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 database and paper 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 provides a great reference on the best practice and control strategy for “high-risk” HCPs” in the biopharmaceutical industry.
The database provides two separate lists of Host Cell Proteins (HCPs) specifically focusing on biotherapeutics produced in CHO cells.
The first is a comprehensive list of frequently seen HCPs found throughout different processing steps. This contains 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 second contains the frequently seen 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.
Also included are the function of the protein, the specific type of impact (drug or patient) such as aggregation, fragmentation, modification or immunogenicity and the associated references for each protein. These dynamic lists will continue to be updated when new CHO proteins are identified and/or reported in the literature.
| Identified HCP | MW | pl | UniProt | AAs | Comments | Refs | Link |
|---|---|---|---|---|---|---|---|
| 40S ribosomal protein SA (RPSA) | 19.7 | 9.4 | G3HQX0 | 179 | Aboulaich et al., 2014; Liu et al., 2019 | https://www.uniprot.org/uniprot/G3HQX0 | |
| 60S acidic ribosomal protein P0 | 30.6 | 8.9 | G3HKG9 | 280 | Aboulaich et al., 2014; Liu et al., 2019; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3HKG9 | |
| 78 kDa glucose regulated protein(GRP78, BiP) | 72.4 | 5.1 | G3I8R9 | 654 | Aboulaich et al., 2014; Albrecht et al., 2018b; Chiverton et al., 2016; Falkenberg et al., 2019; Kreimer et al., 2017; Liu et al., 2019; Migani et al., 2017; Zhang et al., 2014; Joucla et al., 2013; Levy et al., 2016 | https://www.uniprot.org/uniprot/G3I8R9 | |
| Actin, cytoplasmic 1 (ACTB) | 41.7 | 5.2 | P48975 | 375 | also by Levy | Aboulaich et al., 2014; Falkenberg et al., 2019; Farrell et al., 2015; Jawa et al., 2016; Zhang et al., 2014 | https://www.uniprot.org/uniprot/P48975 |
| Alpha-enolase (2-phospho-D-glycerate hydro-lyase) | 15.5 | 5 | G3I0W1 | 139 | Liu et al., 2019 | https://www.uniprot.org/uniprot/G3I0W1 | |
| Annexin A2 | 27 | 5.7 | G3IG05 | 244 | Falkenberg et al., 2019; Fukuda et al., 2019 Only mentioned as Annexin in UniProt vs Annexin A2 in Aboulaich; How was Falkenberg determined to be obsolete entry (confirm with Thomas who's an author?)? Didn't locate in Valente 2014 or 2015, delete? Don't have access to Fukuda, couldn't check: does anyone have it? | Aboulaich et al., 2014; Valente et al., 2014 | https://www.uniprot.org/uniprot/G3IG05 |
| Annexin A5 | 36.1 | 4.9 | G3I5A4 | 321 | also in Park | Farrell et al., 2015; Gilgunn & Bones, 2018 | https://www.uniprot.org/uniprot/G3I5A4 |
| C-C motif chemokine | 15.9 | 9.3 | G3GTT2 | 143 | Farrell et al., 2015 | https://www.uniprot.org/uniprot/G3GTT2 | |
