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.

dna sequencing peaks with microscope

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 HCPMWplUniProtAAsCommentsRefsLink
40S ribosomal protein SA (RPSA)19.79.4G3HQX0179Aboulaich et al., 2014; Liu et al., 2019https://www.uniprot.org/uniprot/G3HQX0
60S acidic ribosomal protein P030.68.9G3HKG9280Aboulaich et al., 2014; Liu et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/G3HKG9
78 kDa glucose regulated protein(GRP78, BiP)72.45.1G3I8R9654Aboulaich 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., 2016https://www.uniprot.org/uniprot/G3I8R9
Actin, cytoplasmic 1 (ACTB)41.75.2P48975375also by LevyAboulaich et al., 2014; Falkenberg et al., 2019; Farrell et al., 2015; Jawa et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/P48975
Alpha-enolase (2-phospho-D-glycerate hydro-lyase)15.55G3I0W1139Liu et al., 2019https://www.uniprot.org/uniprot/G3I0W1
Annexin A2275.7G3IG05244Falkenberg 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., 2014https://www.uniprot.org/uniprot/G3IG05
Annexin A536.14.9G3I5A4321also in ParkFarrell et al., 2015; Gilgunn & Bones, 2018https://www.uniprot.org/uniprot/G3I5A4
C-C motif chemokine15.99.3G3GTT2143Farrell et al., 2015https://www.uniprot.org/uniprot/G3GTT2
C-X-C motif chemokine 3 (CXCL3)119.1A4URF0101Farrell et al., 2015; Gilgunn & Bones, 2018; Zhang et al., 2014https://www.uniprot.org/uniprot/A4URF0
Calmodulin (CaM)16.74.1A0A061HUH1149Albrecht et al., 2018b; Liu et al., 2019https://www.uniprot.org/uniprot/A0A061HUH1
Calreticulin (CALR)48.44.3G3HCX8417Farrell et al., 2015; Gilgunn et al., 2019; Valente et al., 2014; Zhang et al., 2014https://www.uniprot.org/uniprot/G3HCX8
Carboxylesterase 1-like protein, Liver (CES1)97.55.9A0A061IFE2882Zhang et al., 2020https://www.uniprot.org/uniprot/A0A061IFE2
Carboxylesterase B-1-like protein, Liver (CES-B1L)77.97.9A0A061I7X9704Zhang et al., 2020https://www.uniprot.org/uniprot/A0A061I7X9
Carboxypeptidase D (Cpd)123.45.8G3HR951106Hu et al., 2016; Dick et al., 2008 (Dick, Qiu, Mahon, Adamo, & Cheng, 2008)https://www.uniprot.org/uniprot/G3HR95
Catalase63.18.3G3GYY6555also ValenteAhluwalia et al., 2017; Liu et al., 2019https://www.uniprot.org/uniprot/G3GYY6
Cathepsin B (CatB)37.55.7G3H0L9339also by Valente & ParkAboulaich 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., 2019https://www.uniprot.org/uniprot/G3H0L9
Cathepsin D (CatD)44.16.5G3I4W7408also 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, 2020https://www.uniprot.org/uniprot/G3I4W7
Cathepsin E (CatE)42.24.7G3HAY9388Yang et al., 2019https://www.uniprot.org/uniprot/G3HAY9
Cathepsin L (CatL)37.36.8G3INC5333also by ValenteGao et al., 2011; Luo et al., 2018; Park et al., 2017https://www.uniprot.org/uniprot/G3INC5
Cathepsin Z (CatZ)347.5Q9EPP7306also by Valente ....Might want to add Migani et al 2017.Brix et al., 2018; Chiverton et al., 2016; Park et al., 2017https://www.uniprot.org/uniprot/Q9EPP7
Chondroitin sulfate proteoglycan 4 (CSPG4)2525.4G3H0E42323Falkenberg et al., 2019; Levy et al., 2016https://www.uniprot.org/uniprot/G3H0E4
