Biology:Transmembrane protein 89

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Short description: Human gene


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Transmembrane protein 89 (TMEM89) is a protein that in humans is encoded by the TMEM89 gene.

Gene

Structure

The TMEM89 gene is found on the minus strand of chromosome 3 (3p21.31) from 48,658,192 to 48,659,288 and is 1,011 nucleotides long.[1][2] The gene has two exons.[1][2] These two exons are not predicted to be alternatively spliced.[1][2]

Gene expression

The TMEM89 gene is most highly expressed in the testis.[1][2] TMEM89 is also found to be expressed at low levels in other tissues such as the stomach, kidneys, heart, ovaries, thyroid, colon, bone marrow, and in adrenal tissues.[1] This gene is also expressed in fetal heart, stomach, kidney, and intestine tissues.[1] Immunohistochemistry data has also found TMEM89 located in the cell membranes of the colon, fallopian tube, kidney, and testis tissues.[3][4] Expression of the TMEM89 gene has also been found in low amounts in the brain tissue from a mouse cerebellum.[5]

Gene expression neighborhood

Human TMEM89 is a part of the Human Protein Atlas expression cluster 23: SpermatidS - Flagellum & Golgi organization.[3][6] The 15 closest expression neighbors include OR4M1, ANTXRL, TGIF2LX, CPXCR1, C3orf84, CXorf66, CLDN17, C11orf94, USP50, SPDYE4, MMP20, SSMEM1, C17orf98, SPACA1, and LYZL1.[6]

Differential gene expression

TMEM89 expression is much higher in amniotic fluid derived hAKPC-P cells compared with immortalized hIPod line cells.[7] TMEM89 expression is higher in cells that have macrophage migration inhibitory factor (MIF) knocked down compared to the control.[8] TMEM89 expression is the lowest in cardiomyocytes from human embryonic stem cells, compared to expression in human embryonic stem cells, embryoid bodies with beating cardiomyocytes, and cardiomyocytes from fetal hearts.[9]

Clinical significance

Gene expression of TMEM89 was found to be upregulated in upper tract urothelial carcinomas, and therefore predicted as a possible biomarker secretory protein for these types of carcinomas.[10] The TMEM89 gene was found to be a potential modifier of autism spectrum disorder severity in a SNP analysis.[citation needed] Gene expression of TMEM89 was also used in a model that predicted the risk score for a potential relapse in stage 1 testicular germ cell tumors.[11]

Human TMEM89 Conceptual Translation[1][12][13][14][15][16][17]

Protein

Structure

Primary

The human TMEM89 protein is 159 amino acids long.[1] This protein has a molecular mass of ~17.5kDa and an isoelectric point of ~10 pI.[2][18] Proteins with a more basic pI are usually associated with the mitochondria or the plasma membrane and have fewer protein interactions.[19][20] The protein structure contains two topological domains (extracellular and cytoplasmic) and a helical transmembrane domain.[13][21][22] The human TMEM89 protein is rich in the amino acids histidine, leucine, and tryptophan.[14] The amino acids aspartate, asparagine, and phenylalanine are present in low amounts in the human TMEM89 protein.[14] Amino acid patterns such as ED are present in the human TMEM89 protein at low amounts, while the pattern KR-ED is present in high amounts.[14] Within the extracellular domain of the human TMEM89 protein, there are 3 cysteines with regular spacing.[14] In the cytoplasmic domain, there are two positive amino acid runs from amino acids 3-5 and 25-27.[14] These different amino acid patterns and protein domains can be visualized in the figures to the right.

Human TMEM89 SOSUI Hydrophobicity and Net Charge Density Graph[21]
SOSUI Human TMEM89 Wheel Plot[21]
Protter Human TMEM89 Snake Plot[22]

Secondary

The TMEM89 protein is only made up of α-helices and strands.[23][24] The α-helices are distributed all throughout the protein in all three domains.[23][24]

Tertiary

The tertiary structure of Human TMEM89 was predicted using Alphafold and I-Tasser software.[23][24] These structures can be seen on the right.

