TMEM144

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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. Conceptual Translation of Transmembrane Protein 144 mRNA transcript sequence with peptide sequence.pdf
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]

Contents

Gene

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

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. Human Transmembrane 144 Protein Tertiary Structure.png
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

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

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

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. Transmembrane Protein 144 schematic diagram.jpg
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

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

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. Vertabrate Ortholog Alignment for Transmembrane Protein 144.pdf
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. Invertebrate Ortholog Alignment with human Transmembrane Protein 144.pdf
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

Genus and speciesCommon nameTaxonomic ClassMedian Date of Divergence (MYA)Accession #Sequence length (aa)Sequence identity (%) Sequence similarity (%)
Homo Sapiens Human Mammalia0NP_060812.2345100.0100.0
Carlito syrichta Philippine tarsier Mammalia69XP_012639059.134594.297.4
Mus musculus House mouse Mammalia87NP_001366471.134885.992.2
Trichosurus vulpecula Brushtail possum Mammalia160XP_036620586.134977.790.3
Chelydra serpentina Snapping turtle Reptilia319KAG6931534.135867.084.1
Gallus gallus Red junglefowl Aves319XP_420383.235766.982.6
Zootoca vivipara Viviparous lizard Reptilia319XP_034969125.136065.982.3
Rana temporaria Common frog Amphibia353XP_040188243.135864.281.0
Protopterus annectens West African lungfish Dipnoi408XP_043918387.140756.469.6
Latimeria chalumnae African coelacanth Coelacanthi414XP_014346971.140756.071.6
Danio rerio Zebrafish Actinopterygii431NP_001005983.138050.064.8
Amblyraja radiata Thorny skate Chondrichthyes464XP_032874310.148645.758.4
Branchiostoma lanceolatum European lancelet Leptocardii556CAH1267272.140244.158.8
Petromyzon marinus Sea lamprey Hyperoartia599XP_032811478.139650.164.9
Ciona intestinalis Vase tunicate Ascidiacea603XP_026696612.139546.659.2
Strongylocentrotus purpuratus Purple sea urchin Echinoidea619XP_030836295.136346.864.7
Echinococcus multilocularis Cyclophyllid tapeworm Cestoda694CDS37915.135141.059.8
Caenorhabditis elegans Roundworm Chromadorea694NP_498062.234538.756.0
Mytilus edulis Blue mussel Bivalvia694CAG2251154.138536.052.0
Schistocerca gregaria Desert locust Insecta694XP_049849104.127825.644.1

Clinical Significance

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

  1. 1 2 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. 1 2 3 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. 1 2 3 4 5 6 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%5B%5D>.
  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. 1 2 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 <https://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. 1 2 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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