Reviewed, UniProtKB/Swiss-Prot P62937 (PPIA_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	165 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cytoplasm
Ligand	Cyclosporin
Molecular function	Isomerase Rotamase
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	initiation of viral infection Inferred from Experiment. Source: Reactome interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW 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 component	cytosol Inferred from direct assay. Source: UniProtKB extracellular region Inferred from Experiment. Source: Reactome nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	peptide binding Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-prolyl cis-trans isomerase activity Inferred from electronic annotation. Source: UniProtKB-KW unfolded 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
PTPRN	Q16849	1	EBI-437708,EBI-728153
SUPT5H	O00267	1	EBI-437708,EBI-710464

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6 Ref.7 Ref.8 Ref.9

Chain

2 – 165

164

Peptidyl-prolyl cis-trans isomerase A

PRO_0000064115

Regions

Domain

7 – 163

157

PPIase cyclophilin-type

Amino acid modifications

Modified residue

2

1

N-acetylvaline; partial Ref.9

Modified residue

21

1

Phosphoserine By similarity

Modified residue

125

1

N6-acetyllysine Ref.13

Modified residue

157

1

Phosphothreonine Ref.12

Cross-link

28

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.14

Experimental info

Mutagenesis

121

1

W → A: 200-fold decrease of sensitivity to CsA. Ref.10

Mutagenesis

121

1

W → F: 75-fold decrease of sensitivity to CsA. Ref.10

Sequence conflict

89

1

I → T in AAH05982. Ref.5

Sequence conflict

106

1

N → I in AAH07104. Ref.5

Sequence conflict

165

1

E → D in CAG32988. Ref.3

Secondary structure

1

.

.

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.

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165

Helix Strand Turn

Details...

Beta strand

5 – 12

8

Beta strand

15 – 24

10

Turn

26 – 28

3

Helix

30 – 41

12

Turn

42 – 44

3

Beta strand

55 – 57

3

Turn

58 – 60

3

Beta strand

61 – 64

4

Turn

67 – 69

3

Beta strand

70 – 73

4

Beta strand

97 – 100

4

Beta strand

108 – 110

3

Beta strand

112 – 117

6

Helix

120 – 122

3

Turn

123 – 125

3

Beta strand

128 – 134

7

Helix

136 – 143

8

Beta strand

156 – 163

8

Sequences

	Sequence		Length	Mass (Da)
	P62937-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 9B2E637A555E4434	FASTA	165	18,012
	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

References

	« Hide 'large scale' referencesShow '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

EMBLGenBankDDBJ

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.

IPI

IPI00419585.

PIR

CSHUA. A94496.

RefSeq

NP_066953.1.

