TMCO4

The most common protein encoded by TMCO4 is 634 amino acids in length with accession number XP_011539488.1.[2]

The molecular weight of TMCO4 is 67.9 kiloDaltons. The isoelectric point is 5.48. As a whole protein, TMCO4 does not have abnormal amino acid distributions. It does have three long stretches of no charge that correspond with the location of the three different transmembrane regions. The first cytosolic domain of TMCO4 does have abnormally high amounts of leucine and glutamic acid and abnormally low amounts of asparagine. The larger lumenal domain of TMCO4 also has an abnormally low amount of asparagine and phenylalanine.

Conceptual translation of TMCO4 page 1. Yellow circles indicate predicted phosphorylation sites and blue circles indicate predicted O-linked glycosylation sites. The highlighting towards the 3' end of the sequence predicts stem loop formations.

Two main areas of interest within the TMCO4 protein are the three transmembrane regions and the large Abhydrolase region.[4] The N-terminus of TMCO4 is predicted to be within the cytosol of the cell, and the C-terminus is predicted to be within the lumen of the endoplasmic retiticulum. TMCO4 is also predicted to have a leucine zipper and a large coiled coil domain.[5]

The secondary structure of TMCO4 is predicted to be dominated by alpha helices based on predictions by iTASSER software.[6]

Many phosphorylation sites were predicted for the two cytosolic regions of TMCO4.[7] O-linked glycosylation sites were predicted to occur in the end of the second lumenal region of TMCO4.[8] These predicted sites can be seen on both the schematic illustration of TMCO4 found above, or in the conceptual translation of TMCO4 found below.

TMCO4 is consistently predicted to be located in the endoplasmic reticulum membrane across many homologs.[5]

Conceptual translation of TMCO4 page 2.

TMCO4 has been found to interact with many proteins. One protein of interest that TMCO4 interacts with is FLT1.[9] FLT1 is a VEGF receptor[10]. VEGF is known to play a significant role in cancer development. Other proteins that TMCO4 has been experimentally shown to interact with are UBB, UBC, KPTN, and BVLF1.[9] UBB and UBC are polyubiquitins that target molecules for degradation, suggesting that TMCO4 is degraded at some point.[11][12] KPTN is a protein that is essential in neuromorphogenesis.[13] BVLF1 is an Epstein-Barr virus protein.[14]

TMCO4 does not have any paralogs.

Orthologs to TMCO4 can be found in bacteria, protists, plants, fungi, trichoplax, invertebrates, fish, amphibians, reptiles, birds and mammals.[15] Some of these orthologs can be found in the table below.[15] The orthologs are sorted in descending order of date of evolution from humans and then descending order of percent sequence identity. TMCO4 is a fast evolving gene that has been highly conserved throughout evolution.[15] Regions of TMCO4 that are highly conserved across the orthologs include the various transmembrane domains and the abhydrolase region.