| C-X-C motif chemokine 3 (CXCL3) | 11 | 9.1 | A4URF0 | 101 | Farrell et al., 2015; Gilgunn & Bones, 2018; Zhang et al., 2014 | https://www.uniprot.org/uniprot/A4URF0 | |
| Calmodulin (CaM) | 16.7 | 4.1 | A0A061HUH1 | 149 | Albrecht et al., 2018b; Liu et al., 2019 | https://www.uniprot.org/uniprot/A0A061HUH1 | |
| Calreticulin (CALR) | 48.4 | 4.3 | G3HCX8 | 417 | Farrell et al., 2015; Gilgunn et al., 2019; Valente et al., 2014; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3HCX8 | |
| Carboxylesterase 1-like protein, Liver (CES1) | 97.5 | 5.9 | A0A061IFE2 | 882 | Zhang et al., 2020 | https://www.uniprot.org/uniprot/A0A061IFE2 | |
| Carboxylesterase B-1-like protein, Liver (CES-B1L) | 77.9 | 7.9 | A0A061I7X9 | 704 | Zhang et al., 2020 | https://www.uniprot.org/uniprot/A0A061I7X9 | |
| Carboxypeptidase D (Cpd) | 123.4 | 5.8 | G3HR95 | 1106 | Hu et al., 2016; Dick et al., 2008 (Dick, Qiu, Mahon, Adamo, & Cheng, 2008) | https://www.uniprot.org/uniprot/G3HR95 | |
| Catalase | 63.1 | 8.3 | G3GYY6 | 555 | also Valente | Ahluwalia et al., 2017; Liu et al., 2019 | https://www.uniprot.org/uniprot/G3GYY6 |
| Cathepsin B (CatB) | 37.5 | 5.7 | G3H0L9 | 339 | also by Valente & Park | Aboulaich et al., 2014; Albrecht et al., 2018b; Levy et al., 2016; Migani et al., 2017; Gao et al., 2011; Yang et al., 2019; Zhang et al., 2016; Zhang et al., 2019 | https://www.uniprot.org/uniprot/G3H0L9 |
| Cathepsin D (CatD) | 44.1 | 6.5 | G3I4W7 | 408 | also by Valente | Albrecht et al., 2018b; Bee et al., 2017; Bee et al., 2015; Fukuda et al., 2019; Park et al., 2017; Ranjan et al., 2019; Robert et al., 2009; Singh et al., 2020; Zhang et al., 2016; Singh, Mishra, Yadav, Budholiya, & Rathore, 2020 | https://www.uniprot.org/uniprot/G3I4W7 |
| Cathepsin E (CatE) | 42.2 | 4.7 | G3HAY9 | 388 | Yang et al., 2019 | https://www.uniprot.org/uniprot/G3HAY9 | |
| Cathepsin L (CatL) | 37.3 | 6.8 | G3INC5 | 333 | also by Valente | Gao et al., 2011; Luo et al., 2018; Park et al., 2017 | https://www.uniprot.org/uniprot/G3INC5 |
| Cathepsin Z (CatZ) | 34 | 7.5 | Q9EPP7 | 306 | also by Valente ....Might want to add Migani et al 2017. | Brix et al., 2018; Chiverton et al., 2016; Park et al., 2017 | https://www.uniprot.org/uniprot/Q9EPP7 |
| Chondroitin sulfate proteoglycan 4 (CSPG4) | 252 | 5.4 | G3H0E4 | 2323 | Falkenberg et al., 2019; Levy et al., 2016 | https://www.uniprot.org/uniprot/G3H0E4 | |
| Clusterin (CLU) | 51.8 | 5.5 | G3HNJ3 | 447 | also by Valente and Park Migani et al., 2017 listed clusterin proteins from 3 other hosts (rat, mouse and another species of hamster) | Aboulaich et al., 2014; Albrecht et al., 2018a; Farrell et al., 2015; Kreimer et al., 2017; Levy et al., 2016; Migani et al., 2017; Singh et al., 2020; Zhang et al., 2014; Doneanu et al., 2012; Levy et al., 2014; Wilson & Easterbrook-Smith, 1992 | https://www.uniprot.org/uniprot/G3HNJ3 |
