# Transmembrane protein 145

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. RNA-sequencing data from NCBI displayed that TMEM145 displays highest expression in the brain with notable expression also in the adrenal glands. Microarray-assessed tissue expression revealed that human TMEM145 is expressed ubiquitously with moderate variation across different tissues. The human TMEM145 protein has a lower than average expression level in comparison to other human proteins. The Human Protein Atlas showed human TMEM145 to have highest expression in the cerebellum with second highest expression in the cerebral cortex. In situ hybridization data from Allen Brain Atlas showed TMEM145 RNA expression in Mus Musculus with highest expression in the cerebellum and dentate gyrus.

## 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.

## 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. The isoelectric point of this protein is 8.8. There are five protein isoforms and all are displayed in the table.
| Isoform | Accession Number | Protein (aa) | Molecular Weight (kDa) |
| Isoform 1 | NP_001353839 | 563 | ~60 |
| Isoform 2 | NP_775904 | 493 | ~52 |
| Isoform X1 | XP_054176598 | 549 | ~60 |
| Isoform X2 | XP_054176599 | 389 | ~45 |
| Isoform X3 | XP_054176600 | 375 | ~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. 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). 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 Species | Common Name | Taxonomic Group | Date of Divergence From the Human Lineage (*MYA) | Accession Number | Sequence Length | Sequence Identity to Human Protein (%) | Sequence Similarity to Human Protein (%) |
| Homo sapiens | Humans | Primate | 0 | NP_001353839 | 563 | 100 | 100 |
| Microcebus murinus | Grey Mouse Lemur | Primate | 74 | XP_012613964.1 | 596 | 92.45 | 93.1 |
| Mus musculus | House Mouse | Rodentia | 87 | NP_001390132.1 | 563 | 96.63 | 97.2 |
| Rhinolophus ferrumequinum | Greater Horseshoe Bat | Chiroptera | 94 | XP_032985445.1 | 563 | 97.16 | 98.4 |
| Phascolarctos cinereus | Koala | Diprotodontia | 160 | XP_020858946.1 | 573 | 92 | 76.9 |
| Dermochelys coriacea | Leatherback Sea Turtle | Testudines | 319 | XP_038239097 | 545 | 77.86 | 80.6 |
| Cuculus canorus | Common Cuckoo | Cuculiformes | 319 | XP_053908563.1 | 557 | 70.76 | 77.1 |
| Python bivittatus | Burmese Python | Squamata | 319 | XP_007430515.2 | 591 | 76.65 | 75.7 |
| Apteryx mantelli | North Island Brown Kiwi | Apterygiformes | 319 | XP_067172958.1 | 563 | 81.17 | 83 |
| Rhinatrema bivittatum | Two-lined Caecilian | Gymnophiona | 352 | XP_029432757.1 | 546 | 77.84 | 81.3 |
| Eleutherodactylus coqui | Puerto Rican Coqui | Anura | 352 | XM_066607125.1 | 547 | 75.09 | 79.3 |
| Bufotes viridis | European Green Toad | Anura | 352 | CAK8626328.1 | 547 | 74.53 | 77.9 |
| Protopterus annectens | West African Lungfish | Ceratodontiformes | 408 | XP_043936719.1 | 588 | 80.82 | 72.6 |
| Danio rerio | Zebrafish | Cypriniformes | 429 | XP_686062.6 | 579 | 68.72 | 71.6 |
| Amphiprion ocellaris | Clown Anemonefish | Perciformes | 429 | XP_023119489.1 | 551 | 67.75 | 73.7 |
| Hypanus sabinus | Atlantic Stingray | Myliobatiformes | 462 | XP_059824187.1 | 534 | 65.48 | 67.7 |
| Branchiostoma floridae | Florida Lancelet | Amphioxiformes | 581 | XP_035675017.1 | 550 | 54.53 | 59.1 |
| Acanthaster planci | Crown-of-thorns Starfish | Valvatida | 619 | XP_022093045.1 | 584 | 47.73 | 58.5 |
| Saccostrea echinata | Blacklip Rock Oyster | Ostreida | 686 | XP_061193107.1 | 567 | 42.22 | 55.8 |
| Oscarella lobularis | Sea Sponge | Homosclerophorida | 758 | XP_065845639.1 | 523 | 37.29 | 55.5 |
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.