TMEM241

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Transmembrane protein 241 (aka C18orf45, hVVT) is a ubiquitous sugar transporter protein which in humans is encoded by the TMEM241 gene.[1]

Gene

In humans, TMEM241 is a 142,188 bp gene located at 18q11.2 which contains 24 exons.[2]

Gene Neighborhood

TMEM241 is located near CABLES1, RIOK3, and NPC1 on chromosome 18.[3]

mRNA

File:3' UTR hairpin.png
TMEM241 Isoform 1 5' UTR (untranslated region) hairpin

The primary mRNA for human TMEM241, isoform 1,[3] contains a 5' UTR hairpin loop conserved in primates.The primary mRNA for human TMEM241 isoform 1 contains binding sites in its 3' UTR for the miRNAs 520f-5p, 378a-5p, and 6866-5p.[4]

Protein

General Properties

There are over 10 transcript variants predicted for the human TMEM241 gene found on BLAST. TMEM241 Isoform 1 is approximately 31 kDa in mass. The protein has an isoelectric point of 8.7. and is particularly rich in the amino acid phenylalanine, containing twice the normal proportion of this amino acid.[5]

Conserved Domains

File:Protein Annotation with 2ndary Structure PS4.png
Structural Details of TMEM241 Isoform 1
File:Alpha helix wheel diagram.png
Alpha helix wheel diagram of TMEM241 isoform 1 showing hydrophobic and hydrophilic region interactions with lipid membrane.

TMEM241 is composed of 9 transmembrane domains forming a hydrophobic integral component of the membrane[2] composed primarily of alpha helices.[6][7][8] TMEM241 contains a VRG4 (Vandate Resistance Glycosylation[9]) domain with homology to the sugar transporter domain VRG4 from Saccharomyces cerevisiae (yeast).[10]

Post-Translational Modification

File:Wikipedia simplified TMEM241.png
TMEM241 Isoform 1 Post translational modification sites

TMEM241 is predicted to undergo various phosphorylations,[11] glycation,[11] palmitoylation.[12] For example, TMEM241 isoform 1[13] has a phosphorylation sites on S6, 64, 170, 177, 291, 295 and 296;[11] glycation sites on K125, 169 and 172;[11] palmitoylation sites on C13, 15, 221.[12]

Interacting Proteins

There is some evidence that this protein may interact with keratin filament based on a two hybrid screen with the keratin protein KRT40.[14]

Expression

TMEM241 is likely to be expressed in all tissues at varying levels from basal to moderate expression.[15] Some studies have found changes in the expression of TMEM241. For instance, in cases of acute megakaryoblastic leukemia, TMEM241 was found to be one of the most upregulated genes.[16] In another case TMEM241 was found to be upregulated during the unfolded protein response following the overexpression of Ero1α (Endoplasmic Reticulum oxidoreduclin 1α).[10]

Homology

TMEM241 is conserved throughout eukaryotes.

Orthologs

File:TMEM241 Time of divergence from humans vs corrected % divergence.png
Divergence Rate of TMEM241

TMEM241 is conserved across all animals and homologs are found throughout eukaryotes. TMEM241 has 19% global identity and 60% identity to GDP-mannose transporter from S. cerevisiae, which contains the VRG4 domain. It is likely that TMEM241 is a GDP-mannose transporter due to this similarity. The graph on the right shows the relative level of conservation of TMEM241 across many species of organism using the principle of a Molecular Clock.

Scientific name Common name Divergence from H. sapiens (m.y.a)[17] Protein Length (amino acids) % Identity to H. sapiens[18][19] Accession number
Homo sapiens Human 0 296 100 NP_116322
Mus musculus Mouse 90.1 297 84 NP_001276595
Calidris pugnax Ruff (bird) 320.5 296 80 XP_003219697
Python bivittatus Python 320.5 296 74 XP_014793906
Xenopus laevis Frog 354.4 293 69 NP_001091222
Salmo salar Salmon 436.8 296 63 XP_014036453
Octopus bimaculoides Octopus 903 291 35 XP_014776992
Halyomorpha halys Stink bug 903 257 32 XP_014284006
Saccharomyces cerevisiae Yeast 1335.5 216 25 AJS02580
Coccomyxa subellipsoidea Green Algae 1570.5 296 28 XP_005651133

Paralogs

TMEM241 has two paralogs in humans which have homologs throughout eukaryotes, UGTREL8[20] and UGTREL7.[21] TMEM241, UGTREL8 and UGTREL7 are a family of sugar transport proteins with close identity to the GDP-mannose transporter identified in S. cerevisiae.

