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Protein

Peptidyl-prolyl cis-trans isomerase A

Gene

PPIA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

Catalytic activityi

Peptidylproline (omega=180) = peptidylproline (omega=0).

Enzyme regulationi

Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase.

GO - Molecular functioni

  • cyclosporin A binding Source: UniProtKB
  • peptidyl-prolyl cis-trans isomerase activity Source: UniProtKB
  • RNA binding Source: UniProtKB
  • unfolded protein binding Source: UniProtKB
  • virion binding Source: UniProtKB

GO - Biological processi

  • entry into host cell Source: Reactome
  • establishment of integrated proviral latency Source: Reactome
  • fusion of virus membrane with host plasma membrane Source: Reactome
  • interleukin-12-mediated signaling pathway Source: Reactome
  • leukocyte migration Source: Reactome
  • lipid particle organization Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • positive regulation of protein secretion Source: UniProtKB
  • positive regulation of viral genome replication Source: UniProtKB
  • protein folding Source: UniProtKB
  • protein peptidyl-prolyl isomerization Source: UniProtKB
  • regulation of viral genome replication Source: UniProtKB
  • RNA-dependent DNA biosynthetic process Source: Reactome
  • uncoating of virus Source: Reactome
  • viral life cycle Source: Reactome
  • viral release from host cell Source: UniProtKB
  • virion assembly Source: Reactome

Keywordsi

Molecular functionIsomerase, Rotamase
Biological processHost-virus interaction

Enzyme and pathway databases

BRENDAi5.2.1.8 2681
ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-162585 Uncoating of the HIV Virion
R-HSA-162588 Budding and maturation of HIV virion
R-HSA-162592 Integration of provirus
R-HSA-162594 Early Phase of HIV Life Cycle
R-HSA-164516 Minus-strand DNA synthesis
R-HSA-164525 Plus-strand DNA synthesis
R-HSA-173107 Binding and entry of HIV virion
R-HSA-175474 Assembly Of The HIV Virion
R-HSA-180689 APOBEC3G mediated resistance to HIV-1 infection
R-HSA-2025928 Calcineurin activates NFAT
R-HSA-210991 Basigin interactions
R-HSA-6798695 Neutrophil degranulation
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-prolyl cis-trans isomerase A (EC:5.2.1.8)
Short name:
PPIase A
Alternative name(s):
Cyclophilin A
Cyclosporin A-binding protein
Rotamase A
Cleaved into the following chain:
Gene namesi
Name:PPIA
Synonyms:CYPA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000196262.13
HGNCiHGNC:9253 PPIA
MIMi123840 gene
neXtProtiNX_P62937

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi121W → A: 200-fold decrease of sensitivity to CsA. 1 Publication1
Mutagenesisi121W → F: 75-fold decrease of sensitivity to CsA. 1 Publication1

Organism-specific databases

DisGeNETi5478
OpenTargetsiENSG00000196262
PharmGKBiPA33574

Chemistry databases

ChEMBLiCHEMBL1949
DrugBankiDB01742 (3r)-1-Acetyl-3-Methylpiperidine
DB00091 Cyclosporine
DB02419 Ethyl Oxo(Piperidin-1-Yl)Acetate
DB00172 L-Proline
GuidetoPHARMACOLOGYi2751

Polymorphism and mutation databases

BioMutaiPPIA
DMDMi51702775

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004232401 – 165Peptidyl-prolyl cis-trans isomerase AAdd BLAST165
Initiator methionineiRemoved; alternateCombined sources5 Publications
ChainiPRO_00000641152 – 165Peptidyl-prolyl cis-trans isomerase A, N-terminally processedAdd BLAST164

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei2N-acetylvaline; partial; in Peptidyl-prolyl cis-trans isomerase A, N-terminally processedCombined sources2 Publications1
Modified residuei28N6-acetyllysine; alternateCombined sources1
Cross-linki28Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki28Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Modified residuei44N6-acetyllysineCombined sources1
Modified residuei76N6-acetyllysineCombined sources1
Modified residuei77PhosphoserineCombined sources1
Modified residuei82N6-acetyllysine; alternateCombined sources1
Cross-linki82Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei93PhosphothreonineCombined sources1
Glycosylationi108N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei125N6-acetyllysineCombined sources1 Publication1
Modified residuei131N6-acetyllysineCombined sources1
Modified residuei133N6-acetyllysineBy similarity1

