HSPE1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHSPE1, heat shock 10kDa protein 1, CPN10, EPF, GROES, HSP10, heat shock protein family E (Hsp10) member 1
External IDsOMIM: 600141 MGI: 104680 HomoloGene: 20500 GeneCards: HSPE1
Orthologs
SpeciesHumanMouse
Entrez

3336

15528

Ensembl

ENSG00000115541

ENSMUSG00000073676

UniProt

P61604

Q64433

RefSeq (mRNA)

NM_002157

NM_008303

RefSeq (protein)

NP_002148

NP_032329

Location (UCSC)Chr 2: 197.5 – 197.5 MbChr 1: 55.13 – 55.13 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Cpn10
gp31 co-chaperonin from bacteriophage t4
Identifiers
SymbolCpn10
PfamPF00166
Pfam clanCL0296
InterProIPR020818
PROSITEPDOC00576
SCOP21lep / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Heat shock 10 kDa protein 1 (Hsp10), also known as chaperonin 10 (cpn10) or early-pregnancy factor (EPF), is a protein that in humans is encoded by the HSPE1 gene. The homolog in E. coli is GroES that is a chaperonin which usually works in conjunction with GroEL.[5]

Structure and function

GroES exists as a ring-shaped oligomer of between six and eight identical subunits, while the 60 kDa chaperonin (cpn60, or groEL in bacteria) forms a structure comprising 2 stacked rings, each ring containing 7 identical subunits.[6] These ring structures assemble by self-stimulation in the presence of Mg2+-ATP. The central cavity of the cylindrical cpn60 tetradecamer provides an isolated environment for protein folding whilst cpn-10 binds to cpn-60 and synchronizes the release of the folded protein in an Mg2+-ATP dependent manner.[7] The binding of cpn10 to cpn60 inhibits the weak ATPase activity of cpn60.

Escherichia coli GroES has also been shown to bind ATP cooperatively, and with an affinity comparable to that of GroEL.[8] Each GroEL subunit contains three structurally distinct domains: an apical, an intermediate and an equatorial domain. The apical domain contains the binding sites for both GroES and the unfolded protein substrate. The equatorial domain contains the ATP-binding site and most of the oligomeric contacts. The intermediate domain links the apical and equatorial domains and transfers allosteric information between them. The GroEL oligomer is a tetradecamer, cylindrically shaped, that is organised in two heptameric rings stacked back to back. Each GroEL ring contains a central cavity, known as the `Anfinsen cage', that provides an isolated environment for protein folding. The identical 10 kDa subunits of GroES form a dome-like heptameric oligomer in solution. ATP binding to GroES may be important in charging the seven subunits of the interacting GroEL ring with ATP, to facilitate cooperative ATP binding and hydrolysis for substrate protein release.

Interactions

GroES has been shown to interact with GroEL.[9][10]

Detection

Early pregnancy factor is tested for rosette inhibition assay. EPF is present in the maternal serum (blood plasma) shortly after fertilization; EPF is also present in cervical mucus [11] and in amniotic fluid.[12]

EPF may be detected in sheep within 72 hours of mating,[13] in mice within 24 hours of mating,[14] and in samples from media surrounding human embryos fertilized in vitro within 48 hours of fertilization[15] (although another study failed to duplicate this finding for in vitro embryos).[16] EPF has been detected as soon as within six hours of mating.[17]

Because the rosette inhibition assay for EPF is indirect, substances that have similar effects may confound the test. Pig semen, like EPF, has been shown to inhibit rosette formation – the rosette inhibition test was positive for one day in sows mated with a vasectomized boar, but not in sows similarly stimulated without semen exposure.[18] A number of studies in the years after the discovery of EPF were unable to reproduce the consistent detection of EPF in post-conception females, and the validity of the discovery experiments was questioned.[19] However, progress in characterization of EPF has been made and its existence is well-accepted in the scientific community.[20][21]

Origin

Early embryos are not believed to directly produce EPF. Rather, embryos are believed to produce some other chemical that induces the maternal system to create EPF.[22][23][24][25][26] After implantation, EPF may be produced by the conceptus directly.[16]

