Full text data of PPIA
PPIA
(CYPA)
[Confidence: high (present in two of the MS resources)]
Peptidyl-prolyl cis-trans isomerase A; PPIase A; 5.2.1.8 (Cyclophilin A; Cyclosporin A-binding protein; Rotamase A; Peptidyl-prolyl cis-trans isomerase A, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Peptidyl-prolyl cis-trans isomerase A; PPIase A; 5.2.1.8 (Cyclophilin A; Cyclosporin A-binding protein; Rotamase A; Peptidyl-prolyl cis-trans isomerase A, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00006664
IPI00006664 peptidylprolyl isomerase A isoform 1 peptidylprolyl isomerase A isoform 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a 5 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a not mentioned n/a found at its expected molecular weight found at molecular weight
IPI00006664 peptidylprolyl isomerase A isoform 1 peptidylprolyl isomerase A isoform 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a 5 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a not mentioned n/a found at its expected molecular weight found at molecular weight
UniProt
P62937
ID PPIA_HUMAN Reviewed; 165 AA.
AC P62937; A8K220; P05092; Q3KQW3; Q6IBU5; Q96IX3; Q9BRU4; Q9BTY9;
read moreAC Q9UC61;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase A;
DE Short=PPIase A;
DE EC=5.2.1.8;
DE AltName: Full=Cyclophilin A;
DE AltName: Full=Cyclosporin A-binding protein;
DE AltName: Full=Rotamase A;
DE Contains:
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase A, N-terminally processed;
GN Name=PPIA; Synonyms=CYPA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Leukemic T-cell;
RX PubMed=3297675;
RA Haendler B., Hofer-Warbinek R., Hofer E.;
RT "Complementary DNA for human T-cell cyclophilin.";
RL EMBO J. 6:947-950(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2197089; DOI=10.1111/j.1432-1033.1990.tb15598.x;
RA Haendler B., Hofer E.;
RT "Characterization of the human cyclophilin gene and of related
RT processed pseudogenes.";
RL Eur. J. Biochem. 190:477-482(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Subthalamic nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow, Brain, Cervix, Colon, Lung, Skeletal muscle, Skin,
RC and Urinary bladder;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-30.
RX PubMed=7657784;
RA Meier U., Beier-Hellwig K., Klug J., Linder D., Beier H.M.;
RT "Identification of cyclophilin A from human decidual and placental
RT tissue in the first trimester of pregnancy.";
RL Hum. Reprod. 10:1305-1310(1995).
RN [9]
RP PROTEIN SEQUENCE OF 2-19.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [10]
RP PROTEIN SEQUENCE OF 2-31; 56-69; 77-118; 132-144 AND 155-165, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 2-28, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT VAL-2, AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [12]
RP MUTAGENESIS OF TRP-121.
RX PubMed=2001362; DOI=10.1021/bi00223a003;
RA Liu J., Chen C.-M., Walsh C.T.;
RT "Human and Escherichia coli cyclophilins: sensitivity to inhibition by
RT the immunosuppressant cyclosporin A correlates with a specific
RT tryptophan residue.";
RL Biochemistry 30:2306-2310(1991).
RN [13]
RP INTERACTION WITH HIV-1 CAPSID PROTEIN.
RX PubMed=8513493; DOI=10.1016/0092-8674(93)90637-6;
RA Luban J., Bossolt K.L., Franke E.K., Kalpana G.V., Goff S.P.;
RT "Human immunodeficiency virus type 1 Gag protein binds to cyclophilins
RT A and B.";
RL Cell 73:1067-1078(1993).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=16527992; DOI=10.1161/01.RES.0000216405.85080.a6;
RA Suzuki J., Jin Z.G., Meoli D.F., Matoba T., Berk B.C.;
RT "Cyclophilin A is secreted by a vesicular pathway in vascular smooth
RT muscle cells.";
RL Circ. Res. 98:811-817(2006).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND VAL-2, AND MASS
RP SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-28; LYS-44; LYS-76; LYS-82;
RP LYS-125 AND LYS-131, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-93, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), AND STRUCTURE BY NMR.
RX PubMed=1896075; DOI=10.1038/353276a0;
RA Kallen J., Spitzfaden C., Zurini M.G.M., Wider G., Widmer H.,
RA Wuethrich K., Walkinshaw M.D.;
RT "Structure of human cyclophilin and its binding site for cyclosporin A
RT determined by X-ray crystallography and NMR spectroscopy.";
RL Nature 353:276-279(1991).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=1946361; DOI=10.1073/pnas.88.21.9483;
RA Ke H., Zydowsky L.D., Liu J., Walsh C.T.;
RT "Crystal structure of recombinant human T-cell cyclophilin A at 2.5-A
RT resolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:9483-9487(1991).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEX WITH CYCLOPHILIN.
RX PubMed=8421501; DOI=10.1038/361091a0;
RA Pfuegl G., Kallen J., Schirmer T., Jansonius J.N., Zurini M.G.M.,
RA Walkinshaw M.D.;
RT "X-ray structure of a decameric cyclophilin-cyclosporin crystal
RT complex.";
RL Nature 361:91-94(1993).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=8263916; DOI=10.1006/jmbi.1993.1664;
RA Mikol V., Kallen J., Pfluegl G., Walkinshaw M.D.;
RT "X-ray structure of a monomeric cyclophilin A-cyclosporin A crystal
RT complex at 2.1-A resolution.";
RL J. Mol. Biol. 234:1119-1130(1993).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=8652511; DOI=10.1021/bi9602775;
RA Zhao Y., Ke H.;
RT "Crystal structure implies that cyclophilin predominantly catalyzes
RT the trans to cis isomerization.";
RL Biochemistry 35:7356-7361(1996).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS).
RX PubMed=9385632;
RA Vajdos F.F., Yoo S., Houseweart M., Sundquist W.I., Hill C.P.;
RT "Crystal structure of cyclophilin A complexed with a binding site
RT peptide from the HIV-1 capsid protein.";
RL Protein Sci. 6:2297-2307(1997).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
RX PubMed=9769216; DOI=10.1006/jmbi.1998.2108;
RA Kallen J., Mikol V., Taylor P., Walkinshaw M.D.;
RT "X-ray structures and analysis of 11 cyclosporin derivatives complexed
RT with cyclophilin A.";
RL J. Mol. Biol. 283:435-449(1998).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH CALCINEURIN B.
RX PubMed=12218175; DOI=10.1073/pnas.192206699;
RA Huai Q., Kim H.Y., Liu Y., Zhao Y., Mondragon A., Liu J.O., Ke H.;
RT "Crystal structure of calcineurin-cyclophilin-cyclosporin shows common
RT but distinct recognition of immunophilin-drug complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:12037-12042(2002).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) IN COMPLEX WITH CALCINEURIN B.
RX PubMed=12357034; DOI=10.1073/pnas.212504399;
RA Jin L., Harrison S.C.;
RT "Crystal structure of human calcineurin complexed with cyclosporin A
RT and human cyclophilin.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13522-13526(2002).
RN [29]
RP STRUCTURE BY NMR OF COMPLEX WITH CYCLOPHILIN.
RX PubMed=8421500; DOI=10.1038/361088a0;
RA Theriault Y., Logan T.M., Meadows R., Yu L., Olejniczak E.T.,
RA Holzman T.F., Simmer R.L., Fesik S.W.;
RT "Solution structure of the cyclosporin A/cyclophilin complex by NMR.";
RL Nature 361:88-91(1993).
RN [30]
RP STRUCTURE BY NMR.
RX PubMed=9299338; DOI=10.1006/jmbi.1997.1220;
RA Ottiger M., Zerbe O., Guentert P., Wuethrich K.;
RT "The NMR solution conformation of unligated human cyclophilin A.";
RL J. Mol. Biol. 272:64-81(1997).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) ALONE AND IN COMPLEX WITH
RP CYCLOSPORINE AND HIV-1 CAPSID, AND ACETYLATION AT LYS-125.
RX PubMed=20364129; DOI=10.1038/nchembio.342;
RA Lammers M., Neumann H., Chin J.W., James L.C.;
RT "Acetylation regulates cyclophilin A catalysis, immunosuppression and
RT HIV isomerization.";
RL Nat. Chem. Biol. 6:331-337(2010).
CC -!- FUNCTION: PPIases accelerate the folding of proteins. It catalyzes
CC the cis-trans isomerization of proline imidic peptide bonds in
CC oligopeptides.
CC -!- CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline
CC (omega=0).
CC -!- ENZYME REGULATION: Binds cyclosporin A (CsA). CsA mediates some of
CC its effects via an inhibitory action on PPIase.
CC -!- SUBUNIT: Interacts with HIV-1 Capsid protein.
CC -!- INTERACTION:
CC Q99IB8:- (xeno); NbExp=2; IntAct=EBI-437708, EBI-6931023;
CC Q72497:gag (xeno); NbExp=6; IntAct=EBI-437708, EBI-1036263;
CC Q16849:PTPRN; NbExp=3; IntAct=EBI-437708, EBI-728153;
CC O00267:SUPT5H; NbExp=2; IntAct=EBI-437708, EBI-710464;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Secreted. Note=Secretion occurs
CC in response to oxidative stress in vascular smooth muscle through
CC a vesicular secretory pathway that involves actin remodeling and
CC myosin II activation, and mediates ERK1/2 activation.
CC -!- PTM: Acetylation at Lys-125 markedly inhibits catalysis of cis to
CC trans isomerization and stabilizes cis rather than trans forms of
CC the HIV-1 capsid. PPIA acetylation also antagonizes the
CC immunosuppressive effects of cyclosporine by inhibiting the
CC sequential steps of cyclosporine binding and calcineurin
CC inhibition.
