Protein:KLK3 |
Protein Summary |
 Gene summary |
| Gene name: KLK3 | ASpdb.0 ID: 354 | Gene | Gene symbol | KLK3 | Gene ID | 354 |
| Gene name | kallikrein related peptidase 3 |
| Synonyms | APS|KLK2A1|PSA|hK3 |
| Cytomap | 19q13.33 |
| Type of gene | protein-coding |
| Description | prostate-specific antigenP-30 antigengamma-seminoproteinkallikrein-3semenogelaseseminin |
| Modification date | 20240305 |
| UniProtAcc | P07288 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | KLK3 | GO:0002803 | positive regulation of antibacterial peptide production | 18714013 |
| Gene | KLK3 | GO:0004175 | endopeptidase activity | 18714013 |
| Gene | KLK3 | GO:0005615 | extracellular space | 8665956 |
| Gene | KLK3 | GO:0032991 | protein-containing complex | 8665956 |
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 |
| P07288-1 | P07288-1_2zch_P.pdb | 2ZCH | X-ray | 2.83 | P | 25 | 261 |
| 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 |
| P07288 | KLK3 | P07288-1 | P07288-2 | 261 | 238 | 211 | 261 | Substitution | GDSGGPLVCNGVLQGITSWGSEPCALPERPSLYTKVVHYRKWIKDTIVANP | WVILITELTMPALPMVLHGSLVPWRGGV | 211 | 238 |
| P07288 | KLK3 | P07288-1 | P07288-3 | 261 | 218 | 69 | 69 | Substitution | N | K | 69 | 69 |
| P07288 | KLK3 | P07288-1 | P07288-3 | 261 | 218 | 70 | 112 | Deletion | none | none | 69 | 69 |
| P07288 | KLK3 | P07288-1 | P07288-4 | 261 | 69 | 69 | 69 | Substitution | N | K | 69 | 69 |
| P07288 | KLK3 | P07288-1 | P07288-4 | 261 | 69 | 70 | 261 | Deletion | none | none | 69 | 69 |
| P07288 | KLK3 | P07288-1 | P07288-5 | 261 | 227 | 211 | 260 | Substitution | GDSGGPLVCNGVLQGITSWGSEPCALPERPSLYTKVVHYRKWIKDTIVAN | VSHPYSQDLEGKGEWG | 211 | 226 |
| Multiple sequence alignment of our canonical and alternatively spliced KLK3 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of KLK3 |
| UniProt-id | ENSG | ENST | ENSP |
| P07288-1 | ENSG00000142515.16 | ENST00000326003.7 | ENSP00000314151.1 |
| P07288-2 | ENSG00000142515.16 | ENST00000360617.7 | ENSP00000353829.2 |
| P07288-3 | ENSG00000142515.16 | ENST00000595952.5 | ENSP00000471155.1 |
| P07288-5 | ENSG00000142515.16 | ENST00000593997.5 | ENSP00000472907.1 |
| UniProt-id | NM ID | NP ID |
| P07288-1 | NM_001648.2 | NP_001639.1 |
| P07288-2 | NM_001030047.1 | NP_001025218.1 |
| P07288-3 | NM_001030048.1 | NP_001025219.1 |
| Amino acid sequences of our canonical and alternatively spliced KLK3 |
| accession_id | Protein sequence |
| P07288-1 | MWVPVVFLTLSVTWIGAAPLILSRIVGGWECEKHSQPWQVLVASRGRAVCGGVLVHPQWVLTAAHCIRNKSVILLGRHSLFHPEDTGQVF QVSHSFPHPLYDMSLLKNRFLRPGDDSSHDLMLLRLSEPAELTDAVKVMDLPTQEPALGTTCYASGWGSIEPEEFLTPKKLQCVDLHVIS |
| P07288-2 | MWVPVVFLTLSVTWIGAAPLILSRIVGGWECEKHSQPWQVLVASRGRAVCGGVLVHPQWVLTAAHCIRNKSVILLGRHSLFHPEDTGQVF QVSHSFPHPLYDMSLLKNRFLRPGDDSSHDLMLLRLSEPAELTDAVKVMDLPTQEPALGTTCYASGWGSIEPEEFLTPKKLQCVDLHVIS |
| P07288-3 | MWVPVVFLTLSVTWIGAAPLILSRIVGGWECEKHSQPWQVLVASRGRAVCGGVLVHPQWVLTAAHCIRKPGDDSSHDLMLLRLSEPAELT DAVKVMDLPTQEPALGTTCYASGWGSIEPEEFLTPKKLQCVDLHVISNDVCAQVHPQKVTKFMLCAGRWTGGKSTCSGDSGGPLVCNGVL |
| P07288-4 | |
| P07288-5 | MWVPVVFLTLSVTWIGAAPLILSRIVGGWECEKHSQPWQVLVASRGRAVCGGVLVHPQWVLTAAHCIRNKSVILLGRHSLFHPEDTGQVF QVSHSFPHPLYDMSLLKNRFLRPGDDSSHDLMLLRLSEPAELTDAVKVMDLPTQEPALGTTCYASGWGSIEPEEFLTPKKLQCVDLHVIS |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| KLK3 (go to UniProt):P07288 |
| 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 |
| P07288 | Domain | 25 | 258 | Note=Peptidase S1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00274 | Type=Substitution;Start=211;End=261 |
| P07288 | Domain | 25 | 258 | Note=Peptidase S1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00274 | Type=Substitution;Start=69;End=69 |
| P07288 | Domain | 25 | 258 | Note=Peptidase S1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00274 | Type=Deletion;Start=70;End=112 |
| P07288 | Domain | 25 | 258 | Note=Peptidase S1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00274 | Type=Substitution;Start=69;End=69 |
| P07288 | Domain | 25 | 258 | Note=Peptidase S1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00274 | Type=Deletion;Start=70;End=261 |
| P07288 | Domain | 25 | 258 | Note=Peptidase S1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00274 | Type=Substitution;Start=211;End=260 |
Gene Isoform Structures and Expression Levels for KLK3 |
| Gene structures of our canonical and alternative spliced genes of KLK3 * 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 P07288-1 |
| 3D view using mol* of P07288-2 |
| 3D view using mol* of P07288-3 |
| 3D view using mol* of P07288-4 |
| 3D view using mol* of P07288-5 |
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 P07288-1 |
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| pLDDT distribution across the protein length of P07288-2 |
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| pLDDT distribution across the protein length of P07288-3 |
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| pLDDT distribution across the protein length of P07288-4 |
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| pLDDT distribution across the protein length of P07288-5 |
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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 P07288-1 |