Human TMEM89 Tertiary Structure With Labeled Domains[23][25]
Human TMEM89 Tertiary Structure with Labeled Charges[25][23]
I-Tasser Human TMEM89 Signal Peptide and Extracellular Domain Structure Prediction[24][25]
I-Tasser and Alphafold Human TMEM89 Signal Peptide and Extracellular Domain Comparison[23][24][25]
I-Tasser Human TMEM89 Cytoplasmic Domain Structure Prediction[25][24]
I-Tasser and Alphafold Human TMEM89 Cytoplasmic Domain Comparison[23][25][24]

Post-translational modifications

The TMEM89 protein has a predicted N-myristylation site from amino acids 47-52, a predicted Src homology 3 (SH3) binding domain from amino acids 106-111, and one conserved predicted phosphorylation site at amino acid S117.[15][17][16] N-myristylation is a protein lipid modification that has roles in protein-protein interactions, cell signaling, and targeting proteins to endomembranes and the plasma membrane.[26] Proteins with SH3 binding domains are usually involved in signal transduction pathways, cytoskeleton organization, membrane trafficking, or organelle assembly.[27] Protein phosphorylation is an important process involved with signal transduction, protein synthesis, cell division, cell growth, development, and aging.[28]

Human TMEM89 Motif Schematic[29][15][17][16]
Human TMEM89 N-myristylation Site Multiple Sequence Alignment[30][15]

Interactions

The human TMEM89 protein interacts with the proteins C4A, RBM15B, GOLGA6A, PFKFB4, DOCK3, MAPKAPK3, ZNF557, and ZBTB47.[31][32]

Homologs

Orthologs

Orthologs of TMEM89 are only found in mammals.[1] The only mammalian taxon that does not contain a TMEM89 ortholog is the monotremes.

Below is a table with information on some of the orthologs of human TMEM89. These orthologs were used to make the multiple sequence alignment and N-myristylation site alignment to the right.

TMEM89 Ortholog Table[33][34][35]
Genus and Species Common Name Taxon Date of Divergence (MYA) NCBI Accession Number Sequence Length (aa) % Identity % Similarity
Homo sapiens Humans Primate 0 NP_001008270.1 159 100 100
Castor canadensis American beaver Rodentia 87 XP_020018275.1 158 73.1 81.2
Urocitellus parryii Arctic ground squirrel Rodentia 87 XP_026239733.1 155 66.0 74.8
Orcinus orca Orca Artiodactyla 94 XP_004283952.1 159 71.9 80.0
Bos taurus Cow Artiodactyla 94 NP_001104538.1 159 63.5 73.5
Odobenus rosmarus divergens Pacific walrus Carnivora 94 XP_004399365.2 159 67.9 77.4
Canis lupus familiaris Dog Carnivora 94 XP_038283783.1 159 65.6 76.2
Talpa occidentalis Spanish mole Eulipotphyla 94 XP_037376292.1 162 66.7 75.3
Condylura cristata Star-nosed mole Eulipotphyla 94 XP_004676653.1 162 63.0 74.1
Pteropus alecto Black flying fox Chiroptera 94 XP_006909233.1 156 65.2 74.5
Desmodus rotundus Common vampire bat Chiroptera 94 XP_024421609.1 159 63.8 74.4
Ceratotherium simum simum Southern white rhinoceros Perissodactyla 94 XP_004419716.1 159 64.2 78.0
Equus caballus Horse Perissodactyla 94 XP_003363167.2 207 49.8 58.9
Manis javanica Malayan pangolin Pholidota 94 KAI5937412.1 158 53.8 67.5
Manis pentadactyla Chinese pangolin Pholidota 94 XP_036733472.1 158 53.1 66.0
Orycteropus afer afer Aardvark Tubulidentata 99 XP_007953489.1 160 68.9 77.0
Loxodonta africana African bush elephant Proboscidea 99 XP_003409726.1 160 68.8 79.4
Dasypus novemcinctus Nine-banded armadillo Cingulata 99 XP_004451990.1 157 67.5 75.0
Sarcophilus harrisii Tasmanian devil Dasyuromorphia 160 XP_031794457.1 168 41.0 52.2
Trichosurus vulpecula Common brushtail possum Diprotodontia 160 XP_036595517.1 168 40.8 51.4
Unrooted Phylogenetic Tree of Human TMEM89 Orthologs[33][36]