| Cofilin-1 (CFL) | 18.5 | 8.2 | G3IDM2 | 166 | Cofilin not in Gilgunn paper | Aboulaich et al., 2014; Albrecht et al., 2018a; Albrecht et al., 2018b; Gilgunn et al., 2019; Liu et al., 2019 | https://www.uniprot.org/uniprot/G3IDM2 |
| Elongation factor 1-alpha (eEF1a) | 50.1 | 9.1 | P62629 | 462 | Falkenberg et al., 2019; Liu et al., 2019; Zhang et al., 2014 | https://www.uniprot.org/uniprot/P62629 | |
| Elongation factor 2 (eEF2) | 95.3 | 6.2 | P09445 | 858 | also valente & falkenberg | Aboulaich et al., 2014; Albrecht et al., 2018b; Jawa et al., 2016; Liu et al., 2019; Zhang et al., 2014 | https://www.uniprot.org/uniprot/P09445 |
| Endoplasmin (HSP90B1) | 92.6 | 4.7 | G3HQM6 | 803 | also Valente | Albrecht et al., 2018b; Falkenberg et al., 2019; Gilgunn et al., 2019; Jawa et al., 2016; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3HQM6 |
| ERP57 protein | 56.8 | 6 | Q91Z81 | 505 | also Valente | Levy et al., 2016; Zhang et al., 2014 | https://www.uniprot.org/uniprot/Q91Z81 |
| Follistatin-related protein 1 (FST1) | 65.4 | 6.2 | G3HAI3 | 583 | Migani listed bovine protein | Levy et al., 2016; Migani et al., 2017; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3HAI3 |
| Fructose-bisphosphate aldolase (FBA) | 39.4 | 8.3 | G3I4H6 | 364 | also by Valente & Park | Chiverton et al., 2016; Liu et al., 2019 | https://www.uniprot.org/uniprot/G3I4H6 |
| Galectin 3 binding protein (Gal-3BP) | 63.8 | 5.1 | G3H3E4 | 574 | also by valente & Park ?. Georgeen Galectin 3 binding protein, Valente and Park entered as references under? comments.??? Could not find it referenced in Valente et al, 2018 or Park et al, 2017? Maybe it was in other Valente and Park publications? - REVIEW AT LATER DATE (not required for paper) | Levy et al., 2016; Singh et al., 2020 | https://www.uniprot.org/uniprot/G3H3E4 |
| Galectin-1 (Gal-1) | 14.8 | 5.5 | P48538 | 135 | Albrecht et al., 2018a; Albrecht et al., 2018b | https://www.uniprot.org/uniprot/P48538 | |
| Galectin-3 (Gal-3) | 32.4 | 6.9 | G3H7B3 | 281 | Aboulaich et al., 2014; Liu et al., 2019 | https://www.uniprot.org/uniprot/G3H7B3 | |
| Glutathione S-transferase P 1 (GSTP1) | 25 | 8.2 | G3I3Y6 | 221 | Also by Valente et al 2018 & Park?. Glutatione S-transferase P 1, I could not find it referenced in Gilgunn & Bones, 2018, but found it referenced in Valente et al, 2018. | Aboulaich et al., 2014; Gilgunn & Bones, 2018; Zhang et al., 2014; Albrecht et al., 2018b | https://www.uniprot.org/uniprot/G3I3Y6 |
| Glyceraldehyde-3-phosphate dehydrogenase (G3P) | 35.7 | 8.5 | P17244 | 333 | Falkenberg refers to a subunit of P17244 - G3IHW0 is poorly reviewed and has low homology with (80%) with P174244?should we remove Falkenberg? | Aboulaich et al., 2014; Albrecht et al., 2018a; Albrecht et al., 2018b; Falkenberg et al., 2019; Levy et al., 2016; Liu et al., 2019; Zhang et al., 2014 | https://www.uniprot.org/uniprot/P17244 |
| Granulins (GRN) | 63.9 | 6 | G3HLK3 | 592 | also by Valente | Jawa et al., 2016; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3HLK3 |