CC -!- SIMILARITY: Belongs to the cyclophilin-type PPIase family. PPIase
CC A subfamily.
CC -!- SIMILARITY: Contains 1 PPIase cyclophilin-type domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ppia/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Cyclophilin entry;
CC URL="http://en.wikipedia.org/wiki/Cyclophilin";
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DR EMBL; Y00052; CAA68264.1; -; mRNA.
DR EMBL; X52851; CAA37039.1; -; Genomic_DNA.
DR EMBL; AK290085; BAF82774.1; -; mRNA.
DR EMBL; CR456707; CAG32988.1; -; mRNA.
DR EMBL; AB451307; BAG70121.1; -; mRNA.
DR EMBL; AB451438; BAG70252.1; -; mRNA.
DR EMBL; AY739283; AAU13906.1; -; Genomic_DNA.
DR EMBL; BC000689; AAH00689.1; -; mRNA.
DR EMBL; BC003026; AAH03026.2; -; mRNA.
DR EMBL; BC005320; AAH05320.1; -; mRNA.
DR EMBL; BC005982; AAH05982.1; -; mRNA.
DR EMBL; BC007104; AAH07104.1; -; mRNA.
DR EMBL; BC013915; AAH13915.1; -; mRNA.
DR EMBL; BC073992; AAH73992.1; -; mRNA.
DR EMBL; BC106030; AAI06031.1; -; mRNA.
DR EMBL; BC137057; AAI37058.1; -; mRNA.
DR EMBL; BC137058; AAI37059.1; -; mRNA.
DR PIR; A94496; CSHUA.
DR RefSeq; NP_066953.1; NM_021130.3.
DR UniGene; Hs.356331; -.
DR PDB; 1AK4; X-ray; 2.36 A; A/B=2-164.
DR PDB; 1AWQ; X-ray; 1.58 A; A=2-165.
DR PDB; 1AWR; X-ray; 1.58 A; A/B/C/D/E/F=2-165.
DR PDB; 1AWS; X-ray; 2.55 A; A=2-165.
DR PDB; 1AWT; X-ray; 2.55 A; A/B/C/D/E/F=2-165.
DR PDB; 1AWU; X-ray; 2.34 A; A=2-165.
DR PDB; 1AWV; X-ray; 2.34 A; A/B/C/D/E/F=2-165.
DR PDB; 1BCK; X-ray; 1.80 A; A=1-165.
DR PDB; 1CWA; X-ray; 2.10 A; A=1-165.
DR PDB; 1CWB; X-ray; 2.20 A; A=1-165.
DR PDB; 1CWC; X-ray; 1.86 A; A=1-165.
DR PDB; 1CWF; X-ray; 1.86 A; A=1-165.
DR PDB; 1CWH; X-ray; 1.86 A; A=1-165.
DR PDB; 1CWI; X-ray; 1.90 A; A=1-165.
DR PDB; 1CWJ; X-ray; 1.80 A; A=1-165.
DR PDB; 1CWK; X-ray; 1.80 A; A=1-165.
DR PDB; 1CWL; X-ray; 1.80 A; A=1-165.
DR PDB; 1CWM; X-ray; 2.00 A; A=1-165.
DR PDB; 1CWO; X-ray; 1.86 A; A=2-164.
DR PDB; 1FGL; X-ray; 1.80 A; A=2-164.
DR PDB; 1M63; X-ray; 2.80 A; C/G=1-165.
DR PDB; 1M9C; X-ray; 2.00 A; A/B=1-164.
DR PDB; 1M9D; X-ray; 1.90 A; A/B=1-164.
DR PDB; 1M9E; X-ray; 1.72 A; A/B=1-163.
DR PDB; 1M9F; X-ray; 1.73 A; A/B=1-164.
DR PDB; 1M9X; X-ray; 1.70 A; A/B/E/F=1-164.
DR PDB; 1M9Y; X-ray; 1.90 A; A/B/E/F=1-164.
DR PDB; 1MF8; X-ray; 3.10 A; C=1-165.
DR PDB; 1MIK; X-ray; 1.76 A; A=1-165.
DR PDB; 1NMK; X-ray; 2.10 A; A/B=1-165.
DR PDB; 1OCA; NMR; -; A=1-165.
DR PDB; 1RMH; X-ray; 2.40 A; A/B=2-165.
DR PDB; 1VBS; X-ray; 2.00 A; A=1-165.
DR PDB; 1VBT; X-ray; 2.30 A; A/B=1-165.
DR PDB; 1W8L; X-ray; 1.80 A; A=2-164.
DR PDB; 1W8M; X-ray; 1.65 A; A=2-164.
DR PDB; 1W8V; X-ray; 1.70 A; A=2-164.
DR PDB; 1YND; X-ray; 1.60 A; A/B=1-165.
DR PDB; 1ZKF; X-ray; 2.55 A; A/B=1-165.
DR PDB; 2ALF; X-ray; 1.90 A; A=2-164.
DR PDB; 2CPL; X-ray; 1.63 A; A=2-164.
DR PDB; 2CYH; X-ray; 1.64 A; A=2-165.
DR PDB; 2RMA; X-ray; 2.10 A; A/C/E/G/I/K/M/O/Q/S=2-164.
DR PDB; 2RMB; X-ray; 2.10 A; A/C/E/G/I/K/M/O/Q/S=2-164.
DR PDB; 2X25; X-ray; 1.20 A; B=2-165.
DR PDB; 2X2A; X-ray; 1.40 A; A/B=1-165.
DR PDB; 2X2C; X-ray; 2.41 A; K/M/O/Q/S=1-165.
DR PDB; 2X2D; X-ray; 1.95 A; B/C=1-165.
DR PDB; 2XGY; X-ray; 1.80 A; B=1-165.
DR PDB; 3CYH; X-ray; 1.90 A; A=2-165.
DR PDB; 3CYS; NMR; -; A=1-165.
DR PDB; 3K0M; X-ray; 1.25 A; A=1-165.
DR PDB; 3K0N; X-ray; 1.39 A; A=1-165.
DR PDB; 3K0O; X-ray; 1.55 A; A=1-165.
DR PDB; 3K0P; X-ray; 1.65 A; A=1-165.
DR PDB; 3K0Q; X-ray; 2.32 A; A=1-165.
DR PDB; 3K0R; X-ray; 2.42 A; A=1-165.
DR PDB; 3ODI; X-ray; 2.20 A; A/C/E/G/I/K/M/O/Q/S=1-165.
DR PDB; 3ODL; X-ray; 2.31 A; A/C/E/G/I/K/M/O/Q/S=1-165.
DR PDB; 3RDD; X-ray; 2.14 A; A=1-165.
DR PDB; 4CYH; X-ray; 2.10 A; A=2-165.
DR PDB; 4IPZ; X-ray; 1.67 A; A=1-165.
DR PDB; 5CYH; X-ray; 2.10 A; A=2-165.
DR PDBsum; 1AK4; -.
DR PDBsum; 1AWQ; -.
DR PDBsum; 1AWR; -.
DR PDBsum; 1AWS; -.
DR PDBsum; 1AWT; -.
DR PDBsum; 1AWU; -.
DR PDBsum; 1AWV; -.
DR PDBsum; 1BCK; -.
DR PDBsum; 1CWA; -.
DR PDBsum; 1CWB; -.
DR PDBsum; 1CWC; -.
DR PDBsum; 1CWF; -.
DR PDBsum; 1CWH; -.
DR PDBsum; 1CWI; -.
DR PDBsum; 1CWJ; -.
DR PDBsum; 1CWK; -.
DR PDBsum; 1CWL; -.
DR PDBsum; 1CWM; -.
DR PDBsum; 1CWO; -.
DR PDBsum; 1FGL; -.
DR PDBsum; 1M63; -.
DR PDBsum; 1M9C; -.
DR PDBsum; 1M9D; -.
DR PDBsum; 1M9E; -.
DR PDBsum; 1M9F; -.
DR PDBsum; 1M9X; -.
DR PDBsum; 1M9Y; -.
DR PDBsum; 1MF8; -.
DR PDBsum; 1MIK; -.
DR PDBsum; 1NMK; -.
DR PDBsum; 1OCA; -.
DR PDBsum; 1RMH; -.
DR PDBsum; 1VBS; -.
DR PDBsum; 1VBT; -.
DR PDBsum; 1W8L; -.
DR PDBsum; 1W8M; -.
DR PDBsum; 1W8V; -.
DR PDBsum; 1YND; -.
DR PDBsum; 1ZKF; -.
DR PDBsum; 2ALF; -.
DR PDBsum; 2CPL; -.
DR PDBsum; 2CYH; -.
DR PDBsum; 2RMA; -.
DR PDBsum; 2RMB; -.
DR PDBsum; 2X25; -.
DR PDBsum; 2X2A; -.
DR PDBsum; 2X2C; -.
DR PDBsum; 2X2D; -.
DR PDBsum; 2XGY; -.
DR PDBsum; 3CYH; -.
DR PDBsum; 3CYS; -.
DR PDBsum; 3K0M; -.
DR PDBsum; 3K0N; -.
DR PDBsum; 3K0O; -.
DR PDBsum; 3K0P; -.
DR PDBsum; 3K0Q; -.
DR PDBsum; 3K0R; -.
DR PDBsum; 3ODI; -.
DR PDBsum; 3ODL; -.
DR PDBsum; 3RDD; -.
DR PDBsum; 4CYH; -.
DR PDBsum; 4IPZ; -.
DR PDBsum; 5CYH; -.
DR ProteinModelPortal; P62937; -.
DR SMR; P62937; 2-165.
DR DIP; DIP-6080N; -.
DR IntAct; P62937; 38.
DR MINT; MINT-4999116; -.
