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Reviewed, UniProtKB/Swiss-Prot P62937 (PPIA_HUMAN)

Last modified July 7, 2009. Version 68. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Peptidyl-prolyl cis-trans isomerase A
      Short name=PPIase A
      Short name=Rotamase A
    EC=5.2.1.8
Alternative name(s):
    Cyclophilin A
    Cyclosporin A-binding protein
Gene names
Name: PPIA
Synonyms: CYPA
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length165 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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

Catalytic activity

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

Enzyme regulation

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

Subunit structure

Interacts with HIV-1 Capsid protein. Ref.11

Subcellular location

Cytoplasm.

Sequence similarities

Belongs to the cyclophilin-type PPIase family. PPIase A subfamily.

Contains 1 PPIase cyclophilin-type domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PTPRNQ168491EBI-437708,EBI-728153
SUPT5HO002671EBI-437708,EBI-710464

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.6 Ref.7 Ref.8 Ref.9
Chain2 – 165164Peptidyl-prolyl cis-trans isomerase A
PRO_0000064115

Regions

Domain7 – 163157PPIase cyclophilin-type

Amino acid modifications

Modified residue21N-acetylvaline; partial Ref.9
Modified residue211Phosphoserine By similarity
Modified residue1251N6-acetyllysine Ref.13
Modified residue1571Phosphothreonine Ref.12
Cross-link28Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.14

Experimental info

Mutagenesis1211W → A: 200-fold decrease of sensitivity to CsA. Ref.10
Mutagenesis1211W → F: 75-fold decrease of sensitivity to CsA. Ref.10
Sequence conflict891I → T in AAH05982. Ref.5
Sequence conflict1061N → I in AAH07104. Ref.5
Sequence conflict1651E → D in CAG32988. Ref.3

Secondary structure

................................ 165
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P62937-1 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 9B2E637A555E4434

FASTA16518,012
        10         20         30         40         50         60 
MVNPTVFFDI AVDGEPLGRV SFELFADKVP KTAENFRALS TGEKGFGYKG SCFHRIIPGF 

        70         80         90        100        110        120 
MCQGGDFTRH NGTGGKSIYG EKFEDENFIL KHTGPGILSM ANAGPNTNGS QFFICTAKTE 