% Identity[18][19] TMEM241

(H.sapiens)

UGTREL7

(H.sapiens)

UGTREL8

(H.sapiens)

GDP Mannose Transporter

(S. cerevisiae)

TMEM241 (H. sapiens) 100% 19.9% 23.9% 19.0%
UGTREL7 (H. sapiens) 19.9% 100% 52.2% 18.8%
UGTREL8 (H. sapiens) 23.9% 52.2% 100% 19.9%
GDP Mannose Transporter

(S. cerivisiae)

19.0% 18.8% 19.9% 100%

References

  1. ↑ "Entrez Gene: Transmembrane protein 241". Retrieved 2013-05-09.
  2. ↑ 2.0 2.1 "TMEM241 transmembrane protein 241 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-02-28.
  3. ↑ 3.0 3.1 "NCBI NM_032933.5". Retrieved 6 February 2016.
  4. ↑ "miRDB - MicroRNA Target Prediction And Functional Study Database". mirdb.org. Retrieved 2016-04-30.
  5. ↑ Brendel, V; Bucher, P; Nourbakhsh, I.R; Blaisdell, B.E; Karlin, S (1992). "Methods and algorithms for statistical analysis of protein sequences". Proc. Natl. Acad. Sci. 89: 2002–2006. doi:10.1073/pnas.89.6.2002. PMC 48584.
  6. ↑ "SOSUI: Result". harrier.nagahama-i-bio.ac.jp. Retrieved 2016-04-24.
  7. ↑ "Phobius". phobius.sbc.su.se. Retrieved 2016-04-24.
  8. ↑ "DAS-TMfilter server". mendel.imp.ac.at. Retrieved 2016-04-24.
  9. ↑ "VRG4 | SGD". www.yeastgenome.org. Retrieved 2016-04-30.
  10. ↑ 10.0 10.1 Hansen, H.G.; Schmidt, J. D.; Soltoft, C. L.; Ramming, T.; Geertz-Hansen, H. M.; Christensen, B.; Sorensen, E. S.; Juncker, A. S.; Appenzeller-Herzog, C.; Ellgaard, L. (1 October 2012). "Hyperactivity of the Ero1 Oxidase Elicits Endoplasmic Reticulum Stress but No Broad Antioxidant Response". Journal of Biological Chemistry. 287 (47): 39513–39523. doi:10.1074/jbc.M112.405050. PMC 3501080.
  11. ↑ 11.0 11.1 11.2 11.3 "Welcome to CBS". www.cbs.dtu.dk. Retrieved 2016-04-24.
  12. ↑ 12.0 12.1 "CSS-Palm - Palmitoylation Site Prediction". csspalm.biocuckoo.org. Retrieved 2016-04-24.
  13. ↑ "transmembrane protein 241 isoform 1 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-04-30.
  14. ↑ "mentha: the interactome browser". mentha.uniroma2.it. Retrieved 2016-05-04.
  15. ↑ "GDS3834 / 12797 / TMEM241". www.ncbi.nlm.nih.gov. Retrieved 2016-04-24.
  16. ↑ Pelleri, Maria; Piovesan, Allison; Caracausi, Maria; Berardi, Anna; Vitale, Lorenza; Strippoli, Pierluigi (2014). "Integrated differential transcriptome maps of Acute Megakaryoblastic Leukemia (AMKL) in children with or without Down Syndrome (DS)". BMC Medical Genomics. 7 (1): 63. doi:10.1186/s12920-014-0063-z.
  17. ↑ Hedges, SB; Marin, J; Suleski, M; Kumar, S. "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2016-04-27.
  18. ↑ 18.0 18.1 Pearson, W.R. (1990). "Rapid and Sensitive Sequence Comparison with FASTP and FASTA". Methods in Enzymology: 63–98. doi:10.1016/0076-6879(90)83007-v.
  19. ↑ 19.0 19.1 "ALIGN". Archived from the original on 2003-08-11.
  20. ↑ "UDP-glucuronic acid/UDP-N-acetylgalactosamine transporter [Homo sapien - Protein - NCBI]". www.ncbi.nlm.nih.gov. Retrieved 2016-02-28.
  21. ↑ "SLC35D1 solute carrier family 35 member D1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-04-26.

Further reading

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