Clusterin (CLU)51.85.5G3HNJ3447also 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, 1992https://www.uniprot.org/uniprot/G3HNJ3
Cofilin-1 (CFL)18.58.2G3IDM2166Cofilin not in Gilgunn paperAboulaich et al., 2014; Albrecht et al., 2018a; Albrecht et al., 2018b; Gilgunn et al., 2019; Liu et al., 2019https://www.uniprot.org/uniprot/G3IDM2
Elongation factor 1-alpha (eEF1a)50.19.1P62629462Falkenberg et al., 2019; Liu et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/P62629
Elongation factor 2 (eEF2)95.36.2P09445858also valente & falkenbergAboulaich et al., 2014; Albrecht et al., 2018b; Jawa et al., 2016; Liu et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/P09445
Endoplasmin (HSP90B1)92.64.7G3HQM6803also ValenteAlbrecht et al., 2018b; Falkenberg et al., 2019; Gilgunn et al., 2019; Jawa et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/G3HQM6
ERP57 protein56.86Q91Z81505also ValenteLevy et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/Q91Z81
Follistatin-related protein 1 (FST1)65.46.2G3HAI3583Migani listed bovine proteinLevy et al., 2016; Migani et al., 2017; Zhang et al., 2014https://www.uniprot.org/uniprot/G3HAI3
Fructose-bisphosphate aldolase (FBA)39.48.3G3I4H6364also by Valente & ParkChiverton et al., 2016; Liu et al., 2019https://www.uniprot.org/uniprot/G3I4H6
Galectin 3 binding protein (Gal-3BP)63.85.1G3H3E4574also 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., 2020https://www.uniprot.org/uniprot/G3H3E4
Galectin-1 (Gal-1)14.85.5P48538135Albrecht et al., 2018a; Albrecht et al., 2018bhttps://www.uniprot.org/uniprot/P48538
Galectin-3 (Gal-3)32.46.9G3H7B3281Aboulaich et al., 2014; Liu et al., 2019https://www.uniprot.org/uniprot/G3H7B3
Glutathione S-transferase P 1 (GSTP1)258.2G3I3Y6221Also 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., 2018bhttps://www.uniprot.org/uniprot/G3I3Y6
Glyceraldehyde-3-phosphate dehydrogenase (G3P)35.78.5P17244333Falkenberg 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., 2014https://www.uniprot.org/uniprot/P17244
Granulins (GRN)63.96G3HLK3592also by ValenteJawa et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/G3HLK3
GTP-binding nuclear protein (RAN)24.58.4G3IHE5216Aboulaich et al., 2014; Gilgunn et al., 2019; Jawa et al., 2016https://www.uniprot.org/uniprot/G3IHE5
Guanine nucleotide-binding protein beta-2-like 1 (RACK1)30.47G3HK00276Aboulaich et al., 2014; Gilgunn et al., 2019https://www.uniprot.org/uniprot/G3HK00
Heat shock cognate 71 kDa protein (HSPA8)70.85.2P19378646removed Gilgunn et al., 2019; protein found in ref, grey: not found in ref - supplementals to be checked prior to removing reference from listAboulaich et al., 2014; Albrecht et al., 2018; Jawa et al., 2016; Liu et al., 2019; Migani et al., 2017https://www.uniprot.org/uniprot/P19378
Heat shock protein HSP 90-alpha (HSP90A)84.85P46633733Albrecht et al., 2018b; Jawa et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/P46633
Heat shock protein HSP 90-beta (HSP90B)47.85.3G3HC84412Albrecht et al., 2018b; Gilgunn et al., 2019; Jawa et al., 2016; Liu et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/G3HC84
Hexosaminidase, beta60.76G3H3P528Li et at., 2021, Biotechnology Progress
