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AMHR2
Identifiers
Aliases	AMHR2, AMHR, MISR2, MISRII, MRII, anti-Mullerian hormone receptor type 2
External IDs	OMIM: 600956; MGI: 105062; HomoloGene: 10746; GeneCards: AMHR2; OMA:AMHR2 - orthologs
Gene location (Human) Chr. Chromosome 12 (human) Band 12q13.13 Start 53,423,855 bp End 53,431,672 bp
Gene location (Mouse) Chr. Chromosome 15 (mouse) Band 15 F3|15 57.58 cM Start 102,353,802 bp End 102,363,068 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal cortex left adrenal gland left adrenal cortex left ovary right ovary left testis body of pancreas right testis skeletal muscle tissue spleen Top expressed in seminiferous tubule spermatocyte facial motor nucleus ovary muscle layer of urethra Gonadal ridge epithelium of urethra epithelium of female urethra soleus muscle lamina propria of vagina More reference expression data BioGPS n/a
Gene ontology Molecular function transferase activity nucleotide binding protein kinase activity hormone binding transforming growth factor beta receptor activity, type II metal ion binding kinase activity protein serine/threonine kinase activity transmembrane receptor protein serine/threonine kinase activity protein binding ATP binding anti-Mullerian hormone receptor activity transforming growth factor beta-activated receptor activity growth factor binding SMAD binding Cellular component integral component of membrane membrane integral component of plasma membrane plasma membrane receptor complex Biological process male gonad development phosphorylation sex differentiation female gonad development negative regulation of anti-Mullerian hormone signaling pathway Mullerian duct regression protein phosphorylation transmembrane receptor protein serine/threonine kinase signaling pathway transforming growth factor beta receptor signaling pathway BMP signaling pathway anti-Mullerian hormone signaling pathway pattern specification process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 269 110542 Ensembl ENSG00000135409 ENSMUSG00000023047 UniProt Q16671 Q8K592 RefSeq (mRNA) NM_001164690 NM_001164691 NM_020547 NM_144547 NM_001356575 RefSeq (protein) NP_001158162 NP_001158163 NP_065434 NP_653130 NP_001343504 Location (UCSC) Chr 12: 53.42 – 53.43 Mb Chr 15: 102.35 – 102.36 Mb PubMed search
Wikidata
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Anti-Müllerian hormone receptor, also known as Müllerian Inhibiting Substance Type II Receptor, is a receptor for the anti-Müllerian hormone (AMH). Furthermore, anti-Müllerian hormone receptor type 2 is a protein in humans that is encoded by the AMHR2 gene.

Structure

AMHR2 belongs to TGF-β type II receptor family and adopts the characteristic three-finger toxin fold. However, it displays a unique extended finger 1 loop (see image) that is critical to effectively binding its ligand, AMH. The palm region and other fingers are also implicated in binding to AMH, but are relatively unremarkable when compared to other TGF-β type II receptors. As such, these interactions do not contribute significantly to the observed ligand specificity for AMH like the finger 1 loop.

Function

The gene is present in both men and women. AMHR2 is a Type 2 receptor that binds AMH (Anti-Müllerian hormone). This hormone is responsible for Müllerian Duct regression in vertebrates once the SRY gene has been expressed. Some animals such as jawless fish do not express either AMH or its receptors. High circulating AMH continues on after testis development and is secreted from the Sertoli Cells. It is also expressed in Leydig cells. It has been reported that the loss of function of the AMHR2 gene results in 50% of XY animals to reverse sex to females and also leads to hyperproliferation of mitotically active germ cells, which leads to the sex reversal. AMH binding to the AMHR2 in mammals causes regression of the oviducts, uterus, and upper 2/3 of the vagina.

Clinical significance

Müllerian inhibiting substance type II receptor (MISIIR), also known as the Anti-Müllerian Hormone Receptor, is expressed by ovarian, breast, and prostate cancers and these cancer cells have been reported to apoptose in response to exposure to the Müllerian inhibiting substance (MIS).

Monoclonal Antibodies have been developed that specifically target MISIIR and may be useful as vehicles for drugs and toxins for targeted cancer therapy.