DR STRING; 9606.ENSP00000419425; -.
DR BindingDB; P62937; -.
DR ChEMBL; CHEMBL1949; -.
DR DrugBank; DB00091; Cyclosporine.
DR DrugBank; DB00172; L-Proline.
DR PhosphoSite; P62937; -.
DR DMDM; 51702775; -.
DR DOSAC-COBS-2DPAGE; P62937; -.
DR OGP; P62937; -.
DR REPRODUCTION-2DPAGE; IPI00419585; -.
DR REPRODUCTION-2DPAGE; P62937; -.
DR SWISS-2DPAGE; P62937; -.
DR UCD-2DPAGE; P62937; -.
DR PaxDb; P62937; -.
DR PeptideAtlas; P62937; -.
DR PRIDE; P62937; -.
DR DNASU; 5478; -.
DR Ensembl; ENST00000468812; ENSP00000419425; ENSG00000196262.
DR GeneID; 5478; -.
DR KEGG; hsa:5478; -.
DR UCSC; uc003tlw.3; human.
DR CTD; 5478; -.
DR GeneCards; GC07P044803; -.
DR HGNC; HGNC:9253; PPIA.
DR HPA; CAB004655; -.
DR MIM; 123840; gene.
DR neXtProt; NX_P62937; -.
DR PharmGKB; PA33574; -.
DR eggNOG; COG0652; -.
DR HOVERGEN; HBG001065; -.
DR InParanoid; P62937; -.
DR KO; K03767; -.
DR OMA; PGPNLVI; -.
DR PhylomeDB; P62937; -.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; PPIA; human.
DR EvolutionaryTrace; P62937; -.
DR GeneWiki; Peptidylprolyl_isomerase_A; -.
DR GenomeRNAi; 5478; -.
DR NextBio; 21206; -.
DR PRO; PR:P62937; -.
DR ArrayExpress; P62937; -.
DR Bgee; P62937; -.
DR CleanEx; HS_PPIA; -.
DR Genevestigator; P62937; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IEA:UniProtKB-KW.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; TAS:UniProtKB.
DR GO; GO:0046790; F:virion binding; NAS:UniProtKB.
DR GO; GO:0030260; P:entry into host cell; TAS:Reactome.
DR GO; GO:0075713; P:establishment of integrated proviral latency; TAS:Reactome.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0034389; P:lipid particle organization; IMP:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IMP:UniProtKB.
DR GO; GO:0006457; P:protein folding; TAS:UniProtKB.
DR GO; GO:0006278; P:RNA-dependent DNA replication; TAS:Reactome.
DR GO; GO:0019061; P:uncoating of virus; TAS:Reactome.
DR GO; GO:0019076; P:viral release from host cell; TAS:UniProtKB.
DR GO; GO:0019068; P:virion assembly; TAS:Reactome.
DR InterPro; IPR002130; Cyclophilin-like_PPIase_dom.
DR InterPro; IPR024936; Cyclophilin-type_PPIase.
DR InterPro; IPR020892; Cyclophilin-type_PPIase_CS.
DR Pfam; PF00160; Pro_isomerase; 1.
DR PIRSF; PIRSF001467; Peptidylpro_ismrse; 1.
DR PRINTS; PR00153; CSAPPISMRASE.
DR SUPFAM; SSF50891; SSF50891; 1.
DR PROSITE; PS00170; CSA_PPIASE_1; 1.
DR PROSITE; PS50072; CSA_PPIASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cyclosporin; Cytoplasm;
KW Direct protein sequencing; Glycoprotein; Host-virus interaction;
KW Isomerase; Isopeptide bond; Phosphoprotein; Reference proteome;
KW Rotamase; Secreted; Ubl conjugation.
FT CHAIN 1 165 Peptidyl-prolyl cis-trans isomerase A.
FT /FTId=PRO_0000423240.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 165 Peptidyl-prolyl cis-trans isomerase A, N-
FT terminally processed.
FT /FTId=PRO_0000064115.
FT DOMAIN 7 163 PPIase cyclophilin-type.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylvaline; partial; in Peptidyl-
FT prolyl cis-trans isomerase A, N-
FT terminally processed.
FT MOD_RES 28 28 N6-acetyllysine; alternate.
FT MOD_RES 44 44 N6-acetyllysine.
FT MOD_RES 76 76 N6-acetyllysine.
FT MOD_RES 82 82 N6-acetyllysine.
FT MOD_RES 93 93 Phosphothreonine.
FT MOD_RES 125 125 N6-acetyllysine.
FT MOD_RES 131 131 N6-acetyllysine.
FT CARBOHYD 108 108 N-linked (GlcNAc...) (Potential).
FT CROSSLNK 28 28 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate.
FT MUTAGEN 121 121 W->A: 200-fold decrease of sensitivity to
FT CsA.
FT MUTAGEN 121 121 W->F: 75-fold decrease of sensitivity to
FT CsA.
FT CONFLICT 89 89 I -> T (in Ref. 7; AAH05982).
FT CONFLICT 106 106 N -> I (in Ref. 7; AAH07104).
FT CONFLICT 165 165 E -> D (in Ref. 4; CAG32988).
FT STRAND 5 12
FT STRAND 15 24
FT TURN 26 28
FT HELIX 30 41
FT TURN 42 44
FT STRAND 52 57
FT TURN 58 60
FT STRAND 61 64
FT TURN 67 69
FT STRAND 70 73
FT STRAND 78 81
FT STRAND 97 100
FT STRAND 102 104
FT STRAND 108 110
FT STRAND 112 117
FT HELIX 120 122
FT TURN 123 125
FT STRAND 128 134
FT HELIX 136 143
FT HELIX 148 150
FT TURN 153 155
FT STRAND 156 164
SQ SEQUENCE 165 AA; 18012 MW; 9B2E637A555E4434 CRC64;
MVNPTVFFDI AVDGEPLGRV SFELFADKVP KTAENFRALS TGEKGFGYKG SCFHRIIPGF
MCQGGDFTRH NGTGGKSIYG EKFEDENFIL KHTGPGILSM ANAGPNTNGS QFFICTAKTE
WLDGKHVVFG KVKEGMNIVE AMERFGSRNG KTSKKITIAD CGQLE
//
ID PPIA_HUMAN Reviewed; 165 AA.
AC P62937; A8K220; P05092; Q3KQW3; Q6IBU5; Q96IX3; Q9BRU4; Q9BTY9;
read moreAC Q9UC61;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase A;
DE Short=PPIase A;
DE EC=5.2.1.8;
DE AltName: Full=Cyclophilin A;
DE AltName: Full=Cyclosporin A-binding protein;
DE AltName: Full=Rotamase A;
DE Contains:
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase A, N-terminally processed;
GN Name=PPIA; Synonyms=CYPA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Leukemic T-cell;
RX PubMed=3297675;
RA Haendler B., Hofer-Warbinek R., Hofer E.;
RT "Complementary DNA for human T-cell cyclophilin.";
RL EMBO J. 6:947-950(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2197089; DOI=10.1111/j.1432-1033.1990.tb15598.x;
RA Haendler B., Hofer E.;
RT "Characterization of the human cyclophilin gene and of related
RT processed pseudogenes.";
RL Eur. J. Biochem. 190:477-482(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Subthalamic nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow, Brain, Cervix, Colon, Lung, Skeletal muscle, Skin,
RC and Urinary bladder;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 2-30.
RX PubMed=7657784;
RA Meier U., Beier-Hellwig K., Klug J., Linder D., Beier H.M.;
RT "Identification of cyclophilin A from human decidual and placental
RT tissue in the first trimester of pregnancy.";
RL Hum. Reprod. 10:1305-1310(1995).
RN [9]
RP PROTEIN SEQUENCE OF 2-19.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [10]
RP PROTEIN SEQUENCE OF 2-31; 56-69; 77-118; 132-144 AND 155-165, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 2-28, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT VAL-2, AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [12]
RP MUTAGENESIS OF TRP-121.
RX PubMed=2001362; DOI=10.1021/bi00223a003;
RA Liu J., Chen C.-M., Walsh C.T.;
RT "Human and Escherichia coli cyclophilins: sensitivity to inhibition by
RT the immunosuppressant cyclosporin A correlates with a specific
RT tryptophan residue.";
RL Biochemistry 30:2306-2310(1991).
RN [13]
RP INTERACTION WITH HIV-1 CAPSID PROTEIN.
RX PubMed=8513493; DOI=10.1016/0092-8674(93)90637-6;
RA Luban J., Bossolt K.L., Franke E.K., Kalpana G.V., Goff S.P.;
RT "Human immunodeficiency virus type 1 Gag protein binds to cyclophilins
RT A and B.";
RL Cell 73:1067-1078(1993).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=16527992; DOI=10.1161/01.RES.0000216405.85080.a6;
RA Suzuki J., Jin Z.G., Meoli D.F., Matoba T., Berk B.C.;
RT "Cyclophilin A is secreted by a vesicular pathway in vascular smooth
RT muscle cells.";
RL Circ. Res. 98:811-817(2006).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND VAL-2, AND MASS
RP SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-28; LYS-44; LYS-76; LYS-82;
RP LYS-125 AND LYS-131, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-93, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), AND STRUCTURE BY NMR.
RX PubMed=1896075; DOI=10.1038/353276a0;
RA Kallen J., Spitzfaden C., Zurini M.G.M., Wider G., Widmer H.,
RA Wuethrich K., Walkinshaw M.D.;
RT "Structure of human cyclophilin and its binding site for cyclosporin A
RT determined by X-ray crystallography and NMR spectroscopy.";
RL Nature 353:276-279(1991).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=1946361; DOI=10.1073/pnas.88.21.9483;
RA Ke H., Zydowsky L.D., Liu J., Walsh C.T.;
RT "Crystal structure of recombinant human T-cell cyclophilin A at 2.5-A
RT resolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:9483-9487(1991).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEX WITH CYCLOPHILIN.
