AiPD: Autoinhibited Protein Database

Q08209

Gene name	PPP3CA
Protein name	Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform
Names	CAM-PRP catalytic subunit, Calmodulin-dependent calcineurin A subunit alpha isoform
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5530
EC number	3.1.3.16: Phosphoric monoester hydrolases
Protein Class	SERINE/THREONINE-PROTEIN PHOSPHATASE 2B CATALYTIC SUBUNIT 1-RELATED (PTHR45673)

Descriptions

Calmodulin-stimulated protein phosphatase (Calcineurin in short) plays a central role in the transduction of intracellular Ca2+-mediated signals in processes involving T-cell activation, development and function of the central nervous system, and cardiac growth. Calcineurin is composed of a catalytic domain at the N terminus, B chain, a regulatory domain (RD), autoinhibitory domain (AID), and C-terminal domain (ATC). The catalytic domain is autoinhibited by the AID region in the absence of calcium and CaM. The conformation of autoinhibited Calcineurin is released by the binding of CaM to the RD with the presence of calcium, leading to activation of the phosphatase.

Autoinhibitory domains (AIDs)

Target domain	1-348 (Calcineurin-like phosphoesterase domain)
Relief mechanism	Partner binding
Assay	Structural analysis

AID

407-414 (Autoinhibitory segment)

Target domain

1-348 (Calcineurin-like phosphoesterase domain)

Relief mechanism

Partner binding (CaM binding to CN)

Assay

Structural analysis

Target domain	1-348 (Calcineurin-like phosphoesterase domain)
Relief mechanism	Partner binding
Assay	Structural analysis

AID

468-490 (Autoinhibitory Domain)

Target domain

1-348 (Calcineurin-like phosphoesterase domain)

Relief mechanism

Partner binding (CaM binding to CN)

Assay

Structural analysis

Accessory elements

No accessory elements

References

Rumi-Masante J et al. (2012) "Structural basis for activation of calcineurin by calmodulin", Journal of molecular biology, 415, 307-17

Li SJ et al. (2016) "Cooperative autoinhibition and multi-level activation mechanisms of calcineurin", Cell research, 26, 336-49

Kissinger CR et al. (1995) "Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex", Nature, 378, 641-4

Ye Q et al. (2008) "The complex structure of calmodulin bound to a calcineurin peptide", Proteins, 73, 19-27

Autoinhibited structure

Activated structure

18 structures for Q08209

Entry ID	Method	Resolution	Chain	Position	Source
1AUI	X-ray	210 A	A	1-521	PDB
1M63	X-ray	280 A	A/E	1-372	PDB
1MF8	X-ray	310 A	A	20-392	PDB
2JOG	NMR	-	A	21-347	PDB
2JZI	NMR	-	B	391-414	PDB
2P6B	X-ray	230 A	A/C	1-380	PDB
2R28	X-ray	186 A	C/D	389-413	PDB
2W73	X-ray	145 A	K/L/M/O	395-411	PDB
3LL8	X-ray	200 A	A/C	14-370	PDB
4F0Z	X-ray	170 A	A	1-370	PDB
4Q5U	X-ray	195 A	C	391-414	PDB
5C1V	X-ray	335 A	A/B	2-346	PDB
5SVE	X-ray	260 A	A	1-370	PDB
6NUC	X-ray	190 A	A	1-370	PDB
6NUF	X-ray	190 A	A	1-370	PDB
6NUU	X-ray	230 A	A	1-370	PDB
6UUQ	X-ray	185 A	A	26-339	PDB
AF-Q08209-F1	Predicted				AlphaFoldDB