       130        140        150        160 
WLDGKHVVFG KVKEGMNIVE AMERFGSRNG KTSKKITIAD CGQLE 

« Hide

References

« Hide 'large scale' references
[1]"Complementary DNA for human T-cell cyclophilin."
Haendler B., Hofer-Warbinek R., Hofer E.
EMBO J. 6:947-950(1987) [PubMed: 3297675] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Leukemic T-cell.
[2]"Characterization of the human cyclophilin gene and of related processed pseudogenes."
Haendler B., Hofer E.
Eur. J. Biochem. 190:477-482(1990) [PubMed: 2197089] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"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].
[4]NIEHS SNPs program
Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Bone marrow, Brain, Cervix, Colon, Lung, Skeletal muscle, Skin and Urinary bladder.
[6]"Identification of cyclophilin A from human decidual and placental tissue in the first trimester of pregnancy."
Meier U., Beier-Hellwig K., Klug J., Linder D., Beier H.M.
Hum. Reprod. 10:1305-1310(1995) [PubMed: 7657784] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-30.
[7]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-19.
Tissue: Platelet.
[8]Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-31; 56-69; 77-118; 132-144 AND 155-165, MASS SPECTROMETRY.
Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[9]Bienvenut W.V., Claeys D.
Submitted (NOV-2005) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-28, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT VAL-2, MASS SPECTROMETRY.
Tissue: Platelet.
[10]"Human and Escherichia coli cyclophilins: sensitivity to inhibition by the immunosuppressant cyclosporin A correlates with a specific tryptophan residue."
Liu J., Chen C.-M., Walsh C.T.
Biochemistry 30:2306-2310(1991) [PubMed: 2001362] [Abstract]
Cited for: MUTAGENESIS OF TRP-121.
[11]"Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B."
Luban J., Bossolt K.L., Franke E.K., Kalpana G.V., Goff S.P.
Cell 73:1067-1078(1993) [PubMed: 8513493] [Abstract]
Cited for: INTERACTION WITH HIV-1 CAPSID PROTEIN.
[12]"Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC."
Gevaert K., Staes A., Van Damme J., De Groot S., Hugelier K., Demol H., Martens L., Goethals M., Vandekerckhove J.
Proteomics 5:3589-3599(2005) [PubMed: 16097034] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-157, MASS SPECTROMETRY.
Tissue: Hepatocyte.
[13]"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey."
Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.
Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-125, MASS SPECTROMETRY.
Tissue: Epithelium.
[14]"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry."
Meierhofer D., Wang X., Huang L., Kaiser P.
J. Proteome Res. 7:4566-4576(2008) [PubMed: 18781797] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-28, MASS SPECTROMETRY.
[15]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]"Structure of human cyclophilin and its binding site for cyclosporin A determined by X-ray crystallography and NMR spectroscopy."
Kallen J., Spitzfaden C., Zurini M.G.M., Wider G., Widmer H., Wuethrich K., Walkinshaw M.D.
Nature 353:276-279(1991) [PubMed: 1896075] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), STRUCTURE BY NMR.
[17]"Crystal structure of recombinant human T-cell cyclophilin A at 2.5-A resolution."
Ke H., Zydowsky L.D., Liu J., Walsh C.T.
Proc. Natl. Acad. Sci. U.S.A. 88:9483-9487(1991) [PubMed: 1946361] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[18]"X-ray structure of a decameric cyclophilin-cyclosporin crystal complex."
Pfuegl G., Kallen J., Schirmer T., Jansonius J.N., Zurini M.G.M., Walkinshaw M.D.
Nature 361:91-94(1993) [PubMed: 8421501] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEX WITH CYCLOPHILIN.
[19]"X-ray structure of a monomeric cyclophilin A-cyclosporin A crystal complex at 2.1-A resolution."
Mikol V., Kallen J., Pfluegl G., Walkinshaw M.D.
J. Mol. Biol. 234:1119-1130(1993) [PubMed: 8263916] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[20]"Crystal structure implies that cyclophilin predominantly catalyzes the trans to cis isomerization."
Zhao Y., Ke H.
Biochemistry 35:7356-7361(1996) [PubMed: 8652511] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[21]"Crystal structure of cyclophilin A complexed with a binding site peptide from the HIV-1 capsid protein."
Vajdos F.F., Yoo S., Houseweart M., Sundquist W.I., Hill C.P.
Protein Sci. 6:2297-2307(1997) [PubMed: 9385632] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS).
[22]"X-ray structures and analysis of 11 cyclosporin derivatives complexed with cyclophilin A."
Kallen J., Mikol V., Taylor P., Walkinshaw M.D.
J. Mol. Biol. 283:435-449(1998) [PubMed: 9769216] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[23]"Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes."
Huai Q., Kim H.Y., Liu Y., Zhao Y., Mondragon A., Liu J.O., Ke H.
Proc. Natl. Acad. Sci. U.S.A. 99:12037-12042(2002) [PubMed: 12218175] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH CALCINEURIN B.
[24]"Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin."
Jin L., Harrison S.C.
Proc. Natl. Acad. Sci. U.S.A. 99:13522-13526(2002) [PubMed: 12357034] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) IN COMPLEX WITH CALCINEURIN B.
[25]"Solution structure of the cyclosporin A/cyclophilin complex by NMR."
Theriault Y., Logan T.M., Meadows R., Yu L., Olejniczak E.T., Holzman T.F., Simmer R.L., Fesik S.W.
Nature 361:88-91(1993) [PubMed: 8421500] [Abstract]
Cited for: STRUCTURE BY NMR OF COMPLEX WITH CYCLOPHILIN.
[26]"The NMR solution conformation of unligated human cyclophilin A."
Ottiger M., Zerbe O., Guentert P., Wuethrich K.
J. Mol. Biol. 272:64-81(1997) [PubMed: 9299338] [Abstract]
Cited for: STRUCTURE BY NMR.
+Additional computationally mapped references.

