TMEM144 explained

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

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. Isoform one consist of 345 amino acids with a total mass of 37.6 kDa.[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.

Expression

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

Cellular Localization

Precise cell localization has multiple predicted locations. Localization tools state TMEM144 is likely found in the plasma membrane, endoplasmic reticulum,[9] Lysosome/Vacuole, or Golgi apparatus.[10] However, an immunofluorescent staining of various human cell lines display localization to the mitochondria.[11]

Post Translational Modifications

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

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. 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.

Ortholog Table

Genus and SpeciesCommon NameTaxonomic ClassMedian Date of Divergence (MYA)Accession #Sequence Length (aa)Sequence Identity (%)Sequence Similarity (%)
Homo SapiensHumanMammalia0NP_060812.2345100.0100.0
Carlito syrichtaPhilippine tarsierMammalia69XP_012639059.134594.297.4
Mus musculusHouse mouseMammalia87NP_001366471.134885.992.2
Trichosurus vulpeculaBrushtail possumMammalia160XP_036620586.134977.790.3
Chelydra serpentinaSnapping turtleReptilia319KAG6931534.135867.084.1
Gallus gallusRed junglefowlAves319XP_420383.235766.982.6
Zootoca viviparaViviparous lizardReptilia319XP_034969125.136065.982.3
Rana temporariaCommon frogAmphibia353XP_040188243.135864.281.0
Protopterus annectensWest African lungfishDipnoi408XP_043918387.140756.469.6
Latimeria chalumnaeAfrican coelacanthCoelacanthi414XP_014346971.140756.071.6
Danio rerioZebrafishActinopterygii431NP_001005983.138050.064.8
Amblyraja radiataThorny skateChondrichthyes464XP_032874310.148645.758.4
Branchiostoma lanceolatumEuropean lanceletLeptocardii556CAH1267272.140244.158.8
Petromyzon marinusSea lampreyHyperoartia599XP_032811478.139650.164.9
Ciona intestinalisVase tunicateAscidiacea603XP_026696612.139546.659.2
Strongylocentrotus purpuratusPurple sea urchinEchinoidea619XP_030836295.136346.864.7
Echinococcus multilocularisCyclophyllid tapewormCestoda694CDS37915.135141.059.8
Caenorhabditis elegansRoundwormChromadorea694NP_498062.234538.756.0
Mytilus edulisBlue musselBivalvia694CAG2251154.138536.052.0
Schistocerca gregariaDesert locustInsecta694XP_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] Whereas in patients with pancreatic cancer, high expression of TMEM144 is associated with poor prognostic outcomes.

Notes and References

  1. NCBI Gene (National Center for Biotechnology Information Gene Database) entry on TMEM144 .
  2. NCBI Nucleotide (National Center for Biotechnology Information Nucleotide Database) entry on TMEM144 .
  3. UniProt entry of TMEM144 .
  4. NCBI Protein (National Center for Biotechnology Information Protein Database) entry on TMEM144 .
  5. ExPASy Compute pI/Mw tool entry on TMEM144 protein .
  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 . An atlas of the protein-coding genes in the human, pig, and mouse brain . Science . 6 March 2020 . 367 . 6482 . 10.1126/science.aay5947 . 32139519 . 212560645 .
  7. 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 . A single–cell type transcriptomics map of human tissues . Science Advances . 30 July 2021 . 7 . 31 . 10.1126/sciadv.abh2169 . 34321199 . 8318366 . 2021SciA....7.2169K .
  8. 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 . RNA-Seq Signatures Normalized by mRNA Abundance Allow Absolute Deconvolution of Human Immune Cell Types . Cell Reports . February 2019 . 26 . 6 . 1627–1640.e7 . 10.1016/j.celrep.2019.01.041 . 30726743 . 6367568 .
  9. PSORT II entry on human TMEM144 protein .
  10. DeepLoc entry of human TMEM144 protein for cell localization prediction .
  11. TMEM144 entry on the Human Protein Atlas .
  12. NetPhos 3.1 entry on human TMEM144 .
  13. GPS SUMO entry on human TMEM144 .
  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. . A reference map of the human binary protein interactome . Nature . 16 April 2020 . 580 . 7803 . 402–408 . 10.1038/s41586-020-2188-x . 32296183 . 7169983 . 2020Natur.580..402L .
  15. TMEM144 entry on IntAct
  16. NCBI BLAST Protein entry on Homo sapiens TMEM144 (NP_060812.2) to identify various orthologs .
  17. TimeTree of Life entry of Homo sapiens compared to ortholog species in Table 1 .
  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 . The testosterone-dependent and independent transcriptional networks in the hypothalamus of Gpr54 and Kiss1 knockout male mice are not fully equivalent . BMC Genomics . December 2011 . 12 . 1 . 209 . 10.1186/1471-2164-12-209 . free . 21527035 . 3111392 .
  19. 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 . Sophia Hober . 18 August 2017 . A pathology atlas of the human cancer transcriptome . Science . 357 . 6352 . 10.1126/science.aan2507 . 28818916 . 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.

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