Protein:CTLA4 |
Protein Summary |
 Gene summary |
| Gene name: CTLA4 | ASpdb.0 ID: 1493 | Gene | Gene symbol | CTLA4 | Gene ID | 1493 |
| Gene name | cytotoxic T-lymphocyte associated protein 4 |
| Synonyms | ALPS5|CD|CD152|CELIAC3|CTLA-4|GRD4|GSE|IDDM12 |
| Cytomap | 2q33.2 |
| Type of gene | protein-coding |
| Description | cytotoxic T-lymphocyte protein 4celiac disease 3cytotoxic T lymphocyte associated antigen 4 short spliced formcytotoxic T-lymphocyte-associated serine esterase-4gluten-sensitive enteropathyinsulin-dependent diabetes mellitus 12ligand and transmembra |
| Modification date | 20240331 |
| UniProtAcc | P16410 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CTLA4 | GO:0005794 | Golgi apparatus | 15814706 |
| Gene | CTLA4 | GO:0009897 | external side of plasma membrane | 18641304 |
| Gene | CTLA4 | GO:0045334 | clathrin-coated endocytic vesicle | 15814706 |
| Gene | CTLA4 | GO:0045590 | negative regulation of regulatory T cell differentiation | 18641304 |
| Gene | CTLA4 | GO:0048471 | perinuclear region of cytoplasm | 15814706 |
| Gene | CTLA4 | GO:0098636 | protein complex involved in cell adhesion | 7544393 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P16410-1 | P16410-1_3osk_B.pdb | 3OSK | X-ray | 1.8 | B | 38 | 160 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P16410 | CTLA4 | P16410-1 | P16410-2 | 223 | 56 | 38 | 204 | Deletion | none | none | 37 | 37 |
| P16410 | CTLA4 | P16410-1 | P16410-3 | 223 | 58 | 38 | 204 | Deletion | none | none | 37 | 37 |
| P16410 | CTLA4 | P16410-1 | P16410-3 | 223 | 58 | 205 | 223 | Substitution | PPTEPECEKQFQPYFIPIN | KEKKPSYNRGLCENAPNRARM | 38 | 58 |
| P16410 | CTLA4 | P16410-1 | P16410-4 | 223 | 79 | 58 | 58 | Substitution | C | S | 58 | 58 |
| P16410 | CTLA4 | P16410-1 | P16410-4 | 223 | 79 | 59 | 204 | Deletion | none | none | 58 | 58 |
| P16410 | CTLA4 | P16410-1 | P16410-4 | 223 | 79 | 205 | 223 | Substitution | PPTEPECEKQFQPYFIPIN | KEKKPSYNRGLCENAPNRARM | 59 | 79 |
| P16410 | CTLA4 | P16410-1 | P16410-5 | 223 | 174 | 153 | 174 | Substitution | DPEPCPDSDFLLWILAAVSSGL | AKEKKPSYNRGLCENAPNRARM | 153 | 174 |
| P16410 | CTLA4 | P16410-1 | P16410-5 | 223 | 174 | 175 | 223 | Deletion | none | none | 174 | 174 |
| Multiple sequence alignment of our canonical and alternatively spliced CTLA4 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CTLA4 |
| UniProt-id | ENSG | ENST | ENSP |
| P16410-1 | ENSG00000163599.18 | ENST00000648405.2 | ENSP00000497102.1 |
| P16410-3 | ENSG00000163599.18 | ENST00000487393.1 | ENSP00000497319.1 |
| P16410-5 | ENSG00000163599.18 | ENST00000295854.10 | ENSP00000295854.6 |
| UniProt-id | NM ID | NP ID |
| P16410-1 | NM_005214.4 | NP_005205.2 |
| P16410-5 | NM_001037631.2 | NP_001032720.1 |
| Amino acid sequences of our canonical and alternatively spliced CTLA4 |
| accession_id | Protein sequence |
| P16410-1 | MACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYM MGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDFLLWILAAVSSGLFFYSFL |
| P16410-2 | |
| P16410-3 | |
| P16410-4 | |
| P16410-5 | MACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYM |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CTLA4 (go to UniProt):P16410 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P16410 | Topological domain | 36 | 161 | Note=Extracellular;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:28484017;Dbxref=PMID:28484017 | Type=Deletion;Start=38;End=204 |
| P16410 | Topological domain | 36 | 161 | Note=Extracellular;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:28484017;Dbxref=PMID:28484017 | Type=Deletion;Start=38;End=204 |
| P16410 | Topological domain | 36 | 161 | Note=Extracellular;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:28484017;Dbxref=PMID:28484017 | Type=Substitution;Start=58;End=58 |
| P16410 | Topological domain | 36 | 161 | Note=Extracellular;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:28484017;Dbxref=PMID:28484017 | Type=Deletion;Start=59;End=204 |