206 variants for Q08209

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV001027515 RCV001267106 CA357950659 rs1553925558 RCV000509875 VAR_080348	92	H>R	Intellectual disability IECEE1 Epileptic encephalopathy, infantile or early childhood, 1 Inborn genetic diseases [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_080349 CA357948414 rs199706529 RCV000509768	281	H>Q	IECEE1 Epileptic encephalopathy, infantile or early childhood, 1 [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt 1000Genomes ExAC dbSNP gnomAD
RCV000624048 RCV000509989 VAR_080350 rs1553923787 CA357948412	282	E>K	IECEE1 Epileptic encephalopathy, infantile or early childhood, 1 Inborn genetic diseases [UniProt, ClinVar]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs1553920383 RCV000677432	419	S>missing	Epileptic encephalopathy, infantile or early childhood, 1 [ClinVar]	Yes	ClinVar dbSNP
rs1727004803 RCV001198048	429	T>missing	Epileptic encephalopathy, infantile or early childhood, 1 [ClinVar]	Yes	ClinVar dbSNP
RCV000735832 rs1560570541	431	M>missing	Epileptic encephalopathy, infantile or early childhood, 1 [ClinVar]	Yes	ClinVar dbSNP
RCV000625968 rs1553920379	438	S>missing	Epileptic encephalopathy, infantile or early childhood, 1 [ClinVar]	Yes	ClinVar dbSNP
rs1578388765 RCV000987459	438	S>missing	Epileptic encephalopathy, infantile or early childhood, 1 [ClinVar]	Yes	ClinVar dbSNP
CA357947963 RCV000509789 rs1553920376	445	Q>*	Epileptic encephalopathy, infantile or early childhood, 1 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV001865669 RCV000510091 VAR_080352 rs1553920374 CA357947948	447	A>T	Epileptic encephalopathy, infantile or early childhood, 1 IECEE1; unknown pathological significance [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
VAR_081902 CA357947765 RCV000735833 rs1560567347	470	F>L	Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development ACCIID [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
CA357947743 rs1560567337 RCV000735834 VAR_081903	473	A>T	Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development ACCIID [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV001031007 rs1726628642	493	D>N	Epileptic encephalopathy, infantile or early childhood, 1 [ClinVar]	Yes	ClinVar dbSNP
rs1175599344 CA357949688	2	S>C		No	ClinGen TOPMed gnomAD
CA357949683 rs1175599344	2	S>F		No	ClinGen TOPMed gnomAD
rs376661307 CA3024650	3	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs774503546 COSM1309570 CA3024651	3	E>K	urinary_tract [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs749627735 CA3024649	4	P>L		No	ClinGen ExAC gnomAD
CA3024647 rs770314812	6	A>T		No	ClinGen ExAC gnomAD
rs1730017441 RCV001090878	8	D>Y		No	ClinVar dbSNP
rs777239762 CA3024645	9	P>R		No	ClinGen ExAC gnomAD
rs746412506 CA3024646	9	P>T		No	ClinGen ExAC TOPMed gnomAD
CA357949500 rs1384222183	13	T>M		No	ClinGen TOPMed
CA357949512 rs1560730716	13	T>P		No	ClinGen Ensembl
rs1232030786 CA357949495	14	T>A		No	ClinGen gnomAD
rs1309941061 CA357949489	14	T>I		No	ClinGen TOPMed gnomAD
CA103004284 rs866171704	15	D>N		No	ClinGen Ensembl
CA357949427 rs1219287075	18	V>L		No	ClinGen gnomAD
CA357951132 rs1418346739	23	F>I		No	ClinGen gnomAD
rs776490146 CA102987409	27	H>Q		No	ClinGen ExAC TOPMed gnomAD
CA357951102 rs1435984083	27	H>Y		No	ClinGen gnomAD
