Protein:TGM2 |
Protein Summary |
 Gene summary |
| Gene name: TGM2 | ASpdb.0 ID: 7052 | Gene | Gene symbol | TGM2 | Gene ID | 7052 |
| Gene name | transglutaminase 2 |
| Synonyms | G(h)|TG(C)|TGC|hTG2|tTG |
| Cytomap | 20q11.23 |
| Type of gene | protein-coding |
| Description | protein-glutamine gamma-glutamyltransferase 2C polypeptide, protein-glutamine-gamma-glutamyltransferaseTGase CTGase HTGase IITGase-2erythrocyte transglutaminaseheart G alpha(h)hhG alpha(h)isopeptidase TGM2protein G alpha(h)protein-glutamine dea |
| Modification date | 20240407 |
| UniProtAcc | P21980 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | TGM2 | GO:0000785 | chromatin | 9575137 |
| Gene | TGM2 | GO:0000786 | nucleosome | 30867594|32273471 |
| Gene | TGM2 | GO:0003810 | protein-glutamine gamma-glutamyltransferase activity | 7649299|9252372|12506096|23941696 |
| Gene | TGM2 | GO:0005509 | calcium ion binding | 23941696 |
| Gene | TGM2 | GO:0005525 | GTP binding | 7649299 |
| Gene | TGM2 | GO:0005634 | nucleus | 9575137 |
| Gene | TGM2 | GO:0005739 | mitochondrion | 24349085 |
| Gene | TGM2 | GO:0005829 | cytosol | 9575137|24349085 |
| Gene | TGM2 | GO:0005886 | plasma membrane | 2578891 |
| Gene | TGM2 | GO:0010467 | gene expression | 30867594 |
| Gene | TGM2 | GO:0014046 | dopamine secretion | 32273471 |
| Gene | TGM2 | GO:0018149 | peptide cross-linking | 9252372|12506096|23941696|30458214 |
| Gene | TGM2 | GO:0018277 | protein deamination | 9623982|20547769 |
| Gene | TGM2 | GO:0031012 | extracellular matrix | 12506096 |
| Gene | TGM2 | GO:0042981 | regulation of apoptotic process | 9252372 |
| Gene | TGM2 | GO:0043277 | apoptotic cell clearance | 19628791 |
| Gene | TGM2 | GO:0050568 | protein-glutamine glutaminase activity | 9623982|20547769 |
| Gene | TGM2 | GO:0050769 | positive regulation of neurogenesis | 30867594 |
| Gene | TGM2 | GO:0071314 | cellular response to cocaine | 32273471 |
| Gene | TGM2 | GO:0120295 | histone serotonyltransferase activity | 30867594 |
| Gene | TGM2 | GO:0120297 | histone dopaminyltransferase activity | 32273471 |
| Gene | TGM2 | GO:0120299 | peptide histaminyltransferase activity | 23797785 |
| Gene | TGM2 | GO:1903351 | cellular response to dopamine | 32273471 |
| Gene | TGM2 | GO:1904015 | cellular response to serotonin | 30867594 |
| Gene | TGM2 | GO:2000425 | regulation of apoptotic cell clearance | 7935379 |
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 |
| P21980-1 | P21980-1_6a8p_A.pdb | 6A8P | X-ray | 2.54 | A | 1 | 687 |
| 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 |
| P21980 | TGM2 | P21980-1 | P21980-2 | 687 | 548 | 539 | 548 | Substitution | EKSVPLCILY | GKALCSWSIC | 539 | 548 |
| P21980 | TGM2 | P21980-1 | P21980-2 | 687 | 548 | 549 | 687 | Deletion | none | none | 548 | 548 |
| P21980 | TGM2 | P21980-1 | P21980-3 | 687 | 349 | 287 | 349 | Substitution | VLRCLGIPTRVVTNYNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQP | GELHAGMWVMSPGRGHEEHWSRNQDIPALVLPPATNTLNALCGLEPVTTLSGPLSNSHPSSGC | 287 | 349 |
| P21980 | TGM2 | P21980-1 | P21980-3 | 687 | 349 | 350 | 687 | Deletion | none | none | 349 | 349 |
| Multiple sequence alignment of our canonical and alternatively spliced TGM2 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of TGM2 |
| UniProt-id | ENSG | ENST | ENSP |
| P21980-1 | ENSG00000198959.12 | ENST00000361475.7 | ENSP00000355330.2 |
| UniProt-id | NM ID | NP ID |
| P21980-1 | NM_001323316.1 | NP_001310245.1 |
| P21980-1 | NM_004613.3 | NP_004604.2 |
| P21980-1 | XM_011529028.1 | XP_011527330.1 |
| P21980-2 | NM_198951.2 | NP_945189.1 |
| Amino acid sequences of our canonical and alternatively spliced TGM2 |
| accession_id | Protein sequence |
| P21980-1 | MAEELVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFSVVTGPAPSQEAGTKARFPLRDAVEEGDWTA TVVDQQDCTLSLQLTTPANAPIGLYRLSLEASTGYQGSSFVLGHFILLFNAWCPADAVYLDSEEERQEYVLTQQGFIYQGSAKFIKNIPW NFGQFEDGILDICLILLDVNPKFLKNAGRDCSRRSSPVYVGRVVSGMVNCNDDQGVLLGRWDNNYGDGVSPMSWIGSVDILRRWKNHGCQ RVKYGQCWVFAAVACTVLRCLGIPTRVVTNYNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVHKSINRSLIVGLKISTKSVGRDEREDITHTYKYPEGSS EEREAFTRANHLNKLAEKEETGMAMRIRVGQSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKYLLNLNLEPFSEK SVPLCILYEKYRDCLTESNLIKVRALLVEPVINSYLLAERDLYLENPEIKIRILGEPKQKRKLVAEVSLQNPLPVALEGCTFTVEGAGLT |