EPF is an immunosuppressant. Along with other substances associated with early embryos, EPF is believed to play a role in preventing the immune system of the pregnant female from attacking the embryo.[17][27] Injecting anti-EPF antibodies into mice after mating significantly reduced the number of successful pregnancies and number of pups;[28][29] no effect on growth was seen when mice embryos were cultured in media containing anti-EPF antibodies.[30] While some actions of EPF are the same in all mammals (namely rosette inhibition), other immunosuppressant mechanism vary between species.[31]

In mice, EPF levels are high in early pregnancy, but on day 15 decline to levels found in non-pregnant mice.[32] In humans, EPF levels are high for about the first twenty weeks, then decline, becoming undetectable within eight weeks of delivery.[33][34]

Clinical utility

Pregnancy testing

It has been suggested that EPF could be used as a marker for a very early pregnancy test, and as a way to monitor the viability of ongoing pregnancies in livestock.[13] Interest in EPF for this purpose has continued,[35] although current test methods have not proved sufficiently accurate for the requirements of livestock management.[36][37][38][39]

In humans, modern pregnancy tests detect human chorionic gonadotropin (hCG). hCG is not present until after implantation, which occurs six to twelve days after fertilization.[40] In contrast, EPF is present within hours of fertilization. While several other pre-implantation signals have been identified, EPF is believed to be the earliest possible marker of pregnancy.[14][41] The accuracy of EPF as a pregnancy test in humans has been found to be high by several studies.[42][43][44][45]

Birth control research

EPF may also be used to determine whether pregnancy prevention mechanism of birth control methods act before or after fertilization. A 1982 study evaluating EPF levels in women with IUDs concluded that post-fertilization mechanisms contribute significantly to the effectiveness of these devices.[46] However, more recent evidence, such as tubal flushing studies indicates that IUDs work by inhibiting fertilization, acting earlier in the reproductive process than previously thought.[47]

For groups that define pregnancy as beginning with fertilization, birth control methods that have postfertilization mechanisms are regarded as abortifacient. There is currently contention over whether hormonal contraception methods have post-fertilization methods, specifically the most popular hormonal method: the combined oral contraceptive pill (COCP). The group Pharmacists for Life has called for a large-scale clinical trial to evaluate EPF in women taking COCPs; this would be the most conclusive evidence available to determine whether COCPs have postfertilization mechanisms.[48]

Infertility and early pregnancy loss

EPF is useful when investigating embryo loss prior to implantation. One study in healthy human women seeking pregnancy detected fourteen pregnancies with EPF. Of these, six were lost within ten days of ovulation (43% rate of early conceptus loss).[49]

Use of EPF has been proposed to distinguish infertility caused by failure to conceive versus infertility caused by failure to implant.[50] EPF has also been proposed as a marker of viable pregnancy, more useful in distinguishing ectopic or other nonviable pregnancies than other chemical markers such as hCG and progesterone.[51][52][53][54]