CA3024564 rs746829234	28	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA3024565 rs770562478	28	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1724781554 RCV001312044	30	T>I		No	ClinVar dbSNP
rs200056844 CA3024562	31	A>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs748137556 CA3024561	33	E>D		No	ClinGen ExAC gnomAD
rs755119794 CA3024560 COSM447171	34	V>A	breast [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA3024559 rs755119794	34	V>G		No	ClinGen ExAC gnomAD
rs1054602875 CA102987408	34	V>L		No	ClinGen Ensembl
CA357951051 rs1351508365	36	D>N		No	ClinGen gnomAD
CA3024558 rs146174889	37	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA357951033 rs1457318131	38	D>G		No	ClinGen TOPMed
rs780337368 CA3024557	38	D>H		No	ClinGen ExAC gnomAD
rs996368040 CA102987407	39	G>R		No	ClinGen Ensembl
CA3024556 rs756386250	41	P>T		No	ClinGen ExAC TOPMed gnomAD
rs767812589 CA3024554	42	R>C		No	ClinGen ExAC gnomAD
rs762386324 CA3024553	42	R>H		No	ClinGen ExAC TOPMed gnomAD
rs762386324 CA357951008	42	R>L		No	ClinGen ExAC TOPMed gnomAD
rs1160406789 CA357950987	45	I>M		No	ClinGen gnomAD
rs1411992353 CA357950969	48	A>S		No	ClinGen gnomAD
rs764832679 CA3024551	48	A>V		No	ClinGen ExAC gnomAD
CA102987405 rs771036944	50	L>F		No	ClinGen Ensembl
CA357950950 rs1258430839	51	M>R		No	ClinGen gnomAD
CA357950937 rs1415693404	52	K>N		No	ClinGen TOPMed
CA357950891 rs1191653592	59	S>N		No	ClinGen gnomAD
rs1191653592 CA357950890	59	S>T		No	ClinGen gnomAD
CA102987404 rs368190241	61	A>T		No	ClinGen ESP
CA3024547 rs760289268	64	I>V		No	ClinGen ExAC gnomAD
CA357950844 rs1243795414	66	T>R		No	ClinGen gnomAD
rs145968865 CA3024545	71	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs141696639 CA3024543	73	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
COSM199991 CA3024544 rs141696639	73	R>Q	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA357950801 rs768666798	74	Q>E		No	ClinGen ExAC TOPMed gnomAD
CA3024542 rs768666798	74	Q>K		No	ClinGen ExAC TOPMed gnomAD
CA3024541 rs749393129	74	Q>P		No	ClinGen ExAC gnomAD
CA3024540 rs371141456	76	K>N		No	ClinGen ESP ExAC gnomAD
rs1436316738 CA357950771	78	L>V		No	ClinGen gnomAD
CA3024539 rs756328481	81	I>V		No	ClinGen ExAC gnomAD
rs1328427827 COSM1049532 CA357950733	83	A>V	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs111452004 CA102977884	96	F>L		No	ClinGen Ensembl
rs1241684644 CA357950564	105	G>R		No	ClinGen gnomAD
rs1312316615 CA357950537	109	A>V		No	ClinGen gnomAD
CA357950532 rs1560606679	110	N>S		No	ClinGen Ensembl
CA3024514 rs778380450	112	R>C		No	ClinGen ExAC gnomAD
rs758954731 CA3024513	112	R>H		No	ClinGen ExAC gnomAD
rs866354491 CA102977883	117	G>E		No	ClinGen Ensembl
rs376535772 CA102977881	119	Y>C		No	ClinGen ESP
rs1385558748 CA357950377	130	V>L		No	ClinGen gnomAD
CA3024495 rs758904818	137	K>E		No	ClinGen ExAC gnomAD
CA357950307 rs1401883929	140	Y>C		No	ClinGen gnomAD
rs748623959 CA3024494	142	K>R		No	ClinGen ExAC gnomAD
CA357950289 rs1477226914	143	T>A		No	ClinGen gnomAD
rs1323355157 CA357950285	143	T>I		No	ClinGen gnomAD
COSM1049531 CA102976791 rs1000796769	165	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated Ensembl
CA3024468 rs777415869	173	R>C		No	ClinGen ExAC TOPMed gnomAD
CA3024467 rs142836504	173	R>H		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA3024469 rs777415869	173	R>S		No	ClinGen ExAC TOPMed gnomAD
CA3024465 rs765118167	174	V>I		No	ClinGen ExAC TOPMed gnomAD
