Protein:HMBS |
Protein Summary |
 Gene summary |
| Gene name: HMBS | ASpdb.0 ID: 3145 | Gene | Gene symbol | HMBS | Gene ID | 3145 |
| Gene name | hydroxymethylbilane synthase |
| Synonyms | ENCEP|LENCEP|PBG-D|PBGD|PORC|UPS |
| Cytomap | 11q23.3 |
| Type of gene | protein-coding |
| Description | porphobilinogen deaminaseporphyria, acute; Chester typepre-uroporphyrinogen synthaseuroporphyrinogen I synthaseuroporphyrinogen I synthetase |
| Modification date | 20240403 |
| UniProtAcc | P08397 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | HMBS | GO:0004418 | hydroxymethylbilane synthase activity | 18004775|18936296 |
| Gene | HMBS | GO:0006783 | heme biosynthetic process | 18936296 |
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 |
| P08397-1 | P08397-1_7aak_A.pdb | 7AAK | X-ray | 1.7 | A | 17 | 361 |
| 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 |
| P08397 | HMBS | P08397-1 | P08397-2 | 361 | 344 | 1 | 17 | Deletion | none | none | 0 | 0 |
| P08397 | HMBS | P08397-1 | P08397-3 | 361 | 321 | 218 | 257 | Deletion | none | none | 217 | 217 |
| P08397 | HMBS | P08397-1 | P08397-4 | 361 | 304 | 1 | 17 | Deletion | none | none | 0 | 0 |
| P08397 | HMBS | P08397-1 | P08397-4 | 361 | 304 | 218 | 257 | Deletion | none | none | 200 | 200 |
| Multiple sequence alignment of our canonical and alternatively spliced HMBS |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of HMBS |
| UniProt-id | ENSG | ENST | ENSP |
| P08397-1 | ENSG00000256269.11 | ENST00000652429.1 | ENSP00000498786.1 |
| P08397-2 | ENSG00000256269.11 | ENST00000392841.1 | ENSP00000376584.1 |
| P08397-2 | ENSG00000256269.11 | ENST00000537841.5 | ENSP00000444730.1 |
| P08397-2 | ENSG00000256269.11 | ENST00000648374.1 | ENSP00000497255.1 |
| P08397-3 | ENSG00000256269.11 | ENST00000544387.5 | ENSP00000438424.1 |
| P08397-4 | ENSG00000256269.11 | ENST00000542729.5 | ENSP00000443058.1 |
| UniProt-id | NM ID | NP ID |
| P08397-1 | NM_000190.3 | NP_000181.2 |
| P08397-2 | NM_001024382.1 | NP_001019553.1 |
| P08397-2 | XM_005271531.1 | XP_005271588.1 |
| P08397-2 | XM_005271532.1 | XP_005271589.1 |
| P08397-2 | XM_017017629.1 | XP_016873118.1 |
| P08397-3 | NM_001258208.1 | NP_001245137.1 |
| P08397-4 | NM_001258209.1 | NP_001245138.1 |
| Amino acid sequences of our canonical and alternatively spliced HMBS |
| accession_id | Protein sequence |
| P08397-1 | MSGNGNAAATAEENSPKMRVIRVGTRKSQLARIQTDSVVATLKASYPGLQFEIIAMSTTGDKILDTALSKIGEKSLFTKELEHALEKNEV DLVVHSLKDLPTVLPPGFTIGAICKRENPHDAVVFHPKFVGKTLETLPEKSVVGTSSLRRAAQLQRKFPHLEFRSIRGNLNTRLRKLDEQ QEFSAIILATAGLQRMGWHNRVGQILHPEECMYAVGQGALGVEVRAKDQDILDLVGVLHDPETLLRCIAERAFLRHLEGGCSVPVAVHTA MKDGQLYLTGGVWSLDGSDSIQETMQATIHVPAQHEDGPEDDPQLVGITARNIPRGPQLAAQNLGISLANLLLSKGAKNILDVARQLNDA |
| P08397-2 | MRVIRVGTRKSQLARIQTDSVVATLKASYPGLQFEIIAMSTTGDKILDTALSKIGEKSLFTKELEHALEKNEVDLVVHSLKDLPTVLPPG FTIGAICKRENPHDAVVFHPKFVGKTLETLPEKSVVGTSSLRRAAQLQRKFPHLEFRSIRGNLNTRLRKLDEQQEFSAIILATAGLQRMG WHNRVGQILHPEECMYAVGQGALGVEVRAKDQDILDLVGVLHDPETLLRCIAERAFLRHLEGGCSVPVAVHTAMKDGQLYLTGGVWSLDG |
| P08397-3 | MSGNGNAAATAEENSPKMRVIRVGTRKSQLARIQTDSVVATLKASYPGLQFEIIAMSTTGDKILDTALSKIGEKSLFTKELEHALEKNEV DLVVHSLKDLPTVLPPGFTIGAICKRENPHDAVVFHPKFVGKTLETLPEKSVVGTSSLRRAAQLQRKFPHLEFRSIRGNLNTRLRKLDEQ QEFSAIILATAGLQRMGWHNRVGQILHPEECMYAVGQEGGCSVPVAVHTAMKDGQLYLTGGVWSLDGSDSIQETMQATIHVPAQHEDGPE |
| P08397-4 | MRVIRVGTRKSQLARIQTDSVVATLKASYPGLQFEIIAMSTTGDKILDTALSKIGEKSLFTKELEHALEKNEVDLVVHSLKDLPTVLPPG FTIGAICKRENPHDAVVFHPKFVGKTLETLPEKSVVGTSSLRRAAQLQRKFPHLEFRSIRGNLNTRLRKLDEQQEFSAIILATAGLQRMG WHNRVGQILHPEECMYAVGQEGGCSVPVAVHTAMKDGQLYLTGGVWSLDGSDSIQETMQATIHVPAQHEDGPEDDPQLVGITARNIPRGP |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| HMBS (go to UniProt):P08397 |
| 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 HMBS |
| Gene structures of our canonical and alternative spliced genes of HMBS * 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 P08397-1 |
| 3D view using mol* of P08397-2 |
| 3D view using mol* of P08397-3 |
| 3D view using mol* of P08397-4 |
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 P08397-1 |
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| pLDDT distribution across the protein length of P08397-2 |
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| pLDDT distribution across the protein length of P08397-3 |
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| pLDDT distribution across the protein length of P08397-4 |
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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 P08397-1 |
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| Ramachandran plot of P08397-3 |
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| Ramachandran plot of P08397-4 |
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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 |
| P08397-1 | 1.078 | 179 | 0.873 | 417.088 | 0.461 | 0.814 | 1.062 | 0.093 | 1.702 | 0.055 | 0.41 | 25,26,28,29,30,31,34,35,60,61,63,64,68,77,81,93,94 ,95,96,97,98,99,145,146,147,149,150,167,168,169,17 0,171,172,173,187,188,189,191,192,195,196,216,217, 218,219,220 |
| P08397-2 | 1.11 | 162 | 0.885 | 427.035 | 0.445 | 0.862 | 1.171 | 0.23 | 1.757 | 0.131 | 0.288 | 8,9,10,11,12,13,14,17,40,43,44,47,51,60,61,64,77,7 8,79,81,82,129,130,132,133,150,151,152,153,154,155 ,156,171,172,174,175,178,179,197,200,201,202,203 |
| P08397-3 | 1.061 | 271 | 0.964 | 670.222 | 0.46 | 0.79 | 1.061 | 0.369 | 1.379 | 0.268 | 0.601 | 25,26,27,28,29,30,31,34,35,57,60,61,63,64,68,69,71 ,72,73,74,75,76,77,78,94,95,96,98,99,101,102,103,1 48,150,167,168,169,170,171,172,173,218,220,221,222 ,223,224,225,245,311,312,314,315,318,319 |
| P08397-4 | 1.112 | 222 | 0.943 | 523.761 | 0.406 | 0.866 | 1.147 | 0.331 | 1.585 | 0.209 | 0.419 | 8,9,11,12,13,14,17,43,44,47,51,59,60,77,78,79,81,8 2,99,100,101,102,103,104,128,129,130,132,133,150,1 51,152,153,154,155,156,170,171,172,173,174,175,178 ,179,189,194,195,196,197,203,204 |
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 P08397-1_P08397-1_7aak_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 P08397-1_7aak_A_P08397-2.pdb |
| 3D view using mol* of P08397-1_7aak_A_P08397-3.pdb |
| 3D view using mol* of P08397-1_7aak_A_P08397-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P08397-1_P08397-2.pdb |
| 3D view using mol* of P08397-1_P08397-3.pdb |
| 3D view using mol* of P08397-1_P08397-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P08397-1_vs_P08397-2.png |
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| ./stats/secondary_structure/figure/P08397-1_vs_P08397-3.png |
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| ./stats/secondary_structure/figure/P08397-1_vs_P08397-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P08397-1_vs_P08397-2.png |
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| ./stats/relative_asa/P08397-1_vs_P08397-3.png |
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| ./stats/relative_asa/P08397-1_vs_P08397-4.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 HMBS |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to HMBS |
| Previous studies relating to the alternative splicing of HMBS and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| HMBS | 7592566 | Porphobilinogen deaminase gene structure and molecular defects. | Porphobilinogen deaminase (PBGD) is the third enzyme of the heme biosynthetic pathway. The half-normal activity of human PBGD causes acute intermittent porphyria (AIP), an autosomal dominant inherited disease. Two PBGD isoforms, one ubiquitous and one erythroid specific, are encoded by a single gene localized to chromosomal region 11q24.1-11q24.2. The 10-kb PBGD gene comprises 15 exons and two distinct promoters initiate the ubiquitous and the erythroid transcripts by alternative splicing. In AIP, diagnosis of asymptomatic heterozygotes is crucial to prevent occurrence of life-threatening acute attacks by avoiding known precipitating factors. Difficulties with the biochemical diagnosis could be overcome by the ability to identify the PBGD gene defects in AIP patients. Mutational analysis of the PBGD gene or the use of intragenic polymorphisms offer accurate identification of the gene carriers. To date, 58 mutations and 10 polymorphisms have been reported at the PBGD locus. The great heterogeneity of the mutations in AIP patients requires appropriate screening and diagnostic strategies to identify gene defects in AIP families. | D017118 | Porphyria, Acute Intermittent |
| HMBS | 7866402 | Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene. | Acute intermittent porphyria (AIP) is an autosomal dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase (HMB-synthase). AIP is an ecogenetic condition, with life-threatening acute attacks precipitated by various factors including drugs, alcohol, fasting, and certain hormones. Biochemical diagnosis is problematic and the identification of mutations in the HMB-synthase gene provides accurate detection of presymptomatic heterozygotes, permitting avoidance of the acute precipitating factors. Two HMB-synthase isozymes are encoded by the HMB-synthase gene: one unique to erythroid cells and the other a housekeeping isozyme present in all cells. These two isozymes arise from a single gene by alternative splicing. The recent isolation of the cDNAs and entire genomic sequence encoding the HMB-synthase isozymes has facilitated the detection of diagnostically useful intragenic polymorphisms and disease-causing mutations. Of the 36 mutations identified to date, most caused the classic form of AIP. These mutations included small deletions and insertions, point mutations and RNA splice junction alterations and resulted in the half-normal activity of both the erythroid-specific and housekeeping isozymes. Most AIP mutations were private; however, certain mutations were frequently found in Dutch (R116W) and Swedish (W198X) AIP families. A variant form of AIP, in which patients have normal erythroid activity, but half-normal activity of the housekeeping isozyme, resulted from two mutations at the exon 1/intron 1 boundary, each altering splicing of the hepatic-specific transcript. In addition, 10 polymorphisms in the HMB-synthase gene have been identified that are useful for the diagnosis of presymptomatic AIP heterozygotes in families whose specific mutations have not been determined. | D017118 | Porphyria, Acute Intermittent |
Clinically important variants in HMBS |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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