MROH6

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]

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 number Accession number Span in nucleotides Aligned length in nucleotides Exons used
MROH6 NM_001100878.2 6,581 3,265 14
X1 XM_011517214.2 6,581 2,641 14
X2 XM_011517215.2 6,581 2,638 14
X3 XM_011517216.3 6,581 2,573 13
X4 XM_011517217.2 6,581 2,507 12
X5 XM_011517220.2 4,974 2,223 11
X6 XM_011517221.3 6,334 2,159 15
X7 XM_047422089.1 6,334 2,156 15
X8 XM_011517222.2 6,581 2,338 14
X9 XM_047422090.1 6,333 2,140 15
X10 XM_047422092.1 6,581 2,317 14
X11 XM_011517223.2 6,581 2,272 13
X12 XM_047422093.1 6,581 2,269 14
X13 XM_047422094.1 6,581 2,254 13
X14 XM_047422095.1 6,581 2,251 13
X15 XM_047422096.1 6,581 2,197 13
X16 XM_006716615.3 4,987 2,263 11
X17 XM_047422097.1 4,987 2,260 11

Protein

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 name Common name Taxon median date of divergence (MYA) Accession # Length (amino acids) % identity to humans % similarity to humans
Homo Sapiens Humans Primates 0.0 NP_001094348.1 719 100.0% 100.0%
Theropithecus gelada Gelada Primates 28.8 XP_025250353.1 717 95.5% 96.9%
Mus musculus House mouse Rodentia 87.0 NP_001269372.1 722 79.8% 85.6%
Ursus maritimus Polar bear Carnivora 94.0 XP_040481956.1 705 79.5% 84.4%
Bos taurus Common cattle Artiodactyl 94.0 XP_002692603.1 711 79.8% 84.6%
Manis javanica Malayan pangolin Pholidota 94.0 KAI5929482.1 691 74.2% 80.2%
Elephas maximus indicus Indian elephant Elephantidae 99.0 XP_049709696.1 717 80.8% 85.8%
Sarcophilus harrisii Tasmanian devil Marsupialia 160.0 XP_031803182.1 735 57.9% 66.7%
Ornithorhynchus anatinus Platypus Monotremes 180.0 XP_039767867.1 832 51.3% 58.9%
Gallus gallus Red junglefowl Galliformes 319.0 XP_040537654.1 651 23.8% 37.7%
Anas platyrhynchos Mallard Anseriformes 319.0 XP_071898069.1 736 20.4% 32.6%
Falco naumanni Lesser kestrel Falconiformes 319.0 XP_040449421.1 583 20.7% 32.7%
Patagioenas fasciata Band-tailed pigeon Columbiformes 319.0 XP_071666853.1 857 22.7% 33.6%
Colius striatus Speckled mousebird Coliiformes 319.0 XP_061870785.1 581 22.0% 32.9%
Candoia aspera Papuan ground boa Serpentes 319.0 XP_063156074.1 775 33.2% 47.0%
Tiliqua scincoides Common blue-tongued skink Scincidae 319.0 XP_066477445.1 734 24.3% 37.4%
Chelonia mydas Green sea turtle Cryptodira 319.0 XP_027683785.3 885 32.0% 42.4%
Emydura macquarii macquarii Macquarie River turtle Pleurodira 319.0 XP_067392966.1 372 19.2% 27.3%
Crocodylus porosus Saltwater crocodile Crocodilians 319.0 XP_019406236.1 169 6.4% 9.6%
Amia calva Ruddy bowfin Actinopterygii 429.0 XP_066543890.1 168 7.2% 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]
Paralog Accession # Length (amino acids) Percent identity to MROH6 Percent similarity to MROH6
MRO NP_114145 248 7.9% 12.5%
MROH1 NP_115826.3 1,641 12.0% 16.9%
MROH2A NP_001381568.1 1,674 10.2% 17.0%
MROH2B NP_775760.3 1,585 10.3% 17.0%
MROH7 NP_001034553.3 1,323 16.0% 23.7%
MROH8 NP_689716.4 1,052 15.8% 27.0%
MROH9 NP_001157101.1 861 18.3% 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. ^ a b c d "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. ^ a b 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). "Maternal DNA methylation signatures of gestational diabetes across all stages of pregnancy". Journal of Translational Medicine. 23 (1) 1424. doi:10.1186/s12967-025-07237-0. medRxiv 10.1101/2025.05.25.25328297. PMC 12729693. PMID 41444904.