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 HCPUniProtMW
(Molecular Weight)
plAAsReferences
40S ribosomal protein SA (RPSA)G3HQX019.79.4179Aboulaich et al., 2014; Liu et al., 2019https://www.uniprot.org/uniprot/G3HQX0
60S acidic ribosomal protein P0G3HKG930.68.9280Aboulaich et al., 2014; Liu et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/G3HKG9
78 kDa glucose regulated protein(GRP78, BiP)G3I8R972.45.1654Aboulaich 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)P4897541.75.2375also 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)G3I0W115.55139Liu et al., 2019https://www.uniprot.org/uniprot/G3I0W1
Annexin A2G3IG05275.7244Falkenberg 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 A5G3I5A436.14.9321also in ParkFarrell et al., 2015; Gilgunn & Bones, 2018https://www.uniprot.org/uniprot/G3I5A4
C-C motif chemokineG3GTT215.99.3143Farrell et al., 2015https://www.uniprot.org/uniprot/G3GTT2
C-X-C motif chemokine 3 (CXCL3)A4URF0119.1101Farrell et al., 2015; Gilgunn & Bones, 2018; Zhang et al., 2014https://www.uniprot.org/uniprot/A4URF0
Calmodulin (CaM)A0A061HUH116.74.1149Albrecht et al., 2018b; Liu et al., 2019https://www.uniprot.org/uniprot/A0A061HUH1
Calreticulin (CALR)G3HCX848.44.3417Farrell 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)A0A061IFE297.55.9882Zhang et al., 2020https://www.uniprot.org/uniprot/A0A061IFE2
Carboxylesterase B-1-like protein, Liver (CES-B1L)A0A061I7X977.97.9704Zhang et al., 2020https://www.uniprot.org/uniprot/A0A061I7X9
Carboxypeptidase D (Cpd)G3HR95123.45.81106Hu et al., 2016; Dick et al., 2008 (Dick, Qiu, Mahon, Adamo, & Cheng, 2008)https://www.uniprot.org/uniprot/G3HR95
CatalaseG3GYY663.18.3555also ValenteAhluwalia et al., 2017; Liu et al., 2019https://www.uniprot.org/uniprot/G3GYY6
Cathepsin B (CatB)G3H0L937.55.7339also 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)G3I4W744.16.5408also 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)G3HAY942.24.7388Yang et al., 2019https://www.uniprot.org/uniprot/G3HAY9
Cathepsin L (CatL)G3INC537.36.8333also by ValenteGao et al., 2011; Luo et al., 2018; Park et al., 2017https://www.uniprot.org/uniprot/G3INC5
Cathepsin Z (CatZ)Q9EPP7347.5306also 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)G3H0E42525.42323Falkenberg et al., 2019; Levy et al., 2016https://www.uniprot.org/uniprot/G3H0E4
Clusterin (CLU)G3HNJ351.85.5447also 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)G3IDM218.58.2166Cofilin 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)P6262950.19.1462Falkenberg et al., 2019; Liu et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/P62629
Elongation factor 2 (eEF2)P0944595.36.2858also 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)G3HQM692.64.7803also 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 proteinQ91Z8156.86505also ValenteLevy et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/Q91Z81
Follistatin-related protein 1 (FST1)G3HAI365.46.2583Migani listed bovine proteinLevy et al., 2016; Migani et al., 2017; Zhang et al., 2014https://www.uniprot.org/uniprot/G3HAI3
Fructose-bisphosphate aldolase (FBA)G3I4H639.48.3364also by Valente & ParkChiverton et al., 2016; Liu et al., 2019https://www.uniprot.org/uniprot/G3I4H6
Galectin 3 binding protein (Gal-3BP)G3H3E463.85.1574also 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)P4853814.85.5135Albrecht et al., 2018a; Albrecht et al., 2018bhttps://www.uniprot.org/uniprot/P48538