rs759365658 CA3024464	176	D>V		No	ClinGen ExAC TOPMed gnomAD
CA3024463 rs138929276	179	M>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1349802521 CA357950004	181	A>G		No	ClinGen gnomAD
CA357949989 rs1441171271	183	D>E		No	ClinGen gnomAD
rs1391497881 CA357949958	188	A>G		No	ClinGen gnomAD
CA357949960 rs1330417912	188	A>S		No	ClinGen gnomAD
CA357949952 rs1172335185	189	A>G		No	ClinGen TOPMed gnomAD
rs1483715092 CA357949943	191	M>L		No	ClinGen TOPMed
rs1182750511 CA357949859	202	L>F		No	ClinGen gnomAD
CA3024456 rs769123247	206	I>M		No	ClinGen ExAC TOPMed gnomAD
rs749789772 CA3024455	208	T>I		No	ClinGen ExAC gnomAD
rs1409640610 CA357949801	210	D>Y		No	ClinGen TOPMed
rs770369705 CA3024453	211	D>G		No	ClinGen ExAC gnomAD
CA3024430 rs778643523	215	L>V		No	ClinGen ExAC gnomAD
rs1475577978 CA357949391	216	D>N		No	ClinGen gnomAD
rs1405078762 CA357949371	218	F>L		No	ClinGen TOPMed
CA3024429 rs754775984	219	K>R		No	ClinGen ExAC gnomAD
CA357949354 rs1184839287	221	P>S		No	ClinGen gnomAD
rs1243748825 CA357949316	227	M>V		No	ClinGen gnomAD
rs756099128 CA3024426	236	L>V		No	ClinGen ExAC TOPMed gnomAD
CA357949213 rs1467830676	241	N>S		No	ClinGen gnomAD
rs749733697 CA102976202	246	E>Q		No	ClinGen Ensembl
rs1033778784 CA102976201	249	T>S		No	ClinGen TOPMed
rs1270922247 CA357949150	250	H>D		No	ClinGen gnomAD
rs1450390683 CA357949129	253	V>I		No	ClinGen TOPMed
rs867979520 CA102976200	261	S>N		No	ClinGen gnomAD
CA3024410 rs748997466	263	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1269263876 CA357948485	271	H>D		No	ClinGen TOPMed
rs1444501462 CA357948480	271	H>Q		No	ClinGen gnomAD
rs1355122946 CA357948474	272	N>S		No	ClinGen gnomAD
rs1434092585 CA357948443	276	S>C		No	ClinGen gnomAD
rs540250871 CA102975023	277	I>L		No	ClinGen ExAC TOPMed gnomAD
CA3024405 rs540250871	277	I>V		No	ClinGen ExAC TOPMed gnomAD
rs185115989 CA3024401	286	A>G		No	ClinGen 1000Genomes ExAC gnomAD
rs542649732 CA3024402	286	A>S		No	ClinGen 1000Genomes ExAC gnomAD
rs185115989 CA102975022	286	A>V		No	ClinGen 1000Genomes ExAC gnomAD
rs1485755431 CA357949784	289	R>H		No	ClinGen TOPMed gnomAD
rs1259403610 CA553702566	291	Y>*		No	ClinGen gnomAD
CA357949701 rs1313190046	295	Q>E		No	ClinGen TOPMed
rs1427394223 CA357949689	296	T>S		No	ClinGen gnomAD
CA3024384 rs752862238	305	I>V		No	ClinGen ExAC gnomAD
rs1578427507 CA357949548	310	N>D		No	ClinGen Ensembl
rs959612309 CA102974762	312	L>I		No	ClinGen TOPMed
rs4146577 CA102974761	318	K>Q		No	ClinGen Ensembl
CA357949048 rs1163377552	320	A>T		No	ClinGen gnomAD
CA3024360 rs768159553	321	V>I		No	ClinGen ExAC gnomAD
CA357949041 rs768159553	321	V>L		No	ClinGen ExAC gnomAD
rs1223403393 CA357948976	329	M>I		No	ClinGen TOPMed
CA357948980 rs1450495357	329	M>T		No	ClinGen gnomAD
rs752223096 CA3024358	335	N>S		No	ClinGen ExAC TOPMed gnomAD
CA357948847 rs1209744818	347	M>T		No	ClinGen gnomAD
CA3024355 rs776210956	348	D>N		No	ClinGen ExAC TOPMed gnomAD
CA357948838 rs1337481113	348	D>V		No	ClinGen gnomAD
CA3024353 rs760412015	351	T>S		No	ClinGen ExAC gnomAD
CA357948765 rs1578413360	359	E>G		No	ClinGen Ensembl
rs1409876017 CA357948678	370	N>S		No	ClinGen TOPMed gnomAD
CA357948668 rs1375394757	371	I>S		No	ClinGen gnomAD
rs1403289502 CA357948617	379	S>A		No	ClinGen gnomAD
CA3024332 rs774161035	383	G>V		No	ClinGen ExAC TOPMed gnomAD
CA3024331 rs768724533	384	F>C		No	ClinGen ExAC gnomAD
