Protein:CD33 |
Protein Summary |
 Gene summary |
| Gene name: CD33 | ASpdb.0 ID: 945 | Gene | Gene symbol | CD33 | Gene ID | 945 |
| Gene name | CD33 molecule |
| Synonyms | CD33rSiglec|SIGLEC-3|SIGLEC3|p67 |
| Cytomap | 19q13.41 |
| Type of gene | protein-coding |
| Description | myeloid cell surface antigen CD33CD33 antigen (gp67)CD33 molecule transcriptgp67sialic acid-binding Ig-like lectin 3 |
| Modification date | 20240323 |
| UniProtAcc | P20138 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CD33 | GO:0002765 | immune response-inhibiting signal transduction | 10887109 |
| Gene | CD33 | GO:0005654 | nucleoplasm | - |
| Gene | CD33 | GO:0005794 | Golgi apparatus | 21278227 |
| Gene | CD33 | GO:0005886 | plasma membrane | 21278227 |
| Gene | CD33 | GO:0009897 | external side of plasma membrane | 20660734 |
| Gene | CD33 | GO:0150102 | negative regulation of monocyte activation | 15597323 |
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 |
| P20138-1 | P20138-1_7aw6_A.pdb | 7AW6 | X-ray | 1.95 | A | 21 | 232 |
| 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 |
| P20138 | CD33 | P20138-1 | P20138-2 | 364 | 310 | 309 | 364 | Substitution | KHQKKSKLHGPTETSSCSGAAPTVEMDEELHYASLNFHGMNPSKDTSTEYSEVRTQ | VR | 309 | 310 |
| P20138 | CD33 | P20138-1 | P20138-3 | 364 | 237 | 13 | 139 | Deletion | none | none | 12 | 12 |
| Multiple sequence alignment of our canonical and alternatively spliced CD33 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CD33 |
| UniProt-id | ENSG | ENST | ENSP |
| P20138-1 | ENSG00000105383.15 | ENST00000262262.5 | ENSP00000262262.3 |
| P20138-2 | ENSG00000105383.15 | ENST00000391796.7 | ENSP00000375673.2 |
| P20138-3 | ENSG00000105383.15 | ENST00000421133.6 | ENSP00000410126.1 |
| UniProt-id | NM ID | NP ID |
| P20138-1 | NM_001772.3 | NP_001763.3 |
| P20138-1 | XM_011527532.2 | XP_011525834.1 |
| P20138-2 | NM_001177608.1 | NP_001171079.1 |
| P20138-3 | NM_001082618.1 | NP_001076087.1 |
| Amino acid sequences of our canonical and alternatively spliced CD33 |
| accession_id | Protein sequence |
| P20138-1 | MPLLLLLPLLWAGALAMDPNFWLQVQESVTVQEGLCVLVPCTFFHPIPYYDKNSPVHGYWFREGAIISRDSPVATNKLDQEVQEETQGRF RLLGDPSRNNCSLSIVDARRRDNGSYFFRMERGSTKYSYKSPQLSVHVTDLTHRPKILIPGTLEPGHSKNLTCSVSWACEQGTPPIFSWL SAAPTSLGPRTTHSSVLIITPRPQDHGTNLTCQVKFAGAGVTTERTIQLNVTYVPQNPTTGIFPGDGSGKQETRAGVVHGAIGGAGVTAL LALCLCLIFFIVKTHRRKAARTAVGRNDTHPTTGSASPKHQKKSKLHGPTETSSCSGAAPTVEMDEELHYASLNFHGMNPSKDTSTEYSE |
| P20138-2 | MPLLLLLPLLWAGALAMDPNFWLQVQESVTVQEGLCVLVPCTFFHPIPYYDKNSPVHGYWFREGAIISRDSPVATNKLDQEVQEETQGRF RLLGDPSRNNCSLSIVDARRRDNGSYFFRMERGSTKYSYKSPQLSVHVTDLTHRPKILIPGTLEPGHSKNLTCSVSWACEQGTPPIFSWL SAAPTSLGPRTTHSSVLIITPRPQDHGTNLTCQVKFAGAGVTTERTIQLNVTYVPQNPTTGIFPGDGSGKQETRAGVVHGAIGGAGVTAL |
| P20138-3 | MPLLLLLPLLWADLTHRPKILIPGTLEPGHSKNLTCSVSWACEQGTPPIFSWLSAAPTSLGPRTTHSSVLIITPRPQDHGTNLTCQVKFA GAGVTTERTIQLNVTYVPQNPTTGIFPGDGSGKQETRAGVVHGAIGGAGVTALLALCLCLIFFIVKTHRRKAARTAVGRNDTHPTTGSAS |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CD33 (go to UniProt):P20138 |
| 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 |
| P20138 | Topological domain | 18 | 259 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=13;End=139 |
| P20138 | Topological domain | 283 | 364 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=309;End=364 |
| P20138 | Domain | 19 | 135 | Note=Ig-like V-type | Type=Deletion;Start=13;End=139 |
| P20138 | Region | 290 | 364 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=309;End=364 |
| P20138 | Motif | 338 | 343 | Note=ITIM motif 1 | Type=Substitution;Start=309;End=364 |
| P20138 | Motif | 356 | 361 | Note=ITIM motif 2 | Type=Substitution;Start=309;End=364 |
| P20138 | Compositional bias | 347 | 364 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=309;End=364 |
Gene Isoform Structures and Expression Levels for CD33 |
| Gene structures of our canonical and alternative spliced genes of CD33 * 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 P20138-1 |
| 3D view using mol* of P20138-2 |
| 3D view using mol* of P20138-3 |
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 P20138-1 |
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| pLDDT distribution across the protein length of P20138-2 |
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| pLDDT distribution across the protein length of P20138-3 |
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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 P20138-1 |
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| Ramachandran plot of P20138-2 |
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| Ramachandran plot of P20138-3 |
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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 |
| P20138-1 | 0.71 | 34 | 0.486 | 68.257 | 0.433 | 0.722 | 1.109 | 0.206 | 1.519 | 0.136 | 0.569 | 62,73,83,85,86,89,109,110,111,112,116