UniGene

Hs.356331
Hs.598115

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AK4	X-ray	2.36	A/B	2-164	[»]
1AWQ	X-ray	1.58	A	2-165	[»]
1AWR	X-ray	1.58	A/B/C/D/E/F	2-165	[»]
1AWS	X-ray	2.55	A	2-165	[»]
1AWT	X-ray	2.55	A/B/C/D/E/F	2-165	[»]
1AWU	X-ray	2.34	A	2-165	[»]
1AWV	X-ray	2.34	A/B/C/D/E/F	2-165	[»]
1BCK	X-ray	1.80	A	1-165	[»]
1CWA	X-ray	2.10	A	1-165	[»]
1CWB	X-ray	2.20	A	1-165	[»]
1CWC	X-ray	1.86	A	1-165	[»]
1CWF	X-ray	1.86	A	1-165	[»]
1CWH	X-ray	1.86	A	1-165	[»]
1CWI	X-ray	1.90	A	1-165	[»]
1CWJ	X-ray	1.80	A	1-165	[»]
1CWK	X-ray	1.80	A	1-165	[»]
1CWL	X-ray	1.80	A	1-165	[»]
1CWM	X-ray	2.00	A	1-165	[»]
1CWO	X-ray	1.86	A	2-164	[»]
1FGL	X-ray	1.80	A	2-164	[»]
1M63	X-ray	2.80	C/G	1-165	[»]
1M9C	X-ray	2.00	A/B	1-164	[»]
1M9D	X-ray	1.90	A/B	1-164	[»]
1M9E	X-ray	1.72	A/B	1-163	[»]
1M9F	X-ray	1.73	A/B	1-164	[»]
1M9X	X-ray	1.70	A/B/E/F	1-164	[»]
1M9Y	X-ray	1.90	A/B/E/F	1-164	[»]
1MF8	X-ray	3.10	C	1-165	[»]
1MIK	X-ray	1.76	A	1-165	[»]
1NMK	X-ray	2.10	A/B	1-165	[»]
1OCA	NMR	-	A	1-165	[»]
1RMH	X-ray	2.40	A/B	2-165	[»]
1VBS	X-ray	2.00	A	1-165	[»]
1VBT	X-ray	2.30	A/B	1-165	[»]
1W8L	X-ray	1.80	A	2-164	[»]
1W8M	X-ray	1.65	A	2-164	[»]
1W8V	X-ray	1.70	A	2-164	[»]
1YND	X-ray	1.60	A/B	1-165	[»]
1ZKF	X-ray	2.55	A/B	1-165	[»]
2ALF	X-ray	1.90	A	2-164	[»]
2CPL	X-ray	1.63	A	2-164	[»]
2CYH	X-ray	1.64	A	2-165	[»]
2RMA	X-ray	2.10	A/C/E/G/I/K/M/O/Q/S	2-164	[»]
2RMB	X-ray	2.10	A/C/E/G/I/K/M/O/Q/S	2-164	[»]
3CYH	X-ray	1.90	A	2-165	[»]
3CYS	NMR	-	A	1-165	[»]
4CYH	X-ray	2.10	A	2-165	[»]
5CYH	X-ray	2.10	A	2-165	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P62937. 11 interactions.

PTM databases

PhosphoSite

P62937.

2-D gel databases

SWISS-2DPAGE

P62937.

Aarhus/Ghent-2DPAGE

2003. NEPHGE.

DOSAC-COBS-2DPAGE

P62937.

OGP

P62937.

PMMA-2DPAGE

P62937.

REPRODUCTION-2DPAGE

IPI00419585.
P62937.

Siena-2DPAGE

P62937.

Proteomic databases

PeptideAtlas

P62937.

PRIDE

P62937.

Genome annotation databases

Ensembl

ENSG00000196262. Homo sapiens. [Contig view]

GeneID

5478.

KEGG

hsa:5478.

UCSC

uc003tlw.1. human.

Organism-specific databases

GeneCards

GC07P044802.
GC07P044803.

H-InvDB

HIX0041072.

HGNC

HGNC:9253. PPIA.

HPA

CAB004655.

MIM

123840. gene.

PharmGKB

PA33574.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P62937.

OMA

P62937. TMELFND.

Enzyme and pathway databases

BRENDA

5.2.1.8. 247.

Reactome

REACT_604. Hemostasis.
REACT_6185. HIV Infection.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P62937.

Bgee

P62937.

CleanEx

HS_PPIA.

GermOnline

ENSG00000196262. Homo sapiens.
ENSG00000198618. Homo sapiens.

Family and domain databases

InterPro

IPR002130. PPIase_cyclophilin.
[Graphical view]

Gene3D

G3DSA:2.40.100.10. PPIase_cyclophilin. 1 hit.

Pfam

PF00160. Pro_isomerase. 1 hit.
[Graphical view]

PRINTS

PR00153. CSAPPISMRASE.

PROSITE

PS00170. CSA_PPIASE_1. 1 hit.
PS50072. CSA_PPIASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00091. Cyclosporine.
DB00172. L-Proline.

NextBio

21206.

SOURCE

Search...

Entry information

Entry name

PPIA_HUMAN

Accession

Primary (citable) accession number: P62937
Secondary accession number(s): P05092 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)