Host cell protein searchable database
Host cell proteins (HCPs) are process-related impurities that may co-purify with biopharmaceutical drug products. Within this class of impurities there are some that are more problematic. These problematic HCPs can be considered high-risk and can include those that are immunogenic, biologically active, or enzymatically active with the potential to degrade either product molecules or excipients used in formulation.
The “High‐risk” host cell proteins (HCPs): A multi‐company collaborative view publication and database produced by the host cell protein workstream provide a comprehensive review/list of potential problematic HCPs that could impact the safety, efficacy, and quality aspects of CHO-produced biologics, during their development and manufacturing. It is a great reference on the best practice and control strategy for “high-risk” HCPs” in the biopharmaceutical industry.
The database currently focuses on the HCPs specifically isolated from biotherapeutics produced in CHO cells, which are frequently seen HCPs found throughout different processing steps. These HCPs were identified by the BioPhorum’s development group’s Host Cell Protein workstream, through literature review and industry survey data.
The team are continuing to work on compiling characterization data for the HCPs, which includes information such as molecular weight, isoelectric point, accession number, number of amino acids, a hyperlink to the UniProt entry (and a list of references) for each protein.
The key purpose of the database is also to provide information on HCPs that are considered to be problematic and therefore “high-risk.” It further classifies them into four major categories based on their impact to:
- Product quality
- Formulation
- Direct biological function in humans
- Immunogenicity.
Ultimately, the team hopes to include information on the function of all the listed proteins, the specific type of impact (drug or patient) such as aggregation, fragmentation, modification or immunogenicity and the associated references for each protein. Currently this information is only listed for the “high risk” HCPs within the database (rows are highlighted in RED and this list may be filtered by clicking the high risk HCP box in the search field below). The dynamic list will continue to be updated when new proteins are identified and/or reported in the literature.
If you wish to contribute to the database, learn how you may access the latest database or hear more about how you can join BioPhorum, please contact info@biophorum.com
Identified HCP (Abbreviation) | High risk? | Mw (kDa) | pI | UniProt Accession No. | No. of amino acids | |||||||||||||||||||||
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60S acidic ribosomal protein P0 | 30.6 | 8.9 | G3HKG9 | 280 |
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40S ribosomal protein SA (RPSA) | 19.7 | 9.4 | G3HQX0 | 179 |
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Cathepsin Z (CatZ) | High Risk | 34 | 7.5 | Q9EPP7 | 306 |
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Cathepsin L (CatL) | High Risk | 37.3 | 6.8 | G3INC5 | 333 |
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Cathepsin E (CatE) | 42.2 | 4.7 | G3HAY9 | 388 |
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Cathepsin D (CatD) | 44.1 | 6.5 | G3I4W7 | 408 |
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Cathepsin B (CatB) | High Risk | 37.5 | 5.7 | G3H0L9 | 339 |
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Catalase | 63.1 | 8.3 | G3GYY6 | 555 |
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Carboxypeptidase D (Cpd) | High Risk | 123.4 | 5.8 | G3HR95 | 1106 |
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Carboxylesterase B-1-like protein, Liver (CES-B1L) | 77.9 | 7.9 | A0A061I7X9 | 704 |
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Carboxylesterase 1-like protein, Liver (CES1) | High Risk | 97.5 | 5.9 | A0A061IFE2 | 882 |
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Calmodulin (CaM) | 16.7 | 4.1 | A0A061HUH1 | 149 |
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C-X-C motif chemokine 3 (CXCL3) | High Risk | 11 | 9.1 | A4URF0 | 101 |
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C-C motif chemokine | 15.9 | 9.3 | G3GTT2 | 143 |
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Annexin A5 | 36.1 | 4.9 | G3I5A4 | 321 |
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Annexin A2 | 27 | 5.7 | G3IG05 | 244 |
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Alpha-enolase (2-phospho-D-glycerate hydro-lyase) | High Risk | 15.5 | 5 | G3I0W1 | 139 |
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Actin, cytoplasmic 1 (ACTB) | 41.7 | 5.2 | P48975 | 375 |
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78 kDa glucose regulated protein(GRP78, BiP) | High Risk | 72.4 | 5.1 | G3I8R9 | 654 |
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Calreticulin (CALR) | 48.4 | 4.3 | G3HCX8 | 417 |
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Galectin-3 (Gal-3) | 32.4 | 6.9 | G3H7B3 | 281 |
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Glutathione S-transferase P 1 (GSTP1) | High Risk | 25 | 8.2 | G3I3Y6 | 221 |
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Glyceraldehyde-3-phosphate dehydrogenase (G3P) | 35.7 | 8.5 | P17244 | 333 |
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Granulins (GRN) | 63.9 | 6 | G3HLK3 | 592 |
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GTP-binding nuclear protein (RAN) | 24.5 | 8.4 | G3IHE5 | 216 |
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Guanine nucleotide-binding protein beta-2-like 1 (RACK1) | 30.4 | 7 | G3HK00 | 276 |
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Heat shock cognate 71 kDa protein (HSPA8) | 70.8 | 5.2 | P19378 | 646 |
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Heat shock protein HSP 90-alpha (HSP90A) | 84.8 | 5 | P46633 | 733 |
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Heat shock protein HSP 90-beta (HSP90B) | 47.8 | 5.3 | G3HC84 | 412 |
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Endoplasmin (HSP90B1) | 92.6 | 4.7 | G3HQM6 | 803 |
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Galectin 3 binding protein (Gal-3BP) | 63.8 | 5.1 | G3H3E4 | 574 |
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Fructose-bisphosphate aldolase (FBA) | 39.4 | 8.3 | G3I4H6 | 364 |
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Follistatin-related protein 1 (FST1) | 65.4 | 6.2 | G3HAI3 | 583 |
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ERP57 protein | 56.8 | 6 | Q91Z81 | 505 |
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Galectin-1 (Gal-1) | 14.8 | 5.5 | P48538 | 135 |
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Elongation factor 2 (eEF2) | 95.3 | 6.2 | P09445 | 858 |
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Elongation factor 1-alpha (eEF1a) | 50.1 | 9.1 | P62629 | 462 |
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Cofilin-1 (CFL) | 18.5 | 8.2 | G3IDM2 | 166 |
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Clusterin (CLU) | High Risk | 51.8 | 5.5 | G3HNJ3 | 447 |
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Chondroitin sulfate proteoglycan 4 (CSPG4) | 252 | 5.4 | G3H0E4 | 2323 |
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Lysosomal Acid Lipase (LAL) | High Risk | 45.6 | 7.3 | G3HQY6 | 397 |
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Lysosomal Phospholipase A2 (LPLA2) | 47.2 | 6.1 | G3HKV9 | 412 |
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Lysosomal protective protein (CTSA) | 54.2 | 5.7 | G3H8V5 | 475 |
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Malate dehydrogenase, cytoplasmic (MDHC) | 36.5 | 6.2 | G3HDQ2 | 334 |
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Matrix metalloproteinase-19 (MMP-19) | High Risk | 58.9 | 7.7 | G3HRK9 | 525 |
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Metalloproteinase inhibitor 1 (TIMP1) | 22.4 | 8.8 | G3IBH0 | 203 |
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Monocyte Chemoattractant Protein-1 (MCP-1) | High Risk | 15.9 | 9.3 | G3GTT2 | 143 |
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Myosin-9 (MYH9) | 225.8 | 5.5 | G3IH63 | 1948 |
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Nidogen-1 (NID1) | 30.1 | 8.4 | G3I3U5 | 278 |
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Inter-alpha-trypsin inhibitor heavy chain H5 isoform X2 (ITIH5L) | 107.9 | 8.5 | G3H7S9 | 983 |
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Legumain (LGMN) | 49.6 | 6.1 | G3I1H5 | 438 |
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Laminin subunit gamma-1 (LAMC1) | 172.1 | 5 | G3HG25 | 1559 |
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Laminin subunit beta-1 (LAMB1) | 178.1 | 4.8 | G3I278 | 1617 |
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lactotransferrin (LTF) | 71.4 | 8.6 | G3HTA2 | 648 |
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Lactadherin (MFG-E8) | 16.1 | 9.5 | G3ICD3 | 140 |
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L-lactate dehydrogenase A chain (LDHA) | 36.5 | 7 | Q06BU8 | 332 |
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Histone H2B Type 1-N (H2B1N) | 13.9 | 10.3 | G3HDU3 | 126 |
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Histone H2A | 26.7 | 10.9 | G3HDS3 | 236 |
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Hexosaminidase, beta | 60.7 | 6 | G3H3P | 528 |
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Lipoprotein Lipase (LPL) | High Risk | 50.5 | 8 | G3H6V7 | 450 |
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Procollagen-lysine 2-oxoglutarate 5-deoxygenase_1 (PLOD1) | High Risk | 76 | 5.8 | G3IIE7 | 659 |
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Phospholipid transfer protein (PLTP) | 54.4 | 6.2 | G3H8V4 | 493 |
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Proteasome subunit alpha type-7 (PSA7) | 23.8 | 8.6 | G3GWR8 | 212 |
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Protein S100-A6 (S10A6) | High Risk | 10 | 5.3 | G3HC31 | 89 |
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Pyruvate Kinase (PK) | High Risk | 51.6 | 7.6 | G3H3Q1 | 472 |
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Serine protease (HTRA1) | High Risk | 28.7 | 6.5 | G3IBF4 | 268 |
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Sialate o-acetylesterase (SIAE) | High Risk | 59.3 | 8.6 | A0A3L7HS03 | 529 |
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Sulfated glycoprotein (SGP-1) | 27.4 | 5.4 | G3I1Y9 | 249 |
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Transforming Growth Factor-b1 (TGF-b1) | High Risk | 26.4 | 8.5 | G3IA12 | 237 |
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Transgelin-2 (TAGLN) | 22.5 | 8.8 | G3H7Z2 | 199 |
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Procollagen C-endopeptidase enhancer (PCPE1) | 55.2 | 8.5 | G3I664 | 509 |
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Plectin-1 (Plec1) | 83.4 | 8.7 | G3HWJ2 | 720 |
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Phospholipase D3 (PLD3) | 54.4 | 6 | G3HNQ5 | 488 |
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Phospholipase B-like 2 (PLBL2) | High Risk | 65.5 | 5.9 | G3I6T1 | 585 |
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Phosphoglycerate mutase 1 (Pgam1) | 20.2 | 7.8 | G3GZW8 | 178 |
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Phosphoglycerate kinase (PGK1) | 44.6 | 8 | P50310 | 417 |
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Peroxiredoxin-1 (PRDX1) | High Risk | 22.3 | 8.2 | Q9JKY1 | 199 |
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Peptidyl-prolyl cis-trans isomerase A (PPIA) | 17.9 | 8.4 | P14851 | 164 |
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Nucleoside diphosphate kinase B (NDPK-B) | 17.3 | 7.8 | G3HBD3 | 152 |
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Nucleobindin-2 (NUCB2) | 50.3 | 5.1 | G3IF52 | 420 |
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Transketolase (TKTase) | 67.7 | 7.6 | G3GUU5 | 623 |
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Triosephosphate isomerase (TPI) | 16.4 | 8.5 | G3HNV4 | 150 |
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Tubulin alpha-1A chain (TBA1A) | 50.1 | 4.9 | P68362 | 451 |
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Tubulin alpha-1C chain (TBA1C) | 49.9 | 5 | P68365 | 449 |
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V-type proton ATPase subunit C 1 (VATC1) | 43.9 | 7 | G3I3N5 | 382 |
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Vimentin (VIME) | 51.8 | 4.9 | P48670 | 448 |
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