RBCC Red Blood Cell Collection

PPIB (CYPB) [Confidence: high (present in two of the MS resources)]
Peptidyl-prolyl cis-trans isomerase B; PPIase B; 5.2.1.8 (CYP-S1; Cyclophilin B; Rotamase B; S-cyclophilin; SCYLP; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt P23284
ID PPIB_HUMAN Reviewed; 216 AA.
AC P23284; A8K534; Q6IBH5; Q9BVK5;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-NOV-2008, sequence version 2.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase B;
DE Short=PPIase B;
DE EC=5.2.1.8;
DE AltName: Full=CYP-S1;
DE AltName: Full=Cyclophilin B;
DE AltName: Full=Rotamase B;
DE AltName: Full=S-cyclophilin;
DE Short=SCYLP;
DE Flags: Precursor;
GN Name=PPIB; Synonyms=CYPB;
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].
RX PubMed=2040592;
RA Spik G., Haendler B., Delmas O., Mariller C., Chamoux M., Maes P.,
RA Tartar A., Montreuil J., Stedman K., Kocher H.P., Keller R.,
RA Hiestand P.C., Movva N.R.;
RT "A novel secreted cyclophilin-like protein (SCYLP).";
RL J. Biol. Chem. 266:10735-10738(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Prostate, and Skin;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 5-216, AND PROTEIN SEQUENCE OF 34-48.
RX PubMed=2000394; DOI=10.1073/pnas.88.5.1903;
RA Price E.R., Zydowsky L.D., Jin M., Hunter C.H., McKeon F.D.,
RA Walsh C.T.;
RT "Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-
RT prolyl isomerase with a signal sequence.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:1903-1907(1991).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-216.
RX PubMed=1710767;
RA Hasel K.W., Glass J.R., Godbout M., Sutcliffe J.G.;
RT "An endoplasmic reticulum-specific cyclophilin.";
RL Mol. Cell. Biol. 11:3484-3491(1991).
RN [10]
RP PROTEIN SEQUENCE OF 52-59; 64-76; 91-101; 138-150; 164-172 AND
RP 197-207, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 72-84 AND 159-165.
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=1530944; DOI=10.1083/jcb.116.1.113;
RA Arber S., Krause K.-H., Caroni P.;
RT "S-cyclophilin is retained intracellularly via a unique COOH-terminal
RT sequence and colocalizes with the calcium storage protein
RT calreticulin.";
RL J. Cell Biol. 116:113-125(1992).
RN [13]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [14]
RP INVOLVEMENT IN OI9.
RX PubMed=19781681; DOI=10.1016/j.ajhg.2009.09.001;
RA van Dijk F.S., Nesbitt I.M., Zwikstra E.H., Nikkels P.G.,
RA Piersma S.R., Fratantoni S.A., Jimenez C.R., Huizer M., Morsman A.C.,
RA Cobben J.M., van Roij M.H., Elting M.W., Verbeke J.I.,
RA Wijnaendts L.C., Shaw N.J., Hogler W., McKeown C., Sistermans E.A.,
RA Dalton A., Meijers-Heijboer H., Pals G.;
RT "PPIB mutations cause severe osteogenesis imperfecta.";
RL Am. J. Hum. Genet. 85:521-527(2009).
RN [15]
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 [16]
RP INTERACTION WITH DYM.
RX PubMed=21280149; DOI=10.1002/humu.21413;
RA Denais C., Dent C.L., Southgate L., Hoyle J., Dafou D., Trembath R.C.,
RA Machado R.D.;
RT "Dymeclin, the gene underlying Dyggve-Melchior-Clausen syndrome,
RT encodes a protein integral to extracellular matrix and Golgi
