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Conceptual translation of Transmembrane Protein 144 mRNA transcript sequence with peptide sequence. DNA annotations mark an upstream in-frame stop codon, start codon, exon borders, stop codon, polyadenylation signals, and polyadenylation sites. Protein annotations mark the ten transmembrane domain regions, internal repeats, and the region of the protein excluded from the second isoform. Amino acids conserved in distant orthologs are bolded.

Transmembrane Protein 144 (TMEM144) is a protein in humans encoded by the TMEM144 gene.[1]

Gene

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Transmembrane Protein 144 is located on the plus strand of chromosome 4 (4q32.1), spanning a total of 40,857 base pairs.[2] The TMEM144 gene transcribes a mRNA sequence 3,210 nucleotides in length and composed of 13 exons.[3]

Protein

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There exist two isoforms of human Transmembrane Protein 144.[3] Isoform one consist of 345 amino acids with a total mass of 37.6 kDa.[1][4] This isoform has a theoretical isoelectric point of 6.63.[5] The second isoform is 169 amino acids long with a mass of 18.3 kDa.[3]

Predicted tertiary structure of human transmembrane protein 144. Regions of dark blue are very high confidence, light blue regions are confident, yellow regions are low confidence, and orange regions are very low confidence.

Expression

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TMEM144 is over-expressed in adult brain tissue with low regional specificity.[6][7] TMEM144 appears enriched in oligodendrocytes[8][7] and immune cells, such as dendritic cells and monocytes.[9][7]

Cellular Localization

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Precise cell localization has multiple predicted locations. Localization tools state TMEM144 is likely found in the plasma membrane, endoplasmic reticulum,[10] Lysosome/Vacuole, or Golgi apparatus.[11] However, an immunofluorescent staining of various human cell lines display localization to the mitochondria.[7]

Post Translational Modifications

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There exists five predicted post translational modifications for TMEM144, including four sites of phosphorylation[12] and a sumoylation site.[13]

Transmembrane Protein 144 schematic with transmembrane domains and predicted post translational modifications. P indicates predicted sites of phosphorylation. SUMO indicates a predicted sumoylation site.

Interacting Proteins

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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.[14][15]

Homology

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Transmembrane Protein 144 arose approximately 694 million years ago in desert locust.[16] It can be found in both vertebrates and invertebrates.[16][17] 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.

Multiple sequence alignment of human Transmembrane Protein 144 with vertebrate orthologs. Some amino acids in the ortholog sequences were cut out at the N-terminus. Amino acids are highlighted by shared properties and structure. Consensus sequences denote highly conserved amino acids with a capital letter, moderately conserved amino acids with a lowercase letter, and low conservation with a dot. A plus or minus symbol in the consensus sequence indicates conserved basic (+) or acidic (-) properties. Transmembrane regions are boxed in orange and exon boundaries are marked in pink.
Multiple sequence alignment of human Transmembrane Protein 144 to invertebrate orthologs. Consensus sequences denote highly conserved amino acids with a capital letter, moderately conserved amino acids with a lowercase letter, and low conservation with a dot. A plus or minus symbol in the consensus sequence indicates conserved basic (+) or acidic (-) properties. Transmembrane regions are boxed in orange and exon boundaries are marked in pink.

Ortholog Table

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Genus and Species Common Name Taxonomic Class Median Date of Divergence (MYA) Accession # Sequence Length (aa) Sequence Identity (%) Sequence Similarity (%)
Homo Sapiens Human Mammalia 0 NP_060812.2 345 100.0 100.0
Carlito syrichta Philippine tarsier Mammalia 69 XP_012639059.1 345 94.2 97.4
Mus musculus House mouse Mammalia 87 NP_001366471.1 348 85.9 92.2
Trichosurus vulpecula Brushtail possum Mammalia 160 XP_036620586.1 349 77.7 90.3
Chelydra serpentina Snapping turtle Reptilia 319 KAG6931534.1 358 67.0 84.1
Gallus gallus Red junglefowl Aves 319 XP_420383.2 357 66.9 82.6
Zootoca vivipara Viviparous lizard Reptilia 319 XP_034969125.1 360 65.9 82.3
Rana temporaria Common frog Amphibia 353 XP_040188243.1 358 64.2 81.0
Protopterus annectens West African lungfish Dipnoi 408 XP_043918387.1 407 56.4 69.6
Latimeria chalumnae African coelacanth Coelacanthi 414 XP_014346971.1 407 56.0 71.6
Danio rerio Zebrafish Actinopterygii 431 NP_001005983.1 380 50.0 64.8
Amblyraja radiata Thorny skate Chondrichthyes 464 XP_032874310.1 486 45.7 58.4
Branchiostoma lanceolatum European lancelet Leptocardii 556 CAH1267272.1 402 44.1 58.8
Petromyzon marinus Sea lamprey Hyperoartia 599 XP_032811478.1 396 50.1 64.9
Ciona intestinalis Vase tunicate Ascidiacea 603 XP_026696612.1 395 46.6 59.2
Strongylocentrotus purpuratus Purple sea urchin Echinoidea 619 XP_030836295.1 363 46.8 64.7
Echinococcus multilocularis Cyclophyllid tapeworm Cestoda 694 CDS37915.1 351 41.0 59.8
Caenorhabditis elegans Roundworm Chromadorea 694 NP_498062.2 345 38.7 56.0
Mytilus edulis Blue mussel Bivalvia 694 CAG2251154.1 385 36.0 52.0
Schistocerca gregaria Desert locust Insecta 694 XP_049849104.1 278 25.6 44.1

