Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Apoa1. (This text reflects annotations as of Wednesday, January 23, 2013.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of September 10, 2007. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.

---

Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes apolipoprotein A-I, which is the major protein component of high density lipoprotein (HDL) in plasma. The protein promotes cholesterol efflux from tissues to the liver for excretion, and it is a cofactor for lecithin cholesterolacyltransferase (LCAT) which is responsible for the formation of most plasma cholesteryl esters. This gene is closely linked with two other apolipoprotein genes on chromosome 11. Defects in this gene are associated with HDL deficiencies, including Tangier disease, and with systemic non-neuropathic amyloidosis. [provided by RefSeq, Jul 2008]

---

Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Apoa1
  • participates in the following biological processes:
    • cholesterol efflux ^{[11, 16, 19, 20]}
    • cholesterol transport ^[26]
    • regulation of intestinal cholesterol absorption ^[1]
    • regulation of protein phosphorylation ^[16]
  • performs the following molecular functions:
    • cholesterol transporter activity ^[11]
    • high-density lipoprotein particle binding ^{[3, 20]}
    • lipid binding ^[7]
    • lipid transporter activity ^[20]
    • lipoprotein particle binding ^[7]
  • is located in the following cellular components:
    • extracellular region ^[28]
    • extracellular space ^{[2, 3, 6, 8, 14, 17, 19, 20, 23, 24, 25, 26]}
• The gene product of Apoa1 has been shown to bind to the gene products of Abca1, Kcnma1. ^{[13, 15]} Researchers have inferred, based on physical interactions, that the gene product of Apoa1
  • performs the following molecular functions:
    • identical protein binding ^{[7, 20]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Apoa1
  • participates in the following biological processes:
    • adrenal gland development ^[18]
    • blood vessel endothelial cell migration ^[21]
    • cholesterol biosynthetic process ^[18]
    • cholesterol efflux ^[24]
    • cholesterol metabolic process ^{[2, 5, 10, 12, 17, 29]}
    • cholesterol transport ^{[22, 25]}
    • endothelial cell proliferation ^[21]
    • glucocorticoid metabolic process ^[18]
    • lipid storage ^[18]
    • lipoprotein biosynthetic process ^[4]
    • phospholipid metabolic process ^[10]
    • positive regulation of transferase activity ^[4]
  • performs the following molecular functions:
    • lipid transporter activity ^[27]
• Researchers have inferred, based on genetic interactions, that the gene product of Apoa1
  • participates in the following biological processes:
    • cholesterol metabolic process based on interactions with Lep, Lepr ^[9]
    • lipoprotein biosynthetic process based on interactions with Apoe ^[3]
    • negative regulation of hydrolase activity based on interactions with Lepr ^[9]

---

Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Apoa1:
  • participates in the following biological processes:
    • cholesterol efflux
    • cholesterol homeostasis
    • cholesterol import
    • cholesterol metabolic process
    • cholesterol transport
    • G-protein coupled receptor signaling pathway
    • high-density lipoprotein particle assembly
    • negative regulation of cell adhesion molecule production
    • negative regulation of cytokine secretion involved in immune response
    • negative regulation of heterotypic cell-cell adhesion
    • negative regulation of inflammatory response
    • negative regulation of interleukin-1 beta secretion
    • negative regulation of lipase activity
    • negative regulation of response to cytokine stimulus
    • negative regulation of tumor necrosis factor-mediated signaling pathway
    • negative regulation of very-low-density lipoprotein particle remodeling
    • organ regeneration
    • peptidyl-methionine modification
    • phosphatidylcholine biosynthetic process
    • phospholipid efflux
    • phospholipid homeostasis
    • phospholipid transport
    • positive regulation of cholesterol esterification
    • positive regulation of hydrolase activity
    • protein oxidation
    • protein stabilization
    • regulation of Cdc42 protein signal transduction
    • reverse cholesterol transport
    • triglyceride homeostasis
  • performs the following molecular functions:
    • apolipoprotein A-I receptor binding
    • apolipoprotein receptor binding
    • beta-amyloid binding
    • cholesterol binding
    • cholesterol transporter activity
    • enzyme binding
    • high-density lipoprotein particle receptor binding
    • identical protein binding
    • lipase inhibitor activity
    • phosphatidylcholine-sterol O-acyltransferase activator activity
    • phospholipid binding
    • phospholipid transporter activity
  • is located in the following cellular components:
    • cytoplasmic vesicle
    • endocytic vesicle
    • extracellular space
    • high-density lipoprotein particle
    • nucleus
    • spherical high-density lipoprotein particle
    • very-low-density lipoprotein particle

---

Summary text based on GO annotations supported by structural data

• Apoa1 encodes a protein or proteins that contain the following InterPro domains: Apolipoprotein A1/A4/E, Apolipoprotein/apolipophorin, indicating that the gene product:
  • participates in the following biological processes:
    • lipid transport
    • lipoprotein metabolic process

---

Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Apoa1 indicates that it:
  • participates in the following biological processes:
    • lipid metabolic process
    • lipid transport
    • steroid metabolic process
    • transport