RX PubMed=8421501; DOI=10.1038/361091a0;
RA Pfuegl G., Kallen J., Schirmer T., Jansonius J.N., Zurini M.G.M.,
RA Walkinshaw M.D.;
RT "X-ray structure of a decameric cyclophilin-cyclosporin crystal
RT complex.";
RL Nature 361:91-94(1993).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=8263916; DOI=10.1006/jmbi.1993.1664;
RA Mikol V., Kallen J., Pfluegl G., Walkinshaw M.D.;
RT "X-ray structure of a monomeric cyclophilin A-cyclosporin A crystal
RT complex at 2.1-A resolution.";
RL J. Mol. Biol. 234:1119-1130(1993).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=8652511; DOI=10.1021/bi9602775;
RA Zhao Y., Ke H.;
RT "Crystal structure implies that cyclophilin predominantly catalyzes
RT the trans to cis isomerization.";
RL Biochemistry 35:7356-7361(1996).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS).
RX PubMed=9385632;
RA Vajdos F.F., Yoo S., Houseweart M., Sundquist W.I., Hill C.P.;
RT "Crystal structure of cyclophilin A complexed with a binding site
RT peptide from the HIV-1 capsid protein.";
RL Protein Sci. 6:2297-2307(1997).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
RX PubMed=9769216; DOI=10.1006/jmbi.1998.2108;
RA Kallen J., Mikol V., Taylor P., Walkinshaw M.D.;
RT "X-ray structures and analysis of 11 cyclosporin derivatives complexed
RT with cyclophilin A.";
RL J. Mol. Biol. 283:435-449(1998).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH CALCINEURIN B.
RX PubMed=12218175; DOI=10.1073/pnas.192206699;
RA Huai Q., Kim H.Y., Liu Y., Zhao Y., Mondragon A., Liu J.O., Ke H.;
RT "Crystal structure of calcineurin-cyclophilin-cyclosporin shows common
RT but distinct recognition of immunophilin-drug complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:12037-12042(2002).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) IN COMPLEX WITH CALCINEURIN B.
RX PubMed=12357034; DOI=10.1073/pnas.212504399;
RA Jin L., Harrison S.C.;
RT "Crystal structure of human calcineurin complexed with cyclosporin A
RT and human cyclophilin.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13522-13526(2002).
RN [29]
RP STRUCTURE BY NMR OF COMPLEX WITH CYCLOPHILIN.
RX PubMed=8421500; DOI=10.1038/361088a0;
RA Theriault Y., Logan T.M., Meadows R., Yu L., Olejniczak E.T.,
RA Holzman T.F., Simmer R.L., Fesik S.W.;
RT "Solution structure of the cyclosporin A/cyclophilin complex by NMR.";
RL Nature 361:88-91(1993).
RN [30]
RP STRUCTURE BY NMR.
RX PubMed=9299338; DOI=10.1006/jmbi.1997.1220;
RA Ottiger M., Zerbe O., Guentert P., Wuethrich K.;
RT "The NMR solution conformation of unligated human cyclophilin A.";
RL J. Mol. Biol. 272:64-81(1997).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) ALONE AND IN COMPLEX WITH
RP CYCLOSPORINE AND HIV-1 CAPSID, AND ACETYLATION AT LYS-125.
RX PubMed=20364129; DOI=10.1038/nchembio.342;
RA Lammers M., Neumann H., Chin J.W., James L.C.;
RT "Acetylation regulates cyclophilin A catalysis, immunosuppression and
RT HIV isomerization.";
RL Nat. Chem. Biol. 6:331-337(2010).
CC -!- FUNCTION: PPIases accelerate the folding of proteins. It catalyzes
CC the cis-trans isomerization of proline imidic peptide bonds in
CC oligopeptides.
CC -!- CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline
CC (omega=0).
CC -!- ENZYME REGULATION: Binds cyclosporin A (CsA). CsA mediates some of
CC its effects via an inhibitory action on PPIase.
CC -!- SUBUNIT: Interacts with HIV-1 Capsid protein.
CC -!- INTERACTION:
CC Q99IB8:- (xeno); NbExp=2; IntAct=EBI-437708, EBI-6931023;
CC Q72497:gag (xeno); NbExp=6; IntAct=EBI-437708, EBI-1036263;
CC Q16849:PTPRN; NbExp=3; IntAct=EBI-437708, EBI-728153;
CC O00267:SUPT5H; NbExp=2; IntAct=EBI-437708, EBI-710464;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Secreted. Note=Secretion occurs
CC in response to oxidative stress in vascular smooth muscle through
CC a vesicular secretory pathway that involves actin remodeling and
CC myosin II activation, and mediates ERK1/2 activation.
CC -!- PTM: Acetylation at Lys-125 markedly inhibits catalysis of cis to
CC trans isomerization and stabilizes cis rather than trans forms of
CC the HIV-1 capsid. PPIA acetylation also antagonizes the
CC immunosuppressive effects of cyclosporine by inhibiting the
CC sequential steps of cyclosporine binding and calcineurin
CC inhibition.
CC -!- SIMILARITY: Belongs to the cyclophilin-type PPIase family. PPIase
CC A subfamily.
CC -!- SIMILARITY: Contains 1 PPIase cyclophilin-type domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ppia/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Cyclophilin entry;
CC URL="http://en.wikipedia.org/wiki/Cyclophilin";
CC -----------------------------------------------------------------------
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DR EMBL; Y00052; CAA68264.1; -; mRNA.
DR EMBL; X52851; CAA37039.1; -; Genomic_DNA.
DR EMBL; AK290085; BAF82774.1; -; mRNA.
DR EMBL; CR456707; CAG32988.1; -; mRNA.
DR EMBL; AB451307; BAG70121.1; -; mRNA.
DR EMBL; AB451438; BAG70252.1; -; mRNA.
DR EMBL; AY739283; AAU13906.1; -; Genomic_DNA.
DR EMBL; BC000689; AAH00689.1; -; mRNA.
DR EMBL; BC003026; AAH03026.2; -; mRNA.
DR EMBL; BC005320; AAH05320.1; -; mRNA.
DR EMBL; BC005982; AAH05982.1; -; mRNA.
DR EMBL; BC007104; AAH07104.1; -; mRNA.
DR EMBL; BC013915; AAH13915.1; -; mRNA.
DR EMBL; BC073992; AAH73992.1; -; mRNA.
DR EMBL; BC106030; AAI06031.1; -; mRNA.
DR EMBL; BC137057; AAI37058.1; -; mRNA.
DR EMBL; BC137058; AAI37059.1; -; mRNA.
DR PIR; A94496; CSHUA.
DR RefSeq; NP_066953.1; NM_021130.3.
DR UniGene; Hs.356331; -.
DR PDB; 1AK4; X-ray; 2.36 A; A/B=2-164.
DR PDB; 1AWQ; X-ray; 1.58 A; A=2-165.
DR PDB; 1AWR; X-ray; 1.58 A; A/B/C/D/E/F=2-165.
DR PDB; 1AWS; X-ray; 2.55 A; A=2-165.
DR PDB; 1AWT; X-ray; 2.55 A; A/B/C/D/E/F=2-165.
DR PDB; 1AWU; X-ray; 2.34 A; A=2-165.
DR PDB; 1AWV; X-ray; 2.34 A; A/B/C/D/E/F=2-165.
DR PDB; 1BCK; X-ray; 1.80 A; A=1-165.
DR PDB; 1CWA; X-ray; 2.10 A; A=1-165.
DR PDB; 1CWB; X-ray; 2.20 A; A=1-165.
DR PDB; 1CWC; X-ray; 1.86 A; A=1-165.
DR PDB; 1CWF; X-ray; 1.86 A; A=1-165.
DR PDB; 1CWH; X-ray; 1.86 A; A=1-165.
DR PDB; 1CWI; X-ray; 1.90 A; A=1-165.
DR PDB; 1CWJ; X-ray; 1.80 A; A=1-165.
DR PDB; 1CWK; X-ray; 1.80 A; A=1-165.
DR PDB; 1CWL; X-ray; 1.80 A; A=1-165.
DR PDB; 1CWM; X-ray; 2.00 A; A=1-165.
DR PDB; 1CWO; X-ray; 1.86 A; A=2-164.
DR PDB; 1FGL; X-ray; 1.80 A; A=2-164.
DR PDB; 1M63; X-ray; 2.80 A; C/G=1-165.
DR PDB; 1M9C; X-ray; 2.00 A; A/B=1-164.
DR PDB; 1M9D; X-ray; 1.90 A; A/B=1-164.
DR PDB; 1M9E; X-ray; 1.72 A; A/B=1-163.
DR PDB; 1M9F; X-ray; 1.73 A; A/B=1-164.
DR PDB; 1M9X; X-ray; 1.70 A; A/B/E/F=1-164.
DR PDB; 1M9Y; X-ray; 1.90 A; A/B/E/F=1-164.
DR PDB; 1MF8; X-ray; 3.10 A; C=1-165.
DR PDB; 1MIK; X-ray; 1.76 A; A=1-165.
DR PDB; 1NMK; X-ray; 2.10 A; A/B=1-165.
DR PDB; 1OCA; NMR; -; A=1-165.
DR PDB; 1RMH; X-ray; 2.40 A; A/B=2-165.
DR PDB; 1VBS; X-ray; 2.00 A; A=1-165.
DR PDB; 1VBT; X-ray; 2.30 A; A/B=1-165.
DR PDB; 1W8L; X-ray; 1.80 A; A=2-164.