Conserved regions

Regions within the cytoplasmic and extracellular domains of the human TMEM89 protein seem to be the most conserved, as seen in figures on the right.[30][33] Some of these conserved amino acids are part of α-helices in the cytoplasmic and extracellular regions.[30][33]

Human TMEM89 Orthologs Multiple Sequence Alignment[30][33]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Database resources of the national center for biotechnology information". Nucleic Acids Research 50 (D1): D20–D26. January 2022. doi:10.1093/nar/gkab1112. PMID 34850941. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 "The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses". Current Protocols in Bioinformatics 54 (1): 1.30.1–1.30.33. June 2016. doi:10.1002/cpbi.5. PMID 27322403. 
  3. ↑ 3.0 3.1 "The Human Protein Atlas". https://www.proteinatlas.org/. 
  4. ↑ "Proteomics. Tissue-based map of the human proteome". Science 347 (6220): 1260419. January 2015. doi:10.1126/science.1260419. PMID 25613900. 
  5. ↑ "A Suite of Transgenic Driver and Reporter Mouse Lines with Enhanced Brain-Cell-Type Targeting and Functionality". Cell 174 (2): 465–480.e22. July 2018. doi:10.1016/j.cell.2018.06.035. PMID 30007418. 
  6. ↑ 6.0 6.1 "A single-cell type transcriptomics map of human tissues". Science Advances 7 (31): eabh2169. July 2021. doi:10.1126/sciadv.abh2169. PMID 34321199. Bibcode: 2021SciA....7.2169K. 
  7. ↑ "A novel source of cultured podocytes". PLOS ONE 8 (12): e81812. 12 December 2013. doi:10.1371/journal.pone.0081812. PMID 24349133. Bibcode: 2013PLoSO...881812D. 
  8. ↑ "A global genomic view of MIF knockdown-mediated cell cycle arrest". Cell Cycle 7 (11): 1678–1692. June 2008. doi:10.4161/cc.7.11.6011. PMID 18469521. 
  9. ↑ "Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes". PLOS ONE 3 (10): e3474. 22 October 2008. doi:10.1371/journal.pone.0003474. PMID 18941512. Bibcode: 2008PLoSO...3.3474C. 
  10. ↑ "Identification of plasma secreted phosphoprotein 1 as a novel biomarker for upper tract urothelial carcinomas". Biomedicine & Pharmacotherapy 113: 108744. May 2019. doi:10.1016/j.biopha.2019.108744. PMID 30844659. 
  11. ↑ "Development and Validation of a Gene Signature for Prediction of Relapse in Stage I Testicular Germ Cell Tumors". Frontiers in Oncology 10: 1147. 30 July 2020. doi:10.3389/fonc.2020.01147. PMID 32850325. 
  12. ↑ "Six-Frame Translation". https://www.bioline.com/media/calculator/01_13.html. 
  13. ↑ 13.0 13.1 "UniProt: the universal protein knowledgebase in 2021". Nucleic Acids Research 49 (D1): D480–D489. January 2021. doi:10.1093/nar/gkaa1100. PMID 33237286. 
  14. ↑ 14.0 14.1 14.2 14.3 14.4 14.5 "Methods and algorithms for statistical analysis of protein sequences". Proceedings of the National Academy of Sciences of the United States of America 89 (6): 2002–2006. March 1992. doi:10.1073/pnas.89.6.2002. PMID 1549558. Bibcode: 1992PNAS...89.2002B. 
  15. ↑ 15.0 15.1 15.2 15.3 "MyHits: improvements to an interactive resource for analyzing protein sequences". Nucleic Acids Research 35 (Web Server issue): W433–W437. July 2007. doi:10.1093/nar/gkm352. PMID 17545200. 
  16. ↑ 16.0 16.1 16.2 "Kinexus PhosphoNET". http://www.phosphonet.ca/. 
  17. ↑ 17.0 17.1 17.2 "The Eukaryotic Linear Motif resource: 2022 release". Nucleic Acids Research 50 (D1): D497–D508. January 2022. doi:10.1093/nar/gkab975. PMID 34718738. 
  18. ↑ "The focusing positions of polypeptides in immobilized pH gradients can be predicted from their amino acid sequences". Electrophoresis 14 (10): 1023–1031. October 1993. doi:10.1002/elps.11501401163. PMID 8125050. 