| P16410 | Topological domain | 36 | 161 | Note=Extracellular;Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:28484017;Dbxref=PMID:28484017 | Type=Substitution;Start=153;End=174 |
| P16410 | Transmembrane | 162 | 182 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=38;End=204 |
| P16410 | Transmembrane | 162 | 182 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=38;End=204 |
| P16410 | Transmembrane | 162 | 182 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=59;End=204 |
| P16410 | Transmembrane | 162 | 182 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=153;End=174 |
| P16410 | Transmembrane | 162 | 182 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=175;End=223 |
| P16410 | Topological domain | 183 | 223 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=38;End=204 |
| P16410 | Topological domain | 183 | 223 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=38;End=204 |
| P16410 | Topological domain | 183 | 223 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=205;End=223 |
| P16410 | Topological domain | 183 | 223 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=59;End=204 |
| P16410 | Topological domain | 183 | 223 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=205;End=223 |
| P16410 | Topological domain | 183 | 223 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=175;End=223 |
| P16410 | Domain | 39 | 140 | Note=Ig-like V-type | Type=Deletion;Start=38;End=204 |
| P16410 | Domain | 39 | 140 | Note=Ig-like V-type | Type=Deletion;Start=38;End=204 |
| P16410 | Domain | 39 | 140 | Note=Ig-like V-type | Type=Substitution;Start=58;End=58 |
| P16410 | Domain | 39 | 140 | Note=Ig-like V-type | Type=Deletion;Start=59;End=204 |
| P16410 | Region | 46 | 50 | Note=Homodimerization;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:21156796;Dbxref=PMID:21156796 | Type=Deletion;Start=38;End=204 |
| P16410 | Region | 46 | 50 | Note=Homodimerization;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:21156796;Dbxref=PMID:21156796 | Type=Deletion;Start=38;End=204 |
| P16410 | Region | 134 | 139 | Note=Important for interaction with CD80 and CD86;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28484017;Dbxref=PMID:28484017 | Type=Deletion;Start=38;End=204 |
| P16410 | Region | 134 | 139 | Note=Important for interaction with CD80 and CD86;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28484017;Dbxref=PMID:28484017 | Type=Deletion;Start=38;End=204 |
| P16410 | Region | 134 | 139 | Note=Important for interaction with CD80 and CD86;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28484017;Dbxref=PMID:28484017 | Type=Deletion;Start=59;End=204 |
| P16410 | Region | 150 | 155 | "Note=Homodimerization;Ontology_term=ECO:0000269 | ECO:0000269;evidence=ECO:0000269|PubMed:21156796 |
| P16410 | Region | 150 | 155 | "Note=Homodimerization;Ontology_term=ECO:0000269 | ECO:0000269;evidence=ECO:0000269|PubMed:21156796 |
| P16410 | Region | 150 | 155 | "Note=Homodimerization;Ontology_term=ECO:0000269 | ECO:0000269;evidence=ECO:0000269|PubMed:21156796 |
| P16410 | Region | 150 | 155 | "Note=Homodimerization;Ontology_term=ECO:0000269 | ECO:0000269;evidence=ECO:0000269|PubMed:21156796 |
Gene Isoform Structures and Expression Levels for CTLA4 |
| Gene structures of our canonical and alternative spliced genes of CTLA4 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P16410-1 |
| 3D view using mol* of P16410-2 |
| 3D view using mol* of P16410-3 |
| 3D view using mol* of P16410-4 |
| 3D view using mol* of P16410-5 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P16410-1 |
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| pLDDT distribution across the protein length of P16410-2 |
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| pLDDT distribution across the protein length of P16410-4 |
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| pLDDT distribution across the protein length of P16410-5 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P16410-1 |
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| Ramachandran plot of P16410-3 |
