Transmembrane protein 145 is a protein, which in humans, is encoded by the TMEM145 gene. TMEM145 has been associated with tumor suppression in breast cancer and prostate cancer.
Gene
The TMEM145 Gene is located on the plus strand of Chromosome 19 at 19q13.2. This gene spans 11,756 nucleotides and contains 15 exons.NCBI Gene entry on TMEM145 . Retrieved September 18, 2024.GeneCards TMEM145. (2024, August 6). Retrieved September 20, 2024 from, https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM145. RNA-sequencing data from NCBI displayed that TMEM145 displays highest expression in the brain with notable expression also in the adrenal glands.NCBI Gene entry on TMEM145 Microarray-assessed tissue expression revealed that human TMEM145 is expressed ubiquitously with moderate variation across different tissues.NCBI GEO TMEM145 entry GDS3113 The human TMEM145 protein has a lower than average expression level in comparison to other human proteins.PaxDB entry on Homo Sapiens TMEM145 The Human Protein Atlas showed human TMEM145 to have highest expression in the cerebellum with second highest expression in the cerebral cortex.The Human Protein Atlas In situ hybridization data from Allen Brain Atlas showed TMEM145 RNA expression in Mus Musculus with highest expression in the cerebellum and dentate gyrus.Allen Brain Atlas Entry on TMEM145
Transcript Based on NCBI Gene, the longest high-quality mRNA sequence is transcript variant 1 (NM_001366910.1) which encodes isoform 1, the longest protein isoform. This mRNA sequence contains 2298 base pairs.NCBI mRNA entry on TMEM145 Isoform 1 Precursor
Protein
The TMEM145 gene encodes transmembrane protein 145 isoform 1 precursor (NP_001353839.1) with a molecular weight of ~ 60kDa and contains 563 amino acids.NCBI Protein entry on TMEM145 The isoelectric point of this protein is 8.8. There are five protein isoforms and all are displayed in the table. IsoformAccession NumberProtein (aa)Molecular Weight (kDa)Isoform 1NP_001353839563~60Isoform 2NP_775904493~52Isoform X1XP_054176598549~60Isoform X2XP_054176599389~45Isoform X3XP_054176600375~43 Table 1. These are the five protein isoforms of TMEM145.
Transmembrane protein 145 isoform 1 is rich in phenylalanine and tyrosine. The subcellular localization of the human TMEM145 protein is the plasma membrane and cytoskeleton. This protein has a signal peptide from amino acid 1-29 and a cleavage site between amino acid 29 and 30.DTU Department of Health Technology. SignalP 6.0 Tool TMEM145 contains a GOLD domain (Golgi dynamics) and a seven-transmembrane domain. The transmembrane domain is a Rhodopsin-like GPCR Transmembrane Domain.
Evolution/Homology Paralog TMEM145 is paralogous to integral membrane protein GPR180 (G-protein coupled receptor).NCBI Gene entry on GPR180 GPR180 is produced in vascular smooth muscle cells.
Orthologs Homo sapiens TMEM145 gene orthologs are found in mammals, birds, reptiles, amphibians, fish, and invertebrates. Table 2 displays some orthologs of TMEM145.
+Genus and SpeciesCommon NameTaxonomic GroupDate of Divergence Fromthe Human Lineage (*MYA)Accession NumberSequence LengthSequence Identity toHuman Protein (%)Sequence Similarity toHuman Protein (%)Homo sapiensHumansPrimate0NP_001353839563100100Microcebus murinusGrey Mouse LemurPrimate74XP_012613964.159692.4593.1Mus musculusHouse MouseRodentia87NP_001390132.156396.6397.2Rhinolophus ferrumequinumGreater Horseshoe BatChiroptera94XP_032985445.156397.1698.4Phascolarctos cinereusKoalaDiprotodontia160XP_020858946.15739276.9Dermochelys coriaceaLeatherback Sea TurtleTestudines319XP_03823909754577.8680.6Cuculus canorusCommon CuckooCuculiformes319XP_053908563.155770.7677.1Python bivittatusBurmese PythonSquamata319XP_007430515.259176.6575.7Apteryx mantelliNorth Island Brown KiwiApterygiformes319XP_067172958.156381.1783Rhinatrema bivittatumTwo-lined CaecilianGymnophiona352XP_029432757.154677.8481.3Eleutherodactylus coquiPuerto Rican CoquiAnura352XM_066607125.154775.0979.3Bufotes viridisEuropean Green ToadAnura352CAK8626328.154774.5377.9Protopterus annectensWest African LungfishCeratodontiformes408XP_043936719.158880.8272.6Danio rerioZebrafishCypriniformes429XP_686062.657968.7271.6Amphiprion ocellarisClown AnemonefishPerciformes429XP_023119489.155167.7573.7Hypanus sabinusAtlantic StingrayMyliobatiformes462XP_059824187.153465.4867.7Branchiostoma floridaeFlorida LanceletAmphioxiformes581XP_035675017.155054.5359.1Acanthaster planciCrown-of-thorns StarfishValvatida619XP_022093045.158447.7358.5Saccostrea echinataBlacklip Rock OysterOstreida686XP_061193107.156742.2255.8Oscarella lobularisSea SpongeHomosclerophorida758XP_065845639.152337.2955.5 Table 2. Incomplete list of orthologs of human TMEM145 (*MYA = millions of years ago).
Clinical Significance An African ancestry-specific allele (rs10423769_A) is a genetic variant affecting alternative splicing for the TMEM145 gene. A protective interaction between this allele and the APOE ε4 allele lowered the odds for Alzheimer's Disease by 75% in APOE ε4 heterozygous carriers. The TMEM145 isoforms were found to be more expressed in the cerebellum than the frontal cortex, suggesting that TMEM145 plays a more significant role in the cerebellum. In studying the bone metastasis-derived PC3 prostate cancer cell line, TMEM145 was one of four genes deleted from chromosome 19 in a homozygous deletion. Upon analyzing the DNA methylation pattern, TMEM145 was found to be hypermethylated during stages 1, 2, and 3 of breast cancer, meaning it may be involved in breast cancer control mechanisms. TMEM145 was one of several genes that were highly up-regulated (>10 fold) in both mouse adrenal tumor and human pheochromocytoma.
References