Clinical Significance

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Transmembrane Protein 144 is predicted to be a direct or indirect negative regulator of kisspeptin.[18] High expression of TMEM144 is prognostically favorable for patient with endometrial cancer.[19][7] Whereas in patients with pancreatic cancer, high expression of TMEM144 is associated with poor prognostic outcomes.[19][7]

References

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  1. ^ a b NCBI Gene (National Center for Biotechnology Information Gene Database) entry on TMEM144 <https://www.ncbi.nlm.nih.gov/gene/55314>.
  2. ^ NCBI Nucleotide (National Center for Biotechnology Information Nucleotide Database) entry on TMEM144 <https://www.ncbi.nlm.nih.gov/nuccore/NM_018342.5>.
  3. ^ a b c UniProt entry of TMEM144 <https://www.uniprot.org/uniprotkb/Q7Z5S9/entry#sequences>.
  4. ^ NCBI Protein (National Center for Biotechnology Information Protein Database) entry on TMEM144 <https://www.ncbi.nlm.nih.gov/protein/NP_060812.2>.
  5. ^ ExPASy Compute pI/Mw tool entry on TMEM144 protein <https://web.expasy.org/compute_pi/>.
  6. ^ Sjöstedt, Evelina; Zhong, Wen; Fagerberg, Linn; Karlsson, Max; Mitsios, Nicholas; Adori, Csaba; Oksvold, Per; Edfors, Fredrik; Limiszewska, Agnieszka; Hikmet, Feria; Huang, Jinrong; Du, Yutao; Lin, Lin; Dong, Zhanying; Yang, Ling; Liu, Xin; Jiang, Hui; Xu, Xun; Wang, Jian; Yang, Huanming; Bolund, Lars; Mardinoglu, Adil; Zhang, Cheng; von Feilitzen, Kalle; Lindskog, Cecilia; Pontén, Fredrik; Luo, Yonglun; Hökfelt, Tomas; Uhlén, Mathias; Mulder, Jan (6 March 2020). "An atlas of the protein-coding genes in the human, pig, and mouse brain". Science. 367 (6482). doi:10.1126/science.aay5947. PMID 32139519. S2CID 212560645.
  7. ^ a b c d e f TMEM144 entry on the Human Protein Atlas <https://www.proteinatlas.org/ENSG00000164124-TMEM144>.
  8. ^ Karlsson, Max; Zhang, Cheng; Méar, Loren; Zhong, Wen; Digre, Andreas; Katona, Borbala; Sjöstedt, Evelina; Butler, Lynn; Odeberg, Jacob; Dusart, Philip; Edfors, Fredrik; Oksvold, Per; von Feilitzen, Kalle; Zwahlen, Martin; Arif, Muhammad; Altay, Ozlem; Li, Xiangyu; Ozcan, Mehmet; Mardinoglu, Adil; Fagerberg, Linn; Mulder, Jan; Luo, Yonglun; Ponten, Fredrik; Uhlén, Mathias; Lindskog, Cecilia (30 July 2021). "A single–cell type transcriptomics map of human tissues". Science Advances. 7 (31). Bibcode:2021SciA....7.2169K. doi:10.1126/sciadv.abh2169. PMC 8318366. PMID 34321199.
  9. ^ Monaco, Gianni; Lee, Bernett; Xu, Weili; Mustafah, Seri; Hwang, You Yi; Carré, Christophe; Burdin, Nicolas; Visan, Lucian; Ceccarelli, Michele; Poidinger, Michael; Zippelius, Alfred; Pedro de Magalhães, João; Larbi, Anis (February 2019). "RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cell Types". Cell Reports. 26 (6): 1627–1640.e7. doi:10.1016/j.celrep.2019.01.041. PMC 6367568. PMID 30726743.
  10. ^ PSORT II entry on human TMEM144 protein <https://psort.hgc.jp/cgi-bin/runpsort.pl[permanent dead link‍]>.
  11. ^ DeepLoc entry of human TMEM144 protein for cell localization prediction <https://services.healthtech.dtu.dk/service.php?DeepLoc-2.0>.
  12. ^ NetPhos 3.1 entry on human TMEM144 <https://services.healthtech.dtu.dk/service.php?NetPhos-3.1>.
  13. ^ GPS SUMO entry on human TMEM144 <http://sumosp.biocuckoo.org/showResult.php Archived 2018-05-06 at the Wayback Machine>.
  14. ^ Luck, Katja; Kim, Dae-Kyum; Lambourne, Luke; Spirohn, Kerstin; Begg, Bridget E.; Bian, Wenting; Brignall, Ruth; Cafarelli, Tiziana; Campos-Laborie, Francisco J.; Charloteaux, Benoit; Choi, Dongsic; Coté, Atina G.; Daley, Meaghan; Deimling, Steven; Desbuleux, Alice; Dricot, Amélie; Gebbia, Marinella; Hardy, Madeleine F.; Kishore, Nishka; Knapp, Jennifer J.; Kovács, István A.; Lemmens, Irma; Mee, Miles W.; Mellor, Joseph C.; Pollis, Carl; Pons, Carles; Richardson, Aaron D.; Schlabach, Sadie; Teeking, Bridget; Yadav, Anupama; Babor, Mariana; Balcha, Dawit; Basha, Omer; Bowman-Colin, Christian; Chin, Suet-Feung; Choi, Soon Gang; Colabella, Claudia; Coppin, Georges; D'Amata, Cassandra; De Ridder, David; De Rouck, Steffi; Duran-Frigola, Miquel; Ennajdaoui, Hanane; Goebels, Florian; Goehring, Liana; Gopal, Anjali; Haddad, Ghazal; Hatchi, Elodie; Helmy, Mohamed; Jacob, Yves; Kassa, Yoseph; Landini, Serena; Li, Roujia; van Lieshout, Natascha; MacWilliams, Andrew; Markey, Dylan; Paulson, Joseph N.; Rangarajan, Sudharshan; Rasla, John; Rayhan, Ashyad; Rolland, Thomas; San-Miguel, Adriana; Shen, Yun; Sheykhkarimli, Dayag; Sheynkman, Gloria M.; Simonovsky, Eyal; Taşan, Murat; Tejeda, Alexander; Tropepe, Vincent; Twizere, Jean-Claude; Wang, Yang; Weatheritt, Robert J.; Weile, Jochen; Xia, Yu; Yang, Xinping; Yeger-Lotem, Esti; Zhong, Quan; Aloy, Patrick; Bader, Gary D.; De Las Rivas, Javier; Gaudet, Suzanne; Hao, Tong; Rak, Janusz; Tavernier, Jan; Hill, David E.; Vidal, Marc; Roth, Frederick P.; Calderwood, Michael A. (16 April 2020). "A reference map of the human binary protein interactome". Nature. 580 (7803): 402–408. Bibcode:2020Natur.580..402L. doi:10.1038/s41586-020-2188-x. PMC 7169983. PMID 32296183.
  15. ^ TMEM144 entry on IntAct <https://www.ebi.ac.uk/intact/search?query=tmem144>
  16. ^ a b 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>.
  17. ^ TimeTree of Life entry of Homo sapiens compared to ortholog species in Table 1 <http://www.timetree.org/>.
  18. ^ Prentice, Leah M; d'Anglemont de Tassigny, Xavier; McKinney, Steven; Ruiz de Algara, Teresa; Yap, Damian; Turashvili, Gulisa; Poon, Steven; Sutcliffe, Margaret; Allard, Pat; Burleigh, Angela; Fee, John; Huntsman, David G; Colledge, William H; Aparicio, Samuel AJ (December 2011). "The testosterone-dependent and independent transcriptional networks in the hypothalamus of Gpr54 and Kiss1 knockout male mice are not fully equivalent". BMC Genomics. 12 (1): 209. doi:10.1186/1471-2164-12-209. PMC 3111392. PMID 21527035.
  19. ^ a b Uhlen, Mathias; Zhang, Cheng; Lee, Sunjae; Sjöstedt, Evelina; Fagerberg, Linn; Bidkhori, Gholamreza; Benfeitas, Rui; Arif, Muhammad; Liu, Zhengtao; Edfors, Fredrik; Sanli, Kemal; von Feilitzen, Kalle; Oksvold, Per; Lundberg, Emma; Hober, Sophia; Nilsson, Peter; Mattsson, Johanna; Schwenk, Jochen M.; Brunnström, Hans; Glimelius, Bengt; Sjöblom, Tobias; Edqvist, Per-Henrik; Djureinovic, Dijana; Micke, Patrick; Lindskog, Cecilia; Mardinoglu, Adil; Ponten, Fredrik (18 August 2017). "A pathology atlas of the human cancer transcriptome". Science. 357 (6352). doi:10.1126/science.aan2507. PMID 28818916.
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