaling.
Reactome	REACT_111102. Signal Transduction. REACT_111217. Metabolism. REACT_115566. Cell Cycle. REACT_116125. Disease. REACT_21300. Mitotic M-M/G1 phases. REACT_604. Hemostasis. REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P62714.
Bgee	P62714.
CleanEx	HS_PPP2CB.
Genevestigator	P62714.
GermOnline	ENSG00000104695. Homo sapiens.
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	P62714.
ChEMBL	CHEMBL2435.
ChiTaRS	PPP2CB. human.
DrugBank	DB00163. Vitamin E.
GenomeRNAi	5516.
NextBio	21334.
SOURCE	Search...

Entry information

Entry name

PP2AB_HUMAN

Accession

Primary (citable) accession number: P62714
Secondary accession number(s): D3DSV4, P11082, Q6FHK5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	July 19, 2004
Last modified:	May 1, 2013
This is version 100 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.