CLPS (Colipase) Gene in Humans – Functional Annotation and Research Overview OpenAI o3-deep-research-2025-06-26 72 citations 2025-11-03T21:38:56.053646

CLPS (Colipase) Gene in Humans – Functional Annotation and Research Overview

Overview and Gene Product Identity

The human CLPS gene encodes colipase, a small protein cofactor essential for pancreatic triglyceride lipase activity and dietary fat digestion (gosset.ai). Colipase is produced as a 112–amino acid preproprotein (UniProt P04118) that includes a signal peptide and an activation segment (pmc.ncbi.nlm.nih.gov). It is exclusively expressed in the exocrine pancreas – particularly in acinar cells – and secreted into pancreatic juice as procolipase (www.ncbi.nlm.nih.gov). During digestion, procolipase is activated by trypsin cleavage in the duodenum, yielding active colipase and releasing a small N-terminal pentapeptide called enterostatin (gosset.ai) (pmc.ncbi.nlm.nih.gov). The CLPS gene is located on chromosome 6p21.31 (pmc.ncbi.nlm.nih.gov) and exhibits highly tissue-specific expression (e.g. ~17,700 RPKM in pancreas, with essentially no expression in other tissues) (www.ncbi.nlm.nih.gov). This extreme enrichment reflects colipase’s dedicated role in pancreatic exocrine function.

Molecular Function and Mechanism of Colipase

Colipase itself has no enzymatic activity; instead, it serves as a critical cofactor that enables pancreatic triglyceride lipase (PTL) to function optimally in the intestinal lumen (gosset.ai). One colipase binds stoichiometrically to one lipase molecule, targeting the C-terminal, non-catalytic domain of PTL (www.genecards.org). This interaction stabilizes lipase in an open, active conformation and expands its hydrophobic surface, greatly enhancing the enzyme’s ability to bind lipid substrates (www.genecards.org). Colipase also has a high affinity for lipid–water interfaces: it can bind to emulsified dietary fat droplets (micelles) and simultaneously tether the lipase enzyme there (gosset.ai). In essence, colipase anchors and stabilizes pancreatic lipase at the lipid interface even in the presence of bile salts, which would otherwise displace or inhibit the enzyme (gosset.ai) (www.ncbi.nlm.nih.gov). By counteracting bile salt-mediated inhibition, colipase permits pancreatic lipase to efficiently hydrolyze triglycerides into fatty acids and 2-monoglycerides – the absorbable forms of fat (gosset.ai) (www.ncbi.nlm.nih.gov).

Key mechanism: In the intestinal lumen, dietary fats are first emulsified by bile. Pancreatic lipase alone has reduced activity on emulsified triglycerides when bile acids are present, because bile acids can strip lipase off the fat droplet surface. Colipase is indispensable for lipase function under these conditions (pubmed.ncbi.nlm.nih.gov). It acts as a bridging molecule, one side binding tightly to lipase and the other embedding into the lipid droplet. Classic experiments demonstrated that beyond a certain interfacial tension (as occurs in bile-rich micelles), lipase cannot adsorb to fat droplets without colipase (pubmed.ncbi.nlm.nih.gov). Colipase thus restores or “reactivates” lipase activity in the intestinal environment (pmc.ncbi.nlm.nih.gov). In vivo, pancreatic triglyceride lipase is essentially ineffective without its colipase partner (pubmed.ncbi.nlm.nih.gov) – together, they form a 1:1 lipase–colipase complex that is the active unit for fat breakdown. Structural studies confirm the strength and specificity of this complex: colipase–lipase binding is stabilized by multiple hydrogen bonds and extensive surface contacts (~80 van der Waals interactions) at the interface of colipase and the lipase’s C-terminal domain (pmc.ncbi.nlm.nih.gov). Through these interactions, colipase prevents lipase denaturation at the water–lipid interface and maintains the enzyme in the correct orientation for catalysis (pubmed.ncbi.nlm.nih.gov). The net effect is a dramatic increase in the efficiency of triglyceride hydrolysis in the small intestine.