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| Ramachandran plot of P07288-2 |
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| Ramachandran plot of P07288-4 |
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| Ramachandran plot of P07288-5 |
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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 |
| P07288-1 | 1.03 | 178 | 1.024 | 474.026 | 0.49 | 0.743 | 1.008 | 0.63 | 1.109 | 0.568 | 1.136 | 65,68,101,105,106,108,109,110,111,117,120,159,162, 163,164,165,188,189,190,207,208,209,210,213,227,22 8,229,230,231,232,234,235,236,239,241 |
| P07288-2 | 1.061 | 128 | 1.136 | 417.431 | 0.661 | 0.676 | 0.821 | 1.159 | 0.644 | 1.801 | 1.442 | 38,53,61,121,137,138,139,140,141,142,143,144,145,1 46,147,150,151,152,153,195,196,197,215,216,218,225 ,226,227,228,229 |
| P07288-3 | 0.889 | 76 | 0.898 | 193.109 | 0.679 | 0.644 | 0.9 | 0.562 | 0.944 | 0.595 | 1.042 | 65,116,119,120,122,145,146,147,164,165,166,167,168 ,169,170,184,185,186,187,188,189,191,192,196,197,1 98 |
| P07288-4 | 0.432 | 8 | 0.36 | 18.179 | 0.862 | 0.537 | 0.696 | 0.42 | 0.699 | 0.601 | 1.049 | 23,25,28,29,30,31
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| P07288-5 | 1.061 | 535 | 1.085 | 1398.068 | 0.47 | 0.77 | 0.988 | 0.809 | 0.972 | 0.832 | 1.209 | 18,19,20,21,22,23,24,25,36,38,39,41,43,46,47,48,49 ,50,51,52,53,61,62,63,65,68,72,74,77,80,81,101,105 ,106,108,109,110,111,115,116,117,118,119,120,121,1 39,141,142,144,145,146,148,152,153,154,155,156,157 ,158,159,167,176,178,179,180,181,182,187,188,189,1 90,191,192,194,195,196,197,198,199,208,209,210,211 ,212,213,224,225,226,227 |
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 P07288-1_P07288-1_2zch_P.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P07288-1_2zch_P_P07288-2.pdb |
| 3D view using mol* of P07288-1_2zch_P_P07288-3.pdb |
| 3D view using mol* of P07288-1_2zch_P_P07288-4.pdb |
| 3D view using mol* of P07288-1_2zch_P_P07288-5.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P07288-1_P07288-2.pdb |
| 3D view using mol* of P07288-1_P07288-3.pdb |
| 3D view using mol* of P07288-1_P07288-4.pdb |
| 3D view using mol* of P07288-1_P07288-5.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P07288-1_vs_P07288-2.png |
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| ./stats/secondary_structure/figure/P07288-1_vs_P07288-3.png |
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| ./stats/secondary_structure/figure/P07288-1_vs_P07288-4.png |
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| ./stats/secondary_structure/figure/P07288-1_vs_P07288-5.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P07288-1_vs_P07288-2.png |
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| ./stats/relative_asa/P07288-1_vs_P07288-3.png |
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| ./stats/relative_asa/P07288-1_vs_P07288-4.png |
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| ./stats/relative_asa/P07288-1_vs_P07288-5.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 KLK3 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P07288 | KLK3 | DB04839 | Cyproterone acetate | approved, investigational | |
| P07288 | KLK3 | DB02998 | Metribolone | experimental | activator |
| P07288 | KLK3 | DB00834 | Mifepristone | approved, investigational | |
| P07288 | KLK3 | DB16019 | Gallium Ga-68 gozetotide | approved | binder |
| P07288 | KLK3 | DB16778 | Lutetium Lu-177 vipivotide tetraxetan | approved | binder |
Related Diseases to KLK3 |
| Previous studies relating to the alternative splicing of KLK3 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| KLK3 | 2458104 | Molecular cloning and characterization of novel prostate antigen cDNA's. | Three different prostate antigen cDNA's were isolated from a PC 82 prostate tumor cDNA library. PA 75 has a size of 1.4 kb and contains the almost complete information for the 35 kD prostate antigen preproprotein. The 1.6 kb PA 525 cDNA lacks about 0.2 kb of the 3'-non coding region and contains an additional internal 0.4 kb fragment as a result of alternative splicing. PA 424 represents a 0.6 kb variant of PA 75. It contains a 0.15 kb internal fragment and a poly(A) tail preceded by an AAGAAA motive at the 3'-end. The predicted protein products of PA 525 and PA 424 will be different from PA 75 at the C-terminal end. In RNA preparations of two human prostate tumors (PC 82 and PC EW) seven different prostate antigen transcripts can be detected ranging in size from 0.5 kb to 5.6 kb. PA 75 cDNA represents the major 1.5 kb mRNA. PA 424 correlates with a 0.9 kb transcript and PA 525 with a 1.9 kb mRNA species. | D011471 | Prostatic Neoplasms |
