MROH6

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Predicted tertiary protein structure of Maestro Heat-Like Repeat Family Member 6, generated by the program Alphafold MROH6 Protein Structure.png
Predicted tertiary protein structure of Maestro Heat-Like Repeat Family Member 6, generated by the program Alphafold

Maestro heat-like repeat family member 6 (MROH6), also known as c8orf73, is a protein which in humans is encoded by the MROH6 gene. [1] The word 'maestro' itself is an acronym, standing for Male-Specific Transcription in the Developing Reproductive Organs (MRO). MRO genes belong to the MROH family, which includes MROH1, MROH2B, MROH7, MROH8, and MROH9. [2]

Contents

Gene

The genomic location of MROH6 in humans is on chromosome 8 (8q24.3), spanning 6,581 base pairs, from base pair 143,566,192 to 143,572,772. The gene contains a total of 15 exons. [1]

Transcript

The MROH6 gene encodes 17 known mRNA transcript variants. The longest transcript variant is simply referred to as MROH6, which is 3,265 nucleotides long and contains 14 exons. [1]

Table 1: MROH6 isoforms.
Transcript variant numberAccession numberSpan in nucleotidesAligned length in nucleotidesExons used
MROH6NM_001100878.26,5813,26514
X1XM_011517214.26,5812,64114
X2XM_011517215.26,5812,63814
X3XM_011517216.36,5812,57313
X4XM_011517217.26,5812,50712
X5XM_011517220.24,9742,22311
X6XM_011517221.36,3342,15915
X7XM_047422089.16,3342,15615
X8XM_011517222.26,5812,33814
X9XM_047422090.16,3332,14015
X10XM_047422092.16,5812,31714
X11XM_011517223.26,5812,27213
X12XM_047422093.16,5812,26914
X13XM_047422094.16,5812,25413
X14XM_047422095.16,5812,25113
X15XM_047422096.16,5812,19713
X16XM_006716615.34,9872,26311
X17XM_047422097.14,9872,26011

Protein

Diagram of the human MROH6 protein showcasing domains/motifs and post-translational modification sites. Human MROH6 Diagram.png
Diagram of the human MROH6 protein showcasing domains/motifs and post-translational modification sites.
Conceptual translation of the MROH6 protein in humans MROH6 Conceptual Translation.png
Conceptual translation of the MROH6 protein in humans

The protein encoded by the primary isoform of MROH6 is 719 amino acids long. [1]

Domains

A notable feature of the MROH6 protein is the presence of seven HEAT repeats, which are protein tandem repeat structural motifs. HEAT repeats are composed of two alpha helices linked by a short loop. These repeats give MROH6 and its gene family its name, as well as directing the function of the protein. [3]

Structure

MROH6 consists primarily of alpha helices. The protein structure lacks any beta sheets. [4]

Regulation

Gene level

MROH6 demonstrates broad expression throughout the human body. However, it shows noticeably higher expression in certain tissues, such as the esophagus. In human fetal development, high expression is shown in the stomach, lung, intestine, and adrenal gland. RNA sequencing data also shows high expression in the cerebellum, liver, lung, placenta, small intestine, and stomach. The Human Protein Atlas indicates high expression in the bone marrow, esophagus, skin, and stomach. [5]

Protein Level

The protein is predicted to be localized within the cytoplasm, nucleus, and mitochondria. [6]

Evolution

Orthologs

Orthologs of the MROH6 protein were found to exist in amniotes as well as the genome of Amia calva . Despite the presence of the gene in Amia calva, orthologs of MROH6 have not been found in any other fish nor in amphibians.