Histone H2A26.710.9G3HDS3236also in LevyLiu et al., 2019https://www.uniprot.org/uniprot/G3HDS3
Histone H2B Type 1-N (H2B1N)13.910.3G3HDU3126 Aboulaich et al., 2014; Gilgunn et al., 2019https://www.uniprot.org/uniprot/G3HDU3
Inter-alpha-trypsin inhibitor heavy chain H5 isoform X2 (ITIH5L)107.98.5G3H7S9983Falkenberg et al., 2019; Levy et al., 2016https://www.uniprot.org/uniprot/G3H7S9
L-lactate dehydrogenase A chain (LDHA)36.57Q06BU8332Aboulaich et al., 2014; Albrecht et al., 2018bhttps://www.uniprot.org/uniprot/Q06BU8
Lactadherin (MFG-E8)16.19.5G3ICD3140Aboulaich et al., 2014; Levy et al., 2016https://www.uniprot.org/uniprot/G3ICD3
lactotransferrin (LTF)71.48.6G3HTA2648Kreimer et al., 2017; Liu et al., 2019https://www.uniprot.org/uniprot/G3HTA2
Laminin subunit beta-1 (LAMB1)178.14.8G3I2781617Levy et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/G3I278
Laminin subunit gamma-1 (LAMC1)172.15G3HG251559Gilgunn et al., 2019; Levy et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/G3HG25
Legumain (LGMN)49.66.1G3I1H5438Albrecht et al., 2018b; Levy et al., 2016; Migani et al., 2017https://www.uniprot.org/uniprot/G3I1H5
Lipoprotein Lipase (LPL)50.58G3H6V7450Chiu et al., 2017; Levy et al., 2014; McShan et al., 2016; Levy et al., 2016; Singh et al., 2020https://www.uniprot.org/uniprot/G3H6V7
Lysosomal Acid Lipase (LAL)45.67.3G3HQY6397Levy et al., 2014; McShan et al., 2016; Kreimer et al., 2017; Valente et al., 2015https://www.uniprot.org/uniprot/G3HQY6
Lysosomal Phospholipase A2 (LPLA2)47.26.1G3HKV9412Chiu et al., 2017; Hall et al., 2016; McShan et al., 2016; Shayman et al., 2011https://www.uniprot.org/uniprot/G3HKV9
Lysosomal protective protein (CTSA)54.25.7G3H8V5475Levy et al, 2014, Migani et al., 2017, Valente et al., 2015https://www.uniprot.org/uniprot/G3H8V5
Malate dehydrogenase, cytoplasmic (MDHC)36.56.2G3HDQ2334Albrecht et al., 2018a; Albrecht et al., 2018b; Gilgunn et al., 2019https://www.uniprot.org/uniprot/G3HDQ2
Matrix metalloproteinase-19 (MMP-19)58.97.7G3HRK9525Aboulaich et al., 2014; Farrell et al., 2015; Gilgunn & Bones, 2018; Levy et al., 2016; https://www.uniprot.org/uniprot/G3HRK9
Metalloproteinase inhibitor 1 (TIMP1)22.48.8G3IBH0203Aboulaich et al., 2014; Albrecht et al., 2018b; Levy et al., 2016https://www.uniprot.org/uniprot/G3IBH0
Monocyte Chemoattractant Protein-1 (MCP-1)15.99.3G3GTT2143Leister et al., 2019; Yoshimura & Leonard, 1989https://www.uniprot.org/uniprot/G3GTT2
Myosin-9 (MYH9)225.85.5G3IH631948Gilgunn et al., 2019; Liu et al., 2019https://www.uniprot.org/uniprot/G3IH63
Nidogen-1 (NID1)30.18.4G3I3U5278Aboulaich et al., 2014; Levy et al., 2016; Zhang et al., 2014; Singh et al., 2020https://www.uniprot.org/uniprot/G3I3U5
Nucleobindin-2 (NUCB2)50.35.1G3IF52420Levy et al., 2016; Migani et al., 2017https://www.uniprot.org/uniprot/G3IF52
Nucleoside diphosphate kinase B (NDPK-B)17.37.8G3HBD3152Aboulaich et al., 2014; Albrecht et al., 2018bhttps://www.uniprot.org/uniprot/G3HBD3
Peptidyl-prolyl cis-trans isomerase A (PPIA)17.98.4P14851164Aboulaich et al., 2014; Falkenberg et al., 2019; https://www.uniprot.org/uniprot/P14851
