TISIDB

Summary
Symbol	TTLL3
Name	tubulin tyrosine ligase-like family member 3
Aliases	DKFZP434B103; HOTTL; tubulin tyrosine ligase-like family, member 3; tubulin--tyrosine ligase-like protein 3; ......
Chromosomal Location	3p25.3
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	Cytoplasm, cytoskeleton Cell projection, cilium Cytoplasm, cytoskeleton, cilium axoneme
Domain	PF03133 Tubulin-tyrosine ligase family
Function	Monoglycylase which modifies alpha- and beta-tubulin, generating side chains of glycine on the gamma-carboxyl groups of specific glutamate residues within the C-terminal tail of alpha- and beta-tubulin. Involved in the side-chain initiation step of the glycylation reaction by adding a single glycine chain to generate monoglycine side chains. Not involved in elongation step of the polyglycylation reaction.

> Gene Ontology [ TOP ]
Biological Process	GO:0000226 microtubule cytoskeleton organization GO:0001578 microtubule bundle formation GO:0010927 cellular component assembly involved in morphogenesis GO:0018094 protein polyglycylation GO:0030031 cell projection assembly GO:0035082 axoneme assembly GO:0042384 cilium assembly GO:0044782 cilium organization GO:0060271 cilium morphogenesis
Molecular Function	GO:0016874 ligase activity GO:0016879 ligase activity, forming carbon-nitrogen bonds GO:0016881 acid-amino acid ligase activity GO:0070735 protein-glycine ligase activity GO:0070736 protein-glycine ligase activity, initiating
Cellular Component	GO:0005874 microtubule GO:0005929 cilium GO:0005930 axoneme GO:0044441 ciliary part GO:0097014 ciliary plasm

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	TTLL3
Name	tubulin tyrosine ligase-like family member 3
Aliases	DKFZP434B103; HOTTL; tubulin tyrosine ligase-like family, member 3; tubulin--tyrosine ligase-like protein 3; ......
Chromosomal Location	3p25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TTLL3 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	TTLL3
Name	tubulin tyrosine ligase-like family member 3
Aliases	DKFZP434B103; HOTTL; tubulin tyrosine ligase-like family, member 3; tubulin--tyrosine ligase-like protein 3; ......
Chromosomal Location	3p25.3
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

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Statistical results of TTLL3 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	TTLL3
Name	tubulin tyrosine ligase-like family member 3
Aliases	DKFZP434B103; HOTTL; tubulin tyrosine ligase-like family, member 3; tubulin--tyrosine ligase-like protein 3; ......
Chromosomal Location	3p25.3
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 TTLL3 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	-0.401	0.156
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.89	0.255
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.048	0.943
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.225	0.558
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.043	0.988
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.565	0.88
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.166	0.656
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.336	0.754
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.662	0.549
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.438	0.767
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	1.142	0.563
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.103	0.298

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TTLL3 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	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
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	11.1	0	11.1	0.0181
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	11.1	0	11.1	0.0286
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	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	0	0	0	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	TTLL3
Name	tubulin tyrosine ligase-like family member 3
Aliases	DKFZP434B103; HOTTL; tubulin tyrosine ligase-like family, member 3; tubulin--tyrosine ligase-like protein 3; ......
Chromosomal Location	3p25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TTLL3. 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	TTLL3
Name	tubulin tyrosine ligase-like family member 3
Aliases	DKFZP434B103; HOTTL; tubulin tyrosine ligase-like family, member 3; tubulin--tyrosine ligase-like protein 3; ......
Chromosomal Location	3p25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TTLL3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TTLL3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TTLL3
Name	tubulin tyrosine ligase-like family member 3
Aliases	DKFZP434B103; HOTTL; tubulin tyrosine ligase-like family, member 3; tubulin--tyrosine ligase-like protein 3; ......
Chromosomal Location	3p25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TTLL3. 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	TTLL3
Name	tubulin tyrosine ligase-like family member 3
Aliases	DKFZP434B103; HOTTL; tubulin tyrosine ligase-like family, member 3; tubulin--tyrosine ligase-like protein 3; ......
Chromosomal Location	3p25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TTLL3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TTLL3
Name	tubulin tyrosine ligase-like family member 3
Aliases	DKFZP434B103; HOTTL; tubulin tyrosine ligase-like family, member 3; tubulin--tyrosine ligase-like protein 3; ......
Chromosomal Location	3p25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TTLL3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TTLL3
Name	tubulin tyrosine ligase-like family member 3
Aliases	DKFZP434B103; HOTTL; tubulin tyrosine ligase-like family, member 3; tubulin--tyrosine ligase-like protein 3; ......
Chromosomal Location	3p25.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TTLL3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting TTLL3.

ID	Name	Drug Type	Targets	#Targets
DB00277	Theophylline	Small Molecule	ADORA1, ADORA2A, ADORA2B, CPNE1, HDAC2, HM13, NOMO1, PARP1, PDE3A, ......	14

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