FAM46C

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
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View/Edit Human

Protein FAM46C also known as family with sequence similarity 46, member C is a protein that, in humans, is encoded by the FAM46C gene 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[1] and contains 4 nematode prion-like proteins. FAM46C was placed into group XXV of the nucleotidyltransferase superfamily[1] 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.[2] Deletion and/ or mutation of FAM46C has been associated with impaired overall survival in Myeloma patients.[3]

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+ early erythroid, various B-cells, T-cells, and lymphocytes, as well as all tissues associated with testes.[4]

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

Paralogs

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

File:FAM46C Paralog Table.png
This table lists human FAM46C paralogs, indicating relevant NCBI accession numbers (current as of May 2013), as well as nucleotide and protein alignment scores calculated using the ALIGN algorithm and cross-checked with NCBI BLAST search.
File:Ortholog table.png
Orthologs of FAM46C are listed in order of date of divergence from the human lineage, as determined by a search of the publicly available Timetree database. Note that all values are considered approximate and are used solely as bioinformatic data compiled via free public databases of published research.

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

File:PHYRE2 FAM46C prediction.png
This PHYRE2 FAM46C structure prediction was annotated with brackets to demonstrate regions of conserved structure prediction through the Trichoplax ortholog. Note that many of the structures seem to have originated as shorter segments of what exists in human FAM46C 9if we are to take high confidence predictions as most probable structures).

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[5] 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

File:FAM46C Ortholog Unrooted Tree.png
FAM46C Ortholog Unrooted Tree

Based on multiple sequence alignments generated by ClustalW 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, DUF1693 (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[6] 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[7]

Protein Evidence Accession Database
DAZAP2 2-hybrid AAR11454 MINT
TRIP6 2-hybrid CAA05080 MINT
PLK4 2-hybrid NM_014264 MINT
AP2B1 2-hybrid NM_001030006 MINT

References

  1. 1.0 1.1 Kuchta K, Knizewski L, Wyrwicz LS, Rychlewski L, Ginalski K (December 2009). "Comprehensive classification of nucleotidyltransferase fold proteins: identification of novel families and their representatives in human". Nucleic Acids Res. 37 (22): 7701–14. doi:10.1093/nar/gkp854. PMC 2794190. PMID 19833706.
  2. Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM (April 2011). "A diverse range of gene products are effectors of the type I interferon antiviral response". Nature. 472 (7344): 481–5. doi:10.1038/nature09907. PMC 3409588. PMID 21478870.
  3. Boyd KD, Ross FM, Walker BA, Wardell CP, Tapper WJ, Chiecchio L, Dagrada G, Konn ZJ, Gregory WM, Jackson GH, Child JA, Davies FE, Morgan GJ (December 2011). "Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival". Clin. Cancer Res. 17 (24): 7776–84. doi:10.1158/1078-0432.CCR-11-1791. PMID 21994415.
  4. http://biogps.org/#goto=genereport&id=54855
  5. Kelley LA, Sternberg MJ (2009). "Protein structure prediction on the Web: a case study using the Phyre server". Nat Protoc. 4 (3): 363–71. doi:10.1038/nprot.2009.2. PMID 19247286.
  6. Horton P, Nakai K (1997). "Better prediction of protein cellular localization sites with the k nearest neighbors classifier". Proc Int Conf Intell Syst Mol Biol. 5: 147–52. PMID 9322029.
  7. "FAM46C PSICQUIC View". Retrieved 11 May 2013.

External links

  • [2] - The homepage of the Full-length long Japan human genomic sequencing project

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