TISIDB

Summary
Symbol	SYVN1
Name	synovial apoptosis inhibitor 1, synoviolin
Aliases	HRD1; DER3; HMG-coA reductase degradation 1 homolog (S. cerevisiae); HMG-coA reductase degradation 1 homolog ......
Chromosomal Location	11q13
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 membrane Multi-pass membrane protein
Domain	PF13639 Ring finger domain
Function	Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114, PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218, PubMed:17170702, PubMed:22607976, PubMed:26471130). Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (PubMed:12459480, PubMed:12646171, PubMed:12975321, PubMed:14593114, PubMed:16289116, PubMed:16847254, PubMed:17059562, PubMed:17141218, PubMed:17170702, PubMed:22607976, PubMed:26471130). Also promotes the degradation of normal but naturally short-lived proteins such as SGK. Protects cells from ER stress-induced apoptosis. Protects neurons from apoptosis induced by polyglutamine-expanded huntingtin (HTT) or unfolded GPR37 by promoting their degradation (PubMed:17141218). Sequesters p53/TP53 in the cytoplasm and promotes its degradation, thereby negatively regulating its biological function in transcription, cell cycle regulation and apoptosis (PubMed:17170702). Mediates the ubiquitination and subsequent degradation of cytoplasmic NFE2L1 (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0000209 protein polyubiquitination GO:0006486 protein glycosylation GO:0006487 protein N-linked glycosylation GO:0006517 protein deglycosylation GO:0006986 response to unfolded protein GO:0009100 glycoprotein metabolic process GO:0009101 glycoprotein biosynthetic process GO:0010498 proteasomal protein catabolic process GO:0018196 peptidyl-asparagine modification GO:0018279 protein N-linked glycosylation via asparagine GO:0030433 ER-associated ubiquitin-dependent protein catabolic process GO:0030968 endoplasmic reticulum unfolded protein response GO:0030970 retrograde protein transport, ER to cytosol GO:0031647 regulation of protein stability GO:0032527 protein exit from endoplasmic reticulum GO:0034620 cellular response to unfolded protein GO:0034976 response to endoplasmic reticulum stress GO:0035966 response to topologically incorrect protein GO:0035967 cellular response to topologically incorrect protein GO:0036498 IRE1-mediated unfolded protein response GO:0036503 ERAD pathway GO:0036507 protein demannosylation GO:0036508 protein alpha-1,2-demannosylation GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043413 macromolecule glycosylation GO:0050821 protein stabilization GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0070085 glycosylation GO:0070936 protein K48-linked ubiquitination GO:0097193 intrinsic apoptotic signaling pathway GO:1902235 regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902532 negative regulation of intracellular signal transduction GO:1903513 endoplasmic reticulum to cytosol transport GO:1903573 negative regulation of response to endoplasmic reticulum stress GO:1904380 endoplasmic reticulum mannose trimming GO:2001233 regulation of apoptotic signaling pathway GO:2001234 negative regulation of apoptotic signaling pathway GO:2001242 regulation of intrinsic apoptotic signaling pathway GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
Molecular Function	GO:0002020 protease binding GO:0004842 ubiquitin-protein transferase activity GO:0016874 ligase activity GO:0019787 ubiquitin-like protein transferase activity GO:0051082 unfolded protein binding GO:0051087 chaperone binding GO:0051117 ATPase binding GO:0061630 ubiquitin protein ligase activity GO:0061659 ubiquitin-like protein ligase activity GO:1904264 ubiquitin protein ligase activity involved in ERAD pathway GO:1990381 ubiquitin-specific protease binding
Cellular Component	GO:0000151 ubiquitin ligase complex GO:0000153 cytoplasmic ubiquitin ligase complex GO:0000835 ER ubiquitin ligase complex GO:0000836 Hrd1p ubiquitin ligase complex GO:0000839 Hrd1p ubiquitin ligase ERAD-L complex GO:0005790 smooth endoplasmic reticulum GO:0030176 integral component of endoplasmic reticulum membrane GO:0031227 intrinsic component of endoplasmic reticulum membrane GO:0036513 Derlin-1 retrotranslocation complex GO:0044322 endoplasmic reticulum quality control compartment

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04120 Ubiquitin mediated proteolysis hsa04141 Protein processing in endoplasmic reticulum
Reactome	R-HSA-446203: Asparagine N-linked glycosylation R-HSA-901042: Calnexin/calreticulin cycle R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-901032: ER Quality Control Compartment (ERQC) R-HSA-5358346: Hedgehog ligand biogenesis R-HSA-5387390: Hh mutants abrogate ligand secretion R-HSA-5362768: Hh mutants that don't undergo autocatalytic processing are degraded by ERAD R-HSA-381070: IRE1alpha activates chaperones R-HSA-392499: Metabolism of proteins R-HSA-532668: N-glycan trimming in the ER and Calnexin/Calreticulin cycle R-HSA-597592: Post-translational protein modification R-HSA-162582: Signal Transduction R-HSA-5358351: Signaling by Hedgehog R-HSA-381119: Unfolded Protein Response (UPR) R-HSA-381038: XBP1(S) activates chaperone genes

