SMCO4

SMCO4 (Single-pass membrane protein with coiled-coil domains 4) is a human gene that encodes the FN5 protein. The FN5 protein is a single-pass transmembrane protein, which means that one end of the protein will remain in the cytoplasm, while the other end of the protein is exposed to the interior of the cell.

SMCO4
Identifiers
AliasesSMCO4, C11orf75, FN5, single-pass membrane protein with coiled-coil domains 4
External IDsOMIM: 609477 HomoloGene: 137340 GeneCards: SMCO4
Gene location (Human)
Chr.Chromosome 11 (human)[1]
Band11q21Start93,478,472 bp[1]
End93,543,391 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

56935

n/a

Ensembl

ENSG00000166002

n/a

UniProt

Q9NRQ5

n/a

RefSeq (mRNA)

NM_020179

n/a

RefSeq (protein)

NP_064564

n/a

Location (UCSC)Chr 11: 93.48 – 93.54 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Gene Properties

The SMCO4 gene is located on chromosome 11, with specific chromosomal coordinates of 11q13.3-q23.3 in Homo sapiens.[3] SMCO4 has two common aliases: C11orf75 (Chromosome 11 Open Reading Frame 75) and FN5.[4]

mRNA features

SMCO4 has 7 isoforms in Homo sapiens.[5] The SMCO4 isoform 1 has 9 exons, while the rest of the isoforms have varying amounts of exons. These isoforms are listed in the table below, with their accession numbers for reference.

Isoform SMCO4 isoform x1 SMCO4 isoform x2 SMCO4 isoform x3 SMCO4 isoform x4 SMCO4 isoform x5 SMCO4 isoform x6 SMCO4 isoform x6
NCBI accession # XM_011542907.1 XM_011542908.2 XM_011542909.1 XM_011542910.2 XM_017018019.1 XM_017018020.1 XM_011542911.2

Protein
Sequence Length (bp) Protein Sequence Length (aa)[3] Molecular Weight (kD)[6] Isoelectric Point[6]
979 59 6.7 10.75

MRQLKGKPKKETSKDKKERKQAMQEARQQITTVVLPTLAVVVLLIVVFVYVATRPTITE

The protein that is encoded by SMCO4 is rich in phosphorylable amino acids and has a high pH. There are no predicted protein repeats. There is evidence that the protein is present in the outer membrane of the mitochondria.[7] The absence of an N-terminal signal peptide shows that the protein does not have the ability to leave the organelle it is in, which correlates with the knowledge that it is a transmembrane protein.

Structure

The structure of the FN5 protein is not yet known, but the protein qualities are useful in predicting the protein's structure. There is no evidence that the protein would take on any Beta-turns; its secondary structure would be composed of only alpha-helixes. There are two separate helixes: the transmembrane helix and the alpha helix.

This image is an animated rendition of a possible structure that the FN5 protein would take on. The C-terminus is shown in red, and the N-terminus is shown in blue.

Expression
This image, from the Protein Atlas database, shows the expression levels of the SMCO4 gene in different areas throughout the body

Expression Analysis

SMCO4 expression in humans was predicted to be highest in the salivary glands.[8][9] Overall, there was RNA tissue expression shown in 37 human tissues and expression of the protein in 71 cell types.[9]

Regulation of Expression

SMCO4 is not ubiquitously expressed throughout humans. There is evidence that the expression of SMCO4 is easily manipulated by many different factors, making constant expression unlikely. One example of this expression regulation comes from an experiment that showed increased SMCO4 expression in the presence of Gamma-tocotrienol.[10][11]

Predicted Interactions

SMCO4 is predicted to interact with the following proteins:[12]

BNIP3L BCL2/adenovirus E1B 19kDa protein-interacting protein 3-like
SYNE4 Spectrin Repeat Containing Nuclear Envelope Family Member 4
CCDC155 Coiled-Coil Domain Containing 155

Conservation

Two microRNAs, miR-124-3p.1 and miR-183-5p.1, are thought to be highly conserved throughout variety of vertebrates. TheseicroRio RNAs are both neuronal in nature.[13]

Orthologs

Orthologs of SMCO4 were found in a variety of species, including mammals, birds, reptiles, amphibians, insects and parasites. The primates were consistently found to have the highest sequence identity with the human SMCO4 sequence, followed closely by an extinct fish species called Latimeria chalumnae. There was no evidence of SMCO4 presence in yeast species.

References
  1. GRCh38: Ensembl release 89: ENSG00000166002 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. Kehrer-Sawatzki H, Moschgath E, Maier C, Legius E, Elgar G, Krone W (June 2000). "Characterization of the Fugu rubripes NLK and FN5 genes flanking the NF1 (Neurofibromatosis type 1) gene in the 5' direction and mapping of the human counterparts". Gene. 251 (1): 63–71. doi:10.1016/s0378-1119(00)00188-8. PMID 10863097.
  4. https://genecards.weizmann.ac.il/geneloc-bin/display_map.pl?range_type=within_id&chr_nr=11&around_id=574243&around_marker=SMCO4&start_bp=93478472&end_bp=93586855&plus_minus_Mb=4&match=exact&range=on&genes=on&enhancers=on&entity=gene#574243. Missing or empty |title= (help)
  5. "SMCO4 single-pass membrane protein with coiled-coil domains 4 [ Homo sapiens (human)]".
  6. http://seqtool.sdsc.edu/CGI/BW.cgi. Missing or empty |title= (help)
  7. PSORT II Server. GenScript http://www.genscript.com/tools/psort. Missing or empty |title= (help)
  8. "EST Profile".
  9. "SMCO4".
  10. "Gamma-tocotrienol effect on breast cancer MCF-7 cells".
  11. "Tocotrienols: A new way to combat cancer".
  12. "107 binary interactions found for search term SMCO4". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-25.
  13. Dostie J, Mourelatos Z, Yang M, Sharma A, Dreyfuss G (February 2003). "Numerous microRNPs in neuronal cells containing novel microRNAs". RNA. 9 (2): 180–6. doi:10.1261/rna.2141503. PMC 1370383. PMID 12554860.
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