DR PDB; 1W8M; X-ray; 1.65 A; A=2-164.
DR PDB; 1W8V; X-ray; 1.70 A; A=2-164.
DR PDB; 1YND; X-ray; 1.60 A; A/B=1-165.
DR PDB; 1ZKF; X-ray; 2.55 A; A/B=1-165.
DR PDB; 2ALF; X-ray; 1.90 A; A=2-164.
DR PDB; 2CPL; X-ray; 1.63 A; A=2-164.
DR PDB; 2CYH; X-ray; 1.64 A; A=2-165.
DR PDB; 2RMA; X-ray; 2.10 A; A/C/E/G/I/K/M/O/Q/S=2-164.
DR PDB; 2RMB; X-ray; 2.10 A; A/C/E/G/I/K/M/O/Q/S=2-164.
DR PDB; 2X25; X-ray; 1.20 A; B=2-165.
DR PDB; 2X2A; X-ray; 1.40 A; A/B=1-165.
DR PDB; 2X2C; X-ray; 2.41 A; K/M/O/Q/S=1-165.
DR PDB; 2X2D; X-ray; 1.95 A; B/C=1-165.
DR PDB; 2XGY; X-ray; 1.80 A; B=1-165.
DR PDB; 3CYH; X-ray; 1.90 A; A=2-165.
DR PDB; 3CYS; NMR; -; A=1-165.
DR PDB; 3K0M; X-ray; 1.25 A; A=1-165.
DR PDB; 3K0N; X-ray; 1.39 A; A=1-165.
DR PDB; 3K0O; X-ray; 1.55 A; A=1-165.
DR PDB; 3K0P; X-ray; 1.65 A; A=1-165.
DR PDB; 3K0Q; X-ray; 2.32 A; A=1-165.
DR PDB; 3K0R; X-ray; 2.42 A; A=1-165.
DR PDB; 3ODI; X-ray; 2.20 A; A/C/E/G/I/K/M/O/Q/S=1-165.
DR PDB; 3ODL; X-ray; 2.31 A; A/C/E/G/I/K/M/O/Q/S=1-165.
DR PDB; 3RDD; X-ray; 2.14 A; A=1-165.
DR PDB; 4CYH; X-ray; 2.10 A; A=2-165.
DR PDB; 4IPZ; X-ray; 1.67 A; A=1-165.
DR PDB; 5CYH; X-ray; 2.10 A; A=2-165.
DR PDBsum; 1AK4; -.
DR PDBsum; 1AWQ; -.
DR PDBsum; 1AWR; -.
DR PDBsum; 1AWS; -.
DR PDBsum; 1AWT; -.
DR PDBsum; 1AWU; -.
DR PDBsum; 1AWV; -.
DR PDBsum; 1BCK; -.
DR PDBsum; 1CWA; -.
DR PDBsum; 1CWB; -.
DR PDBsum; 1CWC; -.
DR PDBsum; 1CWF; -.
DR PDBsum; 1CWH; -.
DR PDBsum; 1CWI; -.
DR PDBsum; 1CWJ; -.
DR PDBsum; 1CWK; -.
DR PDBsum; 1CWL; -.
DR PDBsum; 1CWM; -.
DR PDBsum; 1CWO; -.
DR PDBsum; 1FGL; -.
DR PDBsum; 1M63; -.
DR PDBsum; 1M9C; -.
DR PDBsum; 1M9D; -.
DR PDBsum; 1M9E; -.
DR PDBsum; 1M9F; -.
DR PDBsum; 1M9X; -.
DR PDBsum; 1M9Y; -.
DR PDBsum; 1MF8; -.
DR PDBsum; 1MIK; -.
DR PDBsum; 1NMK; -.
DR PDBsum; 1OCA; -.
DR PDBsum; 1RMH; -.
DR PDBsum; 1VBS; -.
DR PDBsum; 1VBT; -.
DR PDBsum; 1W8L; -.
DR PDBsum; 1W8M; -.
DR PDBsum; 1W8V; -.
DR PDBsum; 1YND; -.
DR PDBsum; 1ZKF; -.
DR PDBsum; 2ALF; -.
DR PDBsum; 2CPL; -.
DR PDBsum; 2CYH; -.
DR PDBsum; 2RMA; -.
DR PDBsum; 2RMB; -.
DR PDBsum; 2X25; -.
DR PDBsum; 2X2A; -.
DR PDBsum; 2X2C; -.
DR PDBsum; 2X2D; -.
DR PDBsum; 2XGY; -.
DR PDBsum; 3CYH; -.
DR PDBsum; 3CYS; -.
DR PDBsum; 3K0M; -.
DR PDBsum; 3K0N; -.
DR PDBsum; 3K0O; -.
DR PDBsum; 3K0P; -.
DR PDBsum; 3K0Q; -.
DR PDBsum; 3K0R; -.
DR PDBsum; 3ODI; -.
DR PDBsum; 3ODL; -.
DR PDBsum; 3RDD; -.
DR PDBsum; 4CYH; -.
DR PDBsum; 4IPZ; -.
DR PDBsum; 5CYH; -.
DR ProteinModelPortal; P62937; -.
DR SMR; P62937; 2-165.
DR DIP; DIP-6080N; -.
DR IntAct; P62937; 38.
DR MINT; MINT-4999116; -.
DR STRING; 9606.ENSP00000419425; -.
DR BindingDB; P62937; -.
DR ChEMBL; CHEMBL1949; -.
DR DrugBank; DB00091; Cyclosporine.
DR DrugBank; DB00172; L-Proline.
DR PhosphoSite; P62937; -.
DR DMDM; 51702775; -.
DR DOSAC-COBS-2DPAGE; P62937; -.
DR OGP; P62937; -.
DR REPRODUCTION-2DPAGE; IPI00419585; -.
DR REPRODUCTION-2DPAGE; P62937; -.
DR SWISS-2DPAGE; P62937; -.
DR UCD-2DPAGE; P62937; -.
DR PaxDb; P62937; -.
DR PeptideAtlas; P62937; -.
DR PRIDE; P62937; -.
DR DNASU; 5478; -.
DR Ensembl; ENST00000468812; ENSP00000419425; ENSG00000196262.
DR GeneID; 5478; -.
DR KEGG; hsa:5478; -.
DR UCSC; uc003tlw.3; human.
DR CTD; 5478; -.
DR GeneCards; GC07P044803; -.
DR HGNC; HGNC:9253; PPIA.
DR HPA; CAB004655; -.
DR MIM; 123840; gene.
DR neXtProt; NX_P62937; -.
DR PharmGKB; PA33574; -.
DR eggNOG; COG0652; -.
DR HOVERGEN; HBG001065; -.
DR InParanoid; P62937; -.
DR KO; K03767; -.
DR OMA; PGPNLVI; -.
DR PhylomeDB; P62937; -.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_604; Hemostasis.
DR ChiTaRS; PPIA; human.
DR EvolutionaryTrace; P62937; -.
DR GeneWiki; Peptidylprolyl_isomerase_A; -.
DR GenomeRNAi; 5478; -.
DR NextBio; 21206; -.
DR PRO; PR:P62937; -.
DR ArrayExpress; P62937; -.
DR Bgee; P62937; -.
DR CleanEx; HS_PPIA; -.
DR Genevestigator; P62937; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IEA:UniProtKB-KW.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; TAS:UniProtKB.
DR GO; GO:0046790; F:virion binding; NAS:UniProtKB.
DR GO; GO:0030260; P:entry into host cell; TAS:Reactome.
DR GO; GO:0075713; P:establishment of integrated proviral latency; TAS:Reactome.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0034389; P:lipid particle organization; IMP:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IMP:UniProtKB.
DR GO; GO:0006457; P:protein folding; TAS:UniProtKB.
DR GO; GO:0006278; P:RNA-dependent DNA replication; TAS:Reactome.
DR GO; GO:0019061; P:uncoating of virus; TAS:Reactome.
DR GO; GO:0019076; P:viral release from host cell; TAS:UniProtKB.
DR GO; GO:0019068; P:virion assembly; TAS:Reactome.
DR InterPro; IPR002130; Cyclophilin-like_PPIase_dom.
DR InterPro; IPR024936; Cyclophilin-type_PPIase.
DR InterPro; IPR020892; Cyclophilin-type_PPIase_CS.
DR Pfam; PF00160; Pro_isomerase; 1.
DR PIRSF; PIRSF001467; Peptidylpro_ismrse; 1.
DR PRINTS; PR00153; CSAPPISMRASE.
DR SUPFAM; SSF50891; SSF50891; 1.
DR PROSITE; PS00170; CSA_PPIASE_1; 1.
DR PROSITE; PS50072; CSA_PPIASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cyclosporin; Cytoplasm;
KW Direct protein sequencing; Glycoprotein; Host-virus interaction;
KW Isomerase; Isopeptide bond; Phosphoprotein; Reference proteome;
KW Rotamase; Secreted; Ubl conjugation.
FT CHAIN 1 165 Peptidyl-prolyl cis-trans isomerase A.
FT /FTId=PRO_0000423240.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 165 Peptidyl-prolyl cis-trans isomerase A, N-
FT terminally processed.
FT /FTId=PRO_0000064115.
FT DOMAIN 7 163 PPIase cyclophilin-type.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylvaline; partial; in Peptidyl-
FT prolyl cis-trans isomerase A, N-
FT terminally processed.
FT MOD_RES 28 28 N6-acetyllysine; alternate.
FT MOD_RES 44 44 N6-acetyllysine.
FT MOD_RES 76 76 N6-acetyllysine.
FT MOD_RES 82 82 N6-acetyllysine.
FT MOD_RES 93 93 Phosphothreonine.
