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Reviewed, UniProtKB/Swiss-Prot P62937 (PPIA_HUMAN)

Last modified November 4, 2008. Version 57. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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)
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.

Subcellular location

Cytoplasm.

Sequence similarities

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

Contains 1 PPIase cyclophilin-type domain.

Ontologies

Keywords

   Biological processHost-virus interaction
   Cellular componentCytoplasm
   LigandCyclosporin
   Molecular functionIsomerase
Rotamase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Direct protein sequencing

Gene Ontology (GO)

   Biological processinitiation of viral infection

Inferred from Experiment. Source: Reactome

protein folding

Traceable author statement. Source: UniProtKB

provirus integration

Inferred from Experiment. Source: Reactome

regulation of viral genome replication

Inferred from mutant phenotype. Source: UniProtKB

   Cellular componentcytosol

Inferred from direct assay. Source: UniProtKB

extracellular region

Inferred from Experiment. Source: Reactome

nucleus

Inferred from direct assay. Source: UniProtKB

   Molecular functionunfolded protein binding

Traceable author statement. Source: UniProtKB

virion binding

Non-traceable author statement. Source: UniProtKB

Complete GO annotation...

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
Chain2 – 165164Peptidyl-prolyl cis-trans isomerase A
PRO_0000064115

Regions

Domain7 – 163157PPIase cyclophilin-type

Amino acid modifications

Modified residue21N-acetylvaline; partial
Modified residue211Phosphoserine By similarity
Modified residue1251N6-acetyllysine
Modified residue1571Phosphothreonine

Experimental info

Mutagenesis1211W → A: 200-fold decrease of sensitivity to CsA
Mutagenesis1211W → F: 75-fold decrease of sensitivity to CsA
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, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."
Livingston R.J., Rieder M.J., Chung M.-W., Ritchie T.K., Olson A.N., Nguyen C.P., Nguyen D.A., Poel C.L., Chambers S.W., Schackwitz W.S., Sherwood J.K., Sherwood A.M., Leithauser B.J., Nickerson D.A.
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]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.
[9]Lubec G., Afjehi-Sadat L.
Submitted (MAR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-19; 56-69 AND 77-91, MASS SPECTROMETRY.
Tissue: Brain and Cajal-Retzius cell.
[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]"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.
[15]"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).
[16]"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.
[17]"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).
[18]"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).
[19]"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).
[20]"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).
[21]"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.
[22]"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.
[23]"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.
[24]"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

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.
PIRCSHUA. A94496.
RefSeqNP_066953.1.
UniGeneHs.356331
Hs.598115

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1AK4X-ray2.36A/B1-165[»]
1AWQX-ray1.58A1-165[»]
1AWRX-ray1.58A/B/C/D/E/F1-165[»]
1AWSX-ray2.55A1-165[»]
1AWTX-ray2.55A/B/C/D/E/F1-165[»]
1AWUX-ray2.34A1-165[»]
1AWVX-ray2.34A/B/C/D/E/F1-165[»]
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/B1-165[»]
1VBSX-ray2.00A1-165[»]
1VBTX-ray2.30A/B1-165[»]
1W8LX-ray1.80A1-165[»]
1W8MX-ray1.65A1-165[»]
1W8VX-ray1.70A1-165[»]
1YNDX-ray1.60A/B1-165[»]
1ZKFX-ray2.55A/B1-165[»]
2ALFX-ray1.90A1-165[»]
2CPLX-ray1.63A1-165[»]
2CYHX-ray1.64A1-165[»]
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[»]
3CYHX-ray1.90A1-165[»]
3CYSNMR-A1-165[»]
4CYHX-ray2.10A1-165[»]
5CYHX-ray2.10A1-165[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP62937.

PTM databases

PhosphoSiteP62937.

Polymorphism databases