---

References

1. Boisvert WA et al. (1999) ApoA1 reduces free cholesterol accumulation in atherosclerotic lesions of ApoE-deficient mice transplanted with ApoE-expressing macrophages. Arterioscler Thromb Vasc Biol, 19:525-30. (PubMed:10073953)
2. Cabana VG et al. (1999) SAA-only HDL formed during the acute phase response in apoA-I+/+ and apoA-I-/- mice. J Lipid Res, 40:1090-103. (PubMed:10357841)
3. Cabana VG et al. (2004) Influence of apoA-I and apoE on the formation of serum amyloid A-containing lipoproteins in vivo and in vitro. J Lipid Res, 45:317-25. (PubMed:14595002)
4. Chroni A et al. (2005) Point mutations in apolipoprotein A-I mimic the phenotype observed in patients with classical lecithin:cholesterol acyltransferase deficiency. Biochemistry, 44:14353-66. (PubMed:16245952)
5. Fagan AM et al. (2004) ApoAI deficiency results in marked reductions in plasma cholesterol but no alterations in amyloid-beta pathology in a mouse model of Alzheimer's disease-like cerebral amyloidosis. Am J Pathol, 165:1413-22. (PubMed:15466405)
6. Francone OL et al. (2003) Abnormal phospholipid composition impairs HDL biogenesis and maturation in mice lacking Abca1. Biochemistry, 42:8569-78. (PubMed:12859204)
7. Gong EL et al. (1994) Structural and functional properties of human and mouse apolipoprotein A-I. Biochim Biophys Acta, 1213:335-42. (PubMed:8049247)
8. Goodrum JF et al. (1995) Nerve regeneration and cholesterol reutilization occur in the absence of apolipoproteins E and A-I in mice. J Neurochem, 64:408-16. (PubMed:7798939)
9. Gruen ML et al. (2005) Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I. J Lipid Res, 46:2007-14. (PubMed:15995171)
10. Hajri T et al. (1998) The acute phase response in apolipoprotein A-1 knockout mice: apolipoprotein serum amyloid A and lipid distribution in plasma high density lipoproteins. Biochim Biophys Acta, 1394:209-18. (PubMed:9795222)
11. Hirsch-Reinshagen V et al. (2004) Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain. J Biol Chem, 279:41197-207. (PubMed:15269218)
12. Hughes SD et al. (1997) HDL deficiency in genetically engineered mice requires elevated LDL to accelerate atherogenesis. Arterioscler Thromb Vasc Biol, 17:1725-9. (PubMed:9327769)
13. Kathiresan T et al. (2009) A protein interaction network for the large conductance Ca2+-activated K+ channel in the mouse cochlea. Mol Cell Proteomics, null:null. (PubMed:19423573)
14. Lusis AJ et al. (1983) Genetic control of lipid transport in mice. II. Genes controlling structure of high density lipoproteins. J Biol Chem, 258:5071-8. (PubMed:6403543)
15. Maric J et al. (2005) Intracellular lipidation of newly synthesized apolipoprotein A-I in primary murine hepatocytes. J Biol Chem, 280:39942-9. (PubMed:16204232)
16. Martinez LO et al. (2003) Phosphorylation of a pest sequence in ABCA1 promotes calpain degradation and is reversed by ApoA-I. J Biol Chem, 278:37368-74. (PubMed:12869555)
17. Parks JS et al. (1995) Effect of apolipoprotein A-I deficiency on lecithin:cholesterol acyltransferase activation in mouse plasma. J Lipid Res, 36:349-55. (PubMed:7751823)
18. Plump AS et al. (1996) Apolipoprotein A-I is required for cholesteryl ester accumulation in steroidogenic cells and for normal adrenal steroid production. J Clin Invest, 97:2660-71. (PubMed:8647961)
19. Plump AS et al. (1997) ApoA-I knockout mice: characterization of HDL metabolism in homozygotes and identification of a post-RNA mechanism of apoA-I up-regulation in heterozygotes. J Lipid Res, 38:1033-47. (PubMed:9186920)
20. Reschly EJ et al. (2002) Apolipoprotein A-I alpha -helices 7 and 8 modulate high density lipoprotein subclass distribution. J Biol Chem, 277:9645-54. (PubMed:11744719)
21. Seetharam D et al. (2006) High-density lipoprotein promotes endothelial cell migration and reendothelialization via scavenger receptor-B type I. Circ Res, 98:63-72. (PubMed:16339487)
22. Spady DK et al. (1998) Kinetic characteristics and regulation of HDL cholesteryl ester and apolipoprotein transport in the apoA-I-/- mouse. J Lipid Res, 39:1483-92. (PubMed:9684752)
23. Srivastava RA et al. (1992) Dietary fatty acids and dietary cholesterol differ in their effect on the in vivo regulation of apolipoprotein A-I and A-II gene expression in inbred strains of mice. Biochim Biophys Acta, 1125:251-61. (PubMed:1596514)
24. Stein O et al. (1997) Delayed loss of cholesterol from a localized lipoprotein depot in apolipoprotein A-I-deficient mice. Proc Natl Acad Sci U S A, 94:9820-4. (PubMed:9275209)
25. Voyiaziakis E et al. (1998) ApoA-I deficiency causes both hypertriglyceridemia and increased atherosclerosis in human apoB transgenic mice. J Lipid Res, 39:313-21. (PubMed:9507992)
26. Webb NR et al. (1997) Adenoviral vector-mediated overexpression of serum amyloid A in apoA-I-deficient mice. J Lipid Res, 38:1583-90. (PubMed:9300780)
27. Williamson R et al. (1992) Marked reduction of high density lipoprotein cholesterol in mice genetically modified to lack apolipoprotein A-I. Proc Natl Acad Sci U S A, 89:7134-8. (PubMed:1496008)
28. Wolfrum C et al. (2005) Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis. Nat Med, 11:418-22. (PubMed:15793583)
29. Zabalawi M et al. (2007) Inflammation and skin cholesterol in LDLr-/-, apoA-I-/- mice: link between cholesterol homeostasis and self-tolerance? J Lipid Res, 48:52-65. (PubMed:17071966)

---

---

Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

---