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| P20138-2 | 0.554 | 23 | 0.42 | 61.74 | 0.671 | 0.601 | 0.914 | 0.097 | 1.203 | 0.081 | 0.754 | 15,17,18,21,22,127,128,129,130,131
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| P20138-3 | 0.607 | 29 | 0.473 | 84.378 | 0.618 | 0.616 | 0.849 | 0.457 | 1.236 | 0.37 | 0.688 | 12,13,14,15,16,17,89,94,96,97
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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 P20138-1_P20138-1_7aw6_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 P20138-1_7aw6_A_P20138-2.pdb |
| 3D view using mol* of P20138-1_7aw6_A_P20138-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P20138-1_P20138-2.pdb |
| 3D view using mol* of P20138-1_P20138-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P20138-1_vs_P20138-2.png |
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| ./stats/secondary_structure/figure/P20138-1_vs_P20138-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P20138-1_vs_P20138-2.png |
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| ./stats/relative_asa/P20138-1_vs_P20138-3.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 CD33 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P20138 | CD33 | DB06318 | AVE9633 | investigational | |
| P20138 | CD33 | DB00056 | Gemtuzumab ozogamicin | approved, investigational | antibody, regulator |
Related Diseases to CD33 |
| Previous studies relating to the alternative splicing of CD33 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CD33 | 24381305 | CD33: increased inclusion of exon 2 implicates the Ig V-set domain in Alzheimer's disease susceptibility. | We previously demonstrated that the Alzheimer's disease (AD) associated risk allele, rs3865444(C), results in a higher surface density of CD33 on monocytes. Here, we find alternative splicing of exon 2 to be the primary mechanism of the genetically driven differential expression of CD33 protein. We report that the risk allele, rs3865444(C), is associated with greater cell surface expression of CD33 in both subjects of European and African-American ancestry and that there is a single haplotype influencing CD33 surface expression. A meta-analysis of the two populations narrowed the number of significant SNPs in high linkage disequilibrium (LD) (r(2) > 0.8) with rs3865444 to just five putative causal variants associated with increased protein expression. Using gene expression data from flow-sorted CD14(+)CD16(-) monocytes from 398 healthy subjects of three populations, we show that the rs3865444(C) risk allele is strongly associated with greater expression of CD33 exon 2 (pMETA = 2.36 × 10(-60)). Western blotting confirms increased protein expression of the full-length CD33 isoform containing exon 2 relative to the rs3865444(C) allele (P < 0.0001). Of the variants in strong LD with rs3865444, rs12459419, which is located in a putative SRSF2 splice site of exon 2, is the most likely candidate to mediate the altered alternative splicing of CD33's Immunoglobulin V-set domain 2 and ultimately influence AD susceptibility. | D000544 | Alzheimer Disease |
| CD33 | 24381305 | CD33: increased inclusion of exon 2 implicates the Ig V-set domain in Alzheimer's disease susceptibility. | We previously demonstrated that the Alzheimer's disease (AD) associated risk allele, rs3865444(C), results in a higher surface density of CD33 on monocytes. Here, we find alternative splicing of exon 2 to be the primary mechanism of the genetically driven differential expression of CD33 protein. We report that the risk allele, rs3865444(C), is associated with greater cell surface expression of CD33 in both subjects of European and African-American ancestry and that there is a single haplotype influencing CD33 surface expression. A meta-analysis of the two populations narrowed the number of significant SNPs in high linkage disequilibrium (LD) (r(2) > 0.8) with rs3865444 to just five putative causal variants associated with increased protein expression. Using gene expression data from flow-sorted CD14(+)CD16(-) monocytes from 398 healthy subjects of three populations, we show that the rs3865444(C) risk allele is strongly associated with greater expression of CD33 exon 2 (pMETA = 2.36 × 10(-60)). Western blotting confirms increased protein expression of the full-length CD33 isoform containing exon 2 relative to the rs3865444(C) allele (P < 0.0001). Of the variants in strong LD with rs3865444, rs12459419, which is located in a putative SRSF2 splice site of exon 2, is the most likely candidate to mediate the altered alternative splicing of CD33's Immunoglobulin V-set domain 2 and ultimately influence AD susceptibility. | D020022 | Genetic Predisposition to Disease |
Clinically important variants in CD33 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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