RT organization and is associated with protein secretion pathways
RT critical in bone development.";
RL Hum. Mutat. 32:231-239(2011).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 39-216.
RX PubMed=8197205; DOI=10.1073/pnas.91.11.5183;
RA Mikol V., Kallen J., Walkinshaw M.D.;
RT "X-ray structure of a cyclophilin B/cyclosporin complex: comparison
RT with cyclophilin A and delineation of its calcineurin-binding
RT domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:5183-5186(1994).
RN [18]
RP VARIANT OI9 ARG-9.
RX PubMed=20089953; DOI=10.1056/NEJMoa0907705;
RA Barnes A.M., Carter E.M., Cabral W.A., Weis M., Chang W.,
RA Makareeva E., Leikin S., Rotimi C.N., Eyre D.R., Raggio C.L.,
RA Marini J.C.;
RT "Lack of cyclophilin B in osteogenesis imperfecta with normal collagen
RT folding.";
RL N. Engl. J. Med. 362:521-528(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: Cyclosporin A (CsA) inhibits CYPB.
CC -!- SUBUNIT: Interacts with DYM.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. Melanosome.
CC Note=Identified by mass spectrometry in melanosome fractions from
CC stage I to stage IV.
CC -!- DISEASE: Osteogenesis imperfecta 9 (OI9) [MIM:259440]: A form of
CC osteogenesis imperfecta, a connective tissue disorder
CC characterized by low bone mass, bone fragility and susceptibility
CC to fractures after minimal trauma. Disease severity ranges from
CC very mild forms without fractures to intrauterine fractures and
CC perinatal lethality. Extraskeletal manifestations, which affect a
CC variable number of patients, are dentinogenesis imperfecta,
CC hearing loss, and blue sclerae. OI9 is a severe autosomal
CC recessive form of the disorder. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cyclophilin-type PPIase family. PPIase
CC B subfamily.
CC -!- SIMILARITY: Contains 1 PPIase cyclophilin-type domain.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-9 is the initiator.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA52150.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ppib/";
CC -!- WEB RESOURCE: Name=Osteogenesis imperfecta variant database;
CC Note=Peptidyl-prolyl cis-trans isomerase B (PPIB);
CC URL="http://oi.gene.le.ac.uk/home.php?select_db=PPIB";
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DR EMBL; M63573; AAA36601.1; -; mRNA.
DR EMBL; AK291149; BAF83838.1; -; mRNA.
DR EMBL; CR456829; CAG33110.1; -; mRNA.
DR EMBL; AY962310; AAX44050.1; -; Genomic_DNA.
DR EMBL; AC100840; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77669.1; -; Genomic_DNA.
DR EMBL; BC001125; AAH01125.1; -; mRNA.
DR EMBL; BC008848; AAH08848.1; -; mRNA.
DR EMBL; BC020800; AAH20800.1; -; mRNA.
DR EMBL; BC032138; AAH32138.1; -; mRNA.
DR EMBL; M60857; AAA52150.1; ALT_INIT; mRNA.
DR EMBL; M60457; AAA35733.1; -; mRNA.
DR PIR; A39118; CSHUB.
DR RefSeq; NP_000933.1; NM_000942.4.
DR UniGene; Hs.434937; -.
DR PDB; 1CYN; X-ray; 1.85 A; A=39-216.
DR PDB; 3ICH; X-ray; 1.20 A; A=34-216.
DR PDB; 3ICI; X-ray; 1.70 A; A/B=34-216.
DR PDBsum; 1CYN; -.
DR PDBsum; 3ICH; -.
DR PDBsum; 3ICI; -.
DR ProteinModelPortal; P23284; -.
DR SMR; P23284; 37-216.
DR IntAct; P23284; 14.
DR MINT; MINT-1142578; -.
