MSMB

Beta-microseminoprotein is a protein that in humans is encoded by the MSMB gene.{{cite journal |vauthors=Ulvsback M, Spurr NK, Lundwall A | title = Assignment of the human gene for beta-microseminoprotein (MSMB) to chromosome 10 and demonstration of related genes in other vertebrates | journal = Genomics | volume = 11 | issue = 4 | pages = 920–4 |date=Mar 1992 | pmid = 1783399 | doi =10.1016/0888-7543(91)90015-7 }}{{cite web | title = Entrez Gene: MSMB microseminoprotein, beta-| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4477}} For historical reasons, the scientific literature may also refer to this protein as Prostate secretory protein 94 (PSP94), microseminoprotein (MSP), microseminoprotein-beta (MSMB), beta-inhibitin, prostatic inhibin peptide (PIP), and inhibitin like material (ILM).

Distribution

MSMB is one of the three major proteins secreted by the epithelial cells of the prostate{{cite journal |vauthors=Lilja H, Abrahamsson PA | title = Three predominant proteins secreted by the human prostate gland | journal = Prostate | volume = 12 | issue = 1 | pages = 29–38 | year = 1988 | pmid = 3347596 | doi = 10.1002/pros.2990120105| s2cid = 12843459 }} and has a concentration in seminal plasma of 0.5 to 1 mg/mL{{cite journal |vauthors=Valtonen-André C, Sävblom C, Fernlund P, Lilja H, Giwercman A, Lundwall A | title = Beta-microseminoprotein in serum correlates with the levels in seminal plasma of young, healthy males | journal = J. Androl. | volume = 29 | issue = 3 | pages = 330–7 | year = 2008 | pmid = 18222915 | doi = 10.2164/jandrol.107.003616 | doi-access = free }} Two comprehensive studies of beta-microseminoprotein in tissue have shown that it is secreted by epithelial cells in many other organs: liver, lung, breast, kidney, colon, stomach, pancreas, esophagus, duodenum, salivary glands, fallopian tube, corpus uteri, bulbourethral glands and cervix.{{cite journal |vauthors=Weiber H, Andersson C, Murne A, Rannevik G, Lindström C, Lilja H, Fernlund P | title = Beta microseminoprotein is not a prostate-specific protein. Its identification in mucous glands and secretions | journal = Am. J. Pathol. | volume = 137 | issue = 3 | pages = 593–603 |date=September 1990 | pmid = 2205099 | pmc = 1877516 }}{{cite journal |vauthors=Ohkubo I, Tada T, Ochiai Y, Ueyama H, Eimoto T, Sasaki M | title = Human seminal plasma beta-microseminoprotein: its purification, characterization, and immunohistochemical localization | journal = Int. J. Biochem. Cell Biol. | volume = 27 | issue = 6 | pages = 603–11 |date=June 1995 | pmid = 7671139 | doi = 10.1016/1357-2725(95)00021-G }} This list corresponds closely to the sites from which all late onset cancers develop.{{cite book |vauthors=Laurence M | date = 2018 | title = PSP94, what is it good for? Sixth edition}}

Evolution and structure

MSMB is a rapidly evolving protein.{{cite journal |vauthors=Nolet S, St-Louis D, Mbikay M, Chrétien M | title = Rapid evolution of prostatic protein PSP94 suggested by sequence divergence between rhesus monkey and human cDNAs | journal = Genomics | volume = 9 | issue = 4 | pages = 775–7 |date=April 1991 | pmid = 2037304 | doi = 10.1016/0888-7543(91)90375-o}} Solution structures of human and porcine MSMB show remarkable similarity despite having only 51% of amino acids in common.{{cite journal |vauthors=Ghasriani H, Teilum K, Johnsson Y, Fernlund P, Drakenberg T | title = Solution structures of human and porcine beta-microseminoprotein | journal = J. Mol. Biol. | volume = 362 | issue = 3 | pages = 502–15 |date=September 2006 | pmid = 16930619 | doi = 10.1016/j.jmb.2006.07.029 }} The C-terminus domain of MSMB contains two two-stranded β-sheets; these have no resemblance to other structural motifs. The rapid evolution of MSMB can be attributed to either sexual selection or innate pathogen defense;{{cite journal |vauthors=Clark NL, Swanson WJ | title = Pervasive adaptive evolution in primate seminal proteins | journal = PLOS Genet. | volume = 1 | issue = 3 | pages = e35 |date=September 2005 | pmid = 16170411 | pmc = 1201370 | doi = 10.1371/journal.pgen.0010035 | doi-access = free }} {{open access}} the wide distribution of MSMB in the body and the fungicidal properties of the C-terminus suggest that innate pathogen defense plays a role in driving this evolution.{{cite journal |vauthors=Edström Hägerwall AM, Rydengård V, Fernlund P, Mörgelin M, Baumgarten M, Cole AM, Malmsten M, Kragelund BB, Sørensen OE | title = β-Microseminoprotein endows post coital seminal plasma with potent candidacidal activity by a calcium- and pH-dependent mechanism | journal = PLOS Pathog. | volume = 8 | issue = 4 | pages = e1002625 | year = 2012 | pmid = 22496651 | pmc = 3320615 | doi = 10.1371/journal.ppat.1002625 | doi-access = free }} {{open access}}