Post-translational modificationi

Acetylation at Lys-125 markedly inhibits catalysis of cis to trans isomerization and stabilizes cis rather than trans forms of the HIV-1 capsid. PPIA acetylation also antagonizes the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition.2 Publications

Keywords - PTMi

Acetylation, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP62937
PaxDbiP62937
PeptideAtlasiP62937
PRIDEiP62937
TopDownProteomicsiP62937-1 [P62937-1]

2D gel databases

DOSAC-COBS-2DPAGEiP62937
OGPiP62937
REPRODUCTION-2DPAGEiIPI00419585
P62937
SWISS-2DPAGEiP62937
UCD-2DPAGEiP62937

PTM databases

iPTMnetiP62937
PhosphoSitePlusiP62937
SwissPalmiP62937

Expressioni

Gene expression databases

BgeeiENSG00000196262
CleanExiHS_PPIA
ExpressionAtlasiP62937 baseline and differential
GenevisibleiP62937 HS

Organism-specific databases

HPAiCAB004655
HPA058345

Interactioni

Subunit structurei

Interacts with HIV-1 Capsid protein.4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • unfolded protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111474, 120 interactors
CORUMiP62937
DIPiDIP-6080N
IntActiP62937, 67 interactors
MINTiP62937
STRINGi9606.ENSP00000419425

