TMEM44

Gene

TMEM44 gene has 14 transcipts (splice variants). The whole span of the gene is 46,016 base pairs long, while the mRNA sequence of TMEM44 is 1,483 base pairs long, with 13 exons. Exon 1 and 2 partial are part of 5'-UTR, and the partial exon 2 is only highly conserved in primates.[6]

Regulation

There are 5 experimentally verified promoters, and 4 predicted ones. Promoter GXP_232172, which is promoter set 5 is the longest with 1,276 base pairs and a total of 11 coding transcripts.[7]

Expression

There is an overall low level expression of TMEM44 gene throughout the body parts and throughout the developmental stages of humans. Some parts where TMEM44 expression is detected are in bone, brain, eye, ovary, pancreas and uterus. Some expression was also detected under certain health conditions including gastrointestinal tumor, glioma, ovarian tumor, pancreatic tumor, muscle tissue tumor and uterine tumor.[8]

Locus

TMEM44 gene is located near the end of the long arm of chromosome 3 (3q29) in humans (Homo sapiens).[9]

TMEM44 gene on human chromosome 3

Protein

TMEM44 is 428 amino acids in length. The molecular weight of the protein is 47.1kDa, and its formula is C2086H3315N585O611S22, with a total of 6,619 atoms.[10] The theoretical isoelectric point (pI) of TMEM44 is 8.12.[11] The instability index (II) of TMEM44 is 47.96, which classifies the protein as unstable. There are 12 isoforms of TMEM44, with isofrom c being the longest.[9] The function of TMEM44 is currently unknown.

Subcellular Localization

The C-terminus of TMEM44 is found in the cytoplasm, and the protein is predicted to be integrated within the membrane of the endoplasmic reticulum.[12]

Secondary Structure

TMEM44 has 41.12% of alpha helix, 15.65% of extended strand and 43.22% of random coil.[13]

3D of partial TMEM44 protein from sequence 119 to 267 (identity 13%)

Transmembrane Region Allocation

There are seven predicted transmembrane domains in TMEM44 protein.

Phobius posterior probabilities of human TMEM44 protein

Interacting Proteins

GSK3B (Glycogen synthase kinase 3 beta), KAT6B (Histone acetyltransferase KAT6B/Histone acetyltransferase MYST4), TMEM31 (Transmembrane protein 31), SPAG9 (sperm associated antigen 9) and TNKS (tankyrase-1) are predicted to interact with TMEM44.[14][15][16]

Post-Translational Modification

TMEM44 undergoes threonine, tyrosine and serine phosphorylations.[17] Many serine phosphorylation takes place near the C-terminus, causing it to be negatively charged.

Predicted phosphorylation sites in human TMEM44 protein

The Glycine (G) found nearest from the C-terminus is predicted to have glycosylphosphatidylinositol (GPI) attached, which anchors the protein to the cellular plasma membrane.[18]

The first 45 amino acids serve as a signal peptide cleavage site.[19]

Orthologs

Orthologs with the TMEM44 protein include amphibians, birds, fish, and mammals. The closest ortholog from human with TMEM44 is common chimpanzee (Pan troglodytes) with 98% identity, and the most distantly related ortholog is common carp (Cyprinus carpio) with 27% identity.[20]

12 selected orthologs of TMEM44 are shown below.

Orthologs of TMEM44
sequence number genus species common name date of divergence/MYA NCBI[21] accession number identity/%
Homo sapiens human 0 AAI44160.1 100
1 Macaca fascicularis crab-eating macaque 29 XP_005545405.1 94
2 Rhinolophus sinicus Chinese rufous horseshoe bat 96 XP_019578895.1 80
3 Condylura cristata star-nosed mole 96 XP_012585115.1 79
4 Enhydra lutris kenyoni sea otter 96 XP_022370817.1 78
5 Sorex araneus common shrew 96 XP_012791655.1 63
6 Chrysemys picta bellii painted turtle 312 XP_023967126.1 51
7 Nipponia nippon crested ibis 312 XP_009466798.1 42
8 Xenopus tropicalis western clawed frog 353 XP_012818195.1 39
9 Salvelinus alpinus arctic char 435 XP_023859379.1 35
10 Hippocampus comes tiger tail seahorse 435 XP_019735697.1 33
11 Oreochromis niloticus Nile tilapia 435 XP_013119610.1 30
12 Monopterus albus Asian swamp eel 435 XP_020452501.1 29

TMEM44 is generally fast evolving, with about 0.310 changes of amino acids per 100 over a million year.

Graph of Corrected Amino Acids Changes per 100 residues (m) over Time showing the rough rate of TMEM44 (red) compared to the other proteins

Paralogs

Predicted paralogous proteins of TMEM44 are C9IZ85, F8WCY1, F8WE47, H7C3X7, J3KQW3, Q6PL43, and Q96I73.[22]

References

  1. GRCh38: Ensembl release 89: ENSG00000145014 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000022537 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: Transmembrane protein 44". Retrieved 2018-05-01.
  6. "Homo sapiens transmembrane protein 44, mRNA (cDNA clone IMAGE:4747146) - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-02-18.
  7. "Genomatix - NGS Data Analysis & Personalized Medicine". www.genomatix.de. Retrieved 2018-05-05.
  8. Group, Schuler. "EST Profile - Hs.478729". www.ncbi.nlm.nih.gov. Retrieved 2018-04-23.
  9. "TMEM44 transmembrane protein 44 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-02-15.
  10. "ExPASy - ProtParam tool". web.expasy.org. Retrieved 2018-04-22.
  11. "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 2018-05-05.
  12. "PSORT WWW Server". psort.hgc.jp. Retrieved 2018-05-05.
  13. UCBL, Institut de Biologie et Chimie des Proteines - UMR5086 - CNRS -. "NPS@ : GOR4 secondary structure prediction". npsa-prabi.ibcp.fr. Retrieved 2018-05-05.
  14. IntAct. "https://www.ebi.ac.uk/intact/". www.ebi.ac.uk. Retrieved 2018-04-22. External link in |title= (help)
  15. Lab, Mike Tyers. "BioGRID | Database of Protein, Chemical, and Genetic Interactions". thebiogrid.org. Retrieved 2018-04-22.
  16. "The Molecular INTeraction Database – An ELIXIR Core Resource". mint.bio.uniroma2.it. Retrieved 2018-04-22.
  17. "NetPhos 3.1 Server". www.cbs.dtu.dk. Retrieved 2018-04-22.
  18. "GPI Prediction Server". mendel.imp.ac.at. Retrieved 2018-05-05.
  19. "ProP 1.0 Server". www.cbs.dtu.dk. Retrieved 2018-05-05.
  20. "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2018-02-18.
  21. "Home - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-05-05.
  22. .Database, GeneCards Human Gene. "TMEM44 Gene - GeneCards | TMM44 Protein | TMM44 Antibody". www.genecards.org. Retrieved 2018-04-23.
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