CA3024307 rs536640678	387	A>T		No	ClinGen 1000Genomes ExAC gnomAD
rs569765595 CA3024306	388	T>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA3024305 rs776993681	393	K>N		No	ClinGen ExAC gnomAD
CA357948307 rs1270077332	395	V>G		No	ClinGen gnomAD
rs1201745966 CA357948297	397	R>G		No	ClinGen gnomAD
rs1429103068 CA357948290	398	N>H		No	ClinGen gnomAD
rs1727467178 RCV001216094	406	M>I		No	ClinVar dbSNP
rs1436739036 CA357948231	406	M>K		No	ClinGen gnomAD
rs769247405 CA3024273	419	S>C		No	ClinGen ExAC gnomAD
CA357948125 rs1303693414	419	S>N		No	ClinGen gnomAD
CA3024272 COSM3824844 rs745416220	422	T>M	breast [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs1372357775 CA357948093	425	G>S		No	ClinGen gnomAD
rs1560570546 RCV000762100	426	L>missing		No	ClinVar dbSNP
CA357948059 rs1308518859	430	G>D		No	ClinGen gnomAD
rs1175529557 CA357948055	431	M>V		No	ClinGen TOPMed
CA357948028 rs369318194	434	S>R		No	ClinGen ESP TOPMed gnomAD
rs746729174 CA3024269	441	K>R		No	ClinGen ExAC gnomAD
rs1179419824 CA357947979	442	Q>L		No	ClinGen gnomAD
CA357947954 rs1473264145	446	S>N		No	ClinGen gnomAD
CA357947906 rs1330073156	451	A>V		No	ClinGen gnomAD
rs749840124 CA3024251	452	I>V		No	ClinGen ExAC TOPMed gnomAD
rs763442265 CA3024233	464	Q>K		No	ClinGen ExAC gnomAD
RCV001008246 rs1578382902	465	H>missing		No	ClinVar dbSNP
CA357947798 rs1374390478	465	H>R		No	ClinGen gnomAD
CA357947770 rs1160055643	469	S>T		No	ClinGen TOPMed
CA3024232 rs775976578	472	E>K		No	ClinGen ExAC gnomAD
rs368195162 CA102969036	478	R>Q		No	ClinGen ESP TOPMed
rs1360040556 CA357947673	483	M>V		No	ClinGen TOPMed
rs867473896 CA102969035	484	P>S		No	ClinGen Ensembl
CA357947660 rs1394307680	485	P>T		No	ClinGen gnomAD
CA357947651 rs1296940907	486	R>H		No	ClinGen TOPMed
CA102969033 rs878969404	490	M>I		No	ClinGen Ensembl
rs1373331738 CA357947615	491	P>R		No	ClinGen TOPMed
rs771722172 CA3024228	492	S>C		No	ClinGen ExAC gnomAD
CA102969032 rs1003181111	494	A>D		No	ClinGen TOPMed gnomAD
CA357947599 rs778848431	494	A>S		No	ClinGen ExAC TOPMed gnomAD
COSM166947 CA3024226 rs778848431	494	A>T	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
rs768576482 CA3024225	495	N>S		No	ClinGen ExAC gnomAD
rs867409069 CA102969031	496	L>F		No	ClinGen gnomAD
CA357947589 rs867409069	496	L>I		No	ClinGen gnomAD
rs1230679427 CA357947569	499	I>V		No	ClinGen gnomAD
CA357947556 rs1332460277	500	N>K		No	ClinGen gnomAD
rs1578382769 CA357947559	500	N>S		No	ClinGen Ensembl
CA357947532 rs1390292432	504	T>N		No	ClinGen TOPMed gnomAD
CA357947531 rs1390292432	504	T>S		No	ClinGen TOPMed gnomAD
CA357947524 rs1369276872	505	S>L		No	ClinGen gnomAD
rs1343836557 CA357947519	506	E>G		No	ClinGen TOPMed gnomAD
rs374275483 CA3024223	507	T>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs750488827 CA3024221	509	G>S		No	ClinGen ExAC gnomAD
rs781181414 CA3024220	510	T>M		No	ClinGen ExAC TOPMed gnomAD
rs781181414 CA357947494	510	T>R		No	ClinGen ExAC TOPMed gnomAD
rs1171177832 CA357947495	510	T>S		No	ClinGen gnomAD
rs751843872 CA3024218	512	S>G		No	ClinGen ExAC gnomAD
CA3024217 rs199874915	513	N>S		No	ClinGen ExAC TOPMed gnomAD
CA357947467 rs1184186677	514	G>A		No	ClinGen gnomAD
CA357947437 rs1277738384	518	S>N		No	ClinGen TOPMed gnomAD
CA3024215 rs753154536	520	I>T		No	ClinGen ExAC gnomAD
rs1578382624 CA357947414	521	Q>R		No	ClinGen Ensembl