FT MOD_RES 125 125 N6-acetyllysine.
FT MOD_RES 131 131 N6-acetyllysine.
FT CARBOHYD 108 108 N-linked (GlcNAc...) (Potential).
FT CROSSLNK 28 28 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate.
FT MUTAGEN 121 121 W->A: 200-fold decrease of sensitivity to
FT CsA.
FT MUTAGEN 121 121 W->F: 75-fold decrease of sensitivity to
FT CsA.
FT CONFLICT 89 89 I -> T (in Ref. 7; AAH05982).
FT CONFLICT 106 106 N -> I (in Ref. 7; AAH07104).
FT CONFLICT 165 165 E -> D (in Ref. 4; CAG32988).
FT STRAND 5 12
FT STRAND 15 24
FT TURN 26 28
FT HELIX 30 41
FT TURN 42 44
FT STRAND 52 57
FT TURN 58 60
FT STRAND 61 64
FT TURN 67 69
FT STRAND 70 73
FT STRAND 78 81
FT STRAND 97 100
FT STRAND 102 104
FT STRAND 108 110
FT STRAND 112 117
FT HELIX 120 122
FT TURN 123 125
FT STRAND 128 134
FT HELIX 136 143
FT HELIX 148 150
FT TURN 153 155
FT STRAND 156 164
SQ SEQUENCE 165 AA; 18012 MW; 9B2E637A555E4434 CRC64;
MVNPTVFFDI AVDGEPLGRV SFELFADKVP KTAENFRALS TGEKGFGYKG SCFHRIIPGF
MCQGGDFTRH NGTGGKSIYG EKFEDENFIL KHTGPGILSM ANAGPNTNGS QFFICTAKTE
WLDGKHVVFG KVKEGMNIVE AMERFGSRNG KTSKKITIAD CGQLE
//
MIM
123840
*RECORD*
*FIELD* NO
123840
*FIELD* TI
*123840 PEPTIDYL-PROLYL ISOMERASE A; PPIA
;;CYCLOPHILIN A; CYPA;;
CYPH
*FIELD* TX
read moreCLONING
Cyclophilin is a specific high-affinity binding protein for the
immunosuppressant agent cyclosporin A. Because of its dramatic effects
on decreasing morbidity and increasing survival rates in human
transplants, the molecular mechanism of immunosuppression by cyclosporin
A has been a matter of much interest. Liu et al. (1990) cloned human
cDNA for T-cell CYPH and constructed an expression vector under control
of the tac promoter for efficient expression in E. coli.
GENE FUNCTION
Cyclophilin A (also designated peptidyl-prolyl cis/trans isomerase A or
PPIA) is a member of the immunophilin class of proteins that all possess
peptidyl-prolyl cis/trans isomerase activity and, therefore, are
believed to be involved in protein folding and/or intracellular protein
transport. Luban et al. (1993) showed that cyclophilin A binds to the
Gag protein of human immunodeficiency virus type 1 (HIV-1). This
interaction can be inhibited by the immunosuppressant cyclosporin A and
also by nonimmunosuppressive, cyclophilin A-binding cyclosporin A
derivatives, which were also shown to exhibit potent anti-HIV-1
activity. Thus, cyclophilin A may have an essential function in HIV-1
replication.
Pushkarsky et al. (2001) identified CD147 (BSG; 109480) as a receptor
for extracellular CYPA. They found that CD147 enhanced HIV-1 infection
through interaction with CYPA incorporated into virions.
Virus-associated CYPA coimmunoprecipitated with CD147 from infected
cells, and antibody to CD147 inhibited HIV-1 entry. Viruses whose
replication did not require CYPA were resistant to the inhibitory effect
of anti-CD147 antibody. Pushkarsky et al. (2001) concluded that HIV-1
entry depends on an interaction between virus-associated CYPA and CD147
on a target cell.
Towers et al. (2003) demonstrated that HIV-1 sensitivity to restriction
factors is modulated by CYPA. In certain nonhuman primate cells, the
HIV-1 capsid protein (CA)-CYPA interaction is essential for restriction:
HIV-1 infectivity is increased greater than 100-fold by cyclosporin A, a
competitive inhibitor of the interaction, or by an HIV-1 CA mutation
that disrupts CYPA binding. Conversely, disruption of CA-CYPA
interaction in human cells reveals that CYPA protects HIV-1 from the
Ref-1 restriction factor. Towers et al. (2003) concluded that their
findings suggest that HIV-1 has coopted a host cell protein to
counteract restriction factors expressed by human cells and this
adaptation can confer sensitivity to restriction in unnatural hosts.
Manel et al. (2010) showed that, when dendritic cell resistance to
infection is circumvented, HIV-1 induces dendritic cell maturation, an
antiviral type I interferon response, and activation of T cells. This
innate response is dependent on the interaction of newly synthesized
HIV-1 capsid with cellular cyclophilin A (CYPA) and the subsequent
activation of the transcription factor IRF3 (603734). Because the
peptidylprolyl isomerase CYPA also interacts with HIV-1 capsid to
promote infectivity, the results of Manel et al. (2010) indicated that
capsid conformation has evolved under opposing selective pressures for
infectivity versus furtiveness. Thus, a cell-intrinsic sensor for HIV-1
exists in dendritic cells and mediates an antiviral immune response, but
it is not typically engaged owing to the absence of dendritic cell
infection.
Using different Apoe (107741) transgenic mice, including mice with
ablation and/or inhibition of CypA, Bell et al. (2012) showed that
expression of Apoe4 and lack of murine Apoe, but not Apoe2 and Apoe3,
leads to blood brain barrier breakdown by activating a proinflammatory
CypA-Nfkb (164011)-Mmp9 (120361) pathway in pericytes. This, in turn,
leads to neuronal uptake of multiple blood-derived neurotoxic proteins,
and microvascular and cerebral blood flow reductions. Bell et al. (2012)
showed that the vascular defects in Apoe-deficient and Apoe4-expressing
mice precede neuronal dysfunction and can initiate neurodegenerative
changes. Astrocyte-secreted Apoe3, but not Apoe4, suppressed the
CypA-Nfkb-Mmp9 pathway in pericytes through a lipoprotein receptor. Bell
et al. (2012) concluded that CypA is a key target for treating
APOE4-mediated neurovascular injury and the resulting neuronal
dysfunction and degeneration.
Rasaiyaah et al. (2013) showed that HIV-1 capsid mutants N74D and P90A,
which are impaired for interaction with cofactors (CPSF6; 604979) and
cyclophilins (NUP358, 601181 and CYPA), respectively, cannot replicate
in primary human monocyte-derived macrophages because they trigger
innate sensors leading to nuclear translocation of NFKB and IRF3, the
production of soluble type I IFN, and induction of an antiviral state.
Depletion of CPSF6 with short hairpin RNA expression allowed wildtype
virus to trigger innate sensors and IFN production. In each case,
suppressed replication was rescued by IFN-receptor blockade,
demonstrating a role for IFN in restriction. IFN production is dependent
on viral reverse transcription but not integration, indicating that a
viral reverse transcription product comprises the HIV-1
pathogen-associated molecular pattern. Finally, Rasaiyaah et al. (2013)
demonstrated that they could pharmacologically induce wildtype HIV-1
infection to stimulate IFN secretion and an antiviral state using a
nonimmunosuppressive cyclosporine analog. The authors concluded that
HIV-1 has evolved to use CPSF6 and cyclophilins to cloak its
replication, allowing evasion of innate immune sensors and induction of
a cell-autonomous innate immune response in primary human macrophages.
MAPPING
Using a panel of somatic rodent/human cell hybrids and PCR technology,
Willenbrink et al. (1995) mapped the cyclophilin gene (designated PPIA)
on chromosome 7 and 4 pseudogenes (PPIP2, PPIP3, PPIP4, and PPIP6) to
chromosomes 14, 10, 18, and 3, respectively. Using chromosome 7 and
chromosome 10 deletion hybrid panels, they further localized the PPIA
coding gene to 7p13-p11.2, as confirmed by fluorescence in situ
hybridization (FISH) analysis, and a pseudogene (PPIP3) to the region
10q11.2-q23.
Braaten et al. (1996) mapped the PPIA gene to 7p13 by FISH.
BIOCHEMICAL FEATURES
- Crystal Structure
Fraser et al. (2009) introduced dual strategies of ambient temperature
x-ray crystallographic data collection and automated electron density
sampling to structurally unravel interconverting substrates of the human
proline isomerase cyclophilin A. A conservative mutation outside the
active site was designed to stabilize features of the previously hidden
minor conformation. This mutation not only inverted the equilibrium
between the substrates, but also caused large, parallel reductions in
the conformational interconversion rates and the catalytic rate. Fraser
et al. (2009) concluded that their studies introduced crystallographic
approaches to define functional minor protein conformations and, in
combination with NMR analysis of the enzyme dynamics in solution, show
how collective motions directly contribute to the catalytic power of an
enzyme.
ANIMAL MODEL
Sayah et al. (2004) showed that knockdown of owl monkey CYPA by RNA
interference (RNAi) correlated with suppression of anti-HIV-1 activity.
However, reintroduction of CYPA to RNAi-treated cells did not restore
antiviral activity. A search for additional RNAi targets identified
TRIMCYP, an RNAi-responsive mRNA encoding a TRIM5 (608487)/CYPA fusion
protein. TRIMCYP accounts for post-entry restriction of HIV-1 in owl
monkeys and blocks HIV-1 infection when transferred to otherwise
infectable human or rat cells. Sayah et al. (2004) suggested that
TRIMCYP arose after the divergence of New and Old World primates when a
LINE-1 retrotransposon catalyzed the insertion of a CYPA cDNA into the
TRIM5 locus. They concluded that this was the first vertebrate example
of a chimeric gene generated by this mechanism of exon shuffling.