Biological Role in Digestion and Physiology

Dietary fat digestion: Colipase plays a central role in lipid catabolism as part of the pancreatic enzyme system. It is required for the normal digestion and absorption of long-chain dietary triglycerides in the small intestine (www.ncbi.nlm.nih.gov). The lipase–colipase enzyme system acts in the lumen of the duodenum and jejunum to generate fatty acids and monoglycerides, which are then absorbed by enterocytes. In the absence of functional colipase, pancreatic lipase cannot properly act on emulsified fats, leading to severe fat malabsorption. This is evidenced clinically and in animal models – colipase deficiency or inactivity causes steatorrhea (excess fat in stool) and symptoms of exocrine pancreatic insufficiency (gosset.ai). For example, patients or experimental animals lacking colipase activity exhibit oily diarrhea and weight loss due to undigested fat, underscoring the cofactor’s essential role in nutrient absorption (gosset.ai). Consistently, pancreatic enzyme replacement therapies for pancreatic insufficiency (e.g. pancrelipase supplements) rely on sources that provide not only lipase but also colipase activity to ensure efficacy (pmc.ncbi.nlm.nih.gov) (gosset.ai).

Pathways and interactions: Colipase operates at the intersection of digestive pathways: it is secreted alongside pancreatic lipase (encoded by the PNLIP gene) into the duodenum as part of the pancreatic juice. There, it interacts with other key molecules of fat digestion – notably bile salts (taurocholate, etc.) and the lipid substrate itself. Colipase doesn’t participate in classic signaling cascades, but its action is integral to the biochemical pathway of triglyceride breakdown. In a broader nutritional context, colipase function ensures that dietary fats (which are hydrophobic) can be broken down in an aqueous environment and absorbed. Additionally, colipase may assist other fat-degrading enzymes: while pancreatic triglyceride lipase is its primary partner, colipase can also bind and support pancreatic lipase-related proteins on certain substrates (pmc.ncbi.nlm.nih.gov), though pancreatic PTL is the main enzyme requiring colipase (pmc.ncbi.nlm.nih.gov). In neonates (who have low pancreatic lipase expression immediately after birth), colipase is present and might contribute to fat digestion via alternate lipases (e.g. human milk bile-salt stimulated lipase or gastric lipase); this suggests a possible supportive role for colipase in early life nutrition (pmc.ncbi.nlm.nih.gov). Notably, colipase itself is not a signaling molecule, but interestingly, its precursor peptide has been implicated in metabolic signaling (see below). Overall, colipase’s activity is tightly linked to the digestive process and is a critical factor in the intestinal phase of fat metabolism.

Activation, Regulation, and Enterostatin

Newly synthesized colipase is an inactive zymogen (procolipase) that undergoes proteolytic activation. In the pancreatic acinar cell, procolipase (approximately 10 kDa) is packaged into zymogen granules and co-released with digestive enzymes. Trypsin (another pancreatic enzyme) cleaves procolipase in the duodenum, removing a 5-amino-acid activation peptide from the N-terminus (pmc.ncbi.nlm.nih.gov). This cleavage converts the inactive precursor into active colipase capable of binding lipase. The small liberated peptide is enterostatin (sequence Val-Pro-Asp-Pro-Arg in humans) (pmc.ncbi.nlm.nih.gov). Intriguingly, enterostatin is biologically active on its own: it has been shown in rodents and other animals to function as a satiety or signaling peptide related to fat intake. Erlanson-Albertsson and colleagues first proposed enterostatin as a feedback signal for dietary fat regulation (pmc.ncbi.nlm.nih.gov). In rats, peripheral or central administration of enterostatin selectively reduces fat consumption (i.e. the animals eat less fat) (pmc.ncbi.nlm.nih.gov). For example, Okada et al. (1991) demonstrated that enterostatin treatment led to significantly decreased fat intake in rats (pmc.ncbi.nlm.nih.gov). The working model is that when the pancreas secretes more procolipase (for fat digestion), more enterostatin is generated in the gut, which then signals the brain to curb appetite for fatty foods (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This provides a negative feedback loop to prevent overconsumption of fat. Consistent with this idea, high-fat feeding increases CLPS (procolipase) expression in the pancreas (pmc.ncbi.nlm.nih.gov), presumably producing more enterostatin to limit further fat intake. However, this regulatory mechanism is complex and species-dependent. In humans, the physiological role of enterostatin remains less clear – some studies explored associations of CLPS gene variants with obesity and feeding behavior. For instance, Wermter et al. (2010) found no strong genetic association between common CLPS polymorphisms and early-onset obesity in humans (pmc.ncbi.nlm.nih.gov), suggesting that if enterostatin influences appetite, its impact might be subtle or compensable. Nonetheless, the procolipase–enterostatin system illustrates how closely pancreatic digestive function is linked to nutritional feedback signals.