As a tumour marker

Although almost exclusively associated with pregnancy, EPF-like activity has also been detected in tumors of germ cell origin[55][56] and in other types of tumors.[57] Its utility as a tumour marker, to evaluate the success of surgical treatment, has been suggested.[58]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000115541 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000073676 - 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: HSPE1 heat shock 10kDa protein 1 (chaperonin 10)".
  6. ↑ Hemmingsen SM, Woolford C, van der Vies SM, Tilly K, Dennis DT, Georgopoulos CP, Hendrix RW, Ellis RJ (May 1988). "Homologous plant and bacterial proteins chaperone oligomeric protein assembly". Nature. 333 (6171): 330–4. Bibcode:1988Natur.333..330H. doi:10.1038/333330a0. PMID 2897629. S2CID 4325057.
  7. ↑ Schmidt A, Schiesswohl M, Völker U, Hecker M, Schumann W (June 1992). "Cloning, sequencing, mapping, and transcriptional analysis of the groESL operon from Bacillus subtilis". J. Bacteriol. 174 (12): 3993–9. doi:10.1128/jb.174.12.3993-3999.1992. PMC 206108. PMID 1350777.
  8. ↑ Martin J, Geromanos S, Tempst P, Hartl FU (November 1993). "Identification of nucleotide-binding regions in the chaperonin proteins GroEL and GroES". Nature. 366 (6452): 279–82. Bibcode:1993Natur.366..279M. doi:10.1038/366279a0. PMID 7901771. S2CID 4243962.
  9. ↑ Samali A, Cai J, Zhivotovsky B, Jones DP, Orrenius S (April 1999). "Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells". EMBO J. 18 (8): 2040–8. doi:10.1093/emboj/18.8.2040. PMC 1171288. PMID 10205158.
  10. ↑ Lee KH, Kim HS, Jeong HS, Lee YS (October 2002). "Chaperonin GroESL mediates the protein folding of human liver mitochondrial aldehyde dehydrogenase in Escherichia coli". Biochem. Biophys. Res. Commun. 298 (2): 216–24. doi:10.1016/S0006-291X(02)02423-3. PMID 12387818.
  11. ↑ Cheng SJ, Zheng ZQ (Feb 2004). "Early pregnancy factor in cervical mucus of pregnant women". American Journal of Reproductive Immunology. 51 (2): 102–5. doi:10.1046/j.8755-8920.2003.00136.x. PMID 14748834. S2CID 40837910.
  12. ↑ Zheng ZQ, Qin ZH, Ma AY, Qiao CX, Wang H (1990). "Detection of early pregnancy factor-like activity in human amniotic fluid". American Journal of Reproductive Immunology. 22 (1–2): 9–11. doi:10.1111/j.1600-0897.1990.tb01025.x. PMID 2346595. S2CID 85106990.
  13. 1 2 Morton H, Clunie GJ, Shaw FD (Mar 1979). "A test for early pregnancy in sheep". Research in Veterinary Science. 26 (2): 261–2. doi:10.1016/S0034-5288(18)32933-3. PMID 262615.
  14. 1 2 Cavanagh AC, Morton H, Rolfe BE, Gidley-Baird AA (Apr 1982). "Ovum factor: a first signal of pregnancy?". American Journal of Reproductive Immunology. 2 (2): 97–101. doi:10.1111/j.1600-0897.1982.tb00093.x. PMID 7102890. S2CID 9624692.
  15. ↑ Smart YC, Cripps AW, Clancy RL, Roberts TK, Lopata A, Shutt DA (Jan 1981). "Detection of an immunosuppressive factor in human preimplantation embryo cultures". The Medical Journal of Australia. 1 (2): 78–9. doi:10.5694/j.1326-5377.1981.tb135326.x. PMID 7231254. S2CID 12267649.
  16. 1 2 Nahhas F, Barnea E (1990). "Human embryonic origin early pregnancy factor before and after implantation". American Journal of Reproductive Immunology. 22 (3–4): 105–8. doi:10.1111/j.1600-0897.1990.tb00651.x. PMID 2375830. S2CID 21055879.
