P16298 (PP2BB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
CAM-PRP catalytic subunit
Calmodulin-dependent calcineurin A subunit beta isoform

Gene names

Name:	PPP3CB
Synonyms:	CALNA2, CALNB, CNA2

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	524 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin.
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 1 Fe3+ ion per subunit By similarity. Binds 1 zinc ion per subunit By similarity.
Subunit structure	Composed of two components (A and B), the A component is the catalytic subunit and the B component confers calcium sensitivity.
Sequence similarities	Belongs to the PPP phosphatase family. PP-2B subfamily.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Ligand	Calmodulin-binding Iron Metal-binding Zinc
Molecular function	Hydrolase Protein phosphatase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell differentiation Inferred from electronic annotation. Source: Compara T cell homeostasis Inferred from electronic annotation. Source: Compara T cell proliferation Non-traceable author statement PubMed 8978785. Source: UniProtKB axon extension Traceable author statement PubMed 21531385. Source: UniProtKB calcium ion-dependent exocytosis Inferred from sequence or structural similarity. Source: UniProtKB cellular response to drug Inferred from direct assay PubMed 11005320. Source: UniProtKB heart development Inferred from electronic annotation. Source: Compara learning Traceable author statement PubMed 21531385. Source: UniProtKB memory Traceable author statement PubMed 21531385. Source: UniProtKB negative regulation of T cell mediated cytotoxicity Inferred from electronic annotation. Source: Compara positive regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription, DNA-dependent Non-traceable author statement PubMed 8978785. Source: UniProtKB protein dephosphorylation Inferred from sequence or structural similarity. Source: UniProtKB protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of synaptic plasticity Traceable author statement PubMed 21531385. Source: UniProtKB response to cytokine stimulus Inferred from electronic annotation. Source: Compara signal transduction Non-traceable author statement PubMed 8978785. Source: UniProtKB social behavior Inferred from expression pattern PubMed 21531385. Source: UniProtKB
Cellular_component	calcineurin complex Inferred from direct assay PubMed 8524402. Source: UniProtKB cytosol Traceable author statement. Source: Reactome plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from direct assay PubMed 8524402. Source: UniProtKB calmodulin binding Inferred from direct assay PubMed 11005320Ref.1. Source: UniProtKB calmodulin-dependent protein phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB drug binding Inferred from direct assay PubMed 11005320. Source: UniProtKB protein phosphatase 2B binding Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Irak1	Q99J34	2	EBI-1759540,EBI-6117042	From a different organism.
IRF2	P14316	2	EBI-1759540,EBI-2866589

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist. Calcineurin A beta isoform consists of at least two isoenzymes that may result from alternative splicing events.

Isoform 1 (identifier: P16298-1)

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 2 (identifier: P16298-2)

The sequence of this isoform differs from the canonical sequence as follows:
     137-137: E → EHVLGTEDISINPHNNINE
     456-524: ATVEAIEAEK...NHGTGNHTAQ → GNDVMQLAVP...LLFFSSCLSS

Isoform 3 (identifier: P16298-3)

The sequence of this isoform differs from the canonical sequence as follows:
     395-395: D → DV
     456-465: Missing.

Isoform 4 (identifier: P16298-4)

The sequence of this isoform differs from the canonical sequence as follows:
     395-395: D → DV

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 524	524	Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform		PRO_0000058825
Regions
	Region	1 – 310	310	Catalytic
	Region	256 – 262	7	Calcineurin B binding-site 1 Potential
	Region	305 – 310	6	Calcineurin B binding-site 2 Potential
	Region	401 – 423	23	Calmodulin-binding Potential
	Region	474 – 496	23	Inhibitory domain
	Compositional bias	11 – 21	11	Poly-Pro
Sites
	Active site	160	1	Proton donor By similarity
	Metal binding	99	1	Iron By similarity
	Metal binding	101	1	Iron By similarity
	Metal binding	127	1	Iron By similarity
	Metal binding	127	1	Zinc By similarity
	Metal binding	159	1	Zinc By similarity
	Metal binding	208	1	Zinc By similarity
	Metal binding	290	1	Zinc By similarity
Natural variations
	Alternative sequence	137	1	E → EHVLGTEDISINPHNNINE in isoform 2.		VSP_005096
	Alternative sequence	395	1	D → DV in isoform 3 and isoform 4.		VSP_043803
	Alternative sequence	456 – 524	69	ATVEA…NHTAQ → GNDVMQLAVPQMDWGTPHSF ANNSHNACREFLLFFSSCLS S in isoform 2.		VSP_005097
	Alternative sequence	456 – 465	10	Missing in isoform 3.		VSP_012617

