Transmembrane Protein 144 (TMEM144) is a protein in humans encoded by the TMEM144 gene.NCBI Gene (National Center for Biotechnology Information Gene Database) entry on TMEM144 <https://www.ncbi.nlm.nih.gov/gene/55314>.
Gene Transmembrane Protein 144 is located on the plus strand of chromosome 4 (4q32.1), spanning a total of 40,857 base pairs.NCBI Nucleotide (National Center for Biotechnology Information Nucleotide Database) entry on TMEM144 <https://www.ncbi.nlm.nih.gov/nuccore/NM_018342.5>. The TMEM144 gene transcribes a mRNA sequence 3,210 nucleotides in length and composed of 13 exons.UniProt entry of TMEM144 <https://www.uniprot.org/uniprotkb/Q7Z5S9/entry#sequences>.
Protein There exist two isoforms of human Transmembrane Protein 144. Isoform one consist of 345 amino acids with a total mass of 37.6 kDa.NCBI Protein (National Center for Biotechnology Information Protein Database) entry on TMEM144 <https://www.ncbi.nlm.nih.gov/protein/NP_060812.2>. This isoform has a theoretical isoelectric point of 6.63.ExPASy Compute pI/Mw tool entry on TMEM144 protein <https://web.expasy.org/compute_pi/>. The second isoform is 169 amino acids long with a mass of 18.3 kDa.
Expression TMEM144 is over-expressed in adult brain tissue with low regional specificity. TMEM144 appears enriched in oligodendrocytes and immune cells, such as dendritic cells and monocytes.
Cellular Localization Precise cell localization has multiple predicted locations. Localization tools state TMEM144 is likely found in the plasma membrane, endoplasmic reticulum,PSORT II entry on human TMEM144 protein <https://psort.hgc.jp/cgi-bin/runpsort.pl>. Lysosome/Vacuole, or Golgi apparatus.DeepLoc entry of human TMEM144 protein for cell localization prediction <https://services.healthtech.dtu.dk/service.php?DeepLoc-2.0>. However, an immunofluorescent staining of various human cell lines display localization to the mitochondria.TMEM144 entry on the Human Protein Atlas <https://www.proteinatlas.org/ENSG00000164124-TMEM144>.
Post Translational Modifications There exists five predicted post translational modifications for TMEM144, including four sites of phosphorylationNetPhos 3.1 entry on human TMEM144 <https://services.healthtech.dtu.dk/service.php?NetPhos-3.1>. and a sumoylation site.GPS SUMO entry on human TMEM144 <http://sumosp.biocuckoo.org/showResult.php >.
Interacting Proteins Several proteins have been observed to be physically associated with TMEM144, including Transmembrane Protein 237, Homocysteine-Responsive Endoplasmic Reticulum-Resident Ubiquitin-Like Domain Member 2 Protein, Translocase of Inner Mitochondrial Membrane Domain-Containing Protein 1, Free Fatty Acid Receptor 2, Aquaporin 6, Serine Rich Single-Pass Membrane Protein 1, and Adrenoceptor Beta 2.TMEM144 entry on IntAct <https://www.ebi.ac.uk/intact/search?query=tmem144>
Homology Transmembrane Protein 144 arose approximately 694 million years ago in desert locust. It can be found in both vertebrates and invertebrates.NCBI BLAST Protein entry on Homo sapiens TMEM144 (NP_060812.2) to identify various orthologs <https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins>.TimeTree of Life entry of Homo sapiens compared to ortholog species in Table 1 <https://www.timetree.org/>. It takes TMEM144 approximately 6.8 million years to make a 1% change to its amino acid sequence, indicating a moderately low rate of evolution.
Ortholog Table Genus and species Common name Taxonomic Class Median Date of Divergence (MYA) Accession # Sequence length (aa) Sequence identity (%) Sequence similarity (%)Homo SapiensHumanMammalia0NP_060812.2345100.0100.0Carlito syrichtaPhilippine tarsierMammalia69XP_012639059.134594.297.4Mus musculusHouse mouseMammalia87NP_001366471.134885.992.2Trichosurus vulpeculaBrushtail possumMammalia160XP_036620586.134977.790.3Chelydra serpentinaSnapping turtleReptilia319KAG6931534.135867.084.1Gallus gallusRed junglefowlAves319XP_420383.235766.982.6Zootoca viviparaViviparous lizardReptilia319XP_034969125.136065.982.3Rana temporariaCommon frogAmphibia353XP_040188243.135864.281.0Protopterus annectensWest African lungfishDipnoi408XP_043918387.140756.469.6Latimeria chalumnaeAfrican coelacanthCoelacanthi414XP_014346971.140756.071.6Danio rerioZebrafishActinopterygii431NP_001005983.138050.064.8Amblyraja radiataThorny skateChondrichthyes464XP_032874310.148645.758.4Branchiostoma lanceolatumEuropean lanceletLeptocardii556CAH1267272.140244.158.8Petromyzon marinusSea lampreyHyperoartia599XP_032811478.139650.164.9Ciona intestinalisVase tunicateAscidiacea603XP_026696612.139546.659.2Strongylocentrotus purpuratusPurple sea urchinEchinoidea619XP_030836295.136346.864.7Echinococcus multilocularisCyclophyllid tapewormCestoda694CDS37915.135141.059.8Caenorhabditis elegansRoundwormChromadorea694NP_498062.234538.756.0Mytilus edulisBlue musselBivalvia694CAG2251154.138536.052.0Schistocerca gregariaDesert locustInsecta694XP_049849104.127825.644.1
Clinical Significance Transmembrane Protein 144 is predicted to be a direct or indirect negative regulator of kisspeptin. High expression of TMEM144 is prognostically favorable for patient with endometrial cancer. Whereas in patients with pancreatic cancer, high expression of TMEM144 is associated with poor prognostic outcomes.
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