Protein FAM46C also known as family with sequence similarity 46, member C is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that, in humans, is encoded by the ''FAM46C''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

at locus 1p12 spanning base pairs from 118,148,556 to 118,171,011.

Summary

FAM46C is a protein of unknown function consisting of 391 amino acid residues that are translated from an mRNA consisting of 5720 base pairs. FAM46C was initially sequenced as part of the Full-length long Japan genomic sequencing project. FAM46C is found on chromosome 1 at the locus 1p12 FAM46C contains one domain of unknown function, DUF1693, and as such has been placed in the DUF1693 protein family. This protein family has been established as a part of the Nucleotidyltransferase superfamily and contains 4 nematode prion-like proteins. FAM46C was placed into group XXV of the

nucleotidyltransferase Nucleotidyltransferases are transferase enzymes of phosphorus-containing groups, e.g., substituents of nucleotidylic acids or simply nucleoside monophosphates. The general reaction of transferring a nucleoside monophosphate moiety from A to B, can ...

superfamily along with 3 other ''Homo sapiens'' FAM46 proteins ( A, B, D). It has been suggested that FAM46C may be functionally involved with the Type 1 interferon response. Deletion and/ or mutation of FAM46C has been associated with impaired overall survival in

Myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemi ...

patients.

Gene

''Homo sapiens'' FAM46C spans 22,456 bases on chromosome 1. Microarray data suggests that human FAM46C displays elevated expression levels in bone marrow,

CD71 Transferrin receptor protein 1 (TfR1), also known as Cluster of Differentiation 71 (CD71), is a protein that in humans is encoded by the ''TFRC'' gene. TfR1 is required for iron import from transferrin into cells by endocytosis. Structure and func ...

+ early

erythroid Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hol ...

, various B-cells,

T-cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

s, and

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

s, as well as all tissues associated with

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoste ...

Evolution and homology

''Homo sapiens'' FAM46C is highly conserved in close orthologs with only small changes in protein AA sequence when comparing to other mammals. FAM46C and specifically the DUF1693 is traceable throughout the known

metazoans Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...

, with a distant homolog found in ''Trichoplax adhaerens'', a member of the basal multicellular organismal group

Placozoa The Placozoa are a basal form of marine free-living (non-parasitic) multicellular organism. They are the simplest in structure of all animals. Three genera have been found: the classical ''Trichoplax adhaerens'', '' Hoilungia hongkongensis'', a ...

Paralogs

''Homo sapiens'' FAM46C is paralogous to 3 separate known FAM46 proteins, all of which contain DUF1693. FAM46C Paralog Table

Orthologs

There are numerous FAM46C orthologs present throughout the current catalog of multicellular organisms, all of which exhibit impressive conservation of domain of unknown function 1693. The most notable ortholog is taken to be TRIADDRAFT14293, a gene of the species ''Trichoplax adhaerens''. This ortholog provides evidence that FAM46C is a member of a group of proteins containing highly conserved amino acid residues, and as such it is thought to provide some highly important function, as would be expected when considering its possible nucleotidyltransferase activity.

Homologous domains

In order to determine possible conserved structures, a predictive approach was utilized with regards to comparison of FAM46C with the most distant homolog available, that of ''Trichoplax adhearens''.

PHYRE2 Phyre and Phyre2 (Protein Homology/AnalogY Recognition Engine; pronounced as 'fire') are free web-based services for protein structure prediction. Phyre is among the most popular methods for protein structure prediction having been cited over 150 ...

was used to predict protein secondary structure of human FAM46C as well as trichoplax TRIADDRAFT-14293. We are able to visualize possible structures predicted with high confidence in both the human gene, as well as the placozoan gene. This preliminary prediction offers some insight into important structures, most probably of catalytic and/or binding function.

Phylogeny

Based on multiple sequence alignments generated by

ClustalW Clustal is a series of widely used computer programs used in bioinformatics for multiple sequence alignment. There have been many versions of Clustal over the development of the algorithm that are listed below. The analysis of each tool and its ...

an unrooted phylogenetic tree was generated for select FAM46C orthologs in order to demonstrate the diverse occurrences of FAM46C-like genes throughout the current evolutionary catalog. For posterity, many orthologs were omitted (see ortholog table above; many were omitted from this table as well).

Protein structure

"Homo sapiens" FAM46C encodes a 391 amino acid protein with no known isoforms. "Homo sapiens" FAM46C has not been crystallized and its secondary structure has not yet been determined as of May 2013. FAM46C has a predicted isoelectric point of 5.338. The protein contains one domain of unknown function, DUF169
(Pfam: PF07984)
A Leucine zipper pattern was found beginning at Lys113 and ending at Lys134. This could help distinguish nuclear proteins from non-nuclear proteins, however all other subsets of analyses using PSORTII have predicted that FAM46C is strictly a cytosolic protein. No other significant protein structural motifs have been predicted.

Protein-protein interactions

FAM46C has been experimentally shown to interact physically with at least 4 separate proteins, with other interactions that have been predicted

References

{{Reflist, 35em

External links

- The homepage of the Full-length long Japan human genomic sequencing project Genes on human chromosome 1