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 2005. Version 2. Checksum: 7661183F3C2362C8	FASTA	524	59,024
	10 20 30 40 50 60 MAAPEPARAA PPPPPPPPPP PGADRVVKAV PFPPTHRLTS EEVFDLDGIP RVDVLKNHLV 70 80 90 100 110 120 KEGRVDEEIA LRIINEGAAI LRREKTMIEV EAPITVCGDI HGQFFDLMKL FEVGGSPANT 130 140 150 160 170 180 RYLFLGDYVD RGYFSIECVL YLWVLKILYP STLFLLRGNH ECRHLTEYFT FKQECKIKYS 190 200 210 220 230 240 ERVYEACMEA FDSLPLAALL NQQFLCVHGG LSPEIHTLDD IRRLDRFKEP PAFGPMCDLL 250 260 270 280 290 300 WSDPSEDFGN EKSQEHFSHN TVRGCSYFYN YPAVCEFLQN NNLLSIIRAH EAQDAGYRMY 310 320 330 340 350 360 RKSQTTGFPS LITIFSAPNY LDVYNNKAAV LKYENNVMNI RQFNCSPHPY WLPNFMDVFT 370 380 390 400 410 420 WSLPFVGEKV TEMLVNVLSI CSDDELMTEG EDQFDGSAAA RKEIIRNKIR AIGKMARVFS 430 440 450 460 470 480 VLREESESVL TLKGLTPTGM LPSGVLAGGR QTLQSATVEA IEAEKAIRGF SPPHRICSFE 490 500 510 520 EAKGLDRINE RMPPRKDAVQ QDGFNSLNTA HATENHGTGN HTAQ
	Isoform 2 [UniParc]. Checksum: 1B0BFA63FB98E06D	FASTA	514	58,013
	10 20 30 40 50 60 MAAPEPARAA PPPPPPPPPP PGADRVVKAV PFPPTHRLTS EEVFDLDGIP RVDVLKNHLV 70 80 90 100 110 120 KEGRVDEEIA LRIINEGAAI LRREKTMIEV EAPITVCGDI HGQFFDLMKL FEVGGSPANT 130 140 150 160 170 180 RYLFLGDYVD RGYFSIEHVL GTEDISINPH NNINECVLYL WVLKILYPST LFLLRGNHEC 190 200 210 220 230 240 RHLTEYFTFK QECKIKYSER VYEACMEAFD SLPLAALLNQ QFLCVHGGLS PEIHTLDDIR 250 260 270 280 290 300 RLDRFKEPPA FGPMCDLLWS DPSEDFGNEK SQEHFSHNTV RGCSYFYNYP AVCEFLQNNN 310 320 330 340 350 360 LLSIIRAHEA QDAGYRMYRK SQTTGFPSLI TIFSAPNYLD VYNNKAAVLK YENNVMNIRQ 370 380 390 400 410 420 FNCSPHPYWL PNFMDVFTWS LPFVGEKVTE MLVNVLSICS DDELMTEGED QFDGSAAARK 430 440 450 460 470 480 EIIRNKIRAI GKMARVFSVL REESESVLTL KGLTPTGMLP SGVLAGGRQT LQSGNDVMQL 490 500 510 AVPQMDWGTP HSFANNSHNA CREFLLFFSS CLSS
	Isoform 3 [UniParc]. Checksum: A6762D9468A09B51	FASTA	515	58,081
	10 20 30 40 50 60 MAAPEPARAA PPPPPPPPPP PGADRVVKAV PFPPTHRLTS EEVFDLDGIP RVDVLKNHLV 70 80 90 100 110 120 KEGRVDEEIA LRIINEGAAI LRREKTMIEV EAPITVCGDI HGQFFDLMKL FEVGGSPANT 130 140 150 160 170 180 RYLFLGDYVD RGYFSIECVL YLWVLKILYP STLFLLRGNH ECRHLTEYFT FKQECKIKYS 190 200 210 220 230 240 ERVYEACMEA FDSLPLAALL NQQFLCVHGG LSPEIHTLDD IRRLDRFKEP PAFGPMCDLL 250 260 270 280 290 300 WSDPSEDFGN EKSQEHFSHN TVRGCSYFYN YPAVCEFLQN NNLLSIIRAH EAQDAGYRMY 310 320 330 340 350 360 RKSQTTGFPS LITIFSAPNY LDVYNNKAAV LKYENNVMNI RQFNCSPHPY WLPNFMDVFT 370 380 390 400 410 420 WSLPFVGEKV TEMLVNVLSI CSDDELMTEG EDQFDVGSAA ARKEIIRNKI RAIGKMARVF 430 440 450 460 470 480 SVLREESESV LTLKGLTPTG MLPSGVLAGG RQTLQSAIRG FSPPHRICSF EEAKGLDRIN 490 500 510 ERMPPRKDAV QQDGFNSLNT AHATENHGTG NHTAQ
	Isoform 4 [UniParc]. Checksum: ADB0ECB75371B574	FASTA	525	59,123
	10 20 30 40 50 60 MAAPEPARAA PPPPPPPPPP PGADRVVKAV PFPPTHRLTS EEVFDLDGIP RVDVLKNHLV 70 80 90 100 110 120 KEGRVDEEIA LRIINEGAAI LRREKTMIEV EAPITVCGDI HGQFFDLMKL FEVGGSPANT 130 140 150 160 170 180 RYLFLGDYVD RGYFSIECVL YLWVLKILYP STLFLLRGNH ECRHLTEYFT FKQECKIKYS 190 200 210 220 230 240 ERVYEACMEA FDSLPLAALL NQQFLCVHGG LSPEIHTLDD IRRLDRFKEP PAFGPMCDLL 250 260 270 280 290 300 WSDPSEDFGN EKSQEHFSHN TVRGCSYFYN YPAVCEFLQN NNLLSIIRAH EAQDAGYRMY 310 320 330 340 350 360 RKSQTTGFPS LITIFSAPNY LDVYNNKAAV LKYENNVMNI RQFNCSPHPY WLPNFMDVFT 370 380 390 400 410 420 WSLPFVGEKV TEMLVNVLSI CSDDELMTEG EDQFDVGSAA ARKEIIRNKI RAIGKMARVF 430 440 450 460 470 480 SVLREESESV LTLKGLTPTG MLPSGVLAGG RQTLQSATVE AIEAEKAIRG FSPPHRICSF 490 500 