  17. 1 2 Shaw FD, Morton H (Mar 1980). "The immunological approach to pregnancy diagnosis: a review". The Veterinary Record. 106 (12): 268–70. doi:10.1136/vr.106.12.268. PMID 6966439. S2CID 45876497.
  18. ↑ Koch E, Ellendorff F (May 1985). "Detection of activity similar to that of early pregnancy factor after mating sows with a vasectomized boar". Journal of Reproduction and Fertility. 74 (1): 39–46. doi:10.1530/jrf.0.0740039. PMID 4020773.
  19. ↑ Chard T, Grudzinskas JG (1987). "Early pregnancy factor". Biological Research in Pregnancy and Perinatology. 8 (2 2D Half): 53–6. PMID 3322417.
  20. ↑ Di Trapani G, Orosco C, Perkins A, Clarke F (Mar 1991). "Isolation from human placental extracts of a preparation possessing 'early pregnancy factor' activity and identification of the polypeptide components". Human Reproduction. 6 (3): 450–7. doi:10.1093/oxfordjournals.humrep.a137357. PMID 1955557.
  21. ↑ Cavanagh AC (Jan 1996). "Identification of early pregnancy factor as chaperonin 10: implications for understanding its role". Reviews of Reproduction. 1 (1): 28–32. doi:10.1530/ror.0.0010028. PMID 9414435.
  22. ↑ Orozco C, Perkins T, Clarke FM (Nov 1986). "Platelet-activating factor induces the expression of early pregnancy factor activity in female mice". Journal of Reproduction and Fertility. 78 (2): 549–55. doi:10.1530/jrf.0.0780549. PMID 3806515.
  23. ↑ Roberts TK, Adamson LM, Smart YC, Stanger JD, Murdoch RN (May 1987). "An evaluation of peripheral blood platelet enumeration as a monitor of fertilization and early pregnancy". Fertility and Sterility. 47 (5): 848–54. doi:10.1016/S0015-0282(16)59177-8. PMID 3569561.
  24. ↑ Sueoka K, Dharmarajan AM, Miyazaki T, Atlas SJ, Wallach EE (Dec 1988). "Platelet activating factor-induced early pregnancy factor activity from the perfused rabbit ovary and oviduct". American Journal of Obstetrics and Gynecology. 159 (6): 1580–4. doi:10.1016/0002-9378(88)90598-4. PMID 3207134.
  25. ↑ Cavanagh AC, Morton H, Athanasas-Platsis S, Quinn KA, Rolfe BE (Jan 1991). "Identification of a putative inhibitor of early pregnancy factor in mice". Journal of Reproduction and Fertility. 91 (1): 239–48. CiteSeerX 10.1.1.578.5819. doi:10.1530/jrf.0.0910239. PMID 1995852.
  26. ↑ Cavanagh AC, Rolfe BE, Athanasas-Platsis S, Quinn KA, Morton H (Nov 1991). "Relationship between early pregnancy factor, mouse embryo-conditioned medium and platelet-activating factor". Journal of Reproduction and Fertility. 93 (2): 355–65. doi:10.1530/jrf.0.0930355. PMID 1787455.
  27. ↑ Bose R, Cheng H, Sabbadini E, McCoshen J, MaHadevan MM, Fleetham J (Apr 1989). "Purified human early pregnancy factor from preimplantation embryo possesses immunosuppresive properties". American Journal of Obstetrics and Gynecology. 160 (4): 954–60. doi:10.1016/0002-9378(89)90316-5. PMID 2712125.
  28. ↑ Igarashi S (Feb 1987). "[Significance of early pregnancy factor (EPF) on reproductive immunology]". Nihon Sanka Fujinka Gakkai Zasshi. 39 (2): 189–94. PMID 2950188.
  29. ↑ Athanasas-Platsis S, Quinn KA, Wong TY, Rolfe BE, Cavanagh AC, Morton H (Nov 1989). "Passive immunization of pregnant mice against early pregnancy factor causes loss of embryonic viability". Journal of Reproduction and Fertility. 87 (2): 495–502. doi:10.1530/jrf.0.0870495. PMID 2600905.
  30. ↑ Athanasas-Platsis S, Morton H, Dunglison GF, Kaye PL (Jul 1991). "Antibodies to early pregnancy factor retard embryonic development in mice in vivo". Journal of Reproduction and Fertility. 92 (2): 443–51. doi:10.1530/jrf.0.0920443. PMID 1886100.
