CLPS

UniProt ID: P04118
Organism: Homo sapiens
Review Status: COMPLETE
Aliases:
Colipase Pancreatic colipase
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Gene Description

Pancreatic colipase, the classical small secreted protein (112 AA precursor, ~10 kDa mature) that functions as an essential cofactor for pancreatic triglyceride lipase (PNLIP) in dietary fat digestion. Produced by pancreatic acinar cells and secreted into the duodenum, colipase binds to the C-terminal domain of pancreatic lipase and anchors the enzyme to the lipid-water interface in the presence of bile salts, restoring and stabilizing lipase activity during triglyceride hydrolysis. The protein contains multiple disulfide bonds forming a stable structure and exhibits lipase binding activity. Beyond fat digestion, colipase also participates in retinoid metabolism and shows antimicrobial properties (response to bacterium). CLPS is the archetypal member of the colipase family, with related proteins (LRCOL1, CLPSL1, CLPSL2) functioning in non-pancreatic tissues.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0008047 enzyme activator activity
IBA
GO_REF:0000033
ACCEPT
Summary: Duplicate enzyme activator annotation with IBA evidence.
Reason: Phylogenetically conserved activator function.
Supporting Evidence:
file:human/CLPS/CLPS-deep-research-perplexity.md
See deep research file for comprehensive analysis
GO:0005576 extracellular region
IEA
GO_REF:0000120
ACCEPT
Summary: Duplicate extracellular annotation (IEA).
Reason: Consistent secreted localization.
GO:0006629 lipid metabolic process
IEA
GO_REF:0000043
ACCEPT
Summary: Participates in lipid metabolic process through lipase activation.
Reason: Central to lipid metabolism in digestion.
GO:0007586 digestion
IEA
GO_REF:0000120
ACCEPT
Summary: Essential for dietary fat digestion in small intestine.
Reason: Primary biological process.
GO:0008047 enzyme activator activity
IEA
GO_REF:0000120
ACCEPT
Summary: Colipase is the classic enzyme activator, enabling pancreatic lipase activity for fat digestion.
Reason: Core molecular function, extensively characterized.
GO:0016042 lipid catabolic process
IEA
GO_REF:0000120
ACCEPT
Summary: Colipase enables triglyceride catabolism by lipase.
Reason: Specific lipid catabolic process.
GO:0035473 lipase binding
IEA
GO_REF:0000002
ACCEPT
Summary: Electronic annotation for lipase binding from InterPro domain. Colipase binds pancreatic lipase C-terminal domain.
Reason: Core molecular function, extensively characterized.
GO:0001523 retinoid metabolic process
IEA
GO_REF:0000107
ACCEPT
Summary: Retinoid metabolic process from Ensembl orthology. Colipase complex hydrolyzes retinyl palmitate to retinol.
Reason: Secondary function, colipase-lipase complex processes retinoids.
GO:0009617 response to bacterium
IEA
GO_REF:0000107
ACCEPT
Summary: Colipase shows antimicrobial activity against bacteria.
Reason: Secondary function, antimicrobial properties documented.
GO:0005576 extracellular region
TAS
Reactome:R-HSA-192422
ACCEPT
Summary: Traceable author statement for extracellular localization.
Reason: Well-established secreted protein.
GO:0005576 extracellular region
TAS
Reactome:R-HSA-192434
ACCEPT
Summary: Traceable author statement for extracellular localization.
Reason: Well-established secreted protein.
GO:0005576 extracellular region
TAS
Reactome:R-HSA-975593
ACCEPT
Summary: Traceable author statement for extracellular localization.
Reason: Well-established secreted protein.
GO:0006629 lipid metabolic process
NAS
PMID:2045105
Assignment of the human pancreatic colipase gene to chromoso...
ACCEPT
Summary: Lipid metabolic process accurately represents CLPS role in lipid metabolism through lipase activation.
Reason: Central to lipid metabolism in digestion. While more specific terms like lipid catabolic process could provide additional precision, this annotation accurately captures CLPS function.
Supporting Evidence:
PMID:2045105
Assignment of the human pancreatic colipase gene to chromosome 6p21.1 to pter.

Core Functions

Binding pancreatic triglyceride lipase and anchoring it to lipid-water interface in presence of bile salts to enable efficient dietary triglyceride hydrolysis

Molecular Function:
lipase binding
Cellular Locations:
Supporting Evidence:
  • file:human/CLPS/CLPS-uniprot.txt
    Colipase binds pancreatic lipase C-terminal domain and anchors enzyme at lipid-water interface
  • file:human/LRCOL1/LRCOL1-deep-research-openai.md
    Colipase binds to lipase and anchors it at lipid-water interface, restoring and stabilizing lipase activity during triglyceride hydrolysis

References

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Suggested Questions for Experts

Q: What is the structural basis of colipase-lipase interaction and bile salt resistance?

Suggested experts: Structural biochemists

Suggested Experiments

Experiment: Crystal structure of colipase-lipase complex at lipid interface

Hypothesis: Colipase binds lipase C-terminus and reorients active site

Type: structural analysis

Deep Research

Cyberian

(CLPS-deep-research-cyberian.md)

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Falcon

(CLPS-deep-research-falcon.md)

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OpenAI

(CLPS-deep-research-openai.md)

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Perplexity

(CLPS-deep-research-perplexity-lite.md)

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Perplexity

(CLPS-deep-research-perplexity.md)

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