A syndrome called "Persistent Mullerian Duct Syndrome" (PMDS) can occur in human males and results in the uterus, vagina, and uterus being present in virilized male. PMDS can be caused by a genetic mutation of deletions, or missenses, and these males often have undescended testes or cryptorchidism, where one testis fails to descend outside of the body cavity. The majority of these patients will be infertile. In females that are homozygous for the mutation, no abnormalities have been observed. However, heterozygous females have been observed to reach menopause sooner and display a lowered AMH level which also is an indicator of antral follicle count. It is likely that these females reach menopause sooner from having fewer antral follicles, thus more atresia of follicles prior to developing an antrum. These phenotypes were confirmed to be the cause of an AMHR2 mutation from knock out studies performed in mice.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000135409 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000023047 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: Anti-Mullerian hormone receptor type 2". Retrieved 2018-06-07.
6. ^ PDB: 7L0J​; Hart KN, Stocker WA, Nagykery NG, Walton KL, Harrison CA, Donahoe PK, et al. (June 2021). "Structure of AMH bound to AMHR2 provides insight into a unique signaling pair in the TGF-β family". Proceedings of the National Academy of Sciences of the United States of America. 118 (26): e2104809118. Bibcode:2021PNAS..11804809H. doi:10.1073/pnas.2104809118. PMC 8256043. PMID 34155118.
7. ^ Adolfi MC, Nakajima RT, Nóbrega RH, Schartl M (February 2019). "Intersex, Hermaphroditism, and Gonadal Plasticity in Vertebrates: Evolution of the Müllerian Duct and Amh/Amhr2 Signaling". Annual Review of Animal Biosciences. 7: 149–172. doi:10.1146/annurev-animal-020518-114955. PMID 30303691. S2CID 52954655.
8. Salhi I, Cambon-Roques S, Lamarre I, Laune D, Molina F, Pugnière M, et al. (May 2004). "The anti-Müllerian hormone type II receptor: insights into the binding domains recognized by a monoclonal antibody and the natural ligand". The Biochemical Journal. 379 (Pt 3): 785–793. doi:10.1042/bj20031961. PMC 1224123. PMID 14750901.
9. Masiakos PT, MacLaughlin DT, Maheswaran S, Teixeira J, Fuller AF, Shah PC, et al. (November 1999). "Human ovarian cancer, cell lines, and primary ascites cells express the human Mullerian inhibiting substance (MIS) type II receptor, bind, and are responsive to MIS". Clinical Cancer Research. 5 (11): 3488–3499. PMID 10589763.
10. Yuan QA, Robinson MK, Simmons HH, Russeva M, Adams GP (March 2008). "Isolation of anti-MISIIR scFv molecules from a phage display library by cell sorter biopanning". Cancer Immunology, Immunotherapy. 57 (3): 367–378. doi:10.1007/s00262-007-0376-2. PMC 11031043. PMID 17676323. S2CID 13075446.
11. Yuan QA, Simmons HH, Robinson MK, Russeva M, Marasco WA, Adams GP (August 2006). "Development of engineered antibodies specific for the Müllerian inhibiting substance type II receptor: a promising candidate for targeted therapy of ovarian cancer". Molecular Cancer Therapeutics. 5 (8): 2096–2105. doi:10.1158/1535-7163.MCT-06-0115. PMID 16928831.
12. Salhi I, Cambon-Roques S, Lamarre I, Laune D, Molina F, Pugnière M, et al. (May 2004). "The anti-Müllerian hormone type II receptor: insights into the binding domains recognized by a monoclonal antibody and the natural ligand". The Biochemical Journal. 379 (Pt 3): 785–793. doi:10.1042/BJ20031961. PMC 1224123. PMID 14750901.
13. Mullen RD, Ontiveros AE, Moses MM, Behringer RR (November 2019). "AMH and AMHR2 mutations: A spectrum of reproductive phenotypes across vertebrate species". Developmental Biology. 455 (1): 1–9. doi:10.1016/j.ydbio.2019.07.006. PMC 6754765. PMID 31301298.

• This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Further reading

• Teixeira J, Maheswaran S, Donahoe PK (October 2001). "Müllerian inhibiting substance: an instructive developmental hormone with diagnostic and possible therapeutic applications". Endocrine Reviews. 22 (5): 657–674. doi:10.1210/edrv.22.5.0445. PMID 11588147.
• Picard JY, Belville C (2002). "". Journal de la Société de Biologie (in French). 196 (3): 217–221. doi:10.1051/jbio/2002196030217. PMID 12462075.
• Wang HQ, Takakura K, Takebayashi K, Noda Y (December 2002). "Mutational analysis of the müllerian-inhibiting substance gene and its receptor gene in Japanese women with polycystic ovary syndrome and premature ovarian failure". Fertility and Sterility. 78 (6): 1329–1330. doi:10.1016/s0015-0282(02)04351-0. PMID 12477536.
• Salhi I, Cambon-Roques S, Lamarre I, Laune D, Molina F, Pugnière M, et al. (May 2004). "The anti-Müllerian hormone type II receptor: insights into the binding domains recognized by a monoclonal antibody and the natural ligand". The Biochemical Journal. 379 (Pt 3): 785–793. doi:10.1042/BJ20031961. PMC 1224123. PMID 14750901.
• Kevenaar ME, Themmen AP, Laven JS, Sonntag B, Fong SL, Uitterlinden AG, et al. (June 2007). "Anti-Müllerian hormone and anti-Müllerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women". Human Reproduction. 22 (6): 1547–1554. doi:10.1093/humrep/dem036. PMID 17337470.
• Kevenaar ME, Themmen AP, Laven JS, Sonntag B, Fong SL, Uitterlinden AG, et al. (June 2007). "Anti-Müllerian hormone and anti-Müllerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women". Human Reproduction. 22 (6): 1547–1554. doi:10.1093/humrep/dem036. PMID 17337470.
• Kevenaar ME, Themmen AP, Rivadeneira F, Uitterlinden AG, Laven JS, van Schoor NM, et al. (September 2007). "A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity". Human Reproduction. 22 (9): 2382–2388. doi:10.1093/humrep/dem176. PMID 17636279.
• Kevenaar ME, Themmen AP, Rivadeneira F, Uitterlinden AG, Laven JS, van Schoor NM, et al. (September 2007). "A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity". Human Reproduction. 22 (9): 2382–2388. doi:10.1093/humrep/dem176. PMID 17636279.
• Bakkum-Gamez JN, Aletti G, Lewis KA, Keeney GL, Thomas BM, Navarro-Teulon I, Cliby WA (January 2008). "Müllerian inhibiting substance type II receptor (MISIIR): a novel, tissue-specific target expressed by gynecologic cancers". Gynecologic Oncology. 108 (1): 141–148. doi:10.1016/j.ygyno.2007.09.010. PMID 17988723.

External links

• Anti-Mullerian+hormone+receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

• Biology

• Genes on human chromosome 12
• EC 2.7.11