Alpha-fetoprotein

{{short description|Fetal analogue of serum albumin}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox_gene}} '''Alpha-fetoprotein''' ('''AFP''',<ref>{{Cite encyclopedia |title=AFP |encyclopedia=Henderson's Dictionary of Biological Terms |last=Lawrence |first=Eleanor |edition=10th |page=1 |isbn=0-470-21446-5}}</ref> '''α-fetoprotein'''; also sometimes called '''alpha-1-fetoprotein''', '''alpha-fetoglobulin''', or '''alpha fetal protein''') is a protein<ref name="Tomasi_1977">{{cite journal | vauthors = Tomasi TB | title = Structure and function of alpha-fetoprotein | journal = Annual Review of Medicine | volume = 28 | pages = 453–465 | year = 1977 | pmid = 67821 | doi = 10.1146/annurev.me.28.020177.002321 }}</ref><ref name="Mizejewski_2001">{{cite journal | vauthors = Mizejewski GJ | title = Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants | journal = Experimental Biology and Medicine | location = Maywood, N.J. | volume = 226 | issue = 5 | pages = 377–408 | date = May 2001 | pmid = 11393167 | doi = 10.1177/153537020122600503 | s2cid = 23763069 | url = http://www.ebmonline.org/cgi/content/abstract/226/5/377 | url-access = subscription }}</ref> that in humans is encoded by the ''AFP'' gene.<ref name="Harper_1983">{{cite journal | vauthors = Harper ME, Dugaiczyk A | title = Linkage of the evolutionarily-related serum albumin and alpha-fetoprotein genes within q11-22 of human chromosome 4 | journal = American Journal of Human Genetics | volume = 35 | issue = 4 | pages = 565–572 | date = July 1983 | pmid = 6192711 | pmc = 1685723 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: Alpha-fetoprotein | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=174 }}</ref> The ''AFP'' gene is located on the ''q'' arm of chromosome 4 (4q13.3).<ref>{{cite web | title = Entry - *104150 - ALPHA-FETOPROTEIN; AFP - OMIM | url = https://omim.org/entry/104150?search=afp&highlight=afp | access-date = 2023-06-12 | website = omim.org | language = en-us }}</ref> Maternal AFP serum level is used to screen for Down syndrome, neural tube defects, and other chromosomal abnormalities.<ref>{{cite book | vauthors = Perry SE, Hockenberry MJ, Lowdermilk DL, Wilson D | chapter = 8: Nursing Care of the Family During Pregnancy | title = Maternal Child Nursing Care | location = St. Louis, Missouri | year = 2014 | publisher = Elsevier | isbn = 978-0-323-09610-2 | edition = Fifth | oclc = 858005418 }}</ref>

AFP is a major plasma protein produced by the yolk sac and the fetal liver during fetal development. It is thought to be the fetal analog of serum albumin. AFP binds to copper, nickel, fatty acids and bilirubin<ref name="entrez" /> and is found in monomeric, dimeric and trimeric forms.

== Structure ==

AFP is a glycoprotein of 591 amino acids<ref name="Pucci_1991">{{cite journal | vauthors = Pucci P, Siciliano R, Malorni A, Marino G, Tecce MF, Ceccarini C, Terrana B | title = Human alpha-fetoprotein primary structure: a mass spectrometric study | journal = Biochemistry | volume = 30 | issue = 20 | pages = 5061–5066 | date = May 1991 | pmid = 1709810 | doi = 10.1021/bi00234a032 }}</ref> and a carbohydrate moiety.<ref name="Seregni_1995">{{cite journal | vauthors = Seregni E, Botti C, Bombardieri E | title = Biochemical characteristics and clinical applications of alpha-fetoprotein isoforms | journal = Anticancer Research | volume = 15 | issue = 4 | pages = 1491–1499 | year = 1995 | pmid = 7544570 }}</ref>