No associated diseases with Q08209

8 regional properties for Q08209

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	251 - 504	IPR000719
domain	SH2 domain	130 - 229	IPR000980
domain	Serine-threonine/tyrosine-protein kinase, catalytic domain	252 - 500	IPR001245
domain	SH3 domain	65 - 126	IPR001452
active_site	Tyrosine-protein kinase, active site	366 - 378	IPR008266
binding_site	Protein kinase, ATP binding site	257 - 279	IPR017441
domain	Tyrosine-protein kinase, catalytic domain	251 - 500	IPR020635
domain	Tyrosine-protein kinase Fgr, SH2 domain	128 - 228	IPR035693

Functions

		Description
EC Number	3.1.3.16	Phosphoric monoester hydrolases
Subcellular Localization	Cytoplasm Cell membrane ; Peripheral membrane protein Cell membrane, sarcolemma Cytoplasm, myofibril, sarcomere, Z line Cell projection, dendritic spine	Colocalizes with ACTN1 and MYOZ2 at the Z line in heart and skeletal muscle (By similarity) Recruited to the cell membrane by scaffold protein AKAP5 following L-type Ca(2+)-channel activation (PubMed:22343722)
PANTHER Family	PTHR45673	SERINE/THREONINE-PROTEIN PHOSPHATASE 2B CATALYTIC SUBUNIT 1-RELATED
PANTHER Subfamily	PTHR45673:SF5	PROTEIN PHOSPHATASE 3 CATALYTIC SUBUNIT ALPHA
PANTHER Protein Class	protein phosphatase protein modifying enzyme
PANTHER Pathway Category	CCKR signaling map CaN T cell activation Calcineurin Wnt signaling pathway Calcineurin B cell activation Calcineurin Gonadotropin-releasing hormone receptor pathway Caln

13 GO annotations of cellular component

Name	Definition
calcineurin complex	A heterodimeric calcium ion and calmodulin dependent protein phosphatase composed of catalytic and regulatory subunits; the regulatory subunit is very similar in sequence to calmodulin.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
dendritic spine	A small, membranous protrusion from a dendrite that forms a postsynaptic compartment, typically receiving input from a single presynapse. They function as partially isolated biochemical and an electrical compartments. Spine morphology is variable:they can be thin, stubby, mushroom, or branched, with a continuum of intermediate morphologies. They typically terminate in a bulb shape, linked to the dendritic shaft by a restriction. Spine remodeling is though to be involved in synaptic plasticity.
extrinsic component of plasma membrane	The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to one of its surfaces, but not integrated into the hydrophobic region.
glutamatergic synapse	A synapse that uses glutamate as a neurotransmitter.
mitochondrion	A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
sarcolemma	The outer membrane of a muscle cell, consisting of the plasma membrane, a covering basement membrane (about 100 nm thick and sometimes common to more than one fiber), and the associated loose network of collagen fibers.
Schaffer collateral - CA1 synapse	A synapse between the Schaffer collateral axon of a CA3 pyramidal cell and a CA1 pyramidal cell.
slit diaphragm	A specialized cell-cell junction found between the interdigitating foot processes of the glomerular epithelium (the podocytes) in the vertebrate kidney, which is adapted for facilitating glomerular filtration.
Z disc	Platelike region of a muscle sarcomere to which the plus ends of actin filaments are attached.

9 GO annotations of molecular function

Name	Definition
ATPase binding	Binding to an ATPase, any enzyme that catalyzes the hydrolysis of ATP.
calcium ion binding	Binding to a calcium ion (Ca2+).
calmodulin binding	Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states.
calmodulin-dependent protein phosphatase activity	Catalysis of the reaction: protein serine/threonine phosphate + H2O = protein serine/threonine + phosphate, dependent on the presence of calcium-bound calmodulin.
cyclosporin A binding	Binding to cyclosporin A, a cyclic undecapeptide that contains several N-methylated and unusual amino acids.
enzyme binding	Binding to an enzyme, a protein with catalytic activity.
protein dimerization activity	The formation of a protein dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits.
protein serine/threonine phosphatase activity	Catalysis of the reaction: protein serine phosphate + H2O = protein serine + phosphate, and protein threonine phosphate + H2O = protein threonine + phosphate.
protein-containing complex binding	Binding to a macromolecular complex.