DR STRING; 9606.ENSP00000300026; -.
DR BindingDB; P23284; -.
DR ChEMBL; CHEMBL2075; -.
DR DrugBank; DB00172; L-Proline.
DR PhosphoSite; P23284; -.
DR DMDM; 215273869; -.
DR OGP; P23284; -.
DR REPRODUCTION-2DPAGE; IPI00646304; -.
DR SWISS-2DPAGE; P23284; -.
DR PaxDb; P23284; -.
DR PRIDE; P23284; -.
DR DNASU; 5479; -.
DR Ensembl; ENST00000300026; ENSP00000300026; ENSG00000166794.
DR GeneID; 5479; -.
DR KEGG; hsa:5479; -.
DR UCSC; uc002and.3; human.
DR CTD; 5479; -.
DR GeneCards; GC15M064448; -.
DR HGNC; HGNC:9255; PPIB.
DR HPA; CAB011487; -.
DR HPA; HPA012720; -.
DR MIM; 123841; gene.
DR MIM; 259440; phenotype.
DR neXtProt; NX_P23284; -.
DR Orphanet; 216804; Osteogenesis imperfecta type 2.
DR Orphanet; 216812; Osteogenesis imperfecta type 3.
DR Orphanet; 216820; Osteogenesis imperfecta type 4.
DR PharmGKB; PA33580; -.
DR eggNOG; COG0652; -.
DR HOGENOM; HOG000065981; -.
DR HOVERGEN; HBG001065; -.
DR InParanoid; P23284; -.
DR KO; K03768; -.
DR OMA; PAYANED; -.
DR OrthoDB; EOG7RFTK4; -.
DR PhylomeDB; P23284; -.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR ChiTaRS; PPIB; human.
DR EvolutionaryTrace; P23284; -.
DR GeneWiki; PPIB; -.
DR GenomeRNAi; 5479; -.
DR NextBio; 21210; -.
DR PRO; PR:P23284; -.
DR Bgee; P23284; -.
DR CleanEx; HS_PPIB; -.
DR Genevestigator; P23284; -.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; NAS:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042277; F:peptide binding; IEA:UniProtKB-KW.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; NAS:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; TAS:ProtInc.
DR GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome.
DR GO; GO:0006457; P:protein folding; IEA:UniProtKB-KW.
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; Complete proteome; Cyclosporin;
KW Direct protein sequencing; Disease mutation; Dwarfism;
KW Endoplasmic reticulum; Glycoprotein; Isomerase;
KW Osteogenesis imperfecta; Polymorphism; Reference proteome; Rotamase;
KW Signal.
FT SIGNAL 1 33
FT CHAIN 34 216 Peptidyl-prolyl cis-trans isomerase B.
FT /FTId=PRO_0000025479.
FT DOMAIN 47 204 PPIase cyclophilin-type.
FT MOTIF 213 216 Prevents secretion from ER.
FT CARBOHYD 148 148 N-linked (GlcNAc...) (Potential).
FT VARIANT 9 9 M -> R (in OI9; patients have white
FT sclerae, normal dentition, no rhizomelia
FT or severe deformity of long bones).
FT /FTId=VAR_063436.
FT VARIANT 60 60 V -> L (in dbSNP:rs11558595).
FT /FTId=VAR_047711.
FT CONFLICT 5 5 S -> R (in Ref. 8; AAA52150).
FT CONFLICT 216 216 E -> D (in Ref. 3; CAG33110).
FT STRAND 41 52
FT STRAND 55 64
FT TURN 66 68
FT HELIX 70 81
FT TURN 82 84
FT STRAND 95 97
FT TURN 98 100
FT STRAND 101 104
FT TURN 107 109
FT STRAND 110 113
FT STRAND 137 140
FT STRAND 142 144
FT STRAND 152 157
FT HELIX 160 162
FT TURN 163 165
FT STRAND 168 174
FT HELIX 176 183
FT STRAND 193 195
FT STRAND 197 212
SQ SEQUENCE 216 AA; 23743 MW; 2D0410A07AA9E420 CRC64;
MLRLSERNMK VLLAAALIAG SVFFLLLPGP SAADEKKKGP KVTVKVYFDL RIGDEDVGRV
IFGLFGKTVP KTVDNFVALA TGEKGFGYKN SKFHRVIKDF MIQGGDFTRG DGTGGKSIYG
ERFPDENFKL KHYGPGWVSM ANAGKDTNGS QFFITTVKTA WLDGKHVVFG KVLEGMEVVR
KVESTKTDSR DKPLKDVIIA DCGKIEVEKP FAIAKE
//