Colgan et al. (2005) found that mice deficient in Cypa were resistant to
immunosuppression by cyclosporine both in vitro and in vivo, as assessed
by proliferation, IL2 (147680) secretion, signal transduction, and tumor
rejection. Cypa-deficient mice remained sensitive to FK506. Colgan et
al. (2005) concluded that CYPA is the primary mediator of
immunosuppression by cyclosporine.
*FIELD* SA
Takahashi et al. (1989)
*FIELD* RF
1. Bell, R. D.; Winkler, E. A.; Singh, I.; Sagare, A. P.; Deane, R.;
Wu, Z.; Holtzman, D. M.; Betsholtz, C.; Armulik, A.; Sallstrom, J.;
Berk, B. C.; Zlokovic, B. V.: Apolipoprotein E controls cerebrovascular
integrity via cyclophilin A. Nature 485: 512-516, 2012.
2. Braaten, D.; Wellington, S.; Warburton, D.; Luban, J.: Assignment
of cyclophilin A (PPIA) to human chromosome band 7p13 by in situ hybridization. Cytogenet.
Cell Genet. 74: 262 only, 1996.
3. Colgan, J.; Asmal, M.; Yu, B.; Luban, J.: Cyclophilin A-deficient
mice are resistant to immunosuppression by cyclosporine. J. Immun. 174:
6030-6038, 2005.
4. Fraser, J. S.; Clarkson, M. W.; Degnan, S. C.; Erion, R.; Kern,
D.; Alber, T.: Hidden alternative structures of proline isomerase
essential for catalysis. Nature 462: 669-673, 2009.
5. Liu, J.; Albers, M. W.; Chen, C.-M.; Schreiber, S. L.; Walsh, C.
T.: Cloning, expression, and purification of human cyclophilin in
Escherichia coli and assessment of the catalytic role of cysteines
by site-directed mutagenesis. Proc. Nat. Acad. Sci. 87: 2304-2308,
1990.
6. Luban, J.; Bossolt, K. L.; Franke, E. K.; Kalpana, G. V.; Goff,
S. P.: Human immunodeficiency virus type 1 gag protein binds to cyclophilins
A and B. Cell 73: 1067-1078, 1993.
7. Manel, N.; Hogstad, B.; Wang, Y.; Levy, D. E.; Unutmaz, D.; Littman,
D. R.: A cryptic sensor for HIV-1 activates antiviral innate immunity
in dendritic cells. Nature 467: 214-217, 2010. Note: Erratum: Nature
470: 424 only, 2011.
8. Pushkarsky, T.; Zybarth, G.; Dubrovsky, L.; Yurchenko, V.; Tang,
H.; Guo, H.; Toole, B.; Sherry, B.; Bukrinsky, M.: CD147 facilitates
HIV-1 infection by interacting with virus-associated cyclophilin A. Proc.
Nat. Acad. Sci. 98: 6360-6365, 2001.
9. Rasaiyaah, J.; Tan, C. P.; Fletcher, A. J.; Price, A. J.; Blondeau,
C.; Hilditch, L.; Jacques, D. A.; Selwood, D. L.; James, L. C.; Noursadeghi,
M.; Towers, G. J.: HIV-1 evades innate immune recognition through
specific cofactor recruitment. Nature 503: 402-405, 2013.
10. Sayah, D. M.; Sokolskaja, E.; Berthoux, L.; Luban, J.: Cyclophilin
A retrotransposition into TRIM5 explains owl monkey resistance to
HIV-1. Nature 430: 569-573, 2004.
11. Takahashi, N.; Hayano, T.; Suzuki, M.: Peptidyl-prolyl cis-trans
isomerase is the cyclosporin A-binding protein cyclophilin. Nature 337:
473-475, 1989.
12. Towers, G. J.; Hatziioannou, T.; Cowan, S.; Goff, S. P.; Luban,
J.; Bieniasz, P. D.: Cyclophilin A modulates the sensitivity of HIV-1
to host restriction factors. Nature Med. 9: 1138-1143, 2003.
13. Willenbrink, W.; Halaschek, J.; Schuffenhauer, S.; Kunz, J.; Steinkasserer,
A.: Cyclophilin A, the major intracellular receptor for the immunosuppressant
cyclosporin A, maps to chromosome 7p11.2-p13: four pseudogenes map
to chromosomes 3, 10, 14, and 18. Genomics 28: 101-104, 1995.
*FIELD* CN
Ada Hamosh - updated: 12/09/2013
Ada Hamosh - updated: 6/5/2012
Ada Hamosh - updated: 10/6/2010
Ada Hamosh - updated: 1/6/2010
Paul J. Converse - updated: 8/4/2006
Patricia A. Hartz - updated: 7/14/2005
Ada Hamosh - updated: 8/26/2004
Ada Hamosh - updated: 8/26/2003
Victor A. McKusick - updated: 3/12/1997
*FIELD* CD
Victor A. McKusick: 5/11/1990
*FIELD* ED
alopez: 12/09/2013
alopez: 6/7/2012
terry: 6/5/2012
alopez: 7/6/2011
alopez: 10/7/2010
terry: 10/6/2010
alopez: 1/15/2010
terry: 1/6/2010
mgross: 8/29/2006
terry: 8/4/2006
mgross: 7/14/2005
tkritzer: 8/27/2004
terry: 8/26/2004
alopez: 9/2/2003
alopez: 8/26/2003
terry: 8/26/2003
carol: 7/10/2001
terry: 3/12/1997
terry: 3/3/1997
terry: 6/11/1996
terry: 5/24/1996
mark: 10/2/1995
terry: 9/11/1995
supermim: 3/16/1992
carol: 12/20/1991
carol: 12/12/1991
carol: 3/15/1991
*RECORD*
*FIELD* NO
123840
*FIELD* TI
*123840 PEPTIDYL-PROLYL ISOMERASE A; PPIA
;;CYCLOPHILIN A; CYPA;;
CYPH
*FIELD* TX
read moreCLONING
Cyclophilin is a specific high-affinity binding protein for the
immunosuppressant agent cyclosporin A. Because of its dramatic effects
on decreasing morbidity and increasing survival rates in human
transplants, the molecular mechanism of immunosuppression by cyclosporin
A has been a matter of much interest. Liu et al. (1990) cloned human
cDNA for T-cell CYPH and constructed an expression vector under control
of the tac promoter for efficient expression in E. coli.
GENE FUNCTION
Cyclophilin A (also designated peptidyl-prolyl cis/trans isomerase A or
PPIA) is a member of the immunophilin class of proteins that all possess
peptidyl-prolyl cis/trans isomerase activity and, therefore, are
believed to be involved in protein folding and/or intracellular protein
transport. Luban et al. (1993) showed that cyclophilin A binds to the
Gag protein of human immunodeficiency virus type 1 (HIV-1). This
interaction can be inhibited by the immunosuppressant cyclosporin A and
also by nonimmunosuppressive, cyclophilin A-binding cyclosporin A
derivatives, which were also shown to exhibit potent anti-HIV-1
activity. Thus, cyclophilin A may have an essential function in HIV-1
replication.
Pushkarsky et al. (2001) identified CD147 (BSG; 109480) as a receptor
for extracellular CYPA. They found that CD147 enhanced HIV-1 infection
through interaction with CYPA incorporated into virions.
Virus-associated CYPA coimmunoprecipitated with CD147 from infected
cells, and antibody to CD147 inhibited HIV-1 entry. Viruses whose
replication did not require CYPA were resistant to the inhibitory effect
of anti-CD147 antibody. Pushkarsky et al. (2001) concluded that HIV-1
entry depends on an interaction between virus-associated CYPA and CD147
on a target cell.
Towers et al. (2003) demonstrated that HIV-1 sensitivity to restriction
factors is modulated by CYPA. In certain nonhuman primate cells, the
HIV-1 capsid protein (CA)-CYPA interaction is essential for restriction:
HIV-1 infectivity is increased greater than 100-fold by cyclosporin A, a
competitive inhibitor of the interaction, or by an HIV-1 CA mutation
that disrupts CYPA binding. Conversely, disruption of CA-CYPA
interaction in human cells reveals that CYPA protects HIV-1 from the
Ref-1 restriction factor. Towers et al. (2003) concluded that their
findings suggest that HIV-1 has coopted a host cell protein to
counteract restriction factors expressed by human cells and this
adaptation can confer sensitivity to restriction in unnatural hosts.
Manel et al. (2010) showed that, when dendritic cell resistance to
infection is circumvented, HIV-1 induces dendritic cell maturation, an
antiviral type I interferon response, and activation of T cells. This
innate response is dependent on the interaction of newly synthesized
HIV-1 capsid with cellular cyclophilin A (CYPA) and the subsequent
activation of the transcription factor IRF3 (603734). Because the
peptidylprolyl isomerase CYPA also interacts with HIV-1 capsid to
promote infectivity, the results of Manel et al. (2010) indicated that
capsid conformation has evolved under opposing selective pressures for
infectivity versus furtiveness. Thus, a cell-intrinsic sensor for HIV-1
exists in dendritic cells and mediates an antiviral immune response, but
it is not typically engaged owing to the absence of dendritic cell
infection.