Beyond dietary regulation, the CLPS gene itself appears to be predominantly regulated at the tissue-specific level. It is expressed almost exclusively in pancreatic acinar cells (www.ncbi.nlm.nih.gov), under the control of pancreatic transcription factors and secretagogue signals (e.g. cholecystokinin stimulates its secretion as part of the pancreatic enzyme release). RefSeq annotations note that CLPS has a few transcript variants encoding the same or similar colipase protein (www.ncbi.nlm.nih.gov), but no major isoform with a different function has been reported. The high specificity of expression implies that upstream regulatory elements ensure colipase is produced only where needed (pancreas) and in coordination with lipase and other digestive enzymes.

Structural Features of Colipase

Colipase is a small, cysteine-rich protein composed of about 100 amino acids (excluding the signal and activation peptides). It has a distinctive flattened, globular structure roughly 25×30×35 Å in size (www.sigmaaldrich.com). Uniquely, colipase lacks extensive regular secondary structure – it does not fold into significant alpha-helices or beta-sheets. Instead, its conformation is stabilized by an extended network of five disulfide bonds that span the protein (pmc.ncbi.nlm.nih.gov). The human colipase contains 10 cysteine residues that form 5 intramolecular disulfide bridges (pmc.ncbi.nlm.nih.gov). These disulfides “staple” the protein into a stable shape consisting of several loop regions. In fact, colipase is often described as having four or five finger-like loops protruding from a relatively flat core (pmc.ncbi.nlm.nih.gov). This disulfide-reinforced loop structure is critical for function: it endows colipase with high stability against proteases and bile in the harsh intestinal environment, and it creates distinct interaction surfaces for lipase and lipids (pmc.ncbi.nlm.nih.gov).

One face of the colipase molecule is hydrophilic and interacts with pancreatic lipase, while the opposite face is hydrophobic, formed by the tips of the loops, and inserts into the lipid interface (pmc.ncbi.nlm.nih.gov). This bipartite surface distribution allows colipase to act as a bridge between water-soluble enzymes and hydrophobic fat droplets. Crystallographic studies of the porcine colipase–lipase complex (van Tilbeurgh et al., 1993; Egloff et al., 1995) provided detailed insight: the colipase–lipase interface involves numerous contacts (including ~8 hydrogen bonds) that ensure tight binding (pmc.ncbi.nlm.nih.gov). Meanwhile, the tip of colipase’s loops penetrates into the lipid layer, anchoring the complex at the triglyceride–water boundary. Site-directed mutagenesis experiments have pinpointed specific amino acids on colipase that mediate these interactions. For example, Tyr^55 on human colipase, located on one of the surface loops, is critical for adsorption to bile salt micelles (pmc.ncbi.nlm.nih.gov). A Y55A colipase mutant showed greatly reduced ability to restore lipase activity in the presence of bile, underscoring the importance of this hydrophobic loop residue in binding the lipid interface (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Other loop residues (e.g. Leu^34/Leu^36 on loop 2 and Ile^75/Ile^79 on loop 4) have also been shown to contribute to the lipid-binding surface of colipase (pmc.ncbi.nlm.nih.gov). In contrast, mutations like Phe^84 located in the protein core mainly affect folding stability rather than direct lipid binding (pmc.ncbi.nlm.nih.gov). These findings from Lowe and colleagues (2013) provide a refined understanding of how colipase’s structure dictates its function at a molecular level.