== Function == The function of AFP in adult humans is unknown. AFP is the most abundant plasma protein found in the human fetus. In the fetus, AFP is produced by both the liver and the yolk sac. It is believed to function as a carrier protein (similar to albumin) that transports materials such as fatty acids to cells.<ref>{{cite journal | vauthors = Chen H | title = Regulation and activities of alpha-fetoprotein | journal = Critical Reviews in Eukaryotic Gene Expression | volume = 7 | issue = 1–2 | pages = 11–41 | date = 1997 | pmid = 9034713 | doi = 10.1615/critreveukargeneexpr.v7.i1-2.20 }}</ref> Maternal plasma levels rise until the 32nd week of pregnancy, when they begin to decline.<ref>Mizejewski Gj (2003) Levels of Alpha-Fetoprotein During regnancy and Early Infancy in Normal and Disease States; Obs Gyn Survey 804-82658(12):</ref> They decrease rapidly after birth. Normal adult levels in the newborn are usually reached by the age of 8 to 12 months. While the function in humans is unknown, in rodents it binds estradiol to prevent the transport of this hormone across the placenta to the fetus. The main function of this is to prevent the virilization of female fetuses. As human AFP does not bind estrogen, its function in humans is less clear.<ref name="Carter_2002">{{cite book | vauthors = Carter CS | veditors = JB B | chapter = Neuroendocrinology of sexual behavior in the female | title = Behavioral Endocrinology | location = Cambridge, Massachusetts | pages = 88–89 | year = 2002 | publisher = MIT Press | isbn = 978-0-262-52321-9 | chapter-url = https://books.google.com/books?id=D6TnKbTRBJoC&q=AFP%20binds%20maternal%20estrogen&pg=PA88 }}</ref> In human liver cancer, AFP is found to bind glypican-3 (GPC3), another oncofetal antigen.<ref>{{Cite journal | vauthors = Zhang YF, Lin S, Xiao Z, Ho M | title = A proteomic atlas of glypican-3 interacting partners: Identification of alpha-fetoprotein and other extracellular proteins as potential immunotherapy targets in liver cancer | journal = Proteoglycan Research | volume = 2 | issue = 4 | date = October 2024 | pmid = 39822733 | pmc = 11737099 | doi = 10.1002/pgr2.70004 | language = en | issn = 2832-3556 | doi-access = free }}</ref>

The rodent AFP system can be overridden with massive injections of estrogen, which overwhelm the AFP system and will masculinize the fetus. The masculinizing effect of estrogens may seem counter-intuitive since estrogens are critical for the proper development of female secondary characteristics during puberty. However, this is not the case prenatally. Gonadal hormones from the testes, such as testosterone and anti-Müllerian hormone, are required to cause development of a phenotypic male. Without these hormones, the fetus will develop into a phenotypic female even if genetically XY. The conversion of testosterone into estradiol by aromatase in many tissues may be an important step in masculinization of that tissue.<ref name="Nef_2000">{{cite journal | vauthors = Nef S, Parada LF | title = Hormones in male sexual development | journal = Genes & Development | volume = 14 | issue = 24 | pages = 3075–3086 | date = December 2000 | pmid = 11124800 | doi = 10.1101/gad.843800 | doi-access = free }}</ref><ref name="Elbrecht_1992">{{cite journal | vauthors = Elbrecht A, Smith RG | title = Aromatase enzyme activity and sex determination in chickens. | journal = Science | location = New York, N.Y. | volume = 255 | issue = 5043 | pages = 467–470 | date = Jan 1992 | pmid = 1734525 | doi = 10.1126/science.1734525 | bibcode = 1992Sci...255..467E }}</ref> Masculinization of the brain is thought to occur both by conversion of testosterone into estradiol by aromatase, but also by de novo synthesis of estrogens within the brain.<ref name="Bakker_2008">{{cite journal | vauthors = Bakker J, Baum MJ | title = Role for estradiol in female-typical brain and behavioral sexual differentiation. | journal = Frontiers in Neuroendocrinology | volume = 29 | issue = 1 | pages = 1–16 | date = Jan 2008 | pmid = 17720235 | pmc = 2373265 | doi = 10.1016/j.yfrne.2007.06.001 }}</ref><ref name="Harding_2004">{{cite journal | vauthors = Harding CF | title = Hormonal modulation of singing: hormonal modulation of the songbird brain and singing behavior. | journal = Annals of the New York Academy of Sciences | volume = 1016 | issue = 1 | pages = 524–539 | date = Jun 2004 | pmid = 15313793 | doi = 10.1196/annals.1298.030 | bibcode = 2004NYASA1016..524H | s2cid = 12457330 }}</ref> Thus, AFP may protect the fetus from maternal estradiol that would otherwise have a masculinizing effect on the fetus, but its exact role is still controversial.