MIM 123841
*RECORD*
*FIELD* NO
123841
*FIELD* TI
*123841 PEPTIDYL-PROLYL ISOMERASE B; PPIB
;;CYCLOPHILIN B; CYPB
*FIELD* TX

DESCRIPTION
read more
Cyclophilins, such as CYPB, bind the immunosuppressive drug cyclosporin
A (CsA) with high affinity. CsA blocks helper T-cell activation at a
step between T-cell receptor stimulation and the transcriptional
activation of cytokine genes. Cyclophilins from many species possess
peptidyl-prolyl cis-trans isomerase (PPIase) activity that is blocked by
CsA and therefore may be relevant in CsA-mediated immunosuppression
(Price et al., 1991).

CLONING

Probing with the cyclophilin A (CYPA; 123840) cDNA under reduced
stringencies, Price et al. (1991) identified the CYPB gene. The deduced
protein is 64% identical to CYPA and is distinguished from it by a
signal sequence that probably directs it to the endoplasmic reticulum
(ER). CYPB shows even stronger similarity to yeast CYPB, which also has
an ER-directed signal sequence.

MAPPING

Peddada et al. (1992) used the PCR technique to generate a unique probe
complementary to the hydrophobic 5-prime end of the human cyclophilin B
gene. Using this probe in an analysis of human/hamster hybrid somatic
cell lines, they assigned the CYPB gene to chromosome 15.

GENE FUNCTION

Price et al. (1991) found that the signal sequence was removed from CYPB
upon expression in E. coli, and the processed protein possessed PPIase
activity that was inhibited by CsA.

Yurchenko et al. (2001) determined that CD147 (BSG; 109480) serves as a
receptor for CYPB. CYPB induced Ca(2+) flux, ERK (see MAPK3; 601795)
phosphorylation, and chemotaxis in CD147-transfected Chinese hamster
ovary cells, but not in control cells. The chemotactic response of
primary human neutrophils to CYPB was blocked by antibodies to CD147.

Using CsA as a bioprobe to identify cellular factors involved in
hepatitis C virus (HCV) genome replication, Watashi et al. (2005) showed
that CYPB interacts with HCV RNA polymerase NS5B to directly stimulate
its RNA binding activity. HCV replication could be reduced by RNA
interference-mediated reduction of endogenous CYPB expression or by the
induced loss of NS5B binding to CYPB. Watashi et al. (2005) concluded
that CYPB functions as a stimulatory regulator of NS5B in the HCV
replication machinery and suggested that CYPB could be a target for
antiviral therapy.

MOLECULAR GENETICS

CRTAP (605497), P3H1 (LEPRE1; 610339), and CYPB (PPIB) form an
intracellular collagen-modifying complex that 3-hydroxylates proline at
position 986 (P986) in the alpha-1 chains of collagen type I (120150),
and deficiency of CRTAP or P3H1 has been reported in autosomal recessive
lethal or severe osteogenesis imperfecta (OI; see 610682 and 610915). In
4 patients with osteogenesis imperfecta type IX (OI9; 259440) from 2
unrelated families, van Dijk et al. (2009) analyzed the PPIB gene and
identified homozygosity for a 4-bp deletion (123841.0001) and a nonsense
mutation (123841.0002), respectively. The percentage of 3-hydroxylated
P986 residues in patients with PPIB mutations was decreased in
comparison to controls, but it was higher than in patients with CRTAP or
LEPRE1 mutations. In addition, in bone tissue from patients with CRTAP
or LEPRE1 mutations, CYPB was detected but both CRTAP and P3H1 were
absent, indicating that CYPB is independent of the presence of either
CRTAP or P3H1. Van Dijk et al. (2009) suggested that recessive OI is
caused by a dysfunctional P3H1/CRTAP/CYPB complex rather than by lack of
3-prolyl hydroxylation of a single proline residue in the alpha-1 chains
of collagen type I.