Functional Implications and Current Research

Given its vital role in fat digestion, colipase has been studied in contexts of nutrition, disease, and even evolution. In terms of human health, colipase insufficiency is one contributing factor in malabsorptive disorders. In chronic pancreatitis or cystic fibrosis (where exocrine output is reduced), the lack of pancreatic colipase – alongside lipase – leads to steatorrhea that must be managed with pancreatic enzyme (and cofactor) replacement (pubmed.ncbi.nlm.nih.gov). Rare congenital cases of combined lipase-colipase deficiency have been reported, presenting in early childhood with failure to thrive due to fat malabsorption (pubmed.ncbi.nlm.nih.gov). Such cases highlight colipase’s non-redundant function: other lipases cannot compensate unless colipase is present to facilitate their action. Indeed, colipase is considered essential for normal fat absorption, and there is no known alternate human protein that can substitute for its cofactor activity (pubmed.ncbi.nlm.nih.gov).

At the same time, research has explored whether variations in the CLPS gene or colipase levels could influence metabolic outcomes like obesity and diabetes. While common variants in CLPS do not appear to strongly affect obesity risk (pmc.ncbi.nlm.nih.gov), a specific missense polymorphism has drawn attention. This variant is an arginine-to-cysteine substitution at position 92 (Arg92Cys) in colipase. Arg^92 lies in one of the colipase loops, and introducing an extra cysteine at this position disturbs the protein’s disulfide bond pattern. Studies by D’Silva, Lowe, and colleagues (published 2007–2013) showed that the Arg92Cys variant produces a colipase protein with impaired stability and function. The mutant colipase can still bind lipase and support the breakdown of short-chain triglycerides normally, but it retains only ~50% of wild-type activity when hydrolyzing long-chain triglycerides (pmc.ncbi.nlm.nih.gov). Functionally, the Cys92-colipase has trouble anchoring lipase to larger lipid emulsions, especially after exposure to conditions mimicking the gut. Notably, Cys92-colipase lost its activity upon storage, suggesting a propensity to misfold or aggregate over time (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This misfolding is likely due to the unpaired cysteine forming aberrant disulfide links. Population-genetic analyses further indicated that Arg92Cys in CLPS might be linked to metabolic traits – researchers found this variant at higher frequency in certain groups and proposed it may contribute to increased risk of type 2 diabetes (pmc.ncbi.nlm.nih.gov). The hypothesis is that a chronically less effective colipase could alter fat digestion efficiency or gut signaling in a way that influences metabolic homeostasis (pmc.ncbi.nlm.nih.gov). While more studies are needed to confirm such links, the Arg92Cys case exemplifies how structure–function relationships in colipase are clinically significant. It also underscores that colipase’s integrity (correct cysteine pairing and folding) is crucial for its cofactor activity.

On the translational front, there are currently no drugs targeting colipase directly – and none likely needed, since colipase is not an enzyme but a facilitator protein (gosset.ai). However, understanding colipase has practical implications. Nutritional interventions for patients with pancreatic insufficiency rely on porcine pancreatic extracts containing both lipase and colipase activity to recapitulate the natural digestive process (pmc.ncbi.nlm.nih.gov). Moreover, any future techniques to engineer improved enzyme replacement (for example, genetically engineered lipases) must ensure colipase compatibility. In biotechnology, colipase is sometimes added to in vitro fat digestion assays or industrial processes to enhance lipase performance (pubmed.ncbi.nlm.nih.gov). There is also interest in whether modulating the enterostatin pathway could affect dietary habits or weight loss, though clinical applications there remain speculative (pmc.ncbi.nlm.nih.gov).

Expert Perspectives and Conclusions

Colipase is a quintessential example of a small cofactor protein that enables an enzyme to function under physiological conditions that would otherwise be prohibitive. As early as the 1970s, investigators recognized that pancreatic lipase alone was ineffective in the intestinal lumen and that a heat-stable cofactor was required for triglyceride digestion (pmc.ncbi.nlm.nih.gov). Decades of research have since firmly established colipase’s role in anchoring lipase at the lipid–water interface and preventing bile salt inhibition. Mark Lowe, a leading expert on pancreatic lipases, summarized that “in vivo, lipase action cannot take place without colipase”, emphasizing colipase’s indispensable role (pubmed.ncbi.nlm.nih.gov). Structurally, colipase represents an elegant adaptation: its disulfide-stabilized, amphipathic design allows it to straddle two worlds – water and oil – to bring together enzyme and substrate. Functionally, it acts as a molecular tether and activation platform for pancreatic lipase.

From a biological process standpoint, colipase is tightly integrated into the fat digestion pathway. Its activity exemplifies the cooperative nature of digestion, where multiple components (bile acids, lipase, co-lipase) work in concert to achieve efficient nutrient breakdown. The physiological importance of colipase is further highlighted by the body’s regulatory investment in it – from selective expression in the pancreas to potential feedback signals (enterostatin) that link digestive capacity with feeding behavior (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

In summary, CLPS (colipase) encodes a crucial cofactor that enables dietary triglyceride assimilation in humans. The colipase protein’s specific binding to pancreatic lipase and lipid interfaces overcomes the barriers presented by an aqueous, bile-rich intestinal environment (www.ncbi.nlm.nih.gov). By stabilizing and localizing lipase at the fat droplet surface, colipase ensures that fat is efficiently hydrolyzed and made available for absorption (www.ncbi.nlm.nih.gov) (gosset.ai). Its role is precise and fundamental – rather than broadly pleiotropic – and it illustrates how a small protein can have a large impact on metabolic physiology. Ongoing research, from detailed mutation analyses to clinical genetic studies, continues to refine our understanding of colipase’s function and its implications in health and disease. The current understanding portrays colipase as an essential facilitator of lipid digestion, with a well-defined action mechanism and a clear importance in nutrition and pancreatic function.

References: (Key sources highlighting colipase function, structure, and physiology have been cited in-line, with URLs and publication details provided. These include foundational biochemical studies, structural analyses from the 1990s, and research up through the 2010s examining genetic variants and regulatory aspects of CLPS.)