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04120 Ubiquitin mediated proteolysis
hsa04141 Protein processing in endoplasmic reticulum

Reactome

R-HSA-446203: Asparagine N-linked glycosylation
R-HSA-901042: Calnexin/calreticulin cycle
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-901032: ER Quality Control Compartment (ERQC)
R-HSA-5358346: Hedgehog ligand biogenesis
R-HSA-5387390: Hh mutants abrogate ligand secretion
R-HSA-5362768: Hh mutants that don't undergo autocatalytic processing are degraded by ERAD
R-HSA-381070: IRE1alpha activates chaperones
R-HSA-392499: Metabolism of proteins
R-HSA-532668: N-glycan trimming in the ER and Calnexin/Calreticulin cycle
R-HSA-597592: Post-translational protein modification
R-HSA-162582: Signal Transduction
R-HSA-5358351: Signaling by Hedgehog
R-HSA-381119: Unfolded Protein Response (UPR)
R-HSA-381038: XBP1(S) activates chaperone genes

Summary
Symbol	SYVN1
Name	synovial apoptosis inhibitor 1, synoviolin
Aliases	HRD1; DER3; HMG-coA reductase degradation 1 homolog (S. cerevisiae); HMG-coA reductase degradation 1 homolog ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SYVN1 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

[ TOP ]

Literatures describing the relation between SYVN1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25209846	Hepatocellular Carcinoma	Inhibit immunity	The decreased expression level of CD155 was due to the involvement of the activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1α (IRE1α) pathways.In addition, the IRE1α pathway contributed to the increased expression level of the ER-associated degradation (ERAD)-related molecule HRD1 and facilitated the degradation of CD155

Summary
Symbol	SYVN1
Name	synovial apoptosis inhibitor 1, synoviolin
Aliases	HRD1; DER3; HMG-coA reductase degradation 1 homolog (S. cerevisiae); HMG-coA reductase degradation 1 homolog ......
Chromosomal Location	11q13
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

[ TOP ]

Statistical results of SYVN1 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	logFC: 2.15; FDR: 0.000150	Sensitive to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.52	Sensitive to T cell-mediated killing
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	SYVN1
Name	synovial apoptosis inhibitor 1, synoviolin
Aliases	HRD1; DER3; HMG-coA reductase degradation 1 homolog (S. cerevisiae); HMG-coA reductase degradation 1 homolog ......
Chromosomal Location	11q13
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 SYVN1 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	0.297	0.183
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.827	0.705
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.091	0.955
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.177	0.524
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.181	0.93
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.174	0.948
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.233	0.534
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.376	0.808
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.078	0.964
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.582	0.681
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	0.957	0.654
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.028	0.664

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of SYVN1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% 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	3.7	3.7	0.27
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	14.3	0.238
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	15.4	0.482
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	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
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	SYVN1
Name	synovial apoptosis inhibitor 1, synoviolin
Aliases	HRD1; DER3; HMG-coA reductase degradation 1 homolog (S. cerevisiae); HMG-coA reductase degradation 1 homolog ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SYVN1. 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	SYVN1
Name	synovial apoptosis inhibitor 1, synoviolin
Aliases	HRD1; DER3; HMG-coA reductase degradation 1 homolog (S. cerevisiae); HMG-coA reductase degradation 1 homolog ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SYVN1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SYVN1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SYVN1
Name	synovial apoptosis inhibitor 1, synoviolin
Aliases	HRD1; DER3; HMG-coA reductase degradation 1 homolog (S. cerevisiae); HMG-coA reductase degradation 1 homolog ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SYVN1. 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	SYVN1
Name	synovial apoptosis inhibitor 1, synoviolin
Aliases	HRD1; DER3; HMG-coA reductase degradation 1 homolog (S. cerevisiae); HMG-coA reductase degradation 1 homolog ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SYVN1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SYVN1
Name	synovial apoptosis inhibitor 1, synoviolin
Aliases	HRD1; DER3; HMG-coA reductase degradation 1 homolog (S. cerevisiae); HMG-coA reductase degradation 1 homolog ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SYVN1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SYVN1
Name	synovial apoptosis inhibitor 1, synoviolin
Aliases	HRD1; DER3; HMG-coA reductase degradation 1 homolog (S. cerevisiae); HMG-coA reductase degradation 1 homolog ......
Chromosomal Location	11q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SYVN1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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