Web resources

NIEHS-SNPs
Wikipedia

Cyclophilin entry

Cross-references

Sequence databases

Y00052 mRNA. Translation: CAA68264.1.
X52851 Genomic DNA. Translation: CAA37039.1.
CR456707 mRNA. Translation: CAG32988.1.
AY739283 Genomic DNA. Translation: AAU13906.1.
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.
BC106030 mRNA. Translation: AAI06031.1.
IPIIPI00419585.
PIRCSHUA. A94496.
RefSeqNP_066953.1.
UniGeneHs.356331
Hs.598115

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1AK4X-ray2.36A/B2-164[»]
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-ray1.86A2-164[»]
1FGLX-ray1.80A2-164[»]
1M63X-ray2.80C/G1-165[»]
1M9CX-ray2.00A/B1-164[»]
1M9DX-ray1.90A/B1-164[»]
1M9EX-ray1.72A/B1-163[»]
1M9FX-ray1.73A/B1-164[»]
1M9XX-ray1.70A/B/E/F1-164[»]
1M9YX-ray1.90A/B/E/F1-164[»]
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-ray1.80A2-164[»]
1W8MX-ray1.65A2-164[»]
1W8VX-ray1.70A2-164[»]
1YNDX-ray1.60A/B1-165[»]
1ZKFX-ray2.55A/B1-165[»]
2ALFX-ray1.90A2-164[»]
2CPLX-ray1.63A2-164[»]
2CYHX-ray1.64A2-165[»]
2RMAX-ray2.10A/C/E/G/I/K/M/O/Q/S2-164[»]
2RMBX-ray2.10A/C/E/G/I/K/M/O/Q/S2-164[»]
3CYHX-ray1.90A2-165[»]
3CYSNMR-A1-165[»]
4CYHX-ray2.10A2-165[»]
5CYHX-ray2.10A2-165[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP62937. 11 interactions.

PTM databases

PhosphoSiteP62937.

2-D gel databases

SWISS-2DPAGEP62937.
Aarhus/Ghent-2DPAGE2003. NEPHGE.
DOSAC-COBS-2DPAGEP62937.
OGPP62937.
PMMA-2DPAGEP62937.
REPRODUCTION-2DPAGEIPI00419585.
P62937.
Siena-2DPAGEP62937.

Proteomic databases

PeptideAtlasP62937.
PRIDEP62937.

Genome annotation databases

EnsemblENSG00000196262. Homo sapiens. [Contig view]
GeneID5478.
KEGGhsa:5478.
UCSCuc003tlw.1. human.

Organism-specific databases

GeneCardsGC07P044802.
GC07P044803.
H-InvDBHIX0041072.
HGNCHGNC:9253. PPIA.
HPACAB004655.
MIM123840. gene.
PharmGKBPA33574.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP62937.
OMAP62937. TMELFND.

Enzyme and pathway databases

BRENDA5.2.1.8. 247.
ReactomeREACT_604. Hemostasis.
REACT_6185. HIV Infection.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpressP62937.
BgeeP62937.
CleanExHS_PPIA.
GermOnlineENSG00000196262. Homo sapiens.
ENSG00000198618. Homo sapiens.

Family and domain databases

InterProIPR002130. PPIase_cyclophilin.
[Graphical view]
Gene3DG3DSA:2.40.100.10. PPIase_cyclophilin. 1 hit.
PfamPF00160. Pro_isomerase. 1 hit.
[Graphical view]
PRINTSPR00153. CSAPPISMRASE.
PROSITEPS00170. CSA_PPIASE_1. 1 hit.
PS50072. CSA_PPIASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00091. Cyclosporine.
DB00172. L-Proline.
NextBio21206.
SOURCESearch...

Entry information

Entry namePPIA_HUMAN
AccessionPrimary (citable) accession number: P62937
Secondary accession number(s): P05092 expand/collapse secondary AC list , Q3KQW3, Q6IBU5, Q96IX3, Q9BRU4, Q9BTY9, Q9UC61
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: July 7, 2009
This is version 68 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents