Protein canopy homolog 2 (CNPY2)

The protein contains 182 amino acids for an estimated molecular weight of 20652 Da.

 

Positive regulator of neurite outgrowth by stabilizing myosin regulatory light chain (MRLC). It prevents MIR-mediated MRLC ubiquitination and its subsequent proteasomal degradation. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 68%
Model score: 0

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The reference OMIM entry for this protein is 605861

Canopy 2, zebrafish, homolog of; cnpy2
Transmembrane protein 4; tmem4
Mir-interacting saposin-like protein; msap

CLONING

Instead of an N-terminal cleavable hydrophobic signal sequence (SS), which is found in secreted or type I membrane proteins, type II membrane proteins retain an uncleaved SS, called a signal anchor (SA), in the membrane. With a type I SA, the N terminus is located in the cytosol, whereas with a type II SA the N terminus is located outside the membrane. Yokoyama-Kobayashi et al. (1995) developed an SS detection system, called the fibrin sheet method, based on the detection of secreted protein fused to a urokinase plasminogen activator protein having fibrinolytic activity. Yokoyama-Kobayashi et al. (1999) adopted this system, together with cell-fractionation analysis, to test for fibrinolytic activity on the surface of cells transfected with fused genes. They isolated a cDNA encoding TMEM4, which they termed HP10390, from a gastric adenocarcinoma cDNA library. TMEM4 encodes a predicted 182-amino acid type II transmembrane protein. Using MIR (MYLIP; 610082) as bait in a yeast 2-hybrid screen of a HeLa cell cDNA library, followed by screening a fetal brain cDNA library, Bornhauser et al. (2003) cloned TMEM4, which they designated MSAP. The first 3 to 20 amino acids of MSAP constitute the SA region, which is followed by a saposin (see PSAP; 176801)-like domain interrupted by 2 stretches of 30 and 40 amino acids. Northern blot analysis detected MSAP expression in all adult and fetal tissues examined, with highest levels in adult placenta, liver, and pancreas. Western blot analysis of placenta and brain detected MSAP at an apparent molecular mass of 21 kD. Immunofluorescence microscopy showed colocalization of Msap with Mir in COS-7 cells. In cultured rodent primary hippocampal neurons, the 2 proteins localized around the nucleus and extended into the neurites.

GENE FUNCTION

Bornhauser et al. (2003) found that MIR and MSAP interacted, but only if both proteins were full length. In rodent neuronal precursor cell lines, MSAP overexpression increased the number of cells with neurites, and downregulation of MSAP by RNA silencing inhibited neurite outgrowth. MSAP stimulated neurite outgrowth in the presence or absence of NGF (NGFB; 162030). Coexpression of MIR with MSAP reduced the stimulatory effect of MSAP on neurite outgrowth. MIR overexpression also resulted in ubiquitination of myosin regulatory light chain B (MRLC2; 609211), and this ubiquitination could be counteracted by MSAP overexpression.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the CNPY2 gene to chromosome 12 (TMAP R22439). ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605861 was added.

Feb. 25, 2016: Protein entry updated
Automatic update: model status changed

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed