TISIDB

Summary
Symbol	KRIT1
Name	KRIT1, ankyrin repeat containing
Aliases	CCM1; cerebral cavernous malformations 1; ankyrin repeat-containing protein Krit1; cerebral cavernous malfor ......
Chromosomal Location	7q21.2
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	Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Cell junction. Note=KRIT1 and CDH5 reciprocally regulate their localization to endothelial cell-cell junctions. Association with RAP1 relocalizes KRIT1 from microtubules to cell junction membranes. Translocates from the cytoplasm along microtubules to the cell membrane in a ITGB1BP1-dependent manner.
Domain	PF00373 FERM central domain PF16705 NUDIX
Function	Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity (By similarity). Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation in a NOTCH-dependent and independent manner, and inhibits ERK1/2 phosphorylation indirectly through activation of the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents the interaction between ITGB1 and ITGB1BP1. Microtubule-associated protein that binds to phosphatidylinositol 4,5-bisphosphate (PIP2)-containing membranes in a GTP-bound RAP1-dependent manner. Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2. Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2 levels.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0001667 ameboidal-type cell migration GO:0001935 endothelial cell proliferation GO:0001936 regulation of endothelial cell proliferation GO:0001937 negative regulation of endothelial cell proliferation GO:0007163 establishment or maintenance of cell polarity GO:0010594 regulation of endothelial cell migration GO:0010596 negative regulation of endothelial cell migration GO:0010631 epithelial cell migration GO:0010632 regulation of epithelial cell migration GO:0010633 negative regulation of epithelial cell migration GO:0016525 negative regulation of angiogenesis GO:0030010 establishment of cell polarity GO:0030336 negative regulation of cell migration GO:0032092 positive regulation of protein binding GO:0032878 regulation of establishment or maintenance of cell polarity GO:0040013 negative regulation of locomotion GO:0043393 regulation of protein binding GO:0043542 endothelial cell migration GO:0045454 cell redox homeostasis GO:0045765 regulation of angiogenesis GO:0048514 blood vessel morphogenesis GO:0050673 epithelial cell proliferation GO:0050678 regulation of epithelial cell proliferation GO:0050680 negative regulation of epithelial cell proliferation GO:0051098 regulation of binding GO:0051099 positive regulation of binding GO:0051271 negative regulation of cellular component movement GO:0072577 endothelial cell apoptotic process GO:0090130 tissue migration GO:0090132 epithelium migration GO:1901342 regulation of vasculature development GO:1901343 negative regulation of vasculature development GO:1904019 epithelial cell apoptotic process GO:1904035 regulation of epithelial cell apoptotic process GO:1904036 negative regulation of epithelial cell apoptotic process GO:2000114 regulation of establishment of cell polarity GO:2000146 negative regulation of cell motility GO:2000181 negative regulation of blood vessel morphogenesis GO:2000351 regulation of endothelial cell apoptotic process GO:2000352 negative regulation of endothelial cell apoptotic process
Molecular Function	GO:0005543 phospholipid binding GO:0005546 phosphatidylinositol-4,5-bisphosphate binding GO:0008017 microtubule binding GO:0015631 tubulin binding GO:0030695 GTPase regulator activity GO:0035091 phosphatidylinositol binding GO:0060589 nucleoside-triphosphatase regulator activity GO:1901981 phosphatidylinositol phosphate binding GO:1902936 phosphatidylinositol bisphosphate binding
Cellular Component	GO:0005874 microtubule

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04015 Rap1 signaling pathway
Reactome	-

Summary
Symbol	KRIT1
Name	KRIT1, ankyrin repeat containing
Aliases	CCM1; cerebral cavernous malformations 1; ankyrin repeat-containing protein Krit1; cerebral cavernous malfor ......
Chromosomal Location	7q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between KRIT1 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 ]
There is no record.

Summary
Symbol	KRIT1
Name	KRIT1, ankyrin repeat containing
Aliases	CCM1; cerebral cavernous malformations 1; ankyrin repeat-containing protein Krit1; cerebral cavernous malfor ......
Chromosomal Location	7q21.2
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 KRIT1 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: -3.08; FDR: 0.00700	Resistant 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	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	KRIT1
Name	KRIT1, ankyrin repeat containing
Aliases	CCM1; cerebral cavernous malformations 1; ankyrin repeat-containing protein Krit1; cerebral cavernous malfor ......
Chromosomal Location	7q21.2
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 KRIT1 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	0.028	0.918
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.23	0.878
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.121	0.916
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.15	0.703
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.532	0.757
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.334	0.88
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.006	0.987
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.105	0.948
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.177	0.919
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.169	0.889
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	0.647	0.705
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.021	0.678

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of KRIT1 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	1.4	6	0.177
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	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	9.5	0	9.5	0.492
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	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	2.6	0	2.6	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	6.2	0	6.2	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	KRIT1
Name	KRIT1, ankyrin repeat containing
Aliases	CCM1; cerebral cavernous malformations 1; ankyrin repeat-containing protein Krit1; cerebral cavernous malfor ......
Chromosomal Location	7q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KRIT1. 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	KRIT1
Name	KRIT1, ankyrin repeat containing
Aliases	CCM1; cerebral cavernous malformations 1; ankyrin repeat-containing protein Krit1; cerebral cavernous malfor ......
Chromosomal Location	7q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KRIT1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KRIT1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	KRIT1
Name	KRIT1, ankyrin repeat containing
Aliases	CCM1; cerebral cavernous malformations 1; ankyrin repeat-containing protein Krit1; cerebral cavernous malfor ......
Chromosomal Location	7q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KRIT1. 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	KRIT1
Name	KRIT1, ankyrin repeat containing
Aliases	CCM1; cerebral cavernous malformations 1; ankyrin repeat-containing protein Krit1; cerebral cavernous malfor ......
Chromosomal Location	7q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of KRIT1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	KRIT1
Name	KRIT1, ankyrin repeat containing
Aliases	CCM1; cerebral cavernous malformations 1; ankyrin repeat-containing protein Krit1; cerebral cavernous malfor ......
Chromosomal Location	7q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between KRIT1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	KRIT1
Name	KRIT1, ankyrin repeat containing
Aliases	CCM1; cerebral cavernous malformations 1; ankyrin repeat-containing protein Krit1; cerebral cavernous malfor ......
Chromosomal Location	7q21.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting KRIT1 collected from DrugBank database.

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

Browse KRIT1