| KLK3 | 10646852 | A novel form of prostate-specific antigen transcript produced by alternative splicing. | Molecular characterization of prostate-specific antigen (PSA) has not been well elucidated, despite a great deal of clinical study. We examined the heterogeneity of PSA using reverse transcription-PCR and direct sequencing. A novel, alternatively spliced variant of the PSA transcript was found in prostate cancer (PC), as well as in benign prostatic tissue. This alternative splicing leads to the deletion of 44 amino acid residues (amino acids 45-88) from mature PSA, resulting in the loss of asparagine 45, which is a binding site for a carbohydrate chain. By these nested reverse transcription-PCR systems, this novel, alternatively spliced PSA gene was recognized in 13 of 18 (72.2%) cases with noncancerous prostate tissue, 4 of 5 (80.0%) PC cases, and 3 of 12 (25.0%) blood samples from PC patients (noncancerous prostate tissue group versus blood sample group, P = 0.011). At present, the biological significance of this alternative splicing remains to be established. | D011470 | Prostatic Hyperplasia |
| KLK3 | 10646852 | A novel form of prostate-specific antigen transcript produced by alternative splicing. | Molecular characterization of prostate-specific antigen (PSA) has not been well elucidated, despite a great deal of clinical study. We examined the heterogeneity of PSA using reverse transcription-PCR and direct sequencing. A novel, alternatively spliced variant of the PSA transcript was found in prostate cancer (PC), as well as in benign prostatic tissue. This alternative splicing leads to the deletion of 44 amino acid residues (amino acids 45-88) from mature PSA, resulting in the loss of asparagine 45, which is a binding site for a carbohydrate chain. By these nested reverse transcription-PCR systems, this novel, alternatively spliced PSA gene was recognized in 13 of 18 (72.2%) cases with noncancerous prostate tissue, 4 of 5 (80.0%) PC cases, and 3 of 12 (25.0%) blood samples from PC patients (noncancerous prostate tissue group versus blood sample group, P = 0.011). At present, the biological significance of this alternative splicing remains to be established. | D011471 | Prostatic Neoplasms |
Clinically important variants in KLK3 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Gln39Leu | Benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Gln39Leu | Benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Glu32Lys | Benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Glu32Lys | Benign |
| P07288 | P07288-1 | KLK3 | Duplication | p.Val40fs | not provided |
| P07288 | P07288-1 | KLK3 | Duplication | p.Val40fs | not provided |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Val258Leu | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Val258Leu | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Gly230Asp | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Gly230Asp | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Arg201Cys | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Arg201Cys | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Cys66Arg | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Cys66Arg | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Asp182Val | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Asp182Val | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Val49Leu | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Val49Leu | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Gly221Arg | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Gly221Arg | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Ala135Thr | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Ala135Thr | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Pro37His | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Pro37His | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Ala43Asp | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Ala43Asp | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.His78Gln | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.His78Gln | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Thr13Met | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Thr13Met | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Arg45His | Likely benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Arg45His | Likely benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Cys198Phe | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Cys198Phe | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Arg24Gln | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Arg24Gln | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Arg201His | Likely benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Arg201His | Likely benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Thr227Met | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Thr227Met | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Val55Gly | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Val55Gly | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.His56Arg | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.His56Arg | Uncertain significance |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Ser210Trp | Likely benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Ser210Trp | Likely benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Leu132Ile | Benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Leu132Ile | Benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Arg125Cys | Benign |
| P07288 | P07288-1 | KLK3 | single nucleotide variant | p.Arg125Cys | Benign |
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