Chemistry databases

BindingDBiP62937

Structurei

Secondary structure

1165
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 12Combined sources8
Beta strandi15 – 24Combined sources10
Turni26 – 28Combined sources3
Helixi30 – 41Combined sources12
Turni42 – 44Combined sources3
Beta strandi55 – 57Combined sources3
Turni58 – 60Combined sources3
Beta strandi61 – 64Combined sources4
Turni67 – 69Combined sources3
Beta strandi70 – 73Combined sources4
Beta strandi74 – 77Combined sources4
Beta strandi78 – 81Combined sources4
Beta strandi97 – 100Combined sources4
Beta strandi102 – 104Combined sources3
Beta strandi108 – 110Combined sources3
Beta strandi112 – 117Combined sources6
Helixi120 – 122Combined sources3
Turni123 – 125Combined sources3
Beta strandi128 – 134Combined sources7
Helixi136 – 143Combined sources8
Helixi148 – 150Combined sources3
Beta strandi152 – 154Combined sources3
Beta strandi156 – 164Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AK4X-ray2.36A/B1-165[»]
1AWQX-ray1.58A2-165[»]
1AWRX-ray1.58A/B/C/D/E/F2-165[»]
1AWSX-ray2.55A2-165[»]
1AWTX-ray2.55A/B/C/D/E/F2-165[»]
1AWUX-ray2.34A2-165[»]
1AWVX-ray2.34A/B/C/D/E/F2-165[»]
1BCKX-ray1.80A1-165[»]
1CWAX-ray2.10A1-165[»]
1CWBX-ray2.20A1-165[»]
1CWCX-ray1.86A1-165[»]
1CWFX-ray1.86A1-165[»]
1CWHX-ray1.86A1-165[»]
1CWIX-ray1.90A1-165[»]
1CWJX-ray1.80A1-165[»]
1CWKX-ray1.80A1-165[»]
1CWLX-ray1.80A1-165[»]
1CWMX-ray2.00A1-165[»]
1CWOX-ray1.86A1-165[»]
1FGLX-ray1.80A1-165[»]
1M63X-ray2.80C/G1-165[»]
1M9CX-ray2.00A/B1-165[»]
1M9DX-ray1.90A/B1-165[»]
1M9EX-ray1.72A/B1-164[»]
1M9FX-ray1.73A/B1-165[»]
1M9XX-ray1.70A/B/E/F1-165[»]
1M9YX-ray1.90A/B/E/F1-165[»]
1MF8X-ray3.10C1-165[»]
1MIKX-ray1.76A1-165[»]
1NMKX-ray2.10A/B1-165[»]
1OCANMR-A1-165[»]
1RMHX-ray2.40A/B2-165[»]
1VBSX-ray2.00A1-165[»]
1VBTX-ray2.30A/B1-165[»]
1W8LX-ray1.80A2-165[»]
1W8MX-ray1.65A2-165[»]
1W8VX-ray1.70A2-165[»]
1YNDX-ray1.60A/B1-165[»]
1ZKFX-ray2.55A/B1-165[»]
2ALFX-ray1.90A2-165[»]
2CPLX-ray1.63A1-165[»]
2CYHX-ray1.64A2-165[»]
2MS4NMR-A1-165[»]
2MZUNMR-A1-165[»]
2N0TNMR-A1-165[»]
2RMAX-ray2.10A/C/E/G/I/K/M/O/Q/S1-165[»]
2RMBX-ray2.10A/C/E/G/I/K/M/O/Q/S1-165[»]
2X25X-ray1.20B2-165[»]
2X2AX-ray1.40A/B1-165[»]
2X2CX-ray2.41K/M/O/Q/S1-165[»]
2X2DX-ray1.95B/C1-165[»]
2XGYX-ray1.80B1-165[»]
3CYHX-ray1.90A2-165[»]
3CYSNMR-A1-165[»]
3K0MX-ray1.25A1-165[»]
3K0NX-ray1.39A1-165[»]
3K0OX-ray1.55A1-165[»]
3K0PX-ray1.65A1-165[»]
3K0QX-ray2.32A1-165[»]
3K0RX-ray2.42A1-165[»]
3ODIX-ray2.20A/C/E/G/I/K/M/O/Q/S1-165[»]
3ODLX-ray2.31A/C/E/G/I/K/M/O/Q/S1-165[»]
3RDDX-ray2.14A1-165[»]
4CYHX-ray2.10A2-165[»]
4IPZX-ray1.67A1-165[»]
4N1MX-ray1.15A1-165[»]
4N1NX-ray1.50A1-165[»]
4N1OX-ray1.75A1-165[»]
4N1PX-ray1.90A1-165[»]
4N1QX-ray1.65A1-165[»]
4N1RX-ray1.80A1-165[»]
4N1SX-ray1.47A1-165[»]
4YUGX-ray1.48A1-165[»]
4YUHX-ray1.34A1-165[»]
4YUIX-ray1.38A1-165[»]
4YUJX-ray1.42A1-165[»]
4YUKX-ray1.48A1-165[»]
4YULX-ray1.42A1-165[»]
4YUMX-ray1.50A1-165[»]
4YUNX-ray1.58A1-165[»]
4YUOX-ray1.20A1-165[»]
4YUPX-ray1.75A1-165[»]
5CYHX-ray2.10A2-165[»]
5F66X-ray1.15A1-165[»]
5FJBelectron microscopy9.00C2-165[»]
5KULX-ray1.70A2-165[»]
5KUNX-ray1.70A2-165[»]
5KUOX-ray1.70A2-165[»]
5KUQX-ray1.70A2-165[»]
5KURX-ray1.70A2-165[»]
5KUSX-ray1.70A2-165[»]
5KUUX-ray1.70A2-165[»]
5KUVX-ray1.70A2-165[»]
5KUWX-ray1.70A2-165[»]
5KUZX-ray1.70A2-165[»]
5KV0X-ray1.70A2-165[»]
5KV1X-ray1.70A2-165[»]
5KV2X-ray1.70A2-165[»]
5KV3X-ray1.70A2-165[»]
5KV4X-ray1.70A2-165[»]
5KV5X-ray1.70A2-165[»]
5KV6X-ray1.70A2-165[»]
5KV7X-ray1.70A2-165[»]
5LUDX-ray1.25A1-165[»]
5NOQX-ray1.60A1-165[»]
5NORX-ray1.80A1-165[»]
5NOSX-ray1.35A1-165[»]
5NOTX-ray1.45A1-165[»]
5NOUX-ray1.30A1-165[»]
5NOVX-ray2.00A1-165[»]
5NOWX-ray1.48A1-165[»]
5NOXX-ray1.49A1-165[»]
5NOYX-ray1.43A1-165[»]
5NOZX-ray1.61A1-165[»]
5T9UX-ray2.30A/B/C/D1-164[»]
5T9WX-ray2.00A2-165[»]
5T9ZX-ray1.40A2-164[»]
5TA2X-ray1.48A2-164[»]
5TA4X-ray1.50A2-165[»]
ProteinModelPortaliP62937
SMRiP62937
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP62937

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini7 – 163PPIase cyclophilin-typePROSITE-ProRule annotationAdd BLAST157