In a sister and brother who had moderately severe osteogenesis
imperfecta without rhizomelia, who were born of consanguineous
Senegalese parents, Barnes et al. (2010) identified homozygosity for a
missense mutation in the PPIB gene (123841.0003). The proband had normal
collagen folding and normal prolyl 3-hydroxylation, suggesting that CYPB
is not the exclusive peptidyl-prolyl cis-trans isomerase that catalyzes
the rate-limiting step in collagen folding.

In a Palestinian pedigree segregating moderate and lethal forms of OI,
Barnes et al. (2012) identified a homozygous indel mutation in the
FKBP10 gene (607063.0009) in a proband from one branch of the family
with OI type 11 (610968), and a homozygous deletion in the PPIB gene
(123841.0004) in a proband from another branch of the family with OI
type IX (259940).

ANIMAL MODEL

Hereditary equine regional dermal asthenia (HERDA) is a degenerative
skin disease that affects the Quarter Horse breed. Tryon et al. (2007)
determined that HERDA is due to a missense mutation (gly39 to arg) in
the equine Ppib gene that alters a glycine conserved across vertebrates.
The mutation was homozygous in 64 affected horses and segregated
concordant with inbreeding loops in the genealogy of 11 affected horses.
Screening of control Quarter Horses indicated a 3.5% carrier frequency.

*FIELD* AV
.0001
OSTEOGENESIS IMPERFECTA, TYPE IX
PPIB, 4-BP DEL, 556AAGA

In 2 fetuses with osteogenesis imperfecta type IX (259440) from a
nonconsanguineous northern European family, van Dijk et al. (2009)
identified homozygosity for a 4-bp deletion (556delAAGA) in exon 5 of
the PPIB gene, resulting in a frameshift that replaces 31 highly
conserved C-terminal residues and causes a premature stop in the last
exon (Lys186GlnfsX8). The unaffected parents were heterozygous carriers
of the deletion, which was not found in 192 control alleles.

.0002
OSTEOGENESIS IMPERFECTA, TYPE IX
PPIB, GLN151TER

In 2 sibs with osteogenesis imperfecta type IX (259440) from a
consanguineous Pakistani family, van Dijk et al. (2009) identified
homozygosity for a 451C-T transition in exon 4 of the PPIB gene,
resulting in a gln151-to-ter (Q151X) substitution that removes the last
65 residues at the C terminus. The unaffected parents were heterozygous
carriers of the deletion, which was not found in 192 control alleles.

.0003
OSTEOGENESIS IMPERFECTA, TYPE IX
PPIB, MET9ARG

In a sister and brother who had moderately severe osteogenesis
imperfecta without rhizomelia (OI9; 259440), Barnes et al. (2010)
identified homozygosity for what they designated a 2T-G transversion,
predicted to eliminate the start codon of the PPIB gene. Van Dijk et al.
(2010) stated that using the current PPIB reference sequence
(NM_000942.4), this is a 26T-G transversion resulting in a met9-to-arg
(M9R) substitution, which could account for the relatively milder
phenotype. Using RT-PCR analysis, Barnes et al. (2010) found that PPIB
transcripts in the proband were approximately 55% of normal; CYPB
protein was undetectable in the proband fibroblast lysate or on
immunofluorescence staining of fibroblasts. The proband's type I
collagen showed normal modification and folding. The unaffected
consanguineous Senegalese parents were heterozygous for the mutation, as
were unaffected sibs.

.0004
OSTEOGENESIS IMPERFECTA, TYPE IX
PPIB, 4-BP DEL, 563ACAG

In a Palestinian pedigree segregating moderate and lethal forms of
recessive OI, Barnes et al. (2012) identified in one pedigree branch a
homozygous deletion in the PPIB gene (563_566delACAG) in 2 children with
lethal type IX OI; in another branch, they identified a homozygous
FKBP10 indel mutation (607063.0009) in a child with moderate type XI OI
(610968).