| GTP-binding nuclear protein (RAN) | 24.5 | 8.4 | G3IHE5 | 216 | Aboulaich et al., 2014; Gilgunn et al., 2019; Jawa et al., 2016 | https://www.uniprot.org/uniprot/G3IHE5 | |
| Guanine nucleotide-binding protein beta-2-like 1 (RACK1) | 30.4 | 7 | G3HK00 | 276 | Aboulaich et al., 2014; Gilgunn et al., 2019 | https://www.uniprot.org/uniprot/G3HK00 | |
| Heat shock cognate 71 kDa protein (HSPA8) | 70.8 | 5.2 | P19378 | 646 | removed Gilgunn et al., 2019; protein found in ref, grey: not found in ref - supplementals to be checked prior to removing reference from list | Aboulaich et al., 2014; Albrecht et al., 2018; Jawa et al., 2016; Liu et al., 2019; Migani et al., 2017 | https://www.uniprot.org/uniprot/P19378 |
| Heat shock protein HSP 90-alpha (HSP90A) | 84.8 | 5 | P46633 | 733 | Albrecht et al., 2018b; Jawa et al., 2016; Zhang et al., 2014 | https://www.uniprot.org/uniprot/P46633 | |
| Heat shock protein HSP 90-beta (HSP90B) | 47.8 | 5.3 | G3HC84 | 412 | Albrecht et al., 2018b; Gilgunn et al., 2019; Jawa et al., 2016; Liu et al., 2019; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3HC84 | |
| Hexosaminidase, beta | 60.7 | 6 | G3H3P | 528 | Li et at., 2021, Biotechnology Progress | ||
| Histone H2A | 26.7 | 10.9 | G3HDS3 | 236 | also in Levy | Liu et al., 2019 | https://www.uniprot.org/uniprot/G3HDS3 |
| Histone H2B Type 1-N (H2B1N) | 13.9 | 10.3 | G3HDU3 | 126 | Aboulaich et al., 2014; Gilgunn et al., 2019 | https://www.uniprot.org/uniprot/G3HDU3 | |
| Inter-alpha-trypsin inhibitor heavy chain H5 isoform X2 (ITIH5L) | 107.9 | 8.5 | G3H7S9 | 983 | Falkenberg et al., 2019; Levy et al., 2016 | https://www.uniprot.org/uniprot/G3H7S9 | |
| L-lactate dehydrogenase A chain (LDHA) | 36.5 | 7 | Q06BU8 | 332 | Aboulaich et al., 2014; Albrecht et al., 2018b | https://www.uniprot.org/uniprot/Q06BU8 | |
| Lactadherin (MFG-E8) | 16.1 | 9.5 | G3ICD3 | 140 | Aboulaich et al., 2014; Levy et al., 2016 | https://www.uniprot.org/uniprot/G3ICD3 | |
| lactotransferrin (LTF) | 71.4 | 8.6 | G3HTA2 | 648 | Kreimer et al., 2017; Liu et al., 2019 | https://www.uniprot.org/uniprot/G3HTA2 | |
| Laminin subunit beta-1 (LAMB1) | 178.1 | 4.8 | G3I278 | 1617 | Levy et al., 2016; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3I278 | |
| Laminin subunit gamma-1 (LAMC1) | 172.1 | 5 | G3HG25 | 1559 | Gilgunn et al., 2019; Levy et al., 2016; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3HG25 | |
| Legumain (LGMN) | 49.6 | 6.1 | G3I1H5 | 438 | Albrecht et al., 2018b; Levy et al., 2016; Migani et al., 2017 | https://www.uniprot.org/uniprot/G3I1H5 | |
| Lipoprotein Lipase (LPL) | 50.5 | 8 | G3H6V7 | 450 | Chiu et al., 2017; Levy et al., 2014; McShan et al., 2016; Levy et al., 2016; Singh et al., 2020 | https://www.uniprot.org/uniprot/G3H6V7 | |