Peroxiredoxin-1 (PRDX1)22.38.2Q9JKY1199Aboulaich 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., 2014https://www.uniprot.org/uniprot/Q9JKY1
Phosphoglycerate kinase (PGK1)44.68P50310417Falkenberg et al., 2019; Liu et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/P50310
Phosphoglycerate mutase 1 (Pgam1)20.27.8G3GZW8178Aboulaich et al., 2014; Gilgunn et al., 2019; Liu et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/G3GZW8
Phospholipase B-like 2 (PLBL2)65.55.9G3I6T1585Aboulaich et al., 2014; de Zafra et al., 2015; Fischer et al., 2017; Jawa et al., 2016; Migani et al., 2017https://www.uniprot.org/uniprot/G3I6T1
Phospholipase D3 (PLD3)54.46G3HNQ5488McShan et al., 2016; Zhang et al., 2020https://www.uniprot.org/uniprot/G3HNQ5
Phospholipid transfer protein (PLTP)54.46.2G3H8V4493Gilgunn et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/G3H8V4
Plectin-1 (Plec1)83.48.7G3HWJ2720Aboulaich et al., 2014https://www.uniprot.org/uniprot/G3HWJ2
Procollagen C-endopeptidase enhancer (PCPE1)55.28.5G3I664509Farrell et al., 2015; Levy et al., 2016; Migani et al., 2017; Zhang et al., 2014https://www.uniprot.org/uniprot/G3I664
Procollagen-lysine 2-oxoglutarate 5-deoxygenase_1 (PLOD1)765.8G3IIE7659Hogwood et al., 2016; Jawa et al., 2016https://www.uniprot.org/uniprot/G3IIE7
Proteasome subunit alpha type-7 (PSA7)23.88.6G3GWR8212Aboulaich et al., 2014; Liu et al., 2019https://www.uniprot.org/uniprot/G3GWR8
Protein S100-A6 (S10A6)105.3G3HC3189Aboulaich et al., 2014; Gilgunn & Bones, 2018; Paintlia et al., 2004https://www.uniprot.org/uniprot/G3HC31
Pyruvate Kinase (PK)51.67.6G3H3Q1472Chiverton et al., 2016; Goey et al., 2018; Zhang et al., 2014https://www.uniprot.org/uniprot/G3H3Q1
Serine protease (HTRA1)28.76.5G3IBF4268Aboulaich et al., 2014; Dorai et al., 2011; Falkenberg et al., 2019; Gilgunn & Bones, 2018; Goey et al., 2018; Zhang et al., 2014https://www.uniprot.org/uniprot/G3IBF4
Sialate o-acetylesterase (SIAE)59.38.6A0A3L7HS03529https://www.uniprot.org/uniprot/A0A3L7HS03
Sulfated glycoprotein (SGP-1)27.45.4G3I1Y9249Aboulaich et al., 2014; Singh et al., 2020; Zhang et al., 2014https://www.uniprot.org/uniprot/G3I1Y9
Transforming Growth Factor-b1 (TGF-b1)26.48.5G3IA12237Beatson et al., 2011; Vanderlaan et al., 2018https://www.uniprot.org/uniprot/G3IA12
Transgelin-2 (TAGLN)22.58.8G3H7Z2199Albrecht et al., 2018a; Albrecht et al., 2018bhttps://www.uniprot.org/uniprot/G3H7Z2
Transketolase (TKTase)67.77.6G3GUU5?623Gilgunn et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/G3GUU5
Triosephosphate isomerase (TPI)16.48.5G3HNV4150Aboulaich et al., 2014; Gilgunn et al., 2019https://www.uniprot.org/uniprot/G3HNV4
Tubulin alpha-1A chain (TBA1A)50.14.9P68362451Gilgunn et al., 2019https://www.uniprot.org/uniprot/P68362
Tubulin alpha-1C chain (TBA1C)49.95P68365449 Zhang et al., 2014https://www.uniprot.org/uniprot/P68365
V-type proton ATPase subunit C 1 (VATC1)43.97G3I3N5382Aboulaich et al., 2014https://www.uniprot.org/uniprot/G3I3N5
Vimentin (VIME)51.84.9P48670448Aboulaich et al., 2014; Gilgunn et al., 2019https://www.uniprot.org/uniprot/P48670
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