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P23284 (PPIB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Peptidyl-prolyl cis-trans isomerase B

Short name=PPIase B
EC=5.2.1.8
Alternative name(s):
CYP-S1
Cyclophilin B
Rotamase B
S-cyclophilin
Short name=SCYLP
Gene names
Name:PPIB
Synonyms:CYPB
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length216 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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

Enzyme regulation

Cyclosporin A (CsA) inhibits CYPB.

Subunit structure

Interacts with DYM. Interacts with CALR, CLGN and CANX. Ref.16 Ref.18

Subcellular location

Endoplasmic reticulum lumen. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.12 Ref.13

Involvement in disease

Osteogenesis imperfecta 9 (OI9) [MIM:259440]: A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI9 is a severe autosomal recessive form of the disorder.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.19

Sequence similarities

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

Contains 1 PPIase cyclophilin-type domain.

Caution

It is uncertain whether Met-1 or Met-9 is the initiator.

Sequence caution

The sequence AAA52150.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Dwarfism
Osteogenesis imperfecta
   DomainSignal
   LigandCyclosporin
   Molecular functionIsomerase
Rotamase
   PTMAcetylation
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbone development

Inferred from mutant phenotype Ref.19. Source: UniProt

chaperone-mediated protein folding

Inferred from direct assay PubMed 22665516. Source: UniProt

extracellular matrix organization

Traceable author statement. Source: Reactome

positive regulation of multicellular organism growth

Inferred from mutant phenotype Ref.19. Source: UniProt

protein peptidyl-prolyl isomerization

Inferred from sequence or structural similarity. Source: UniProt

protein stabilization

Inferred from mutant phenotype Ref.19. Source: UniProt

   Cellular_componentendoplasmic reticulum

Inferred from direct assay Ref.19. Source: UniProt

endoplasmic reticulum lumen

Non-traceable author statement Ref.12. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708PubMed 20458337PubMed 23376485. Source: UniProt

macromolecular complex

Inferred from sequence or structural similarity. Source: UniProt

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 21630459. Source: UniProt

   Molecular_functionpeptide binding

Inferred from electronic annotation. Source: UniProtKB-KW

peptidyl-prolyl cis-trans isomerase activity

Non-traceable author statement Ref.8. Source: UniProtKB

poly(A) RNA binding

Inferred from direct assay PubMed 22658674PubMed 22681889. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 22665516. Source: IntAct

protein complex binding

Inferred from sequence or structural similarity. Source: UniProt

unfolded protein binding

Traceable author statement Ref.8. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PDIA4P136673EBI-8771982,EBI-1054653

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3333 Ref.8
Chain34 – 216183Peptidyl-prolyl cis-trans isomerase B
PRO_0000025479

Regions

Domain47 – 204158PPIase cyclophilin-type
Motif213 – 2164Prevents secretion from ER

Amino acid modifications

Modified residue2091N6-acetyllysine; alternate By similarity
Modified residue2091N6-succinyllysine; alternate By similarity
Glycosylation1481N-linked (GlcNAc...) Potential

Natural variations

Natural variant91M → R in OI9; patients have white sclerae, normal dentition, no rhizomelia or severe deformity of long bones. Ref.19
VAR_063436
Natural variant601V → L.
Corresponds to variant rs11558595 [ dbSNP | Ensembl ].
VAR_047711

Experimental info

Mutagenesis1291K → A: Impairs interaction with CLGN and CANX. Ref.18
Sequence conflict51S → R in AAA52150. Ref.8
Sequence conflict2161E → D in CAG33110. Ref.3

Secondary structure

.................................. 216
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P23284 [UniParc].

Last modified November 25, 2008. Version 2.
Checksum: 2D0410A07AA9E420

FASTA21623,743
        10         20         30         40         50         60 
MLRLSERNMK VLLAAALIAG SVFFLLLPGP SAADEKKKGP KVTVKVYFDL RIGDEDVGRV 

        70         80         90        100        110        120 
IFGLFGKTVP KTVDNFVALA TGEKGFGYKN SKFHRVIKDF MIQGGDFTRG DGTGGKSIYG 

       130        140        150        160        170        180 
ERFPDENFKL KHYGPGWVSM ANAGKDTNGS QFFITTVKTA WLDGKHVVFG KVLEGMEVVR 