== Serum levels == {{main|Elevated alpha-fetoprotein}}

=== Maternal ===

Fetal AFP levels can be monitored in the urine of pregnant women. Since AFP is quickly cleared from the mother's serum via her kidneys, maternal urine AFP correlates with fetal serum levels, although the maternal urine level is much lower than the fetal serum level. AFP levels rise until about week 32. Maternal serum alpha-fetoprotein (MSAFP) screening is performed at 16 to 18 weeks of gestation.<ref>{{cite book | veditors = Perry SE | chapter = Chapter 10: Assessment of High Risk Pregnancy | title = Maternal child nursing care : maternity pediatric | location = St. Louis, Missouri | year = 2018 | publisher = Elsevier | isbn = 978-0-323-54938-7 | edition = Sixth | oclc = 999441854 | first1 = Shannon E. | last1 = Perry }}</ref> If MSAFP levels indicate an anomaly, amniocentesis may be offered to the patient.

=== Infants ===

The normal range of AFP for adults and children is variously reported as under 50, under 10, or under 5 ng/mL.<ref name="Ball_1992">{{cite journal | vauthors = Ball D, Rose E, Alpert E | title = Alpha-fetoprotein levels in normal adults | journal = The American Journal of the Medical Sciences | volume = 303 | issue = 3 | pages = 157–159 | date = March 1992 | pmid = 1375809 | doi = 10.1097/00000441-199203000-00004 }}</ref><ref name="Sizaret_1977">{{cite journal | vauthors = Sizaret P, Martel N, Tuyns A, Reynaud S | title = Mean alpha-fetoprotein values of 1,333 males over 15 years by age groups | journal = Digestion | volume = 15 | issue = 2 | pages = 97–103 | date = February 1977 | pmid = 65304 | doi = 10.1159/000197990 }}</ref> At birth, normal infants have AFP levels four or more orders of magnitude above this normal range, that decreases to a normal range over the first year of life.<ref name="Blohm_1998">{{cite journal | vauthors = Blohm ME, Vesterling-Hörner D, Calaminus G, Göbel U | title = Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age | journal = Pediatric Hematology and Oncology | volume = 15 | issue = 2 | pages = 135–142 | year = 1998 | pmid = 9592840 | doi = 10.3109/08880019809167228 }}</ref><ref name="Ohama_1997">{{cite journal | vauthors = Ohama K, Nagase H, Ogino K, Tsuchida K, Tanaka M, Kubo M, Horita S, Kawakami K, Ohmori M | title = Alpha-fetoprotein (AFP) levels in normal children | journal = European Journal of Pediatric Surgery | volume = 7 | issue = 5 | pages = 267–269 | date = October 1997 | pmid = 9402482 | doi = 10.1055/s-2008-1071168 | s2cid = 260137699 }}</ref><ref name="Lee_1989">{{cite journal | vauthors = Lee PI, Chang MH, Chen DS, Lee CY | title = Serum alpha-fetoprotein levels in normal infants: a reappraisal of regression analysis and sex difference | journal = Journal of Pediatric Gastroenterology and Nutrition | volume = 8 | issue = 1 | pages = 19–25 | date = January 1989 | pmid = 2471821 | doi = 10.1097/00005176-198901000-00005 | author2-link = Chang Mei-hwei | author3-link = Ding-Shinn Chen | s2cid = 21104946 | doi-access = free }}</ref><ref name="Blair_1987">{{cite journal | vauthors = Blair JI, Carachi R, Gupta R, Sim FG, McAllister EJ, Weston R | title = Plasma alpha fetoprotein reference ranges in infancy: effect of prematurity | journal = Archives of Disease in Childhood | volume = 62 | issue = 4 | pages = 362–369 | date = April 1987 | pmid = 2439023 | pmc = 1778344 | doi = 10.1136/adc.62.4.362 }}</ref><ref name="Bader_2004">{{cite journal | vauthors = Bader D, Riskin A, Vafsi O, Tamir A, Peskin B, Israel N, Merksamer R, Dar H, David M | title = Alpha-fetoprotein in the early neonatal period--a large study and review of the literature | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 349 | issue = 1–2 | pages = 15–23 | date = November 2004 | pmid = 15469851 | doi = 10.1016/j.cccn.2004.06.020 }}</ref><ref name="Wu_1985">{{cite book | vauthors = Wu JT, Roan Y, Knight JA | veditors = Mizejewski GJ, Porter I | chapter = Serum levels of AFP in normal infants: their clinical and physiological significance | title = Alfa-Fetoprotein and Congenital Disorders | location = New York | pages = 111–122 | year = 1985 | publisher = Academic Press }}</ref>