| Lysosomal Acid Lipase (LAL) | 45.6 | 7.3 | G3HQY6 | 397 | Levy et al., 2014; McShan et al., 2016; Kreimer et al., 2017; Valente et al., 2015 | https://www.uniprot.org/uniprot/G3HQY6 | |
| Lysosomal Phospholipase A2 (LPLA2) | 47.2 | 6.1 | G3HKV9 | 412 | Chiu et al., 2017; Hall et al., 2016; McShan et al., 2016; Shayman et al., 2011 | https://www.uniprot.org/uniprot/G3HKV9 | |
| Lysosomal protective protein (CTSA) | 54.2 | 5.7 | G3H8V5 | 475 | Levy et al, 2014, Migani et al., 2017, Valente et al., 2015 | https://www.uniprot.org/uniprot/G3H8V5 | |
| Malate dehydrogenase, cytoplasmic (MDHC) | 36.5 | 6.2 | G3HDQ2 | 334 | Albrecht et al., 2018a; Albrecht et al., 2018b; Gilgunn et al., 2019 | https://www.uniprot.org/uniprot/G3HDQ2 | |
| Matrix metalloproteinase-19 (MMP-19) | 58.9 | 7.7 | G3HRK9 | 525 | Aboulaich et al., 2014; Farrell et al., 2015; Gilgunn & Bones, 2018; Levy et al., 2016; | https://www.uniprot.org/uniprot/G3HRK9 | |
| Metalloproteinase inhibitor 1 (TIMP1) | 22.4 | 8.8 | G3IBH0 | 203 | Aboulaich et al., 2014; Albrecht et al., 2018b; Levy et al., 2016 | https://www.uniprot.org/uniprot/G3IBH0 | |
| Monocyte Chemoattractant Protein-1 (MCP-1) | 15.9 | 9.3 | G3GTT2 | 143 | Leister et al., 2019; Yoshimura & Leonard, 1989 | https://www.uniprot.org/uniprot/G3GTT2 | |
| Myosin-9 (MYH9) | 225.8 | 5.5 | G3IH63 | 1948 | Gilgunn et al., 2019; Liu et al., 2019 | https://www.uniprot.org/uniprot/G3IH63 | |
| Nidogen-1 (NID1) | 30.1 | 8.4 | G3I3U5 | 278 | Aboulaich et al., 2014; Levy et al., 2016; Zhang et al., 2014; Singh et al., 2020 | https://www.uniprot.org/uniprot/G3I3U5 | |
| Nucleobindin-2 (NUCB2) | 50.3 | 5.1 | G3IF52 | 420 | Levy et al., 2016; Migani et al., 2017 | https://www.uniprot.org/uniprot/G3IF52 | |
| Nucleoside diphosphate kinase B (NDPK-B) | 17.3 | 7.8 | G3HBD3 | 152 | Aboulaich et al., 2014; Albrecht et al., 2018b | https://www.uniprot.org/uniprot/G3HBD3 | |
| Peptidyl-prolyl cis-trans isomerase A (PPIA) | 17.9 | 8.4 | P14851 | 164 | Aboulaich et al., 2014; Falkenberg et al., 2019; | https://www.uniprot.org/uniprot/P14851 | |
| Peroxiredoxin-1 (PRDX1) | 22.3 | 8.2 | Q9JKY1 | 199 | Aboulaich et al., 2014; Albrecht et al., 2018b; Chiverton et al., 2016; Falkenberg et al., 2019; Jawa et al., 2016; Kreimer et al., 2017; Liu et al., 2019; Migani et al., 2017, Zhang et al., 2014 | https://www.uniprot.org/uniprot/Q9JKY1 | |
| Phosphoglycerate kinase (PGK1) | 44.6 | 8 | P50310 | 417 | Falkenberg et al., 2019; Liu et al., 2019; Zhang et al., 2014 | https://www.uniprot.org/uniprot/P50310 | |
| Phosphoglycerate mutase 1 (Pgam1) | 20.2 | 7.8 | G3GZW8 | 178 | Aboulaich et al., 2014; Gilgunn et al., 2019; Liu et al., 2019; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3GZW8 | |
| Phospholipase B-like 2 (PLBL2) | 65.5 | 5.9 | G3I6T1 | 585 | Aboulaich et al., 2014; de Zafra et al., 2015; Fischer et al., 2017; Jawa et al., 2016; Migani et al., 2017 | https://www.uniprot.org/uniprot/G3I6T1 | |