       190        200        210 
KVESTKTDSR DKPLKDVIIA DCGKIEVEKP FAIAKE 

« Hide

References

« Hide 'large scale' references
[1]"A novel secreted cyclophilin-like protein (SCYLP)."
Spik G., Haendler B., Delmas O., Mariller C., Chamoux M., Maes P., Tartar A., Montreuil J., Stedman K., Kocher H.P., Keller R., Hiestand P.C., Movva N.R.
J. Biol. Chem. 266:10735-10738(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]NIEHS SNPs program
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain, Prostate and Skin.
[8]"Human cyclophilin B: a second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence."
Price E.R., Zydowsky L.D., Jin M., Hunter C.H., McKeon F.D., Walsh C.T.
Proc. Natl. Acad. Sci. U.S.A. 88:1903-1907(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-216, PROTEIN SEQUENCE OF 34-48.
[9]"An endoplasmic reticulum-specific cyclophilin."
Hasel K.W., Glass J.R., Godbout M., Sutcliffe J.G.
Mol. Cell. Biol. 11:3484-3491(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-216.
[10]Lubec G., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 52-59; 64-76; 91-101; 138-150; 164-172 AND 197-207, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Fetal brain cortex.
[11]"Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes."
Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J.
Electrophoresis 13:960-969(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 72-84 AND 159-165.
[12]"S-cyclophilin is retained intracellularly via a unique COOH-terminal sequence and colocalizes with the calcium storage protein calreticulin."
Arber S., Krause K.-H., Caroni P.
J. Cell Biol. 116:113-125(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[13]"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.
J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[14]"PPIB mutations cause severe osteogenesis imperfecta."
van Dijk F.S., Nesbitt I.M., Zwikstra E.H., Nikkels P.G., Piersma S.R., Fratantoni S.A., Jimenez C.R., Huizer M., Morsman A.C., Cobben J.M., van Roij M.H., Elting M.W., Verbeke J.I., Wijnaendts L.C., Shaw N.J., Hogler W., McKeown C., Sistermans E.A. expand/collapse author list , Dalton A., Meijers-Heijboer H., Pals G.
Am. J. Hum. Genet. 85:521-527(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN OI9.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Dymeclin, the gene underlying Dyggve-Melchior-Clausen syndrome, encodes a protein integral to extracellular matrix and Golgi organization and is associated with protein secretion pathways critical in bone development."
Denais C., Dent C.L., Southgate L., Hoyle J., Dafou D., Trembath R.C., Machado R.D.
Hum. Mutat. 32:231-239(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DYM.
[17]"X-ray structure of a cyclophilin B/cyclosporin complex: comparison with cyclophilin A and delineation of its calcineurin-binding domain."
Mikol V., Kallen J., Walkinshaw M.D.
Proc. Natl. Acad. Sci. U.S.A. 91:5183-5186(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 39-216.
[18]"Structural basis of cyclophilin B binding by the calnexin/calreticulin P-domain."
Kozlov G., Bastos-Aristizabal S., Maattanen P., Rosenauer A., Zheng F., Killikelly A., Trempe J.F., Thomas D.Y., Gehring K.
J. Biol. Chem. 285:35551-35557(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 34-216 IN COMPLEX WITH CLGN, MUTAGENESIS OF LYS-129, INTERACTION WITH CALR; CANX AND CLGN.
[19]"Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding."
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.
N. Engl. J. Med. 362:521-528(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT OI9 ARG-9.
+Additional computationally mapped references.

Web resources

NIEHS-SNPs
Osteogenesis imperfecta variant database

Peptidyl-prolyl cis-trans isomerase B (PPIB)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M63573 mRNA. Translation: AAA36601.1.
AK291149 mRNA. Translation: BAF83838.1.
CR456829 mRNA. Translation: CAG33110.1.
AY962310 Genomic DNA. Translation: AAX44050.1.
AC100840 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77669.1.
BC001125 mRNA. Translation: AAH01125.1.
BC008848 mRNA. Translation: AAH08848.1.
BC020800 mRNA. Translation: AAH20800.1.
BC032138 mRNA. Translation: AAH32138.1.
M60857 mRNA. Translation: AAA52150.1. Different initiation.
M60457 mRNA. Translation: AAA35733.1.
CCDSCCDS10191.1.
PIRCSHUB. A39118.
RefSeqNP_000933.1. NM_000942.4.
UniGeneHs.434937.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CYNX-ray1.85A39-216[»]
3ICHX-ray1.20A34-216[»]
3ICIX-ray1.70A/B34-216[»]
ProteinModelPortalP23284.
SMRP23284. Positions 37-216.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111475. 46 interactions.
IntActP23284. 23 interactions.
MINTMINT-1142578.
STRING9606.ENSP00000300026.

Chemistry

BindingDBP23284.
ChEMBLCHEMBL2075.
DrugBankDB00172. L-Proline.

PTM databases

PhosphoSiteP23284.

Polymorphism databases

DMDM215273869.

2D gel databases

OGPP23284.
REPRODUCTION-2DPAGEIPI00646304.
SWISS-2DPAGEP23284.

Proteomic databases

MaxQBP23284.
PaxDbP23284.
PRIDEP23284.

Protocols and materials databases

DNASU5479.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000300026; ENSP00000300026; ENSG00000166794.
GeneID5479.
KEGGhsa:5479.
UCSCuc002and.3. human.

Organism-specific databases

CTD5479.
GeneCardsGC15M064448.
HGNCHGNC:9255. PPIB.
HPACAB011487.
HPA012720.
MIM123841. gene.
259440. phenotype.
neXtProtNX_P23284.
Orphanet216804. Osteogenesis imperfecta type 2.
216812. Osteogenesis imperfecta type 3.
216820. Osteogenesis imperfecta type 4.
PharmGKBPA33580.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0652.
HOGENOMHOG000065981.
HOVERGENHBG001065.
InParanoidP23284.
KOK03768.
OMAPAYANED.
OrthoDBEOG7RFTK4.
PhylomeDBP23284.
TreeFamTF354259.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

BgeeP23284.
CleanExHS_PPIB.
GenevestigatorP23284.

Family and domain databases

Gene3D2.40.100.10. 1 hit.
InterProIPR029000. Cyclophilin-like_dom.
IPR024936. Cyclophilin-type_PPIase.
IPR020892. Cyclophilin-type_PPIase_CS.
IPR002130. Cyclophilin-type_PPIase_dom.
[Graphical view]
PfamPF00160. Pro_isomerase. 1 hit.
[Graphical view]
PIRSFPIRSF001467. Peptidylpro_ismrse. 1 hit.
PRINTSPR00153. CSAPPISMRASE.
SUPFAMSSF50891. SSF50891. 1 hit.
PROSITEPS00170. CSA_PPIASE_1. 1 hit.
PS50072. CSA_PPIASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPPIB. human.
EvolutionaryTraceP23284.
GeneWikiPPIB.
GenomeRNAi5479.
NextBio21210.
PROP23284.
SOURCESearch...

Entry information

Entry namePPIB_HUMAN
AccessionPrimary (citable) accession number: P23284
Secondary accession number(s): A8K534, Q6IBH5, Q9BVK5
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 25, 2008
Last modified: July 9, 2014
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM