Protein:KLHL3 |
Protein Summary |
 Gene summary |
| Gene name: KLHL3 | ASpdb.0 ID: 26249 | Gene | Gene symbol | KLHL3 | Gene ID | 26249 |
| Gene name | kelch like family member 3 |
| Synonyms | PHA2D |
| Cytomap | 5q31.2 |
| Type of gene | protein-coding |
| Description | kelch-like protein 3 |
| Modification date | 20240411 |
| UniProtAcc | Q9UH77 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | KLHL3 | GO:0005829 | cytosol | 22406640 |
| Gene | KLHL3 | GO:0006511 | ubiquitin-dependent protein catabolic process | 23453970|23576762 |
| Gene | KLHL3 | GO:0016567 | protein ubiquitination | 23453970 |
| Gene | KLHL3 | GO:0031463 | Cul3-RING ubiquitin ligase complex | 23453970|23576762 |
| Gene | KLHL3 | GO:0043161 | proteasome-mediated ubiquitin-dependent protein catabolic process | 35093948 |
| Gene | KLHL3 | GO:0070294 | renal sodium ion absorption | 35093948 |
| Gene | KLHL3 | GO:0070936 | protein K48-linked ubiquitination | 23576762 |
| Gene | KLHL3 | GO:1990756 | ubiquitin-like ligase-substrate adaptor activity | 23387299|23453970|23576762|35179207 |
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 |
| Q9UH77-1 | Q9UH77-1_5nkp_B.pdb | 5NKP | X-ray | 2.8 | B | 298 | 585 |
| 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 |
| Q9UH77 | KLHL3 | Q9UH77-1 | Q9UH77-2 | 587 | 555 | 1 | 32 | Deletion | none | none | 0 | 0 |
| Q9UH77 | KLHL3 | Q9UH77-1 | Q9UH77-3 | 587 | 505 | 1 | 82 | Deletion | none | none | 0 | 0 |
| Multiple sequence alignment of our canonical and alternatively spliced KLHL3 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of KLHL3 |
| UniProt-id | ENSG | ENST | ENSP |
| Q9UH77-1 | ENSG00000146021.15 | ENST00000309755.9 | ENSP00000312397.4 |
| Q9UH77-2 | ENSG00000146021.15 | ENST00000508657.5 | ENSP00000422099.1 |
| Q9UH77-3 | ENSG00000146021.15 | ENST00000506491.5 | ENSP00000424828.1 |
| UniProt-id | NM ID | NP ID |
| Q9UH77-1 | NM_017415.2 | NP_059111.2 |
| Q9UH77-2 | NM_001257194.1 | NP_001244123.1 |
| Q9UH77-3 | NM_001257195.1 | NP_001244124.1 |
| Amino acid sequences of our canonical and alternatively spliced KLHL3 |
| accession_id | Protein sequence |
| Q9UH77-1 | MEGESVKLSSQTLIQAGDDEKNQRTITVNPAHMGKAFKVMNELRSKQLLCDVMIVAEDVEIEAHRVVLAACSPYFCAMFTGDMSESKAKK IEIKDVDGQTLSKLIDYIYTAEIEVTEENVQVLLPAASLLQLMDVRQNCCDFLQSQLHPTNCLGIRAFADVHTCTDLLQQANAYAEQHFP EVMLGEEFLSLSLDQVCSLISSDKLTVSSEEKVFEAVISWINYEKETRLEHMAKLMEHVRLPLLPRDYLVQTVEEEALIKNNNTCKDFLI EAMKYHLLPLDQRLLIKNPRTKPRTPVSLPKVMIVVGGQAPKAIRSVECYDFEEDRWDQIAELPSRRCRAGVVFMAGHVYAVGGFNGSLR VRTVDVYDGVKDQWTSIASMQERRSTLGAAVLNDLLYAVGGFDGSTGLASVEAYSYKTNEWFFVAPMNTRRSSVGVGVVEGKLYAVGGYD GASRQCLSTVEQYNPATNEWIYVADMSTRRSGAGVGVLSGQLYATGGHDGPLVRKSVEVYDPGTNTWKQVADMNMCRRNAGVCAVNGLLY |
| Q9UH77-2 | MGKAFKVMNELRSKQLLCDVMIVAEDVEIEAHRVVLAACSPYFCAMFTGDMSESKAKKIEIKDVDGQTLSKLIDYIYTAEIEVTEENVQV LLPAASLLQLMDVRQNCCDFLQSQLHPTNCLGIRAFADVHTCTDLLQQANAYAEQHFPEVMLGEEFLSLSLDQVCSLISSDKLTVSSEEK VFEAVISWINYEKETRLEHMAKLMEHVRLPLLPRDYLVQTVEEEALIKNNNTCKDFLIEAMKYHLLPLDQRLLIKNPRTKPRTPVSLPKV MIVVGGQAPKAIRSVECYDFEEDRWDQIAELPSRRCRAGVVFMAGHVYAVGGFNGSLRVRTVDVYDGVKDQWTSIASMQERRSTLGAAVL NDLLYAVGGFDGSTGLASVEAYSYKTNEWFFVAPMNTRRSSVGVGVVEGKLYAVGGYDGASRQCLSTVEQYNPATNEWIYVADMSTRRSG AGVGVLSGQLYATGGHDGPLVRKSVEVYDPGTNTWKQVADMNMCRRNAGVCAVNGLLYVVGGDDGSCNLASVEYYNPVTDKWTLLPTNMS |
| Q9UH77-3 | MSESKAKKIEIKDVDGQTLSKLIDYIYTAEIEVTEENVQVLLPAASLLQLMDVRQNCCDFLQSQLHPTNCLGIRAFADVHTCTDLLQQAN AYAEQHFPEVMLGEEFLSLSLDQVCSLISSDKLTVSSEEKVFEAVISWINYEKETRLEHMAKLMEHVRLPLLPRDYLVQTVEEEALIKNN NTCKDFLIEAMKYHLLPLDQRLLIKNPRTKPRTPVSLPKVMIVVGGQAPKAIRSVECYDFEEDRWDQIAELPSRRCRAGVVFMAGHVYAV GGFNGSLRVRTVDVYDGVKDQWTSIASMQERRSTLGAAVLNDLLYAVGGFDGSTGLASVEAYSYKTNEWFFVAPMNTRRSSVGVGVVEGK LYAVGGYDGASRQCLSTVEQYNPATNEWIYVADMSTRRSGAGVGVLSGQLYATGGHDGPLVRKSVEVYDPGTNTWKQVADMNMCRRNAGV |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| KLHL3 (go to UniProt):Q9UH77 |
| 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 |
| Q9UH77 | Domain | 50 | 117 | Note=BTB;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00037 | Type=Deletion;Start=1;End=82 |
Gene Isoform Structures and Expression Levels for KLHL3 |
| Gene structures of our canonical and alternative spliced genes of KLHL3 * 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 Q9UH77-1 |
| 3D view using mol* of Q9UH77-2 |
| 3D view using mol* of Q9UH77-3 |
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 Q9UH77-1 |
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| pLDDT distribution across the protein length of Q9UH77-2 |
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| pLDDT distribution across the protein length of Q9UH77-3 |
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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 Q9UH77-1 |
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| Ramachandran plot of Q9UH77-2 |
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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 |
| Q9UH77-1 | 1.092 | 243 | 1.073 | 457.562 | 0.388 | 0.836 | 1.02 | 0.639 | 1.13 | 0.565 | 0.885 | 339,340,341,342,343,344,386,387,388,389,390,391,43 3,434,435,436,437,438,482,483,484,485,486,487,528, 529,530,531,532,533,534,577,579,580,581,582 |
| Q9UH77-2 | 1.09 | 247 | 1.041 | 474.712 | 0.436 | 0.833 | 0.982 | 0.53 | 1.222 | 0.434 | 0.837 | 307,308,309,310,311,312,354,355,356,357,358,359,40 1,402,403,404,405,406,449,450,451,452,453,454,455, 463,464,465,466,495,496,497,498,499,500,501,502,54 4,545,546,547,548,549,550,551 |
| Q9UH77-3 | 1.082 | 250 | 1.062 | 470.596 | 0.432 | 0.821 | 0.984 | 0.651 | 1.137 | 0.572 | 0.727 | 219,256,257,258,259,260,261,262,304,305,306,307,30 8,309,351,352,353,354,355,356,400,401,402,403,404, 405,446,447,448,449,450,451,452,453,462,494,495,49 6,497,498,499,500 |
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 Q9UH77-1_Q9UH77-1_5nkp_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 Q9UH77-1_5nkp_B_Q9UH77-2.pdb |
| 3D view using mol* of Q9UH77-1_5nkp_B_Q9UH77-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q9UH77-1_Q9UH77-2.pdb |
| 3D view using mol* of Q9UH77-1_Q9UH77-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q9UH77-1_vs_Q9UH77-2.png |
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| ./stats/secondary_structure/figure/Q9UH77-1_vs_Q9UH77-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q9UH77-1_vs_Q9UH77-2.png |
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| ./stats/relative_asa/Q9UH77-1_vs_Q9UH77-3.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 KLHL3 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to KLHL3 |
| Previous studies relating to the alternative splicing of KLHL3 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| KLHL3 | 10843806 | Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene. | The Drosophila kelch protein is a structural component of ring canals and is required for oocyte maturation. Here, we report the cloning and genomic structure of a new human homologue of kelch, KLHL3. At the amino acid level, KLHL3 shares 77% similarity with Drosophila kelch and 89% similarity with Mayven (KLHL2), another human kelch homolog. The approximately 6.5-kb mRNA has a single open reading frame encoding a protein of 587 amino acids with a predicted molecular mass of 650 kDa. Like kelch and KLHL2, the KLHL3 protein contains a poxvirus and zinc finger domain at the N-terminus and six tandem repeats (kelch repeats) at the C-terminus. At least three isoforms, which differ in the length of the N-terminus, are produced and may be the result of alternative promoter usage. We also identified alternative polyadenylation sites and alternative splicing; thus, as many as 12 mRNA variants and six putative protein isoforms could be produced. The KLHL3 gene is mapped to human chromosome 5, band q31, contains 17 exons, and spans approximately 120 kb of genomic DNA. KLHL3 maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, we detected no inactivating mutations of KLHL3 in malignant myeloid disorders with loss of 5q. | D000208 | Acute Disease |
| KLHL3 | 10843806 | Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene. | The Drosophila kelch protein is a structural component of ring canals and is required for oocyte maturation. Here, we report the cloning and genomic structure of a new human homologue of kelch, KLHL3. At the amino acid level, KLHL3 shares 77% similarity with Drosophila kelch and 89% similarity with Mayven (KLHL2), another human kelch homolog. The approximately 6.5-kb mRNA has a single open reading frame encoding a protein of 587 amino acids with a predicted molecular mass of 650 kDa. Like kelch and KLHL2, the KLHL3 protein contains a poxvirus and zinc finger domain at the N-terminus and six tandem repeats (kelch repeats) at the C-terminus. At least three isoforms, which differ in the length of the N-terminus, are produced and may be the result of alternative promoter usage. We also identified alternative polyadenylation sites and alternative splicing; thus, as many as 12 mRNA variants and six putative protein isoforms could be produced. The KLHL3 gene is mapped to human chromosome 5, band q31, contains 17 exons, and spans approximately 120 kb of genomic DNA. KLHL3 maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, we detected no inactivating mutations of KLHL3 in malignant myeloid disorders with loss of 5q. | D007951 | Leukemia, Myeloid |
| KLHL3 | 10843806 | Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene. | The Drosophila kelch protein is a structural component of ring canals and is required for oocyte maturation. Here, we report the cloning and genomic structure of a new human homologue of kelch, KLHL3. At the amino acid level, KLHL3 shares 77% similarity with Drosophila kelch and 89% similarity with Mayven (KLHL2), another human kelch homolog. The approximately 6.5-kb mRNA has a single open reading frame encoding a protein of 587 amino acids with a predicted molecular mass of 650 kDa. Like kelch and KLHL2, the KLHL3 protein contains a poxvirus and zinc finger domain at the N-terminus and six tandem repeats (kelch repeats) at the C-terminus. At least three isoforms, which differ in the length of the N-terminus, are produced and may be the result of alternative promoter usage. We also identified alternative polyadenylation sites and alternative splicing; thus, as many as 12 mRNA variants and six putative protein isoforms could be produced. The KLHL3 gene is mapped to human chromosome 5, band q31, contains 17 exons, and spans approximately 120 kb of genomic DNA. KLHL3 maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, we detected no inactivating mutations of KLHL3 in malignant myeloid disorders with loss of 5q. | D009190 | Myelodysplastic Syndromes |
Clinically important variants in KLHL3 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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