| P21980-2 | MAEELVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFSVVTGPAPSQEAGTKARFPLRDAVEEGDWTA TVVDQQDCTLSLQLTTPANAPIGLYRLSLEASTGYQGSSFVLGHFILLFNAWCPADAVYLDSEEERQEYVLTQQGFIYQGSAKFIKNIPW NFGQFEDGILDICLILLDVNPKFLKNAGRDCSRRSSPVYVGRVVSGMVNCNDDQGVLLGRWDNNYGDGVSPMSWIGSVDILRRWKNHGCQ RVKYGQCWVFAAVACTVLRCLGIPTRVVTNYNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVHKSINRSLIVGLKISTKSVGRDEREDITHTYKYPEGSS EEREAFTRANHLNKLAEKEETGMAMRIRVGQSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKYLLNLNLEPFSGK |
| P21980-3 | MAEELVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFSVVTGPAPSQEAGTKARFPLRDAVEEGDWTA TVVDQQDCTLSLQLTTPANAPIGLYRLSLEASTGYQGSSFVLGHFILLFNAWCPADAVYLDSEEERQEYVLTQQGFIYQGSAKFIKNIPW NFGQFEDGILDICLILLDVNPKFLKNAGRDCSRRSSPVYVGRVVSGMVNCNDDQGVLLGRWDNNYGDGVSPMSWIGSVDILRRWKNHGCQ |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| TGM2 (go to UniProt):P21980 |
| 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 |
Gene Isoform Structures and Expression Levels for TGM2 |
| Gene structures of our canonical and alternative spliced genes of TGM2 * 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 P21980-1 |
| 3D view using mol* of P21980-2 |
| 3D view using mol* of P21980-3 |
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 P21980-1 |
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| pLDDT distribution across the protein length of P21980-2 |
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| pLDDT distribution across the protein length of P21980-3 |
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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 P21980-1 |
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| Ramachandran plot of P21980-2 |
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| Ramachandran plot of P21980-3 |
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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 |
| P21980-1 | 1.082 | 149 | 0.92 | 361.522 | 0.431 | 0.821 | 1.19 | 0.092 | 1.574 | 0.059 | 0.843 | 398,399,400,401,402,403,414,415,416,417,418,419,42 0,421,422,447,448,452,453,456,457,461,462,464,465, 466,467,468,577,579 |
| P21980-2 | 1.102 | 174 | 1.167 | 963.487 | 0.695 | 0.745 | 0.787 | 0.92 | 0.676 | 1.361 | 0.682 | 171,172,173,301,302,317,320,321,322,323,330,331,33 2,333,403,405,415,416,417,418,419,420,471,473,474, 475,476,477,489,491,493,495,505,506,507,508,509,51 0,511,512,518,520,525,526,527,528,532,534,544,545, 547 |
| P21980-3 | 1.046 | 273 | 1.07 | 913.409 | 0.566 | 0.751 | 0.974 | 0.721 | 0.984 | 0.733 | 1.034 | 148,149,150,151,155,158,159,160,161,162,164,165,16 6,167,168,169,175,182,184,229,231,239,241,277,278, 280,281,282,285,289,293,294,295,296,297,298,299,30 0,304,305,306,307,308,309,310,312,313,314,315,316, 317,318,319,320,324,327,332,333,334 |
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 P21980-1_P21980-1_6a8p_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P21980-1_6a8p_A_P21980-2.pdb |
| 3D view using mol* of P21980-1_6a8p_A_P21980-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P21980-1_P21980-2.pdb |
| 3D view using mol* of P21980-1_P21980-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P21980-1_vs_P21980-2.png |
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| ./stats/secondary_structure/figure/P21980-1_vs_P21980-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P21980-1_vs_P21980-2.png |
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| ./stats/relative_asa/P21980-1_vs_P21980-3.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to TGM2 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P21980 | TGM2 | DB11254 | Hexylresorcinol | approved | inhibitor |
| P21980 | TGM2 | DB04315 | Guanosine-5'-Diphosphate | experimental |
Related Diseases to TGM2 |
| Previous studies relating to the alternative splicing of TGM2 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| TGM2 | 22089883 | Expression of transglutaminase-2 isoforms in normal human tissues and cancer cell lines: dysregulation of alternative splicing in cancer. | The multiple enzymatic activities and functions of transglutaminase type 2 (TG2) may be attributed to alternative TG2 molecules produced by differential splicing of TG2 mRNA. Different RNA transcripts of the human TG2 gene (TGM2) have been identified, but the expression of TG2 multiple transcripts has never been systematically addressed. We have confirmed and rationalized the main TG2 variants and developed a screening assay for the detection of alternative splicing of TG2, based on real-time reverse-transcription PCR. We have quantified the multiple TG2 transcripts in a wide range of normal tissues and in cancer cell lines from four different sites of origin. Our data show a significant correlation in the expression of canonical and alternative TG2 isoforms in normal human tissue, but differences in alternative splicing of TG2 in cancer cell lines, suggesting that in cancer cells the alternative splicing of TG2 is a more active process. | D000230 | Adenocarcinoma |