Galectin-3 (Gal-3)G3H7B332.46.9281Aboulaich et al., 2014; Liu et al., 2019https://www.uniprot.org/uniprot/G3H7B3
Glutathione S-transferase P 1 (GSTP1)G3I3Y6258.2221Also 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)P1724435.78.5333Falkenberg 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)G3HLK363.96592also by ValenteJawa et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/G3HLK3
GTP-binding nuclear protein (RAN)G3IHE524.58.4216Aboulaich 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)G3HK0030.47276Aboulaich et al., 2014; Gilgunn et al., 2019https://www.uniprot.org/uniprot/G3HK00
Heat shock cognate 71 kDa protein (HSPA8)P1937870.85.2646removed 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)P4663384.85733Albrecht et al., 2018b; Jawa et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/P46633
Heat shock protein HSP 90-beta (HSP90B)G3HC8447.85.3412Albrecht 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, betaG3H3P60.76528Li et at., 2021, Biotechnology Progress
Histone H2AG3HDS326.710.9236also in LevyLiu et al., 2019https://www.uniprot.org/uniprot/G3HDS3
Histone H2B Type 1-N (H2B1N)G3HDU313.910.3126 Aboulaich et al., 2014; Gilgunn et al., 2019https://www.uniprot.org/uniprot/G3HDU3
Inter-alpha-trypsin inhibitor heavy chain H5 isoform X2 (ITIH5L)G3H7S9107.98.5983Falkenberg et al., 2019; Levy et al., 2016https://www.uniprot.org/uniprot/G3H7S9
L-lactate dehydrogenase A chain (LDHA)Q06BU836.57332Aboulaich et al., 2014; Albrecht et al., 2018bhttps://www.uniprot.org/uniprot/Q06BU8
Lactadherin (MFG-E8)G3ICD316.19.5140Aboulaich et al., 2014; Levy et al., 2016https://www.uniprot.org/uniprot/G3ICD3
lactotransferrin (LTF)G3HTA271.48.6648Kreimer et al., 2017; Liu et al., 2019https://www.uniprot.org/uniprot/G3HTA2
Laminin subunit beta-1 (LAMB1)G3I278178.14.81617Levy et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/G3I278
Laminin subunit gamma-1 (LAMC1)G3HG25172.151559Gilgunn et al., 2019; Levy et al., 2016; Zhang et al., 2014https://www.uniprot.org/uniprot/G3HG25
Legumain (LGMN)G3I1H549.66.1438Albrecht et al., 2018b; Levy et al., 2016; Migani et al., 2017https://www.uniprot.org/uniprot/G3I1H5
Lipoprotein Lipase (LPL)G3H6V750.58450Chiu 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)G3HQY645.67.3397Levy et al., 2014; McShan et al., 2016; Kreimer et al., 2017; Valente et al., 2015https://www.uniprot.org/uniprot/G3HQY6
Lysosomal Phospholipase A2 (LPLA2)G3HKV947.26.1412Chiu et al., 2017; Hall et al., 2016; McShan et al., 2016; Shayman et al., 2011https://www.uniprot.org/uniprot/G3HKV9
Lysosomal protective protein (CTSA)G3H8V554.25.7475Levy et al, 2014, Migani et al., 2017, Valente et al., 2015https://www.uniprot.org/uniprot/G3H8V5
Malate dehydrogenase, cytoplasmic (MDHC)G3HDQ236.56.2334Albrecht et al., 2018a; Albrecht et al., 2018b; Gilgunn et al., 2019https://www.uniprot.org/uniprot/G3HDQ2
Matrix metalloproteinase-19 (MMP-19)G3HRK958.97.7525Aboulaich et al., 2014; Farrell et al., 2015; Gilgunn & Bones, 2018; Levy et al., 2016; https://www.uniprot.org/uniprot/G3HRK9
Metalloproteinase inhibitor 1 (TIMP1)G3IBH022.48.8203Aboulaich et al., 2014; Albrecht et al., 2018b; Levy et al., 2016https://www.uniprot.org/uniprot/G3IBH0
Monocyte Chemoattractant Protein-1 (MCP-1)G3GTT215.99.3143Leister et al., 2019; Yoshimura & Leonard, 1989https://www.uniprot.org/uniprot/G3GTT2