Table 2: MROH6 orthologs and related properties. [7]
Scientific nameCommon nameTaxonmedian date of divergence (MYA)Accession #Length (amino acids)% identity to humans% similarity to humans
Homo Sapiens HumansPrimates0.0NP_001094348.1719100.0%100.0%
Theropithecus gelada GeladaPrimates28.8XP_025250353.171795.5%96.9%
Mus musculus House mouseRodentia87.0NP_001269372.172279.8%85.6%
Ursus maritimus Polar bearCarnivora94.0XP_040481956.170579.5%84.4%
Bos taurus Common cattleArtiodactyl94.0XP_002692603.171179.8%84.6%
Manis javanica Malayan pangolinPholidota94.0KAI5929482.169174.2%80.2%
Elephas maximus indicus Indian elephantElephantidae99.0XP_049709696.171780.8%85.8%
Sarcophilus harrisii Tasmanian devilMarsupialia160.0XP_031803182.173557.9%66.7%
Ornithorhynchus anatinus PlatypusMonotremes180.0XP_039767867.183251.3%58.9%
Gallus gallus Red junglefowlGalliformes319.0XP_040537654.165123.8%37.7%
Anas platyrhynchos MallardAnseriformes319.0XP_071898069.173620.4%32.6%
Falco naumanni Lesser kestrelFalconiformes319.0XP_040449421.158320.7%32.7%
Patagioenas fasciata Band-tailed pigeonColumbiformes319.0XP_071666853.185722.7%33.6%
Colius striatus Speckled mousebirdColiiformes319.0XP_061870785.158122.0%32.9%
Candoia aspera Papuan ground boaSerpentes319.0XP_063156074.177533.2%47.0%
Tiliqua scincoides Common blue-tongued skinkScincidae319.0XP_066477445.173424.3%37.4%
Chelonia mydas Green sea turtleCryptodira319.0XP_027683785.388532.0%42.4%
Emydura macquarii macquarii Macquarie River turtlePleurodira319.0XP_067392966.137219.2%27.3%
Crocodylus porosus Saltwater crocodileCrocodilians319.0XP_019406236.11696.4%9.6%
Amia calva Ruddy bowfinActinopterygii429.0XP_066543890.11687.2%10.9%

Paralogs

MROH6 has multiple paralogs found in the human genome and is a member of the MROH family, consisting of seven other genes, as well as three pseudogenes. [2]

Table 3: Paralogs of the human MROH6 gene. [8]
ParalogAccession #Length (amino acids)Percent identity to MROH6Percent similarity to MROH6
MRONP_1141452487.9%12.5%
MROH1NP_115826.31,64112.0%16.9%
MROH2ANP_001381568.11,67410.2%17.0%
MROH2BNP_775760.31,58510.3%17.0%
MROH7NP_001034553.31,32316.0%23.7%
MROH8 NP_689716.41,05215.8%27.0%
MROH9 NP_001157101.186118.3%31.1%

Interacting proteins

The MROH6 protein has been shown and predicted to interact with a wide variety of proteins with a wide variety of functions and localization. These include NUDT15, XPO1, NMNAT1, NMNAT2, NMNAT3, NAPRT, FTL, IQGAP1, SMCO3, NADSYN1, and FAAH. [9] [10] [11] [12]

Clinical significance

Little research has been done into MROH6. MROH6 has been identified as a possible contributor to neuroblastoma, with high expression of the protein leading to poor prognosis. [13] Other studies have identified changes in MROH6 expression as a possible contributor to male infertility, changes in interleukin-18 levels, and gestational diabetes mellitus. [14] [15] [16]