  31. ↑ Rolfe BE, Cavanagh AC, Quinn KA, Morton H (Aug 1988). "Identification of two suppressor factors induced by early pregnancy factor". Clinical and Experimental Immunology. 73 (2): 219–25. PMC 1541604. PMID 3180511.
  32. ↑ Takimoto Y, Hishinuma M, Takahashi Y, Kanagawa H (Oct 1989). "Detection of early pregnancy factor in superovulated mice". Nihon Juigaku Zasshi. The Japanese Journal of Veterinary Science. 51 (5): 879–85. doi:10.1292/jvms1939.51.879. PMID 2607739.
  33. ↑ Qin ZH, Zheng ZQ (Jan 1987). "Detection of early pregnancy factor in human sera". American Journal of Reproductive Immunology and Microbiology. 13 (1): 15–8. doi:10.1111/j.1600-0897.1987.tb00082.x. PMID 2436493.
  34. ↑ Wang HN, Zheng ZQ (Jul 1990). "Detection of early pregnancy factor in fetal sera". American Journal of Reproductive Immunology. 23 (3): 69–72. doi:10.1111/j.1600-0897.1990.tb00674.x. PMID 2257053. S2CID 221409934.
  35. ↑ Sakonju I, Enomoto S, Kamimura S, Hamana K (Apr 1993). "Monitoring bovine embryo viability with early pregnancy factor". The Journal of Veterinary Medical Science. 55 (2): 271–4. doi:10.1292/jvms.55.271. PMID 8513008.
  36. ↑ Greco CR, Vivas AB, Bosch RA (1992). "[Evaluation of the method for early pregnancy factor detection (EPF) in swine. Significance in early pregnancy diagnosis]". Acta Physiologica, Pharmacologica et Therapeutica Latinoamericana. 42 (1): 43–50. PMID 1294272.
  37. ↑ Sasser RG, Ruder CA (1987). "Detection of early pregnancy in domestic ruminants". Journal of Reproduction and Fertility. Supplement. 34: 261–71. PMID 3305923.
  38. ↑ Gandy B, Tucker W, Ryan P, Williams A, Tucker A, Moore A, Godfrey R, Willard S (Sep 2001). "Evaluation of the early conception factor (ECF) test for the detection of nonpregnancy in dairy cattle". Theriogenology. 56 (4): 637–47. doi:10.1016/S0093-691X(01)00595-7. PMID 11572444.
  39. ↑ Cordoba MC, Sartori R, Fricke PM (Aug 2001). "Assessment of a commercially available early conception factor (ECF) test for determining pregnancy status of dairy cattle". Journal of Dairy Science. 84 (8): 1884–9. doi:10.3168/jds.S0022-0302(01)74629-2. PMID 11518314.
  40. ↑ Wilcox AJ, Baird DD, Weinberg CR (Jun 1999). "Time of implantation of the conceptus and loss of pregnancy". The New England Journal of Medicine. 340 (23): 1796–9. doi:10.1056/NEJM199906103402304. PMID 10362823.
  41. ↑ Straube W (1989). "[Early embryonal signals]". Zentralblatt für Gynäkologie. 111 (10): 629–33. PMID 2665388.
  42. ↑ Smart YC, Roberts TK, Fraser IS, Cripps AW, Clancy RL (Jun 1982). "Validation of the rosette inhibition test for the detection of early pregnancy in women". Fertility and Sterility. 37 (6): 779–85. doi:10.1016/S0015-0282(16)46338-7. PMID 6177559.
  43. ↑ Bessho T, Taira S, Ikuma K, Shigeta M, Koyama K, Isojima S (Mar 1984). "[Detection of early pregnancy factor in the sera of conceived women before nidation]". Nihon Sanka Fujinka Gakkai Zasshi. 36 (3): 391–6. PMID 6715922.
  44. ↑ Straube W, Tiemann U, Loh M, Schütz M (1989). "Detection of early pregnancy factor (EPF) in pregnant and nonpregnant subjects with the rosette inhibition test". Archives of Gynecology and Obstetrics. 246 (3): 181–7. doi:10.1007/BF00934079. PMID 2619332. S2CID 20531983.
  45. ↑ Fan XG, Zheng ZQ (May 1997). "A study of early pregnancy factor activity in preimplantation". American Journal of Reproductive Immunology. 37 (5): 359–64. doi:10.1111/j.1600-0897.1997.tb00244.x. PMID 9196793. S2CID 71525444.
  46. ↑ Smart YC, Fraser IS, Clancy RL, Roberts TK, Cripps AW (Feb 1982). "Early pregnancy factor as a monitor for fertilization in women wearing intrauterine devices". Fertility and Sterility. 37 (2): 201–4. doi:10.1016/S0015-0282(16)46039-5. PMID 6174375.
  47. ↑ Grimes, David (2007). "Intrauterine Devices (IUDs)". In Hatcher, Robert A.; et al. (eds.). Contraceptive Technology (19th rev. ed.). New York: Ardent Media. p. 120. ISBN 978-0-9664902-0-6.
  48. ↑ Lloyd J DuPlantis, Jr (2001). "Early Pregnancy Factor". Pharmacists for Life, Intl. Retrieved 2007-01-01. {{cite journal}}: Cite journal requires |journal= (help)
  49. ↑ Smart YC, Fraser IS, Roberts TK, Clancy RL, Cripps AW (Sep 1982). "Fertilization and early pregnancy loss in healthy women attempting conception". Clinical Reproduction and Fertility. 1 (3): 177–84. PMID 6196101.
  50. ↑ Mesrogli M, Maas DH, Schneider J (1988). "[Early abortion rate in sterility patients: early pregnancy factor as a parameter]". Zentralblatt für Gynäkologie. 110 (9): 555–61. PMID 3407357.
  51. ↑ Straube W, Loh M, Leipe S (Dec 1988). "[Significance of the detection of early pregnancy factor for monitoring normal and disordered early pregnancy]". Geburtshilfe und Frauenheilkunde. 48 (12): 854–8. doi:10.1055/s-2008-1026640. PMID 2466731. S2CID 260158786.
  52. ↑ Gerhard I, Katzer E, Runnebaum B (1991). "The early pregnancy factor (EPF) in pregnancies of women with habitual abortions". Early Human Development. 26 (2): 83–92. doi:10.1016/0378-3782(91)90012-R. PMID 1720719.
  53. ↑ Shu-Xin H, Zhen-Qun Z (Mar 1993). "A study of early pregnancy factor activity in the sera of patients with unexplained spontaneous abortion". American Journal of Reproductive Immunology. 29 (2): 77–81. doi:10.1111/j.1600-0897.1993.tb00569.x. PMID 8329108. S2CID 22163702.
  54. ↑ Shahani SK, Moniz CL, Bordekar AD, Gupta SM, Naik K (1994). "Early pregnancy factor as a marker for assessing embryonic viability in threatened and missed abortions". Gynecologic and Obstetric Investigation. 37 (2): 73–6. doi:10.1159/000292528. PMID 8150373.
  55. ↑ Rolfe BE, Morton H, Cavanagh AC, Gardiner RA (Mar 1983). "Detection of an early pregnancy factor-like substance in sera of patients with testicular germ cell tumors". American Journal of Reproductive Immunology. 3 (2): 97–100. doi:10.1111/j.1600-0897.1983.tb00223.x. PMID 6859385. S2CID 33423830.
  56. ↑ Mehta AR, Shahani SK (Jul 1987). "Detection of early pregnancy factor-like activity in women with gestational trophoblastic tumors". American Journal of Reproductive Immunology and Microbiology. 14 (3): 67–9. doi:10.1111/j.1600-0897.1987.tb00122.x. PMID 2823620.
  57. ↑ Quinn KA, Athanasas-Platsis S, Wong TY, Rolfe BE, Cavanagh AC, Morton H (Apr 1990). "Monoclonal antibodies to early pregnancy factor perturb tumour cell growth". Clinical and Experimental Immunology. 80 (1): 100–8. doi:10.1111/j.1365-2249.1990.tb06448.x. PMC 1535227. PMID 2323098.
  58. ↑ Bojahr B, Straube W, Reddemann H (1993). "[Case observations on the significance of early pregnancy factor as a tumor marker]". Zentralblatt für Gynäkologie. 115 (3): 125–8. PMID 7682025.

Further reading

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