| TGM2 | 22089883 | Expression of transglutaminase-2 isoforms in normal human tissues and cancer cell lines: dysregulation of alternative splicing in cancer. | The multiple enzymatic activities and functions of transglutaminase type 2 (TG2) may be attributed to alternative TG2 molecules produced by differential splicing of TG2 mRNA. Different RNA transcripts of the human TG2 gene (TGM2) have been identified, but the expression of TG2 multiple transcripts has never been systematically addressed. We have confirmed and rationalized the main TG2 variants and developed a screening assay for the detection of alternative splicing of TG2, based on real-time reverse-transcription PCR. We have quantified the multiple TG2 transcripts in a wide range of normal tissues and in cancer cell lines from four different sites of origin. Our data show a significant correlation in the expression of canonical and alternative TG2 isoforms in normal human tissue, but differences in alternative splicing of TG2 in cancer cell lines, suggesting that in cancer cells the alternative splicing of TG2 is a more active process. | D011471 | Prostatic Neoplasms |
| TGM2 | 22320917 | Regulation of transglutaminase-mediated hepatic cell death in alcoholic steatohepatitis and non-alcoholic steatohepatitis. | Transglutaminase 2 (TG2), catalyzing crosslinking between lysine and glutamine residues, is involved in many liver diseases. We previously reported that TG2, induced in the nucleus of ethanol- or free fatty acids (FFAs)-treated hepatic cells, crosslinks and inactivates a transcription factor Sp1, leading to reduced expression of c-Met and thereby caspase independent hepatic apoptosis in culture systems, animal models, and both alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) patients. FFAs increase endoplasmic reticulum (ER) stress, NFkB activation and nuclear TG2 (nTG2) through pancreatic ER kinase (PERK)-dependent pathway, whereas ethanol induces nTG2 via retinoid signaling. However, the molecular mechanism by which ethanol/FFAs induce nuclear localization of TG2 has been unclear. | D005234 | Fatty Liver |
| TGM2 | 22320917 | Regulation of transglutaminase-mediated hepatic cell death in alcoholic steatohepatitis and non-alcoholic steatohepatitis. | Transglutaminase 2 (TG2), catalyzing crosslinking between lysine and glutamine residues, is involved in many liver diseases. We previously reported that TG2, induced in the nucleus of ethanol- or free fatty acids (FFAs)-treated hepatic cells, crosslinks and inactivates a transcription factor Sp1, leading to reduced expression of c-Met and thereby caspase independent hepatic apoptosis in culture systems, animal models, and both alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) patients. FFAs increase endoplasmic reticulum (ER) stress, NFkB activation and nuclear TG2 (nTG2) through pancreatic ER kinase (PERK)-dependent pathway, whereas ethanol induces nTG2 via retinoid signaling. However, the molecular mechanism by which ethanol/FFAs induce nuclear localization of TG2 has been unclear. | D005235 | Fatty Liver, Alcoholic |
| TGM2 | 22320917 | Regulation of transglutaminase-mediated hepatic cell death in alcoholic steatohepatitis and non-alcoholic steatohepatitis. | Transglutaminase 2 (TG2), catalyzing crosslinking between lysine and glutamine residues, is involved in many liver diseases. We previously reported that TG2, induced in the nucleus of ethanol- or free fatty acids (FFAs)-treated hepatic cells, crosslinks and inactivates a transcription factor Sp1, leading to reduced expression of c-Met and thereby caspase independent hepatic apoptosis in culture systems, animal models, and both alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) patients. FFAs increase endoplasmic reticulum (ER) stress, NFkB activation and nuclear TG2 (nTG2) through pancreatic ER kinase (PERK)-dependent pathway, whereas ethanol induces nTG2 via retinoid signaling. However, the molecular mechanism by which ethanol/FFAs induce nuclear localization of TG2 has been unclear. | D065626 | Non-alcoholic Fatty Liver Disease |
Clinically important variants in TGM2 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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