Incidental Mutation 'R0019:Pcolce2'

• ID: 15571
• Institutional Source: Beutler Lab
• Gene Symbol: Pcolce2
• Ensembl Gene: ENSMUSG00000015354
• Gene Name: procollagen C-endopeptidase enhancer 2
• Synonyms: 2400001O18Rik, Pcpe2
• MMRRC Submission: 038314-MU
• Accession Numbers:

  Ncbi RefSeq: NM_029620.2; MGI:1923727

• Is this an essential gene?: Non essential (E-score: 0.000)
• Stock #: R0019 (G1)
• Status: Validated
• Chromosome: 9
• Chromosomal Location: 95637601-95698096 bp(+) (GRCm38)
• Type of Mutation: critical splice acceptor site
• DNA Base Change (assembly): A to G at 95694964 bp (GRCm38)
• Zygosity: Heterozygous
• Ref Sequence: ENSEMBL: ENSMUSP00000015498
• Gene Model: predicted gene model for transcript(s): [ENSMUST00000015498]
• AlphaFold: Q8R4W6
• Predicted Effect: probably null; Transcript: ENSMUST00000015498
• SMART Domains: Protein: ENSMUSP00000015498; Gene: ENSMUSG00000015354

Domain	Start	End	E-Value	Type
CUB	32	143	1.49e-41	SMART
CUB	153	267	2e-42	SMART
low complexity region	268	293	N/A	INTRINSIC
C345C	307	412	4.1e-23	SMART

• Predicted Effect: noncoding transcript; Transcript: ENSMUST00000151210
• Meta Mutation Damage Score: 0.9489
• Coding Region Coverage:
  • 1x: 83.5%
  • 3x: 78.2%
  • 10x: 64.4%
  • 20x: 48.4%
• Validation Efficiency: 91% (93/102)
• MGI Phenotype: Strain: 3722112; PHENOTYPE: Mice homozygous for a knock-out allele are viable, fertile and grossly normal with no detectable abnormalities in thymus or T cell development. [provided by MGI curators]
• Allele List at MGI:

  All alleles(8) : Targeted(4) Gene trapped(4)

• Posted On: 2012-12-21
• Science Writer: Anne Murray

Protein Function and Prediction

Pcolce2 encodes PCPE2, a ubiquitously expressed type II procollagen C-proteinase enhancer that functions with BMP-1 to produce pNα1(II) chains (1-4). Another study shows that PCPE2 modulates HDL levels (4) and proteolytically processes pro-apolipoprotein (apo) A-I by enhancing the cleavage of the hexapeptide extension present at the N-terminus of apoA-I (3).

Expression/Localization

PCOLCE2 is highly expressed in the adult human aorta and portions of the adult heart (2).  PCOLCE2 is also highly expressed in the pituitary gland, bladder, mammary gland, and trachea (2).

Background

Lipid profiles of Pcolce2 knockout mice showed a marked increase in plasma apoA-I and HDL-cholesterol (HDL-C) levels in PCPE2 KO mice compared with wild-type littermates, regardless of gender or diet (3). In addition, ABCA1-dependent cholesterol efflux is defective (3).

 

Pcolce2^{tm1Ccb/tm1Ccb}; MGI:3722112

involves: 129S1/Sv * 129X1/SvJ

Mice homozygous for a knock-out allele are viable, fertile and grossly normal with no detectable abnormalities in thymus or T cell development (5).

References

  1. Xu, H., Acott, T. S., and Wirtz, M. K. (2000) Identification and Expression of a Novel Type I Procollagen C-Proteinase Enhancer Protein Gene from the Glaucoma Candidate Region on 3q21-q24. Genomics. 66, 264-273.

  2. Steiglitz, B. M., Keene, D. R., and Greenspan, D. S. (2002) PCOLCE2 Encodes a Functional Procollagen C-Proteinase Enhancer (PCPE2) that is a Collagen-Binding Protein Differing in Distribution of Expression and Post-Translational Modification from the Previously Described PCPE1. J Biol Chem. 277, 49820-49830.

  3. Francone, O. L., Ishida, B. Y., de la Llera-Moya, M., Royer, L., Happe, C., Zhu, J., Chalkey, R. J., Schaefer, P., Cox, C., Burlingame, A., Kane, J. P., and Rothblat, G. H. (2011) Disruption of the Murine Procollagen C-Proteinase Enhancer 2 Gene Causes Accumulation of Pro-apoA-I and Increased HDL Levels. J Lipid Res. 52, 1974-1983.

  4. Zhu, J., Gardner, J., Pullinger, C. R., Kane, J. P., Thompson, J. F., and Francone, O. L. (2009) Regulation of apoAI Processing by Procollagen C-Proteinase Enhancer-2 and Bone Morphogenetic Protein-1. J Lipid Res. 50, 1330-1339.

  5. Heinzel, K., and Bleul, C. C. (2007) The Foxn1-Dependent Transcripts PCOLCE2 and mPPP1R16B are Not Required for Normal Thymopoiesis. Eur J Immunol. 37, 2562-2571.