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| Ramachandran plot of P16410-4 |
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| Ramachandran plot of P16410-5 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P16410-1 | 0.548 | 24 | 0.476 | 36.358 | 0.662 | 0.571 | 0.855 | 0.484 | 1.003 | 0.482 | 1.535 | 63,64,65,66,133,135,136,137,138,139,140
|
| P16410-2 | 0.972 | 89 | 1.056 | 208.544 | 0.656 | 0.574 | 0.77 | 0.961 | 0.536 | 1.793 | 1.929 | 20,23,24,27,28,31,34,35,37,39,41,42,43,44,47,48,51 |
| P16410-4 | 0.392 | 8 | 0.266 | 41.16 | 0.826 | 0.574 | 0.794 | 0.035 | 1.057 | 0.033 | 0.274 | 42,43,44,45,46,47,55,57,59
|
| P16410-5 | 0.571 | 26 | 0.386 | 57.281 | 0.644 | 0.594 | 0.924 | 0 | 1.379 | 0 | 1.123 | 48,49,50,52,118,119,120,121,151,152,153,154
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Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P16410-1_P16410-1_3osk_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P16410-1_3osk_B_P16410-2.pdb |
| 3D view using mol* of P16410-1_3osk_B_P16410-3.pdb |
| 3D view using mol* of P16410-1_3osk_B_P16410-4.pdb |
| 3D view using mol* of P16410-1_3osk_B_P16410-5.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P16410-1_P16410-2.pdb |
| 3D view using mol* of P16410-1_P16410-3.pdb |
| 3D view using mol* of P16410-1_P16410-4.pdb |
| 3D view using mol* of P16410-1_P16410-5.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P16410-1_vs_P16410-2.png |
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| ./stats/secondary_structure/figure/P16410-1_vs_P16410-3.png |
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| ./stats/secondary_structure/figure/P16410-1_vs_P16410-4.png |
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| ./stats/secondary_structure/figure/P16410-1_vs_P16410-5.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P16410-1_vs_P16410-2.png |
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| ./stats/relative_asa/P16410-1_vs_P16410-3.png |
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| ./stats/relative_asa/P16410-1_vs_P16410-4.png |
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| ./stats/relative_asa/P16410-1_vs_P16410-5.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P16410 | Region | 134 | 139 | Note=Important for interaction with CD80 and CD86;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28484017;Dbxref=PMID:28484017 | Type=Deletion;Start=38;End=204 |
| P16410 | Region | 134 | 139 | Note=Important for interaction with CD80 and CD86;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28484017;Dbxref=PMID:28484017 | Type=Deletion;Start=38;End=204 |
| P16410 | Region | 134 | 139 | Note=Important for interaction with CD80 and CD86;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28484017;Dbxref=PMID:28484017 | Type=Deletion;Start=59;End=204 |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to CTLA4 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P16410 | CTLA4 | DB11771 | Tremelimumab | approved, investigational | inhibitor, antibody |
| P16410 | CTLA4 | DB06186 | Ipilimumab | approved | inhibitor, antibody |
| P16410 | CTLA4 | DB01281 | Abatacept | approved | inhibitor |
Related Diseases to CTLA4 |
| Previous studies relating to the alternative splicing of CTLA4 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CTLA4 | 17384200 | CTLA-4 polymorphisms and clinical outcome after allogeneic stem cell transplantation from HLA-identical sibling donors. | CTLA-4 is an inhibitory molecule that down-regulates T-cell activation. Although polymorphisms at CTLA-4 have been correlated with autoimmune diseases their association with clinical outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has yet to be explored. A total of 5 CTLA-4 single-nucleotide polymorphisms were genotyped on 536 HLA-identical sibling donors of allo-HSC transplants. Genotypes were tested for an association with patients' posttransplantation outcomes. The effect of the polymorphisms on