TMTC4

The molecular weight for TMTC4 is 85.0 kdal, and there are no positive, negative, or neutral clusters of amino acids or charge runs exceeding the normal lengths. When looking at a distant ortholog (purple sea urchin) the molecular weight of TMTC4 is 85.5 kdal and there, again, are no charge runs, positive, negative or neutral clusters, or unusual spacings. There are strong similarities in protein composition across species. The isoelectric point for the domain of unknown function (DUF 1736) is lower than that of the protein overall.

Schematic illustration of known and predicted domains and motifs for TMTC4

Predicted secondary structure of TMTC4. Starting at blue and going to red, the diagram illustrates the n-terminus through the c-terminus.

TMTC4 has ten transmembrane regions, all of them spaced within the first half of the protein.[6]

TMTC4 is layered with tetratricopeptide (TPR) repeat sequences that are a part of the TPR superfamily of proteins. DUF1736 is present upstream of the TPR region. A seven residue repeat (SRR) is located toward the end of the protein, and it is thought to encode a coiled-coil structure.[7] Another member of the TPR family, PFTA (protein prenyltransferases alpha subunit repeat), is located within the protein's TPR region and is believed to be involved in signal transduction and vesicular traffic regulation.[8] LSPR coagulation factor V, also a repeat motif, is located within the TPR region, and is thought to be a central regulator of hemostasis.[9]

TMTC4 takes on a series of alpha-helix structures, especially within the TPR region, though there are a minimal amount of beta-strand structures spaced throughout the beginning half of the protein.[10]

Predicted post-translational modifications of TMTC4 protein

There are four predicted nuclear localization signals, each tagging the protein for nuclear import.[6] At the very end of the protein, however, there is a predicted ER retention signal which would prevent the protein from leaving the ER. The protein has three predicted N-glycosylation sites, potentially altering its structure and function and there are ten predicted phosphorylation sites, each a possible activation site for a regulatory mechanism.[6]

There is one possible promoter for the TMTC4 gene, located in the 5’ UTR but before the start of the coding sequence.

Ortholog space for TMTC4 spans a large portion of evolutionary time. TMTC4 is present in mammals, reptiles, amphibians, birds, fish, and invertebrates. It is not present in plants, bacteria, archaea, or fungi.[17]

Paralog space for TMTC4 spans the gene family TMTC. There are four genes in this gene family: TMTC1, TMTC2, TMTC3, and TMTC4. TMTC1 and TMTC3 split from TMTC4 about 1200 million years ago, while TMTC2 split from TMTC4 1400 million years ago. Both of these events happened somewhere between invertebrates and plants.