Function

Beta-microseminoprotein is a member of the immunoglobulin binding factor family. This protein has been reported to have inhibin-like properties,{{cite journal |vauthors=Sheth AR, Arabatti N, Carlquist M, Jörnvall H | title = Characterization of a polypeptide from human seminal plasma with inhibin (inhibition of FSH secretion)-like activity | journal = FEBS Lett. | volume = 165 | issue = 1 | pages = 11–5 |date=January 1984 | pmid = 6692908 | doi = 10.1016/0014-5793(84)80004-6| s2cid = 40923254 | doi-access = free }} though this finding has been disputed.{{cite journal |vauthors=Kohan S, Fröysa B, Cederlund E, Fairwell T, Lerner R, Johansson J, Khan S, Ritzen M, Jörnvall H, Cekan S | title = Peptides of postulated inhibin activity. Lack of in vitro inhibin activity of a 94-residue peptide isolated from human seminal plasma, and of a synthetic replicate of its C-terminal 28-residue segment | journal = FEBS Lett. | volume = 199 | issue = 2 | pages = 242–8 |date=April 1986 | pmid = 3084296 | doi = 10.1016/0014-5793(86)80488-4| s2cid = 33940801 }}{{cite journal |vauthors=Gordon WL, Liu WK, Akiyama K, Tsuda R, Hara M, Schmid K, Ward DN | title = Beta-microseminoprotein (beta-MSP) is not an inhibin | journal = Biol. Reprod. | volume = 36 | issue = 4 | pages = 829–35 |date=May 1987 | pmid = 3109514 | doi = 10.1095/biolreprod36.4.829| doi-access = free }} It may have a role as an autocrine and/or paracrine factor in uterine, breast, and other female reproductive tissues.{{citation needed |date=May 2022}} Two alternatively spliced transcript variants encoding different isoforms are described for this gene. Despite having only 4 out of 11 amino acids in common, both the porcine and human fungicidal peptide on MSMB's C-terminus are potently fungicidal in the absence of calcium ions. The protein inhibits growth of cancer cells in an experimental model of prostate cancer,{{cite journal |vauthors=Garde S, Sheth A, Porter AT, Pienta KJ | title = Effect of prostatic inhibin peptide (PIP) on prostate cancer cell growth in vitro and in vivo | journal = Prostate | volume = 22 | issue = 3 | pages = 225–33 | year = 1993 | pmid = 8488155 | doi = 10.1002/pros.2990220305| s2cid = 20872869 }}{{cite journal |vauthors=Shukeir N, Arakelian A, Kadhim S, Garde S, Rabbani SA | title = Prostate secretory protein PSP-94 decreases tumor growth and hypercalcemia of malignancy in a syngenic in vivo model of prostate cancer | journal = Cancer Res. | volume = 63 | issue = 9 | pages = 2072–8 |date=May 2003 | pmid = 12727822 }} though this property is cell line–specific.{{cite journal |vauthors=Pathak BR, Breed AA, Nakhawa VH, Jagtap DD, Mahale SD | title = Growth inhibition mediated by PSP94 or CRISP-3 is prostate cancer cell line specific | journal = Asian J. Androl. | volume = 12 | issue = 5 | pages = 677–89 |date=September 2010 | pmid = 20676114 | pmc = 3739318 | doi = 10.1038/aja.2010.56 }}

Clinical significance

Two large genome-wide association studies showed that decreased expression of the MSMB protein caused by the rs10993994 single nucleotide polymorphism is associated with an increased risk of developing prostate cancer (odds ratio for CT allele pair ~1.2x, and for TT allele pair ~1.6x, when compared to the low risk CC allele pair).{{cite journal |vauthors=Eeles RA, Kote-Jarai Z, Giles GG, Olama AA, Guy M, Jugurnauth SK, Mulholland S, Leongamornlert DA, Edwards SM, Morrison J | title = Multiple newly identified loci associated with prostate cancer susceptibility | journal = Nat. Genet. | volume = 40 | issue = 3 | pages = 316–21 |date=March 2008 | pmid = 18264097 | doi = 10.1038/ng.90 | s2cid = 30968525 |display-authors=etal}} A 2003 study proposed using a truncated form of the MSMB protein called PSP61 as a biomarker for benign prostatic hyperplasia (BPH). This study found PSP61 in the expressed prostatic secretion of 10 out of 10 men suffering from BPH, while not finding it in 10 out of 10 age-matched BPH-free men.{{cite journal |vauthors=Xu K, Wang X, Ling MT, Lee DT, Fan T, Chan FL, Xuan JJ, Tsao SW, Wong YC | title = Identification of a specifically expressed modified form of novel PSP-94 protein in the secretion of benign prostatic hyperplasia | journal = Electrophoresis | volume = 24 | issue = 7–8 | pages = 1311–8 |date=April 2003 | pmid = 12707925 | doi = 10.1002/elps.200390167 | s2cid = 21348603 }} This truncated form of the MSMB protein lacks the fungicidal peptide identified in 2012. The expression of MSMB is found to be decreased in prostate cancer, so it may be usable as a biomarker for prostate cancer.{{cite journal |vauthors=Whitaker HC, Warren AY, Eeles R, Kote-Jarai Z, Neal DE | title = The potential value of microseminoprotein-beta as a prostate cancer biomarker and therapeutic target | journal = Prostate | volume = 70 | issue = 3 | pages = 333–40 |date=February 2010 | pmid = 19790236 | doi = 10.1002/pros.21059 | s2cid = 206397505 }} Urinary MSMB has been found to be superior to urinary PSA at differentiating men with prostate cancer, at all Gleason grades.{{cite journal |vauthors=Whitaker HC, Kote-Jarai Z, Ross-Adams H, Warren AY, Burge J, George A, Bancroft E, Jhavar S, Leongamornlert D, Tymrakiewicz M | title = The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine | journal = PLOS ONE | volume = 5 | issue = 10 | pages = e13363 | year = 2010 | pmid = 20967219 | pmc = 2954177 | doi = 10.1371/journal.pone.0013363 | bibcode = 2010PLoSO...513363W |display-authors=etal| doi-access = free }} {{open access}}

MSMB

Distribution

Evolution and structure

Function

Clinical significance

References

Further reading