TISIDB

Summary
Symbol	PPIB
Name	peptidylprolyl isomerase B (cyclophilin B)
Aliases	CYPB; OI9; CYP-S1; HEL-S-39; SCYLP; PPIase B; S-cyclophilin; cyclophilin-like protein; epididymis secretory ......
Chromosomal Location	15q21-q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Endoplasmic reticulum lumen Melanosome Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:17081065).
Domain	PF00160 Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD
Function	PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

> Gene Ontology [ TOP ]
Biological Process	GO:0000413 protein peptidyl-prolyl isomerization GO:0001501 skeletal system development GO:0006457 protein folding GO:0018208 peptidyl-proline modification GO:0019058 viral life cycle GO:0019079 viral genome replication GO:0031647 regulation of protein stability GO:0035264 multicellular organism growth GO:0035821 modification of morphology or physiology of other organism GO:0040014 regulation of multicellular organism growth GO:0040018 positive regulation of multicellular organism growth GO:0043900 regulation of multi-organism process GO:0043902 positive regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0044788 modulation by host of viral process GO:0044794 positive regulation by host of viral process GO:0044827 modulation by host of viral genome replication GO:0044829 positive regulation by host of viral genome replication GO:0045069 regulation of viral genome replication GO:0045070 positive regulation of viral genome replication GO:0045927 positive regulation of growth GO:0048524 positive regulation of viral process GO:0048638 regulation of developmental growth GO:0048639 positive regulation of developmental growth GO:0050792 regulation of viral process GO:0050821 protein stabilization GO:0051702 interaction with symbiont GO:0051817 modification of morphology or physiology of other organism involved in symbiotic interaction GO:0051851 modification by host of symbiont morphology or physiology GO:0060348 bone development GO:0061077 chaperone-mediated protein folding GO:1903900 regulation of viral life cycle GO:1903902 positive regulation of viral life cycle
Molecular Function	GO:0003755 peptidyl-prolyl cis-trans isomerase activity GO:0005518 collagen binding GO:0016853 isomerase activity GO:0016859 cis-trans isomerase activity GO:0033218 amide binding GO:0042277 peptide binding GO:0051082 unfolded protein binding GO:0070063 RNA polymerase binding
Cellular Component	GO:0005788 endoplasmic reticulum lumen GO:0005790 smooth endoplasmic reticulum GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0030055 cell-substrate junction GO:0034663 endoplasmic reticulum chaperone complex GO:0042470 melanosome GO:0048770 pigment granule

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1650814: Collagen biosynthesis and modifying enzymes R-HSA-1474290: Collagen formation R-HSA-1474244: Extracellular matrix organization

Summary
Symbol	PPIB
Name	peptidylprolyl isomerase B (cyclophilin B)
Aliases	CYPB; OI9; CYP-S1; HEL-S-39; SCYLP; PPIase B; S-cyclophilin; cyclophilin-like protein; epididymis secretory ......
Chromosomal Location	15q21-q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PPIB and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between PPIB and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
21480325	Hepatocellular Carcinoma	Inhibit immunity (T/NK cell function); immunotherapy target	The TAAs consisting of cyclophilin B, squamous cell carcinoma antigen recognized by T cells (SART) 2, SART3, p53, multidrug resistance-associated protein (MRP) 3, alpha-fetoprotein (AFP) and human telomerase reverse transcriptase (hTERT) were frequently recognized by T cells and these TAA-derived peptides were capable of generating peptide-specific CTLs in HCC patients, which suggested that these TAAs are immunogenic. Cyclophilin B, SART2, SART3, p53, MRP3, AFP, and hTERT were immunogenic targets for HCC immunotherapy.

Summary
Symbol	PPIB
Name	peptidylprolyl isomerase B (cyclophilin B)
Aliases	CYPB; OI9; CYP-S1; HEL-S-39; SCYLP; PPIase B; S-cyclophilin; cyclophilin-like protein; epididymis secretory ......
Chromosomal Location	15q21-q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of PPIB in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	PPIB
Name	peptidylprolyl isomerase B (cyclophilin B)
Aliases	CYPB; OI9; CYP-S1; HEL-S-39; SCYLP; PPIase B; S-cyclophilin; cyclophilin-like protein; epididymis secretory ......
Chromosomal Location	15q21-q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of PPIB in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.037	0.914
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.087	0.983
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.115	0.971
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.01	0.983
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.448	0.847
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.588	0.841
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.213	0.637
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.43	0.817
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.029	0.989
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.177	0.953
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.353	0.941
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.017	0.795

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PPIB in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	7.7	-7.7	0.371
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	PPIB
Name	peptidylprolyl isomerase B (cyclophilin B)
Aliases	CYPB; OI9; CYP-S1; HEL-S-39; SCYLP; PPIase B; S-cyclophilin; cyclophilin-like protein; epididymis secretory ......
Chromosomal Location	15q21-q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PPIB. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	PPIB
Name	peptidylprolyl isomerase B (cyclophilin B)
Aliases	CYPB; OI9; CYP-S1; HEL-S-39; SCYLP; PPIase B; S-cyclophilin; cyclophilin-like protein; epididymis secretory ......
Chromosomal Location	15q21-q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PPIB. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PPIB. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PPIB
Name	peptidylprolyl isomerase B (cyclophilin B)
Aliases	CYPB; OI9; CYP-S1; HEL-S-39; SCYLP; PPIase B; S-cyclophilin; cyclophilin-like protein; epididymis secretory ......
Chromosomal Location	15q21-q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PPIB. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	PPIB
Name	peptidylprolyl isomerase B (cyclophilin B)
Aliases	CYPB; OI9; CYP-S1; HEL-S-39; SCYLP; PPIase B; S-cyclophilin; cyclophilin-like protein; epididymis secretory ......
Chromosomal Location	15q21-q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PPIB expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PPIB
Name	peptidylprolyl isomerase B (cyclophilin B)
Aliases	CYPB; OI9; CYP-S1; HEL-S-39; SCYLP; PPIase B; S-cyclophilin; cyclophilin-like protein; epididymis secretory ......
Chromosomal Location	15q21-q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PPIB and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PPIB
Name	peptidylprolyl isomerase B (cyclophilin B)
Aliases	CYPB; OI9; CYP-S1; HEL-S-39; SCYLP; PPIase B; S-cyclophilin; cyclophilin-like protein; epididymis secretory ......
Chromosomal Location	15q21-q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PPIB collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PPIB.

ID	Name	Drug Type	Targets	#Targets
DB00172	L-Proline	Small Molecule	EPRS, L3HYPDH, P3H1, P3H2, P3H3, P4HA1, P4HA2, PARS2, PPIA, PPIB, ......	21
DB04447	1,4-Dithiothreitol	Small Molecule	ALDH1A1, AXIN1, CAMK2A, GSTZ1, HMGCR, LGALS1, MSRA, PPIB, TPI1, TR ......	10

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