*FIELD* RF
1. Barnes, A. M.; Cabral, W. A.; Weis, M.; Makareeva, E.; Mertz, E.
L.; Leikin, S.; Eyre, D.; Trujillo, C.; Marini, J. C.: Absence of
FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished
collagen cross-linking and reduced collagen deposition in extracellular
matrix. Hum. Mutat. 33: 1589-1598, 2012.

2. Barnes, A. M.; Carter, E. M.; Cabral, W. A.; Weis, M.; Chang, W.;
Makareeva, E.; Leikin, S.; Rotimi, C. N.; Eyre, D. R.; Raggio, C.
L.; Marini, J. C.: Lack of cyclophilin B in osteogenesis imperfecta
with normal collagen folding. New Eng. J. Med. 362: 521-528, 2010.

3. Peddada, L. B.; McPherson, J. D.; Law, R.; Wasmuth, J. J.; Youderian,
P.; Deans, R. J.: Somatic cell mapping of the human cyclophilin B
gene (PPIB) to chromosome 15. Cytogenet. Cell Genet. 60: 219-221,
1992.

4. Price, E. R.; Zydowsky, L. D.; Jin, M.; Baker, C. H.; McKeon, F.
D.; Walsh, C. T.: Human cyclophilin B: a second cyclophilin gene
encodes a peptidyl-prolyl isomerase with a signal sequence. Proc.
Nat. Acad. Sci. 88: 1903-1907, 1991.

5. Tryon, R. C.; White, S. D.; Bannasch, D. L.: Homozygosity mapping
approach identifies a missense mutation in equine cyclophilin B (PPIB)
associated with HERDA in the American Quarter Horse. Genomics 90:
93-102, 2007.

6. van Dijk, F. S.; Cobben, J. M.; Pals, G.: Osteogenesis imperfecta,
normal collagen folding, and lack of cyclophilin B. (Letter) New
Eng. J. Med. 362: 1940-1941, 2010.

7. van Dijk, F. S.; Nesbitt, I. M.; Zwikstra, E. H.; Nikkels, P. G.
J.; Piersma, S. R.; Fratantoni, S. A.; Jimenez, C. R.; Huizer, M.;
Morsman, A. C.; Cobben, J. M.; van Roij, M. H. H.; Elting, M. W.;
and 9 others: PPIB mutations cause severe osteogenesis imperfecta. Am.
J. Hum. Genet. 85: 521-527, 2009.

8. Watashi, K.; Ishii, N.; Hijikata, M.; Inoue, D.; Murata, T.; Miyanari,
Y.; Shimotohno, K.: Cyclophilin B is a functional regulator of hepatitis
C virus RNA polymerase. Molec. Cell 19: 111-122, 2005.

9. Yurchenko, V.; O'Connor, M.; Dai, W. W.; Guo, H.; Toole, B.; Sherry,
B.; Bukrinsky, M.: CD147 is a signaling receptor for cyclophilin
B. Biochem. Biophys. Res. Commun. 288: 786-788, 2001.

*FIELD* CN
Nara Sobreira - updated: 03/29/2013
Marla J. F. O'Neill - updated: 6/1/2010
Marla J. F. O'Neill - updated: 10/22/2009
Ada Hamosh - updated: 8/23/2007
Paul J. Converse - updated: 8/2/2005
Patricia A. Hartz - updated: 7/14/2005

*FIELD* CD
Victor A. McKusick: 3/15/1991

*FIELD* ED
carol: 03/29/2013
carol: 10/6/2011
wwang: 6/1/2010
terry: 6/1/2010
carol: 10/22/2009
terry: 10/22/2009
mgross: 8/31/2007
mgross: 8/30/2007
terry: 8/23/2007
wwang: 8/12/2005
terry: 8/2/2005
mgross: 7/14/2005
carol: 8/2/2001
terry: 6/11/1996
terry: 5/24/1996
carol: 5/11/1993
supermim: 3/16/1992
carol: 2/28/1992
carol: 12/12/1991
carol: 3/15/1991

MIM 259440
*RECORD*
*FIELD* NO
259440
*FIELD* TI
#259440 OSTEOGENESIS IMPERFECTA, TYPE IX; OI9
;;OI, TYPE IX
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moreosteogenesis imperfecta type IX (OI9) can be caused by homozygous
mutation in the PPIB gene (123841) on chromosome 15.