Myosin-9 (MYH9)G3IH63225.85.51948Gilgunn et al., 2019; Liu et al., 2019https://www.uniprot.org/uniprot/G3IH63
Nidogen-1 (NID1)G3I3U530.18.4278Aboulaich et al., 2014; Levy et al., 2016; Zhang et al., 2014; Singh et al., 2020https://www.uniprot.org/uniprot/G3I3U5
Nucleobindin-2 (NUCB2)G3IF5250.35.1420Levy et al., 2016; Migani et al., 2017https://www.uniprot.org/uniprot/G3IF52
Nucleoside diphosphate kinase B (NDPK-B)G3HBD317.37.8152Aboulaich et al., 2014; Albrecht et al., 2018bhttps://www.uniprot.org/uniprot/G3HBD3
Peptidyl-prolyl cis-trans isomerase A (PPIA)P1485117.98.4164Aboulaich et al., 2014; Falkenberg et al., 2019; https://www.uniprot.org/uniprot/P14851
Peroxiredoxin-1 (PRDX1)Q9JKY122.38.2199Aboulaich 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)P5031044.68417Falkenberg et al., 2019; Liu et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/P50310
Phosphoglycerate mutase 1 (Pgam1)G3GZW820.27.8178Aboulaich 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)G3I6T165.55.9585Aboulaich 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)G3HNQ554.46488McShan et al., 2016; Zhang et al., 2020https://www.uniprot.org/uniprot/G3HNQ5
Phospholipid transfer protein (PLTP)G3H8V454.46.2493Gilgunn et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/G3H8V4
Plectin-1 (Plec1)G3HWJ283.48.7720Aboulaich et al., 2014https://www.uniprot.org/uniprot/G3HWJ2
Procollagen C-endopeptidase enhancer (PCPE1)G3I66455.28.5509Farrell 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)G3IIE7765.8659Hogwood et al., 2016; Jawa et al., 2016https://www.uniprot.org/uniprot/G3IIE7
Proteasome subunit alpha type-7 (PSA7)G3GWR823.88.6212Aboulaich et al., 2014; Liu et al., 2019https://www.uniprot.org/uniprot/G3GWR8
Protein S100-A6 (S10A6)G3HC31105.389Aboulaich et al., 2014; Gilgunn & Bones, 2018; Paintlia et al., 2004https://www.uniprot.org/uniprot/G3HC31
Pyruvate Kinase (PK)G3H3Q151.67.6472Chiverton et al., 2016; Goey et al., 2018; Zhang et al., 2014https://www.uniprot.org/uniprot/G3H3Q1
Serine protease (HTRA1)G3IBF428.76.5268Aboulaich 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)A0A3L7HS0359.38.6529https://www.uniprot.org/uniprot/A0A3L7HS03
Sulfated glycoprotein (SGP-1)G3I1Y927.45.4249Aboulaich et al., 2014; Singh et al., 2020; Zhang et al., 2014https://www.uniprot.org/uniprot/G3I1Y9
Transforming Growth Factor-b1 (TGF-b1)G3IA1226.48.5237Beatson et al., 2011; Vanderlaan et al., 2018https://www.uniprot.org/uniprot/G3IA12
Transgelin-2 (TAGLN)G3H7Z222.58.8199Albrecht et al., 2018a; Albrecht et al., 2018bhttps://www.uniprot.org/uniprot/G3H7Z2
Transketolase (TKTase)G3GUU5?67.77.6623Gilgunn et al., 2019; Zhang et al., 2014https://www.uniprot.org/uniprot/G3GUU5
Triosephosphate isomerase (TPI)G3HNV416.48.5150Aboulaich et al., 2014; Gilgunn et al., 2019https://www.uniprot.org/uniprot/G3HNV4
Tubulin alpha-1A chain (TBA1A)P6836250.14.9451Gilgunn et al., 2019https://www.uniprot.org/uniprot/P68362
Tubulin alpha-1C chain (TBA1C)P6836549.95449 Zhang et al., 2014https://www.uniprot.org/uniprot/P68365
V-type proton ATPase subunit C 1 (VATC1)G3I3N543.97382Aboulaich et al., 2014https://www.uniprot.org/uniprot/G3I3N5
Vimentin (VIME)P4867051.84.9448Aboulaich et al., 2014; Gilgunn et al., 2019https://www.uniprot.org/uniprot/P48670

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