  19. ↑ "pH-induced intracellular protein transport". Physical Biology 3 (2): 101–106. May 2006. doi:10.1088/1478-3975/3/2/002. PMID 16829696. Bibcode: 2006PhBio...3..101B. 
  20. ↑ "The relationships between the isoelectric point and: length of proteins, taxonomy and ecology of organisms". BMC Genomics 8 (1): 163. June 2007. doi:10.1186/1471-2164-8-163. PMID 17565672. 
  21. ↑ 21.0 21.1 21.2 "SOSUI: classification and secondary structure prediction system for membrane proteins". Bioinformatics 14 (4): 378–379. 1998-05-01. doi:10.1093/bioinformatics/14.4.378. PMID 9632836. 
  22. ↑ 22.0 22.1 "Protter: interactive protein feature visualization and integration with experimental proteomic data". Bioinformatics 30 (6): 884–886. March 2014. doi:10.1093/bioinformatics/btt607. PMID 24162465. 
  23. ↑ 23.0 23.1 23.2 23.3 23.4 23.5 23.6 "Highly accurate protein structure prediction with AlphaFold". Nature 596 (7873): 583–589. August 2021. doi:10.1038/s41586-021-03819-2. PMID 34265844. Bibcode: 2021Natur.596..583J. 
  24. ↑ 24.0 24.1 24.2 24.3 24.4 24.5 24.6 "I-TASSER server: new development for protein structure and function predictions". Nucleic Acids Research 43 (W1): W174–W181. July 2015. doi:10.1093/nar/gkv342. PMID 25883148. 
  25. ↑ 25.0 25.1 25.2 25.3 25.4 25.5 "Cn3D: sequence and structure views for Entrez". Trends in Biochemical Sciences 25 (6): 300–302. June 2000. doi:10.1016/S0968-0004(00)01561-9. PMID 10838572. 
  26. ↑ "Myristoylation: An Important Protein Modification in the Immune Response". Frontiers in Immunology 8: 751. 2017-06-30. doi:10.3389/fimmu.2017.00751. PMID 28713376. 
  27. ↑ "The Eukaryotic Linear Motif resource: 2022 release". Nucleic Acids Research 50 (D1): D497–D508. January 2022. doi:10.1093/nar/gkab975. PMID 34718738. 
  28. ↑ "The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)". International Journal of Molecular Medicine 40 (2): 271–280. August 2017. doi:10.3892/ijmm.2017.3036. PMID 28656226. 
  29. ↑ "IBS: an illustrator for the presentation and visualization of biological sequences". Bioinformatics 31 (20): 3359–3361. October 2015. doi:10.1093/bioinformatics/btv362. PMID 26069263. 
  30. ↑ 30.0 30.1 30.2 30.3 "Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega". Molecular Systems Biology 7 (1): 539. October 2011. doi:10.1038/msb.2011.75. PMID 21988835. 
  31. ↑ "The BioPlex Network: A Systematic Exploration of the Human Interactome". Cell 162 (2): 425–440. July 2015. doi:10.1016/j.cell.2015.06.043. PMID 26186194. 
  32. ↑ "Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals". JAMA Neurology 72 (11): 1313–1323. November 2015. doi:10.1001/jamaneurol.2015.1700. PMID 26366463. 
  33. ↑ 33.0 33.1 33.2 33.3 33.4 Madden, Thomas L.; Tatusov, Roman L.; Zhang, Jinghui (1996) (in en), [9 Applications of network BLAST server], Methods in Enzymology, 266, Elsevier, pp. 131–141, doi:10.1016/s0076-6879(96)66011-x, ISBN 978-0-12-182167-8, PMID 8743682, https://linkinghub.elsevier.com/retrieve/pii/S007668799666011X, retrieved 2022-12-15 
  34. ↑ "TimeTree 5: An Expanded Resource for Species Divergence Times". Molecular Biology and Evolution 39 (8): msac174. August 2022. doi:10.1093/molbev/msac174. PMID 35932227. 
  35. ↑ "A general method applicable to the search for similarities in the amino acid sequence of two proteins". Journal of Molecular Biology 48 (3): 443–453. March 1970. doi:10.1016/0022-2836(70)90057-4. PMID 5420325. 
  36. ↑ "drawtree". https://evolution.genetics.washington.edu/phylip/doc/drawtree.html. 



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