33 GO annotations of biological process

Name	Definition
aging	A developmental process that is a deterioration and loss of function over time. Aging includes loss of functions such as resistance to disease, homeostasis, and fertility, as well as wear and tear. Aging includes cellular senescence, but is more inclusive. May precede death and may succeed developmental maturation (GO:0021700).
brain development	The process whose specific outcome is the progression of the brain over time, from its formation to the mature structure. Brain development begins with patterning events in the neural tube and ends with the mature structure that is the center of thought and emotion. The brain is responsible for the coordination and control of bodily activities and the interpretation of information from the senses (sight, hearing, smell, etc.).
calcineurin-mediated signaling	Any intracellular signal transduction in which the signal is passed on within the cell by activation of a transcription factor as a consequence of dephosphorylation by Ca(2+)-activated calcineurin. The process begins with calcium-dependent activation of the phosphatase calcineurin. Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase with a conserved function in eukaryotic species from yeast to humans. In yeast and fungi, calcineurin regulates stress signaling and cell cycle, and sporulation and virulence in pathogenic fungi. In metazoans, calcineurin is involved in cell commitment, organogenesis and organ development and immune function of T-lymphocytes. By a conserved mechanism, calcineurin phosphatase activates fungal Crz1 and mammalian NFATc by dephosphorylation and translocation of these transcription factors to the nucleus to regulate gene expression.
calcineurin-NFAT signaling cascade	Any intracellular signal transduction in which the signal is passed on within the cell by activation of a member of the NFAT protein family as a consequence of NFAT dephosphorylation by Ca(2+)-activated calcineurin. The cascade begins with calcium-dependent activation of the phosphatase calcineurin. Calcineurin dephosphorylates multiple phosphoserine residues on NFAT, resulting in the translocation of NFAT to the nucleus. The cascade ends with regulation of transcription by NFAT. The calcineurin-NFAT cascade lies downstream of many cell surface receptors, including G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) that signal to mobilize calcium ions (Ca2+).
calcium ion transport	The directed movement of calcium (Ca) ions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
cardiac muscle hypertrophy in response to stress	The physiological enlargement or overgrowth of all or part of the heart muscle due to an increase in size (not length) of individual cardiac muscle fibers, without cell division, as a result of a disturbance in organismal or cellular homeostasis.
cellular response to glucose stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucose stimulus.
dephosphorylation	The process of removing one or more phosphoric (ester or anhydride) residues from a molecule.
excitatory postsynaptic potential	A process that leads to a temporary increase in postsynaptic potential due to the flow of positively charged ions into the postsynaptic cell. The flow of ions that causes an EPSP is an excitatory postsynaptic current (EPSC) and makes it easier for the neuron to fire an action potential.
G1/S transition of mitotic cell cycle	The mitotic cell cycle transition by which a cell in G1 commits to S phase. The process begins with the build up of G1 cyclin-dependent kinase (G1 CDK), resulting in the activation of transcription of G1 cyclins. The process ends with the positive feedback of the G1 cyclins on the G1 CDK which commits the cell to S phase, in which DNA replication is initiated.
multicellular organismal response to stress	Any process that results in a change in state or activity of a multicellular organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating the organism is under stress. The stress is usually, but not necessarily, exogenous (e.g. temperature, humidity, ionizing radiation).
negative regulation of chromatin binding	Any process that stops or reduces the frequency, rate or extent of chromatin binding. Chromatin binding is the selective interaction with chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase.
negative regulation of dendrite morphogenesis	Any process that stops, prevents, or reduces the frequency, rate or extent of dendrite morphogenesis.
negative regulation of insulin secretion	Any process that stops, prevents, or reduces the frequency, rate or extent of the regulated release of insulin.
negative regulation of production of miRNAs involved in gene silencing by miRNA	Any process that stops, prevents or reduces the frequency, rate or extent of maturation of miRNAs.
peptidyl-serine dephosphorylation	The removal of phosphoric residues from peptidyl-O-phospho-L-serine to form peptidyl-serine.
positive regulation of cardiac muscle hypertrophy in response to stress	Any process that activates or increases the frequency, rate or extent of cardiac muscle hypertrophy in response to stress.
positive regulation of cell adhesion	Any process that activates or increases the frequency, rate or extent of cell adhesion.
positive regulation of cell migration	Any process that activates or increases the frequency, rate or extent of cell migration.
positive regulation of connective tissue replacement	Any process that activates or increases the frequency, rate or extent of connective tissue replacement.
positive regulation of DNA-binding transcription factor activity	Any process that activates or increases the frequency, rate or extent of activity of a transcription factor, any factor involved in the initiation or regulation of transcription.
positive regulation of endocytosis	Any process that activates or increases the frequency, rate or extent of endocytosis.
positive regulation of transcription by RNA polymerase II	Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
postsynaptic modulation of chemical synaptic transmission	Any process, acting in the postsynapse that results in modulation of chemical synaptic transmission.
protein dephosphorylation	The process of removing one or more phosphoric residues from a protein.
protein import into nucleus	The directed movement of a protein from the cytoplasm to the nucleus.
response to amphetamine	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an amphetamine stimulus. Amphetamines consist of a group of compounds related to alpha-methylphenethylamine.
response to calcium ion	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a calcium ion stimulus.
skeletal muscle fiber development	The process whose specific outcome is the progression of the skeletal muscle fiber over time, from its formation to the mature structure. Muscle fibers are formed by the maturation of myotubes. They can be classed as slow, intermediate/fast or fast.
skeletal muscle tissue regeneration	The regrowth of skeletal muscle tissue to repair injured or damaged muscle fibers in the postnatal stage.
T cell activation	The change in morphology and behavior of a mature or immature T cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
transition between fast and slow fiber	The process of conversion of fast-contracting muscle fibers to a slower character. This may involve slowing of contractile rate, slow myosin gene induction, increase in oxidative metabolic properties, altered electrophysiology and altered innervation. This process also regulates skeletal muscle adapatation.
wound healing	The series of events that restore integrity to a damaged tissue, following an injury.