Using different Apoe (107741) transgenic mice, including mice with
ablation and/or inhibition of CypA, Bell et al. (2012) showed that
expression of Apoe4 and lack of murine Apoe, but not Apoe2 and Apoe3,
leads to blood brain barrier breakdown by activating a proinflammatory
CypA-Nfkb (164011)-Mmp9 (120361) pathway in pericytes. This, in turn,
leads to neuronal uptake of multiple blood-derived neurotoxic proteins,
and microvascular and cerebral blood flow reductions. Bell et al. (2012)
showed that the vascular defects in Apoe-deficient and Apoe4-expressing
mice precede neuronal dysfunction and can initiate neurodegenerative
changes. Astrocyte-secreted Apoe3, but not Apoe4, suppressed the
CypA-Nfkb-Mmp9 pathway in pericytes through a lipoprotein receptor. Bell
et al. (2012) concluded that CypA is a key target for treating
APOE4-mediated neurovascular injury and the resulting neuronal
dysfunction and degeneration.
Rasaiyaah et al. (2013) showed that HIV-1 capsid mutants N74D and P90A,
which are impaired for interaction with cofactors (CPSF6; 604979) and
cyclophilins (NUP358, 601181 and CYPA), respectively, cannot replicate
in primary human monocyte-derived macrophages because they trigger
innate sensors leading to nuclear translocation of NFKB and IRF3, the
production of soluble type I IFN, and induction of an antiviral state.
Depletion of CPSF6 with short hairpin RNA expression allowed wildtype
virus to trigger innate sensors and IFN production. In each case,
suppressed replication was rescued by IFN-receptor blockade,
demonstrating a role for IFN in restriction. IFN production is dependent
on viral reverse transcription but not integration, indicating that a
viral reverse transcription product comprises the HIV-1
pathogen-associated molecular pattern. Finally, Rasaiyaah et al. (2013)
demonstrated that they could pharmacologically induce wildtype HIV-1
infection to stimulate IFN secretion and an antiviral state using a
nonimmunosuppressive cyclosporine analog. The authors concluded that
HIV-1 has evolved to use CPSF6 and cyclophilins to cloak its
replication, allowing evasion of innate immune sensors and induction of
a cell-autonomous innate immune response in primary human macrophages.
MAPPING
Using a panel of somatic rodent/human cell hybrids and PCR technology,
Willenbrink et al. (1995) mapped the cyclophilin gene (designated PPIA)
on chromosome 7 and 4 pseudogenes (PPIP2, PPIP3, PPIP4, and PPIP6) to
chromosomes 14, 10, 18, and 3, respectively. Using chromosome 7 and
chromosome 10 deletion hybrid panels, they further localized the PPIA
coding gene to 7p13-p11.2, as confirmed by fluorescence in situ
hybridization (FISH) analysis, and a pseudogene (PPIP3) to the region
10q11.2-q23.
Braaten et al. (1996) mapped the PPIA gene to 7p13 by FISH.
BIOCHEMICAL FEATURES
- Crystal Structure
Fraser et al. (2009) introduced dual strategies of ambient temperature
x-ray crystallographic data collection and automated electron density
sampling to structurally unravel interconverting substrates of the human
proline isomerase cyclophilin A. A conservative mutation outside the
active site was designed to stabilize features of the previously hidden
minor conformation. This mutation not only inverted the equilibrium
between the substrates, but also caused large, parallel reductions in
the conformational interconversion rates and the catalytic rate. Fraser
et al. (2009) concluded that their studies introduced crystallographic
approaches to define functional minor protein conformations and, in
combination with NMR analysis of the enzyme dynamics in solution, show
how collective motions directly contribute to the catalytic power of an
enzyme.
ANIMAL MODEL
Sayah et al. (2004) showed that knockdown of owl monkey CYPA by RNA
interference (RNAi) correlated with suppression of anti-HIV-1 activity.
However, reintroduction of CYPA to RNAi-treated cells did not restore
antiviral activity. A search for additional RNAi targets identified
TRIMCYP, an RNAi-responsive mRNA encoding a TRIM5 (608487)/CYPA fusion
protein. TRIMCYP accounts for post-entry restriction of HIV-1 in owl
monkeys and blocks HIV-1 infection when transferred to otherwise
infectable human or rat cells. Sayah et al. (2004) suggested that
TRIMCYP arose after the divergence of New and Old World primates when a
LINE-1 retrotransposon catalyzed the insertion of a CYPA cDNA into the
TRIM5 locus. They concluded that this was the first vertebrate example
of a chimeric gene generated by this mechanism of exon shuffling.
Colgan et al. (2005) found that mice deficient in Cypa were resistant to
immunosuppression by cyclosporine both in vitro and in vivo, as assessed
by proliferation, IL2 (147680) secretion, signal transduction, and tumor
rejection. Cypa-deficient mice remained sensitive to FK506. Colgan et
al. (2005) concluded that CYPA is the primary mediator of
immunosuppression by cyclosporine.
*FIELD* SA
Takahashi et al. (1989)
*FIELD* RF
1. Bell, R. D.; Winkler, E. A.; Singh, I.; Sagare, A. P.; Deane, R.;
Wu, Z.; Holtzman, D. M.; Betsholtz, C.; Armulik, A.; Sallstrom, J.;
Berk, B. C.; Zlokovic, B. V.: Apolipoprotein E controls cerebrovascular
integrity via cyclophilin A. Nature 485: 512-516, 2012.
2. Braaten, D.; Wellington, S.; Warburton, D.; Luban, J.: Assignment
of cyclophilin A (PPIA) to human chromosome band 7p13 by in situ hybridization. Cytogenet.
Cell Genet. 74: 262 only, 1996.
3. Colgan, J.; Asmal, M.; Yu, B.; Luban, J.: Cyclophilin A-deficient
mice are resistant to immunosuppression by cyclosporine. J. Immun. 174:
6030-6038, 2005.
4. Fraser, J. S.; Clarkson, M. W.; Degnan, S. C.; Erion, R.; Kern,
D.; Alber, T.: Hidden alternative structures of proline isomerase
essential for catalysis. Nature 462: 669-673, 2009.
5. Liu, J.; Albers, M. W.; Chen, C.-M.; Schreiber, S. L.; Walsh, C.
T.: Cloning, expression, and purification of human cyclophilin in
Escherichia coli and assessment of the catalytic role of cysteines
by site-directed mutagenesis. Proc. Nat. Acad. Sci. 87: 2304-2308,
1990.
6. Luban, J.; Bossolt, K. L.; Franke, E. K.; Kalpana, G. V.; Goff,
S. P.: Human immunodeficiency virus type 1 gag protein binds to cyclophilins
A and B. Cell 73: 1067-1078, 1993.
7. Manel, N.; Hogstad, B.; Wang, Y.; Levy, D. E.; Unutmaz, D.; Littman,
D. R.: A cryptic sensor for HIV-1 activates antiviral innate immunity
in dendritic cells. Nature 467: 214-217, 2010. Note: Erratum: Nature
470: 424 only, 2011.
8. Pushkarsky, T.; Zybarth, G.; Dubrovsky, L.; Yurchenko, V.; Tang,
H.; Guo, H.; Toole, B.; Sherry, B.; Bukrinsky, M.: CD147 facilitates
HIV-1 infection by interacting with virus-associated cyclophilin A. Proc.
Nat. Acad. Sci. 98: 6360-6365, 2001.
9. Rasaiyaah, J.; Tan, C. P.; Fletcher, A. J.; Price, A. J.; Blondeau,
C.; Hilditch, L.; Jacques, D. A.; Selwood, D. L.; James, L. C.; Noursadeghi,
M.; Towers, G. J.: HIV-1 evades innate immune recognition through
specific cofactor recruitment. Nature 503: 402-405, 2013.
10. Sayah, D. M.; Sokolskaja, E.; Berthoux, L.; Luban, J.: Cyclophilin
A retrotransposition into TRIM5 explains owl monkey resistance to
HIV-1. Nature 430: 569-573, 2004.
11. Takahashi, N.; Hayano, T.; Suzuki, M.: Peptidyl-prolyl cis-trans
isomerase is the cyclosporin A-binding protein cyclophilin. Nature 337:
473-475, 1989.
12. Towers, G. J.; Hatziioannou, T.; Cowan, S.; Goff, S. P.; Luban,
J.; Bieniasz, P. D.: Cyclophilin A modulates the sensitivity of HIV-1
to host restriction factors. Nature Med. 9: 1138-1143, 2003.
13. Willenbrink, W.; Halaschek, J.; Schuffenhauer, S.; Kunz, J.; Steinkasserer,
A.: Cyclophilin A, the major intracellular receptor for the immunosuppressant
cyclosporin A, maps to chromosome 7p11.2-p13: four pseudogenes map
to chromosomes 3, 10, 14, and 18. Genomics 28: 101-104, 1995.
*FIELD* CN
Ada Hamosh - updated: 12/09/2013
Ada Hamosh - updated: 6/5/2012
Ada Hamosh - updated: 10/6/2010
Ada Hamosh - updated: 1/6/2010
Paul J. Converse - updated: 8/4/2006
Patricia A. Hartz - updated: 7/14/2005
Ada Hamosh - updated: 8/26/2004
Ada Hamosh - updated: 8/26/2003
Victor A. McKusick - updated: 3/12/1997
*FIELD* CD
Victor A. McKusick: 5/11/1990
*FIELD* ED
alopez: 12/09/2013
alopez: 6/7/2012
terry: 6/5/2012
alopez: 7/6/2011
alopez: 10/7/2010
terry: 10/6/2010
alopez: 1/15/2010
terry: 1/6/2010
mgross: 8/29/2006
terry: 8/4/2006
mgross: 7/14/2005
tkritzer: 8/27/2004
terry: 8/26/2004
alopez: 9/2/2003
alopez: 8/26/2003
terry: 8/26/2003
carol: 7/10/2001
terry: 3/12/1997
terry: 3/3/1997
terry: 6/11/1996
terry: 5/24/1996
mark: 10/2/1995
terry: 9/11/1995
supermim: 3/16/1992
carol: 12/20/1991
carol: 12/12/1991
carol: 3/15/1991