cytotoxic T-lymphocyte antigen 4 (CTLA-4) mRNA and protein production were determined in 60 healthy control participants. We observed a reduction in the mRNA expression of the soluble CTLA-4 isoform in the presence of a G allele at CT60 and +49. Patients receiving stem cells from a donor with at least 1 G allele in position CT60 had worse overall survival (56.2% vs 69.8% at 5 years; P = .001; hazard ratio [HR], 3.80; 95% confidence interval [CI], 1.75-8.22), due to a higher risk of relapse (P = .049; HR, 1.71; 95% CI, 1.00-2.93). Acute graft-versus-host disease (aGVHD) was more frequent in patients receiving CT60 AA stem cells (P = .033; HR, 1.54; 95% CI, 1.03-2.29). This is the first study to report an association between polymorphisms at CTLA-4 and clinical outcome after allo-HSCT. The CT60 genotype influences relapse and aGVHD, probably due to its action on CTLA-4 alternative splicing. | D006086 | Graft vs Host Disease |
| CTLA4 | 18088253 | Two SNPs in the promoter region of the CTLA-4 gene affect binding of transcription factors and are associated with human myasthenia gravis. | The molecular mechanisms underlying the regulation of the CD152 (CTLA-4) gene are largely unknown. Two single nucleotide polymorphisms (SNPs) located in the promoter region are suspected to contribute to the pathogenesis of myasthenia gravis (MG) through regulation of gene expression. SETTING, SUBJECTS AND DESIGN: One hundred and sixty-five unrelated Swedish-Caucasian patients with MG (103 females and 62 males, age 17 to 92 years) and 148 ethnically matched healthy individuals were studied. Gene typing of two SNPs (T/C(-1772) and A/G(-1661)) and quantification of soluble CD152 were performed in the patients. Besides the association studies, the function of these two SNPs is characterized. | D009157 | Myasthenia Gravis |
| CTLA4 | 18595775 | Identification of CTLA-4 isoforms produced by alternative splicing and their association with myasthenia gravis. | Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness induced by autoantibodies against the acetylcholine receptor. CTLA-4 (CD152) plays an inhibitory role in the immune response and has been suggested to be involved in the pathophysiology of MG. In this study, we focused on alternative CTLA-4 mRNA expression in PBMCs from MG patients. We defined two new isoforms of CTLA-4 mRNA that arise due to alternative splicing. By semi-quantitative RT-PCR analysis, we observed a lower expression of sCTLA-4 mRNA relative to the membrane form in MG patients. In addition, the MG patients had lower levels of sCTLA-4 mRNA in PBMCs compared to healthy controls, as assessed by real-time PCR. One of the spliced isoforms (LCTLA-4) was more prevalent in MG patients compared to healthy controls. The alternative splicing was not associated with sex, thymectomy, serum levels of anti-AChR, immunosuppressive treatment or the four CTLA-4 gene polymorphisms analyzed. This study reveals an abnormal spectrum of mRNA expression of CTLA-4 in MG patients, which marks the importance of studying gene expression of alternative splicing. | D009157 | Myasthenia Gravis |
| CTLA4 | 19570209 | Increased production of soluble CTLA-4 in patients with spondylarthropathies correlates with disease activity. | Spondylarthropathies (SpA) are characterized by abnormal immune responses including T cell activation. Cytotoxic T lymphocyte associated molecule-4 (CTLA-4) is involved in down-regulating immune responses. A soluble form of CTLA-4 (sCTLA-4), resulting from an alternative splicing, has been identified and was found increased in several autoimmune diseases. Here, we evaluated circulating levels of sCTLA-4 as a marker of immune dysregulation in SpA. Intracellular CTLA-4 and levels of CTLA-4 transcript expression in peripheral blood lymphocytes (PBL) were also studied. | D025242 | Spondylarthropathies |
Clinically important variants in CTLA4 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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