Citations

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  35. AnnotationURLCitation(end_index=12451, start_index=12281, title='Procolipase Gene: No Association with Early-Onset Obesity or Fat Intake - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6444705/#:~:text=%2A%201.Erlanson,4887.1992.tb02473.x.%20%5BDOI%5D%20%5BPubMed%5D%20%5BGoogle%20Scholar')
  36. AnnotationURLCitation(end_index=12591, start_index=12452, title='Procolipase Gene: No Association with Early-Onset Obesity or Fat Intake - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6444705/#:~:text=Asp,s.%20%5BDOI%5D%20%5BPubMed%5D%20%5BGoogle%20Scholar')
  37. AnnotationURLCitation(end_index=12936, start_index=12771, title='Procolipase Gene: No Association with Early-Onset Obesity or Fat Intake - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6444705/#:~:text=The%20colipase%20preproprotein%20,activation%20by%20trypsin%2C%20procolipase%20is')
  38. AnnotationURLCitation(end_index=13541, start_index=13388, title='Procolipase Gene: No Association with Early-Onset Obesity or Fat Intake - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6444705/#:~:text=Several%20lines%20of%20evidence%20in,and%20fat%20intake%20in%20humans')
  39. AnnotationURLCitation(end_index=14110, start_index=13974, title='CLPS colipase [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/1208#:~:text=catalytic%20domain%20of%20lipase%2C%20thereby,6%29%20See%20more')
  40. AnnotationURLCitation(end_index=14550, start_index=14393, title='CLPS colipase [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/1208#:~:text=allows%20lipase%20to%20anchor%20noncovalently,provided%20by%20RefSeq%2C%20Nov%202011')
  41. AnnotationURLCitation(end_index=15271, start_index=15058, title='C3028, Colipase from porcine pancreas, Lyophilized powder', type='url_citation', url='https://www.sigmaaldrich.com/SA/en/product/sigma/c3028?srsltid=AfmBOorwrF7JUkn9iJ5Q_C93_5VEpRrrQr8nHxzqQgpJPXr7y0V7G2Z5#:~:text=Description%20,an%20arrangement%20of%20protruding%20fingers')
  42. AnnotationURLCitation(end_index=15635, start_index=15513, title='Crystallographic study of the structure of colipase and of the interaction with pancreatic lipase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2142970/#:~:text=lacks%20well,Upon%20opening%20of%20the')
  43. AnnotationURLCitation(end_index=15883, start_index=15731, title='A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3684974/#:~:text=The%20more%20common%20arginine%2092,The%20addition%20of%20an%20extra')
  44. AnnotationURLCitation(end_index=16245, start_index=16100, title='Crystallographic study of the structure of colipase and of the interaction with pancreatic lipase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2142970/#:~:text=lacks%20well,a%20rather%20hydrophilic%20part%2C%20interacting')
  45. AnnotationURLCitation(end_index=16606, start_index=16484, title='Crystallographic study of the structure of colipase and of the interaction with pancreatic lipase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2142970/#:~:text=lacks%20well,Upon%20opening%20of%20the')
  46. AnnotationURLCitation(end_index=16936, start_index=16814, title='Crystallographic study of the structure of colipase and of the interaction with pancreatic lipase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2142970/#:~:text=lacks%20well,Upon%20opening%20of%20the')
  47. AnnotationURLCitation(end_index=17472, start_index=17327, title='Crystallographic study of the structure of colipase and of the interaction with pancreatic lipase - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2142970/#:~:text=The%20colipase%20surface%20can%20be,Upon%20opening%20of%20the')
  48. AnnotationURLCitation(end_index=17992, start_index=17853, title='Identification of amino acids in human colipase that mediate adsorption to lipid emulsions and mixed micelles - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3642234/#:~:text=36%20on%20the%202,to%20mixed%20micelles%20is%20mediated')
  49. AnnotationURLCitation(end_index=18357, start_index=18192, title='Identification of amino acids in human colipase that mediate adsorption to lipid emulsions and mixed micelles - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3642234/#:~:text=purified%20recombinant%20colipase%20mutants%20and,residues%20Leu%2034%20and%20Leu')
  50. AnnotationURLCitation(end_index=18497, start_index=18358, title='Identification of amino acids in human colipase that mediate adsorption to lipid emulsions and mixed micelles - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3642234/#:~:text=36%20on%20the%202,to%20mixed%20micelles%20is%20mediated')
  51. AnnotationURLCitation(end_index=18831, start_index=18658, title='Identification of amino acids in human colipase that mediate adsorption to lipid emulsions and mixed micelles - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3642234/#:~:text=acrylamide%20quenching%20curves%20to%20characterize,to%20mixed%20micelles%20is%20mediated')
  52. AnnotationURLCitation(end_index=19100, start_index=18961, title='Identification of amino acids in human colipase that mediate adsorption to lipid emulsions and mixed micelles - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3642234/#:~:text=36%20on%20the%202,to%20mixed%20micelles%20is%20mediated')