DESCRIPTION

Osteogenesis imperfecta is a connective tissue disorder characterized
clinically by bone fragility and increased susceptibility to fractures.
Osteogenesis imperfecta type IX is a severe autosomal recessive form of
the disorder (summary by van Dijk et al., 2009).

CLINICAL FEATURES

In an inbred Irish Traveller family, Williams et al. (1989) described
severe Sillence type II/III (166210/259420) osteogenesis imperfecta in 3
consecutively born children with first-cousin parents. Three other
children were unaffected. There had been other infants in the kindred
with lethal OI. The first sib, a male, died at age 6 weeks. The second,
a girl, was living at age 7 years and attended a normal school with the
aid of an electric cart. The third was diagnosed by ultrasound, and
pregnancy was terminated at 30 weeks' gestation. The lumbar spine of the
mother was interpreted as showing early osteoporosis; the age of the
parents was not given. Studies in the children showed overhydroxylation
of type I collagen components over the entire length of the collagen and
procollagen triple helix, suggesting overmodification of type I
collagen. Linkage studies excluded both the COL1A1 (120150) and the
COL1A2 (120160) genes as the site of the mutation in this disorder (Daw
et al., 1988).

Van Dijk et al. (2009) studied 2 fetuses with osteogenesis imperfecta
from a nonconsanguineous northern European family; radiographs and
autopsy at 16 weeks' and 22 weeks' gestation, respectively, showed
absence of rib fractures with shortened, bowed, and fractured long bones
without evidence of rhizomelia, consistent with a diagnosis of Sillence
OI type II. Weight and head circumference were normal for gestational
age, and no other abnormalities were noted. Bone histology confirmed the
diagnosis of OI, and overmodification of collagen type I in fibroblasts
was evident on electrophoresis. Van Dijk et al. (2009) also studied 2
sibs with OI from a consanguineous Pakistani family, the older of whom
was born with multiple long-bone fractures and had a large head with
large anterior fontanel and gray-colored sclerae, flexed and abducted
hips, short bowed femurs with anterior bowing of the tibiae, and joint
hypermobility, especially of the finger and hip joints, consistent with
a diagnosis of Sillence OI type III. There was no evidence of
dentinogenesis imperfecta. The older sib, who had never walked, used a
wheelchair at age 8 years and had kyphoscoliosis of the thoracic and
lumbar spine, with a height at the 50th percentile for a 17-month-old
child.

Barnes et al. (2010) studied a 4-year-old girl and her 12-year-old
brother, born of consanguineous Senegalese parents, who had moderately
severe osteogenesis imperfecta. The affected sibs did not have
rhizomelia or severe deformity of the long bones, and their skin was
normal in appearance and extensibility. Although they had moderate axial
growth deficiency, their hand length and segmental proportions were
appropriate for their age. Both children had white sclerae and normal
dentition. The brother, whose osteogenesis imperfecta was milder than
that of his sister, also had sickle cell disease.

MOLECULAR GENETICS

In 4 patients from 2 unrelated families with severe osteogenesis
imperfecta, van Dijk et al. (2009) analyzed the PPIB gene and identified
homozygosity for a frameshift (123841.0001) and a nonsense (123841.0002)
mutation, respectively.

In a sister and brother who had moderately severe osteogenesis
imperfecta without rhizomelia, who were born of consanguineous
Senegalese parents, Barnes et al. (2010) identified homozygosity for a
missense mutation in the PPIB gene (123841.0003). The proband had normal
collagen folding and normal prolyl 3-hydroxylation, suggesting that CYPB
is not the exclusive peptidyl-prolyl cis-trans isomerase that catalyzes
the rate-limiting step in collagen folding.