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0865 Eukaryota
COG0652 LUCA
GeneTreeiENSGT00760000119119
HOGENOMiHOG000065981
HOVERGENiHBG001065
InParanoidiP62937
KOiK03767
OMAiFFINFKD
OrthoDBiEOG091G0BGL
PhylomeDBiP62937
TreeFamiTF316719

Family and domain databases

Gene3Di2.40.100.10, 1 hit
InterProiView protein in InterPro
IPR029000 Cyclophilin-like_dom_sf
IPR024936 Cyclophilin-type_PPIase
IPR020892 Cyclophilin-type_PPIase_CS
IPR002130 Cyclophilin-type_PPIase_dom
PANTHERiPTHR11071 PTHR11071, 1 hit
PfamiView protein in Pfam
PF00160 Pro_isomerase, 1 hit
PIRSFiPIRSF001467 Peptidylpro_ismrse, 1 hit
PRINTSiPR00153 CSAPPISMRASE
SUPFAMiSSF50891 SSF50891, 1 hit
PROSITEiView protein in PROSITE
PS00170 CSA_PPIASE_1, 1 hit
PS50072 CSA_PPIASE_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P62937-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVNPTVFFDI AVDGEPLGRV SFELFADKVP KTAENFRALS TGEKGFGYKG
60 70 80 90 100
SCFHRIIPGF MCQGGDFTRH NGTGGKSIYG EKFEDENFIL KHTGPGILSM
110 120 130 140 150
ANAGPNTNGS QFFICTAKTE WLDGKHVVFG KVKEGMNIVE AMERFGSRNG
160
KTSKKITIAD CGQLE
Length:165
Mass (Da):18,012
Last modified:January 23, 2007 - v2
Checksum:i9B2E637A555E4434
GO
Isoform 2 (identifier: P62937-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: Missing.

Show »
Length:105
Mass (Da):11,418
Checksum:i4629A635A48F744B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti89I → T in AAH05982 (PubMed:15489334).Curated1
Sequence conflicti106N → I in AAH07104 (PubMed:15489334).Curated1
Sequence conflicti165E → D in CAG32988 (Ref. 4) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0560501 – 60Missing in isoform 2. 2 PublicationsAdd BLAST60

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00052 mRNA Translation: CAA68264.1
X52851 Genomic DNA Translation: CAA37039.1
AK290085 mRNA Translation: BAF82774.1
AK293003 mRNA Translation: BAF85692.1
CR456707 mRNA Translation: CAG32988.1
AB451307 mRNA Translation: BAG70121.1
AB451438 mRNA Translation: BAG70252.1
AY739283 Genomic DNA Translation: AAU13906.1
AC004854 Genomic DNA No translation available.
AC013436 Genomic DNA No translation available.
BC000689 mRNA Translation: AAH00689.1
BC003026 mRNA Translation: AAH03026.2
BC005320 mRNA Translation: AAH05320.1
BC005982 mRNA Translation: AAH05982.1
BC007104 mRNA Translation: AAH07104.1
BC013915 mRNA Translation: AAH13915.1
BC073992 mRNA Translation: AAH73992.1
BC093076 mRNA Translation: AAH93076.1
BC106030 mRNA Translation: AAI06031.1
BC137057 mRNA Translation: AAI37058.1
BC137058 mRNA Translation: AAI37059.1
CCDSiCCDS5494.1 [P62937-1]
CCDS75592.1 [P62937-2]
PIRiA94496 CSHUA
RefSeqiNP_001287910.1, NM_001300981.1 [P62937-2]
NP_066953.1, NM_021130.4 [P62937-1]
UniGeneiHs.356331

Genome annotation databases

EnsembliENST00000355968; ENSP00000430817; ENSG00000196262 [P62937-2]
ENST00000468812; ENSP00000419425; ENSG00000196262 [P62937-1]
ENST00000489459; ENSP00000427976; ENSG00000196262 [P62937-2]
ENST00000620047; ENSP00000479961; ENSG00000196262 [P62937-2]
GeneIDi5478
KEGGihsa:5478
UCSCiuc064djo.1 human [P62937-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPPIA_HUMAN
AccessioniPrimary (citable) accession number: P62937
Secondary accession number(s): A8K220
, P05092, Q3KQW3, Q567Q0, Q6IBU5, Q96IX3, Q9BRU4, Q9BTY9, Q9UC61
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: April 25, 2018
This is version 163 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health