References

  1. 1 2 3 4 "MROH6 maestro heat like repeat family member 6 [ Homo sapiens (human) ]". National Center for Biotechnology Information . U.S. National Library of Medicine . Retrieved 29 July 2025.
  2. 1 2 Kenigsberg, Shlomit; Lima, Patricia D. A.; Maghen, Leila; Wyse, Brandon A.; Lackan, Chantal; Cheung, Annie N. Y.; Tsang, Benjamin K.; Librach, Clifford L. (2017-04-13). "The elusive MAESTRO gene: Its human reproductive tissue-specific expression pattern". PLOS ONE . 12 (4) e0174873. Bibcode:2017PLoSO..1274873K. doi: 10.1371/journal.pone.0174873 . ISSN   1932-6203. PMC   5391009 . PMID   28406912.
  3. Kobe, Bostjan; Gleichmann, Thomas; Horne, James; Jennings, Ian G.; Scotney, Pierre D.; Teh, Trazel (1999-05-05). "Turn up the HEAT". Structure. 7 (5): R91 –R97. doi: 10.1016/S0969-2126(99)80060-4 . ISSN   0969-2126. PMID   10378263.
  4. Powell, Harold R.; Islam, Suhail A.; David, Alessia; Sternberg, Michael J.E. (2025). "Phyre2.2: A Community Resource for Template-based Protein Structure Prediction". Journal of Molecular Biology. 437 (15) 168960. doi: 10.1016/j.jmb.2025.168960 . PMC   7617537 . PMID   40133783.
  5. "MROH6 protein expression summary". The Human Protein Atlas . The Human Protein Atlas. Retrieved 3 August 2025.
  6. "PSORT II prediction". PSORT. Retrieved 3 August 2025.
  7. "MROH6 - maestro heat like repeat family member 6". National Center for Biotechnology Information . U.S. National Library of Medicine . Retrieved 11 August 2025.
  8. Madeira, Fábio; Madhusoodanan, Nandana; Lee, Joonheung; Eusebi, Alberto; Niewielska, Ania; Tivey, Adrian R N; Lopez, Rodrigo; Butcher, Sarah (2024-07-05). "The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024" (PDF). Nucleic Acids Research. 52 (W1): W521 –W525. doi: 10.1093/nar/gkae241 . ISSN   0305-1048. PMC   11223882 . PMID   38597606 . Retrieved 29 July 2025.
  9. "MROH6 Result Summary". BioGRID . BioGRID. Retrieved 3 August 2025.
  10. "IMEx". EMBL-EBI . European Molecular Biology Laboratory . Retrieved 3 August 2025.
  11. Calderone, Alberto; Castagnoli, Luisa; Cesareni, Gianni (2013). "mentha: a resource for browsing integrated protein-interaction networks". Nature Methods. 10 (8): 690–691. doi: 10.1038/nmeth.2561 . ISSN   1548-7091. PMID   23900247 . Retrieved 3 August 2025.
  12. "STRING - SEARCH - Single Protein by Name / Identifier". STRING . STRING Consortium. Retrieved 3 August 2025.
  13. Oswald, Sally (2023). A proteomics investigation into the role of zDHHC23 and MROH6 in neuroblastoma. University of Liverpool (Thesis). doi:10.17638/03169651 . Retrieved 29 July 2025.
  14. Borgmann, Jennifer; Tüttelmann, Frank; Dworniczak, Bernd; Röpke, Albrecht; Song, Hye-Won; Kliesch, Sabine; Wilkinson, Miles F.; Laurentino, Sandra; Gromoll, Jörg (2016-09-15). "The human RHOX gene cluster: target genes and functional analysis of gene variants in infertile men" (PDF). Human Molecular Genetics . 25 (22): 4898–4910. doi: 10.1093/hmg/ddw313 . ISSN   0964-6906. PMC   6281360 . PMID   28171660 . Retrieved 11 August 2025.
  15. Johansson, Åsa; Eriksson, Niclas; Becker, Richard C.; Storey, Robert F.; Himmelmann, Anders; Hagström, Emil; Varenhorst, Christoph; Axelsson, Tomas; Barratt, Bryan J.; James, Stefan K.; Katus, Hugo A.; Steg, Philippe Gabriel; Syvänen, Ann-Christine; Wallentin, Lars; Siegbahn, Agneta (2015). "NLRC4 Inflammasome Is an Important Regulator of Interleukin-18 Levels in Patients With Acute Coronary Syndromes: Genome-Wide Association Study in the PLATelet inhibition and patient Outcomes Trial (PLATO)". Circulation: Cardiovascular Genetics . 8 (3): 498–506. doi: 10.1161/CIRCGENETICS.114.000724 . ISSN   1942-325X. PMID   25747584.
  16. Srour, Luma; Bejaoui, Yosra; Jerobin, Jayakumar; Dweik, Manar; Sankar, Aswathy; Qannan, Abeer; Allouche Colak, Nassima; Chagoury, Odette; Yousri, Noha A.; Farrell, Thomas; Fthenou, Eleni; Bashir, Mohammed; El Hajj, Nady (2025-05-25), Maternal DNA Methylation Signatures of Gestational Diabetes across all Stages of Pregnancy, doi: 10.1101/2025.05.25.25328297 , retrieved 11 August 2025