13 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P23287	CNA1	Serine/threonine-protein phosphatase 2B catalytic subunit A1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	PR
P48452	PPP3CA	Protein phosphatase 3 catalytic subunit alpha	Bos taurus (Bovine)	SS
Q27889	Pp2B-14D	Serine/threonine-protein phosphatase 2B catalytic subunit 2	Drosophila melanogaster (Fruit fly)	SS
P48456	CanA1	Serine/threonine-protein phosphatase 2B catalytic subunit 1	Drosophila melanogaster (Fruit fly)	SS
Q9VXF1	CanA-14F	Serine/threonine-protein phosphatase 2B catalytic subunit 3	Drosophila melanogaster (Fruit fly)	SS
P48454	PPP3CC	Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform	Homo sapiens (Human)	SS
P16298	PPP3CB	Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform	Homo sapiens (Human)	EV
P48453	Ppp3cb	Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform	Mus musculus (Mouse)	SS
P48455	Ppp3cc	Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform	Mus musculus (Mouse)	PR
P63328	Ppp3ca	Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform	Mus musculus (Mouse)	EV
P20651	Ppp3cb	Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform	Rattus norvegicus (Rat)	SS
P63329	Ppp3ca	Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform	Rattus norvegicus (Rat)	SS
Q0G819	tax-6	Serine/threonine-protein phosphatase 2B catalytic subunit	Caenorhabditis elegans	SS

10	20	30	40	50	60
MSEPKAIDPK	LSTTDRVVKA	VPFPPSHRLT	AKEVFDNDGK	PRVDILKAHL	MKEGRLEESV
70	80	90	100	110	120
ALRIITEGAS	ILRQEKNLLD	IDAPVTVCGD	IHGQFFDLMK	LFEVGGSPAN	TRYLFLGDYV
130	140	150	160	170	180
DRGYFSIECV	LYLWALKILY	PKTLFLLRGN	HECRHLTEYF	TFKQECKIKY	SERVYDACMD
190	200	210	220	230	240
AFDCLPLAAL	MNQQFLCVHG	GLSPEINTLD	DIRKLDRFKE	PPAYGPMCDI	LWSDPLEDFG
250	260	270	280	290	300
NEKTQEHFTH	NTVRGCSYFY	SYPAVCEFLQ	HNNLLSILRA	HEAQDAGYRM	YRKSQTTGFP
310	320	330	340	350	360
SLITIFSAPN	YLDVYNNKAA	VLKYENNVMN	IRQFNCSPHP	YWLPNFMDVF	TWSLPFVGEK
370	380	390	400	410	420
VTEMLVNVLN	ICSDDELGSE	EDGFDGATAA	ARKEVIRNKI	RAIGKMARVF	SVLREESESV
430	440	450	460	470	480
LTLKGLTPTG	MLPSGVLSGG	KQTLQSATVE	AIEADEAIKG	FSPQHKITSF	EEAKGLDRIN
490	500	510	520
ERMPPRRDAM	PSDANLNSIN	KALTSETNGT	DSNGSNSSNI	Q