In a Palestinian pedigree segregating moderate and lethal forms of OI,
Barnes et al. (2012) identified a homozygous indel mutation in the
FKBP10 gene (607063.0009) in a proband from one branch of the family
with OI type 11 (610968), and a homozygous deletion in the PPIB gene
(123841.0004) in a proband from another branch of the family with OI
type IX (259940).

*FIELD* SA
Sillence et al. (1979)
*FIELD* RF
1. Barnes, A. M.; Cabral, W. A.; Weis, M.; Makareeva, E.; Mertz, E.
L.; Leikin, S.; Eyre, D.; Trujillo, C.; Marini, J. C.: Absence of
FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished
collagen cross-linking and reduced collagen deposition in extracellular
matrix. Hum. Mutat. 33: 1589-1598, 2012.

2. Barnes, A. M.; Carter, E. M.; Cabral, W. A.; Weis, M.; Chang, W.;
Makareeva, E.; Leikin, S.; Rotimi, C. N.; Eyre, D. R.; Raggio, C.
L.; Marini, J. C.: Lack of cyclophilin B in osteogenesis imperfecta
with normal collagen folding. New Eng. J. Med. 362: 521-528, 2010.

3. Daw, S.; Nicholls, A. C.; Williams, M.; Sykes, B.; Pope, F. M.
: Autosomal recessive osteogenesis imperfecta: excess post translational
modification of collagen not linked to either COL1A1 or COL1A2. (Abstract) J.
Med. Genet. 25: 275 only, 1988.

4. Sillence, D. O.; Senn, A.; Danks, D. M.: Genetic heterogeneity
in osteogenesis imperfecta. J. Med. Genet. 16: 101-116, 1979.

5. van Dijk, F. S.; Nesbitt, I. M.; Zwikstra, E. H.; Nikkels, P. G.
J.; Piersma, S. R.; Fratantoni, S. A.; Jimenez, C. R.; Huizer, M.;
Morsman, A. C.; Cobben, J. M.; van Roij, M. H. H.; Elting, M. W.;
and 9 others: PPIB mutations cause severe osteogenesis imperfecta. Am.
J. Hum. Genet. 85: 521-527, 2009.

6. Williams, E. M.; Nicholls, A. C.; Daw, S. C. M.; Mitchell, N.;
Levin, L. S.; Green, B.; MacKenzie, J.; Evans, D.-R.; Chudleigh, P.
A.; Pope, F. M.: Phenotypical features of an unique Irish family
with severe autosomal recessive osteogenesis imperfecta. Clin. Genet. 35:
181-190, 1989.

*FIELD* CS
INHERITANCE:
Autosomal recessive

GROWTH:
[Height];
Short limb dwarfism

HEAD AND NECK:
[Eyes];
White to gray sclerae

SKELETAL:
Numerous multiple fractures present at birth;
[Spine];
Scoliosis;
Kyphosis;
[Limbs];
Bowing of limbs due to multiple fractures

MOLECULAR BASIS:
Caused by mutation in the peptidyl-prolyl isomerase B gene (PPIB,
123841.0001)

*FIELD* CD
John F. Jackson: 6/15/1995

*FIELD* ED
joanna: 12/06/2011

*FIELD* CN
Nara Sobreira - updated: 03/29/2013
Marla J. F. O'Neill - updated: 6/1/2010
Marla J. F. O'Neill - updated: 5/24/2010

*FIELD* CD
Victor A. McKusick: 3/21/1989

*FIELD* ED
carol: 03/29/2013
carol: 11/14/2011
carol: 10/6/2011
wwang: 6/1/2010
terry: 6/1/2010
carol: 5/24/2010
carol: 10/22/2009
mimadm: 3/11/1994
supermim: 3/17/1992
supermim: 3/20/1990
ddp: 10/27/1989
root: 3/21/1989