P23284 (PPIB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	216 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Catalytic activity	Peptidylproline (omega=180) = peptidylproline (omega=0).
Enzyme regulation	Cyclosporin A (CsA) inhibits CYPB.
Subunit structure	Interacts with DYM. Ref.16
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 connective tissue disorder characterized by bone fragility, low bone mass, bowing of limbs due to multiple fractures. Short limb dwarfism and blue sclerae are observed in some but not all patients. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.18
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 component	Endoplasmic reticulum
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dwarfism Osteogenesis imperfecta
Domain	Signal
Ligand	Cyclosporin
Molecular function	Isomerase Rotamase
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	extracellular matrix organization Traceable author statement. Source: Reactome protein folding Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum lumen Non-traceable author statement Ref.12. Source: UniProtKB melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	peptide binding Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-prolyl cis-trans isomerase activity Non-traceable author statement Ref.8. Source: UniProtKB unfolded protein binding Traceable author statement Ref.8. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 33

33

Ref.8

Chain

34 – 216

183

Peptidyl-prolyl cis-trans isomerase B

PRO_0000025479

Regions

Domain

47 – 204

158

PPIase cyclophilin-type

Motif

213 – 216

4

Prevents secretion from ER

Amino acid modifications

Glycosylation

148

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

9

1

M → R in OI9; patients have white sclerae, normal dentition, no rhizomelia or severe deformity of long bones. Ref.18

VAR_063436

Natural variant

60

1

V → L.
Corresponds to variant rs11558595 [ dbSNP | Ensembl ].

VAR_047711

Experimental info

Sequence conflict

5

1

S → R in AAA52150. Ref.8

Sequence conflict

216

1

E → D in CAG33110. Ref.3

Secondary structure

1

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216

Helix Strand Turn

Details...

Beta strand

41 – 52

12

Beta strand

55 – 64

10

Turn

66 – 68

3

Helix

70 – 81

12

Turn

82 – 84

3

Beta strand

95 – 97

3

Turn

98 – 100

3

Beta strand

101 – 104

4

Turn

107 – 109

3

Beta strand

110 – 113

4

Beta strand

137 – 140

4

Beta strand

142 – 144

3

Beta strand

152 – 157

6

Helix

160 – 162

3

Turn

163 – 165

3

Beta strand

168 – 174

7

Helix

176 – 183

8

Beta strand

193 – 195

3

Beta strand

197 – 212

16

Sequences

	Sequence		Length	Mass (Da)
	P23284 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 2D0410A07AA9E420	FASTA	216	23,743
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, 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], MASS SPECTROMETRY. 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. , 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]	"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.

IPI

IPI00646304.

PIR

CSHUB. A39118.

RefSeq

NP_000933.1. NM_000942.4.

UniGene

Hs.434937.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CYN	X-ray	1.85	A	39-216	[»]
3ICH	X-ray	1.20	A	34-216	[»]
3ICI	X-ray	1.70	A/B	34-216	[»]

ProteinModelPortal

P23284.

ModBase

Search...

Protein-protein interaction databases

IntAct

P23284. 13 interactions.

MINT

MINT-1142578.

STRING

9606.ENSP00000300026.

PTM databases

PhosphoSite

P23284.

Polymorphism databases

DMDM

215273869.

2D gel databases

OGP

P23284.

REPRODUCTION-2DPAGE

IPI00646304.

SWISS-2DPAGE

P23284.

Proteomic databases

PaxDb

P23284.

PRIDE

P23284.

Protocols and materials databases

DNASU

5479.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000300026; ENSP00000300026; ENSG00000166794.

GeneID

5479.

KEGG

hsa:5479.

UCSC

uc002and.3. human.

Organism-specific databases

CTD

5479.

GeneCards

GC15M064448.

HGNC

HGNC:9255. PPIB.

HPA

CAB011487.
HPA012720.

MIM

123841. gene.
259440. phenotype.

neXtProt

NX_P23284.

Orphanet

216804. Osteogenesis imperfecta type 2.
216812. Osteogenesis imperfecta type 3.
216820. Osteogenesis imperfecta type 4.

PharmGKB

PA33580.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0652.

HOGENOM

HOG000065981.

HOVERGEN

HBG001065.

InParanoid

P23284.

KO

K03768.

OMA

CERRMKF.

OrthoDB

EOG43XV4N.

PhylomeDB

P23284.

Enzyme and pathway databases

Pathway_Interaction_DB

syndecan_1_pathway. Syndecan-1-mediated signaling events.

Reactome

REACT_118779. Extracellular matrix organization.

Gene expression databases

Bgee

P23284.

CleanEx

HS_PPIB.

Genevestigator

P23284.

GermOnline

ENSG00000166794. Homo sapiens.

Family and domain databases

InterPro

IPR002130. Cyclophilin-like_PPIase_dom.
IPR024936. Cyclophilin-type_PPIase.
IPR020892. Cyclophilin-type_PPIase_CS.
[Graphical view]

Pfam

PF00160. Pro_isomerase. 1 hit.
[Graphical view]

PIRSF

PIRSF001467. Peptidylpro_ismrse. 1 hit.

PRINTS

PR00153. CSAPPISMRASE.

SUPFAM

SSF50891. CSA_PPIase. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

BindingDB

P23284.

ChEMBL

CHEMBL2075.

ChiTaRS

PPIB. human.

DrugBank

DB00172. L-Proline.

EvolutionaryTrace

P23284.

GenomeRNAi

5479.

NextBio

21210.

SOURCE

Search...

Entry information

Entry name

PPIB_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 140 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.