510 520 EEAKGLDRIN ERMPPRKDAV QQDGFNSLNT AHATENHGTG NHTAQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human calcineurin A: evidence for two isozymes and identification of a polyproline structural domain." Guerini D., Klee C.B. Proc. Natl. Acad. Sci. U.S.A. 86:9183-9187(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[2]	"Identification of a third alternatively spliced cDNA encoding the catalytic subunit of protein phosphatase 2B beta." McPartlin A.E., Barker H.M., Cohen P.T.W. Biochim. Biophys. Acta 1088:308-310(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Teratocarcinoma.
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). Tissue: Testis.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M29551 mRNA. Translation: AAA35706.1. M29550 mRNA. Translation: AAA35705.1. AJ488506 mRNA. Translation: CAD32694.1. AL353731, AL359074 Genomic DNA. Translation: CAI52487.1. AL359074, AL353731 Genomic DNA. Translation: CAI52473.1. CH471083 Genomic DNA. Translation: EAW54497.1. CH471083 Genomic DNA. Translation: EAW54498.1. BC028049 mRNA. Translation: AAH28049.1.
IPI	IPI00027809. IPI00181738. IPI00218862. IPI00872930.
PIR	A36222. B36222.
RefSeq	NP_001135825.1. NM_001142353.1. NP_001135826.1. NM_001142354.1. NP_066955.1. NM_021132.2.
UniGene	Hs.500067.
3D structure databases
ProteinModelPortal	P16298.
ModBase	Search...
Protein-protein interaction databases
IntAct	P16298. 4 interactions.
STRING	9606.ENSP00000378306.
PTM databases
PhosphoSite	P16298.
Polymorphism databases
DMDM	60659599.
Proteomic databases
PaxDb	P16298.
PRIDE	P16298.
Protocols and materials databases
DNASU	5532.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360663; ENSP00000353881; ENSG00000107758. ENST00000394822; ENSP00000378299; ENSG00000107758. ENST00000394828; ENSP00000378305; ENSG00000107758. ENST00000394829; ENSP00000378306; ENSG00000107758.
GeneID	5532.
KEGG	hsa:5532.
UCSC	uc001jue.3. human. uc001jui.2. human.
Organism-specific databases
CTD	5532.
GeneCards	GC10M075196.
HGNC	HGNC:9315. PPP3CB.
HPA	HPA008233.
MIM	114106. gene.
neXtProt	NX_P16298.
PharmGKB	PA33679.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0639.
HOGENOM	HOG000172699.
HOVERGEN	HBG002819.
KO	K04348.
OMA	DQFDVKV.
OrthoDB	EOG4PVNZK.
Enzyme and pathway databases
Pathway_Interaction_DB	bcr_5pathway. BCR signaling pathway. tcrcalciumpathway. Calcium signaling in the CD4+ TCR pathway. cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells. il12_stat4pathway. IL12 signaling mediated by STAT4. il12_2pathway. IL12-mediated signaling events. nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
Reactome	REACT_111102. Signal Transduction. REACT_118664. Calcineurin Dephosphorylates NFATC1/2/3.
Gene expression databases
ArrayExpress	P16298.
Bgee	P16298.
CleanEx	HS_PPP3CB.
Genevestigator	P16298.
GermOnline	ENSG00000107758. 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	P16298.
ChEMBL	CHEMBL5278.
ChiTaRS	PPP3CB. human.
GenomeRNAi	5532.
NextBio	21430.
SOURCE	Search...

Entry information

Entry name

PP2BB_HUMAN

Accession

Primary (citable) accession number: P16298
Secondary accession number(s): P16299 , Q5F2F9, Q8N1F0, Q8N3W4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	February 1, 2005
Last modified:	May 1, 2013
This is version 103 of the entry and version 2 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.