| Phospholipase D3 (PLD3) | 54.4 | 6 | G3HNQ5 | 488 | McShan et al., 2016; Zhang et al., 2020 | https://www.uniprot.org/uniprot/G3HNQ5 | |
| Phospholipid transfer protein (PLTP) | 54.4 | 6.2 | G3H8V4 | 493 | Gilgunn et al., 2019; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3H8V4 | |
| Plectin-1 (Plec1) | 83.4 | 8.7 | G3HWJ2 | 720 | Aboulaich et al., 2014 | https://www.uniprot.org/uniprot/G3HWJ2 | |
| Procollagen C-endopeptidase enhancer (PCPE1) | 55.2 | 8.5 | G3I664 | 509 | Farrell et al., 2015; Levy et al., 2016; Migani et al., 2017; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3I664 | |
| Procollagen-lysine 2-oxoglutarate 5-deoxygenase_1 (PLOD1) | 76 | 5.8 | G3IIE7 | 659 | Hogwood et al., 2016; Jawa et al., 2016 | https://www.uniprot.org/uniprot/G3IIE7 | |
| Proteasome subunit alpha type-7 (PSA7) | 23.8 | 8.6 | G3GWR8 | 212 | Aboulaich et al., 2014; Liu et al., 2019 | https://www.uniprot.org/uniprot/G3GWR8 | |
| Protein S100-A6 (S10A6) | 10 | 5.3 | G3HC31 | 89 | Aboulaich et al., 2014; Gilgunn & Bones, 2018; Paintlia et al., 2004 | https://www.uniprot.org/uniprot/G3HC31 | |
| Pyruvate Kinase (PK) | 51.6 | 7.6 | G3H3Q1 | 472 | Chiverton et al., 2016; Goey et al., 2018; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3H3Q1 | |
| Serine protease (HTRA1) | 28.7 | 6.5 | G3IBF4 | 268 | Aboulaich et al., 2014; Dorai et al., 2011; Falkenberg et al., 2019; Gilgunn & Bones, 2018; Goey et al., 2018; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3IBF4 | |
| Sialate o-acetylesterase (SIAE) | 59.3 | 8.6 | A0A3L7HS03 | 529 | https://www.uniprot.org/uniprot/A0A3L7HS03 | ||
| Sulfated glycoprotein (SGP-1) | 27.4 | 5.4 | G3I1Y9 | 249 | Aboulaich et al., 2014; Singh et al., 2020; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3I1Y9 | |
| Transforming Growth Factor-b1 (TGF-b1) | 26.4 | 8.5 | G3IA12 | 237 | Beatson et al., 2011; Vanderlaan et al., 2018 | https://www.uniprot.org/uniprot/G3IA12 | |
| Transgelin-2 (TAGLN) | 22.5 | 8.8 | G3H7Z2 | 199 | Albrecht et al., 2018a; Albrecht et al., 2018b | https://www.uniprot.org/uniprot/G3H7Z2 | |
| Transketolase (TKTase) | 67.7 | 7.6 | G3GUU5? | 623 | Gilgunn et al., 2019; Zhang et al., 2014 | https://www.uniprot.org/uniprot/G3GUU5 | |
| Triosephosphate isomerase (TPI) | 16.4 | 8.5 | G3HNV4 | 150 | Aboulaich et al., 2014; Gilgunn et al., 2019 | https://www.uniprot.org/uniprot/G3HNV4 | |
| Tubulin alpha-1A chain (TBA1A) | 50.1 | 4.9 | P68362 | 451 | Gilgunn et al., 2019 | https://www.uniprot.org/uniprot/P68362 | |
| Tubulin alpha-1C chain (TBA1C) | 49.9 | 5 | P68365 | 449 | Zhang et al., 2014 | https://www.uniprot.org/uniprot/P68365 | |
| V-type proton ATPase subunit C 1 (VATC1) | 43.9 | 7 | G3I3N5 | 382 | Aboulaich et al., 2014 | https://www.uniprot.org/uniprot/G3I3N5 | |
| Vimentin (VIME) | 51.8 | 4.9 | P48670 | 448 | Aboulaich et al., 2014; Gilgunn et al., 2019 | https://www.uniprot.org/uniprot/P48670 |