  53. AnnotationURLCitation(end_index=19917, start_index=19760, title='Enzyme replacement therapy for pancreatic insufficiency: present and future - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/21753892/#:~:text=Enzyme%20replacement%20therapy%20for%20pancreatic,This%20treatment%20is%20safe')
  54. AnnotationURLCitation(end_index=20220, start_index=20078, title='Isolated congenital lipase-colipase deficiency - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/6714581/#:~:text=Isolated%20congenital%20lipase,a%20history%20of%20passing%20oily')
  55. AnnotationURLCitation(end_index=20691, start_index=20529, title='[Recent findings on pancreatic lipase and colipase] - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/6373427/#:~:text=hand%2C%20the%20enzyme%20is%20stabilized,hydrophobic%20region%20and%20by%20ionizable')
  56. AnnotationURLCitation(end_index=21084, start_index=20931, title='Procolipase Gene: No Association with Early-Onset Obesity or Fat Intake - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6444705/#:~:text=Several%20lines%20of%20evidence%20in,and%20fat%20intake%20in%20humans')
  57. AnnotationURLCitation(end_index=21878, start_index=21736, title='A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3684974/#:~:text=yeast%20expression%20system%20and%20compared,Cys92%20fully')
  58. AnnotationURLCitation(end_index=22305, start_index=22146, title='A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3684974/#:~:text=triglycerides%20but%20only%20had%2050,lipase%20on%20an%20emulsion%20surface')
  59. AnnotationURLCitation(end_index=22458, start_index=22306, title='A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3684974/#:~:text=The%20more%20common%20arginine%2092,The%20addition%20of%20an%20extra')
  60. AnnotationURLCitation(end_index=22967, start_index=22796, title='A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3684974/#:~:text=that%20the%20Arg92Cys%20polymorphism%20decreases,development%20of%20type%202%20diabetes')
  61. AnnotationURLCitation(end_index=23302, start_index=23131, title='A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3684974/#:~:text=that%20the%20Arg92Cys%20polymorphism%20decreases,development%20of%20type%202%20diabetes')
  62. AnnotationURLCitation(end_index=23843, start_index=23761, title='Gosset', type='url_citation', url='https://gosset.ai/targets/colipase/#:~:text=Mechanism%20of%20Action')
  63. AnnotationURLCitation(end_index=24271, start_index=24101, title='Delayed release pancrelipase for treatment of pancreatic exocrine insufficiency associated with chronic pancreatitis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2710383/#:~:text=preparations%20Porcine%20pancreatic%20enzymes%20are,be%20degraded%20in%20the%20stomach')
  64. AnnotationURLCitation(end_index=24737, start_index=24560, title='Production of recombinant porcine colipase secreted by Pichia pastoris and its application to improve dietary fat digestion and growth of postweaning piglets - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19194948/#:~:text=Production%20of%20recombinant%20porcine%20colipase,secretion%20cassette%20was%20constructed%20with')
  65. AnnotationURLCitation(end_index=25077, start_index=24907, title='Procolipase Gene: No Association with Early-Onset Obesity or Fat Intake - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6444705/#:~:text=%2A%201.Erlanson,4887.1992.tb02473.x.%20%5BDOI%5D%20%5BPubMed%5D%20%5BGoogle%20Scholar')
  66. AnnotationURLCitation(end_index=25663, start_index=25482, title='Colipase enhances hydrolysis of dietary triglycerides in the absence of bile salts - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC371277/#:~:text=Colipase%20enhances%20hydrolysis%20of%20dietary,and%20License%20information%20PMCID%3A%20PMC371277')
  67. AnnotationURLCitation(end_index=26155, start_index=25993, title='[Recent findings on pancreatic lipase and colipase] - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/6373427/#:~:text=hand%2C%20the%20enzyme%20is%20stabilized,hydrophobic%20region%20and%20by%20ionizable')
  68. AnnotationURLCitation(end_index=27134, start_index=26969, title='Procolipase Gene: No Association with Early-Onset Obesity or Fat Intake - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6444705/#:~:text=The%20colipase%20preproprotein%20,activation%20by%20trypsin%2C%20procolipase%20is')
  69. AnnotationURLCitation(end_index=27263, start_index=27135, title='Procolipase Gene: No Association with Early-Onset Obesity or Fat Intake - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6444705/#:~:text=%5BPubMed%5D%20%5BGoogle%20Scholar%5D%20,Pro')
  70. AnnotationURLCitation(end_index=27704, start_index=27547, title='CLPS colipase [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/1208#:~:text=catalytic%20domain%20of%20lipase%2C%20thereby,provided%20by%20RefSeq%2C%20Nov%202011')
  71. AnnotationURLCitation(end_index=28014, start_index=27857, title='CLPS colipase [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/1208#:~:text=catalytic%20domain%20of%20lipase%2C%20thereby,provided%20by%20RefSeq%2C%20Nov%202011')
  72. AnnotationURLCitation(end_index=28169, start_index=28015, title='Gosset', type='url_citation', url='https://gosset.ai/targets/colipase/#:~:text=anchoring%20and%20stabilizing%20the%20enzyme,therapies%20targeting%20this%20molecule%20directly')