TISIDB

Summary
Symbol	HYOU1
Name	hypoxia up-regulated 1
Aliases	ORP150; HSP12A; Grp170; glucose-regulated protein 170; GRP-170; ORP-150; 150 kDa oxygen-regulated protein; 1 ......
Chromosomal Location	11q23.1-q23.3
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.
Domain	PF00012 Hsp70 protein
Function	Has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. May play a role as a molecular chaperone and participate in protein folding.

> Gene Ontology [ TOP ]
Biological Process	GO:0001666 response to hypoxia GO:0002931 response to ischemia GO:0006888 ER to Golgi vesicle-mediated transport GO:0006898 receptor-mediated endocytosis GO:0006986 response to unfolded protein GO:0030968 endoplasmic reticulum unfolded protein response 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:0036293 response to decreased oxygen levels GO:0036294 cellular response to decreased oxygen levels GO:0036483 neuron intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0036498 IRE1-mediated unfolded protein response GO:0043523 regulation of neuron apoptotic process GO:0043524 negative regulation of neuron apoptotic process GO:0048193 Golgi vesicle transport GO:0051402 neuron apoptotic process GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0070482 response to oxygen levels GO:0070997 neuron death GO:0071453 cellular response to oxygen levels GO:0071456 cellular response to hypoxia GO:0097193 intrinsic apoptotic signaling pathway GO:1900037 regulation of cellular response to hypoxia GO:1900038 negative regulation of cellular response to hypoxia GO:1901214 regulation of neuron death GO:1901215 negative regulation of neuron death 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:1903297 regulation of hypoxia-induced intrinsic apoptotic signaling pathway GO:1903298 negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway GO:1903381 regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway GO:1903382 negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway GO:1903573 negative regulation of response to endoplasmic reticulum stress GO:1990144 intrinsic apoptotic signaling pathway in response to hypoxia 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:0051087 chaperone 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:0030139 endocytic vesicle GO:0031983 vesicle lumen GO:0034663 endoplasmic reticulum chaperone complex GO:0060205 cytoplasmic membrane-bounded vesicle lumen GO:0071682 endocytic vesicle lumen

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04141 Protein processing in endoplasmic reticulum
Reactome	R-HSA-2173782: Binding and Uptake of Ligands by Scavenger Receptors R-HSA-381070: IRE1alpha activates chaperones R-HSA-392499: Metabolism of proteins R-HSA-3000484: Scavenging by Class F Receptors R-HSA-381119: Unfolded Protein Response (UPR) R-HSA-5653656: Vesicle-mediated transport R-HSA-381038: XBP1(S) activates chaperone genes

Summary
Symbol	HYOU1
Name	hypoxia up-regulated 1
Aliases	ORP150; HSP12A; Grp170; glucose-regulated protein 170; GRP-170; ORP-150; 150 kDa oxygen-regulated protein; 1 ......
Chromosomal Location	11q23.1-q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HYOU1 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 HYOU1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
16424054	Melanoma	Promote immunity	Chaperoning function of stress protein grp170, a member of the hsp70 superfamily, is responsible for its immunoadjuvant activity. In this study, we determine the ability of grp170 and its structural domains to (a) bind to and present melanoma-associated antigen gp100 to the immune system and (b) to bind to receptors on APCs. Therefore, these studies suggest that molecular chaperoning is involved in stress protein interactions with APCs, antigen binding, and in eliciting antitumor immunity, thus bridging this ancient function of stress proteins in prokaryotes to their ability to elicit immunity in higher organisms.
24218449	Melanoma	Promote immunity	Directing the clinically relevant, melanoma Ag gp100 to mouse-derived DCs by molecular adjuvant and chaperone Grp170 substantially facilitates Ag access to the ER. Grp170 also strengthens the interaction of internalized protein Ag with molecular components involved in ER-associated protein dislocation and/or degradation, which culminates in cytosolic translocation for proteasome-dependent degradation and processing.
16849461	Melanoma	Promote immunity	The continued secretion of grp170 dramatically reduced the tumorigenicity of B16 tumor cells in vivo, although the modification did not alter its transformation phenotype and cell growth rate. C57BL/6 mice that rejected grp170-secreting B16 tumor cells (B16-sgrp170) developed a strong CTL response recognizing melanocyte differentiation Ag TRP2 and were resistant to subsequent tumor challenge.

Summary
Symbol	HYOU1
Name	hypoxia up-regulated 1
Aliases	ORP150; HSP12A; Grp170; glucose-regulated protein 170; GRP-170; ORP-150; 150 kDa oxygen-regulated protein; 1 ......
Chromosomal Location	11q23.1-q23.3
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 HYOU1 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	HYOU1
Name	hypoxia up-regulated 1
Aliases	ORP150; HSP12A; Grp170; glucose-regulated protein 170; GRP-170; ORP-150; 150 kDa oxygen-regulated protein; 1 ......
Chromosomal Location	11q23.1-q23.3
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

[ TOP ]

Points in the above scatter plot represent the expression difference of HYOU1 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	-0.101	0.714
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.286	0.91
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.034	0.985
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.268	0.523
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.295	0.901
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.233	0.938
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.143	0.773
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.004	0.998
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.382	0.858
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.279	0.886
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	0.602	0.833
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.088	0.242

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of HYOU1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	2.7	4.7	0.294
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	1.7	5.7	0.231
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	HYOU1
Name	hypoxia up-regulated 1
Aliases	ORP150; HSP12A; Grp170; glucose-regulated protein 170; GRP-170; ORP-150; 150 kDa oxygen-regulated protein; 1 ......
Chromosomal Location	11q23.1-q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HYOU1. 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	HYOU1
Name	hypoxia up-regulated 1
Aliases	ORP150; HSP12A; Grp170; glucose-regulated protein 170; GRP-170; ORP-150; 150 kDa oxygen-regulated protein; 1 ......
Chromosomal Location	11q23.1-q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HYOU1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HYOU1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HYOU1
Name	hypoxia up-regulated 1
Aliases	ORP150; HSP12A; Grp170; glucose-regulated protein 170; GRP-170; ORP-150; 150 kDa oxygen-regulated protein; 1 ......
Chromosomal Location	11q23.1-q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HYOU1. 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	HYOU1
Name	hypoxia up-regulated 1
Aliases	ORP150; HSP12A; Grp170; glucose-regulated protein 170; GRP-170; ORP-150; 150 kDa oxygen-regulated protein; 1 ......
Chromosomal Location	11q23.1-q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HYOU1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HYOU1
Name	hypoxia up-regulated 1
Aliases	ORP150; HSP12A; Grp170; glucose-regulated protein 170; GRP-170; ORP-150; 150 kDa oxygen-regulated protein; 1 ......
Chromosomal Location	11q23.1-q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HYOU1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HYOU1
Name	hypoxia up-regulated 1
Aliases	ORP150; HSP12A; Grp170; glucose-regulated protein 170; GRP-170; ORP-150; 150 kDa oxygen-regulated protein; 1 ......
Chromosomal Location	11q23.1-q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HYOU1 collected from DrugBank database.

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

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