During this time, the normal range of AFP levels spans approximately two orders of magnitude.<ref name="Lee_1989" /> Correct evaluation of ''abnormal'' AFP levels in infants must take into account these normal patterns.<ref name="Lee_1989" />

Very high AFP levels may be subject to hooking (see tumor marker), which results in the level being reported significantly lower than the actual concentration.<ref name="Jassam_2006">{{cite journal | vauthors = Jassam N, Jones CM, Briscoe T, Horner JH | title = The hook effect: a need for constant vigilance | journal = Annals of Clinical Biochemistry | volume = 43 | issue = Pt 4 | pages = 314–317 | date = July 2006 | pmid = 16824284 | doi = 10.1258/000456306777695726 | doi-access = free }}</ref> This is important for analysis of a series of AFP tumor marker tests, e.g. in the context of post-treatment early surveillance of cancer survivors, where the rate of decrease of AFP has diagnostic value.

== Clinical significance == {{main|Elevated alpha-fetoprotein}} Measurement of AFP is generally used in two clinical contexts. First, it is measured in pregnant women through the analysis of maternal blood or amniotic fluid as a screening test for certain developmental abnormalities, such as aneuploidy. Second, serum AFP level is elevated in people with certain tumors, and so it is used as a biomarker to follow these diseases. Some of these diseases are listed below: * ''Developmental birth defects associated with elevated AFP'' **Omphalocele<ref name="Szabo_1990">{{cite journal | vauthors = Szabó M, Veress L, Münnich A, Papp Z | title = [Alpha fetoprotein concentration in the amniotic fluid in normal pregnancy and in pregnancy complicated by fetal anomaly] | journal = Orvosi Hetilap | volume = 131 | issue = 39 | pages = 2139–2142 | date = September 1990 | pmid = 1699194 | language = hu }}</ref><ref name="Rosen_2005">{{cite journal | vauthors = Rosen T, D'Alton ME | title = Down syndrome screening in the first and second trimesters: what do the data show? | journal = Seminars in Perinatology | volume = 29 | issue = 6 | pages = 367–375 | date = December 2005 | pmid = 16533649 | doi = 10.1053/j.semperi.2006.01.001 }}</ref> **Gastroschisis ** Neural tube defects: elevated α-fetoprotein in amniotic fluid and maternal serum<ref name="Tao p 1" /><ref name="Bredaki_2012">{{cite journal | vauthors = Bredaki FE, Poon LC, Birdir C, Escalante D, Nicolaides KH | title = First-trimester screening for neural tube defects using alpha-fetoprotein | journal = Fetal Diagnosis and Therapy | volume = 31 | issue = 2 | pages = 109–114 | year = 2012 | pmid = 22377693 | doi = 10.1159/000335677 | s2cid = 57465 }}</ref> * ''Tumors associated with elevated AFP'' ** Hepatocellular carcinoma<ref name="Tao p 1">Le, Tao. First Aid for the USMLE Step 1 2013. New York: McGraw-Hill Medical, 2013. Print.</ref><ref>{{cite journal | vauthors = Ertle J, Heider D, Wichert M, Keller B, Kueper R, Hilgard P, Gerken G, Schlaak J | title = A combination of α-fetoprotein and des-γ-carboxy prothrombin is superior in detection of hepatocellular carcinoma. | journal = Digestion | volume = 87 | issue = 2 | pages = 121–131 | date = 2013 | pmid = 23406785 | doi = 10.1159/000346080 | s2cid = 25266129 }}</ref> ** Metastatic disease affecting the liver ** Nonseminomatous germ cell tumors ** Yolk sac tumor<ref name="Tao p 1" /> * ''Other conditions associated with elevated AFP'' ** Ataxia telangiectasia: elevated AFP is used as one factor in diagnosis<ref name="Taylor_2005">{{cite journal | vauthors = Taylor AM, Byrd PJ | title = Molecular pathology of ataxia telangiectasia | journal = Journal of Clinical Pathology | volume = 58 | issue = 10 | pages = 1009–1015 | date = October 2005 | pmid = 16189143 | pmc = 1770730 | doi = 10.1136/jcp.2005.026062 }}</ref>

A peptide derived from AFP that is referred to as AFPep is claimed to possess anti-cancer properties.<ref name="Mesfin_2000">{{cite journal | vauthors = Mesfin FB, Bennett JA, Jacobson HI, Zhu S, Andersen TT | title = Alpha-fetoprotein-derived antiestrotrophic octapeptide | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1501 | issue = 1 | pages = 33–43 | date = April 2000 | pmid = 10727847 | doi = 10.1016/S0925-4439(00)00008-9 | doi-access = free }}</ref>

In the treatment of testicular cancer it is paramount to differentiate seminomatous and nonseminomatous tumors. This is typically done pathologically after removal of the testicle and confirmed by tumor markers. However, if the pathology is pure seminoma but the AFP is elevated, the tumor is treated as a nonseminomatous tumor because it contains yolk sac (nonseminomatous) components.<ref name="Schmoldt_1975">{{cite journal | vauthors = Schmoldt A, Benthe HF, Haberland G | title = Digitoxin metabolism by rat liver microsomes | journal = Biochemical Pharmacology | volume = 24 | issue = 17 | pages = 1639–1641 | date = September 1975 | pmid = 10 | doi = 10.1016/0006-2952(75)90094-5 | url = https://www.sciencedirect.com/science/article/abs/pii/0006295275900945 | hdl = 10033/333424 | hdl-access = free | url-access = subscription }}</ref>

==References== {{reflist|30em}}

==Further reading== {{refbegin|colwidth=35em}} *{{cite journal | vauthors = Nahon JL | title = The regulation of albumin and alpha-fetoprotein gene expression in mammals | journal = Biochimie | volume = 69 | issue = 5 | pages = 445–459 | date = May 1987 | pmid = 2445387 | doi = 10.1016/0300-9084(87)90082-4 }} *{{cite journal | vauthors = Tilghman SM | title = The structure and regulation of the alpha-fetoprotein and albumin genes | journal = Oxford Surveys on Eukaryotic Genes | volume = 2 | pages = 160–206 | year = 1989 | pmid = 2474300 }} *{{cite journal | vauthors = Mizejewski GJ | title = Biological role of alpha-fetoprotein in cancer: prospects for anticancer therapy | journal = Expert Review of Anticancer Therapy | volume = 2 | issue = 6 | pages = 709–735 | date = Dec 2002 | pmid = 12503217 | doi = 10.1586/14737140.2.6.709 | s2cid = 8321005 }} *{{cite journal | vauthors = Yachnin S, Hsu R, Heinrikson RL, Miller JB | title = Studies on human alpha-fetoprotein. Isolation and characterization of monomeric and polymeric forms and amino-terminal sequence analysis | journal = Biochimica et Biophysica Acta | volume = 493 | issue = 2 | pages = 418–428 | date = Aug 1977 | pmid = 70228 | doi = 10.1016/0005-2795(77)90198-2 }} *{{cite journal | vauthors = Aoyagi Y, Ikenaka T, Ichida F | title = Comparative chemical structures of human alpha-fetoproteins from fetal serum and from ascites fluid of a patient with hepatoma | journal = Cancer Research | volume = 37 | issue = 10 | pages = 3663–3667 | date = Oct 1977 | pmid = 71198 }} *{{cite journal | vauthors = Aoyagi Y, Ikenaka T, Ichida F | title = Copper(II)-binding ability of human alpha-fetoprotein | journal = Cancer Research | volume = 38 | issue = 10 | pages = 3483–3486 | date = Oct 1978 | pmid = 80265 }} *{{cite journal | vauthors = Aoyagi Y, Ikenaka T, Ichida F | title = alpha-Fetoprotein as a carrier protein in plasma and its bilirubin-binding ability | journal = Cancer Research | volume = 39 | issue = 9 | pages = 3571–3574 | date = Sep 1979 | pmid = 89900 }} *{{cite journal | vauthors = Torres JM, Anel A, Uriel J | title = Alpha-fetoprotein-mediated uptake of fatty acids by human T lymphocytes | journal = Journal of Cellular Physiology | volume = 150 | issue = 3 | pages = 456–462 | date = Mar 1992 | pmid = 1371512 | doi = 10.1002/jcp.1041500305 | s2cid = 32015210 }} *{{cite journal | vauthors = Greenberg F, Faucett A, Rose E, Bancalari L, Kardon NB, Mizejewski G, Haddow JE, Alpert E | title = Congenital deficiency of alpha-fetoprotein | journal = American Journal of Obstetrics and Gynecology | volume = 167 | issue = 2 | pages = 509–511 | date = Aug 1992 | pmid = 1379776 | doi = 10.1016/S0002-9378(11)91441-0 }} *{{cite journal | vauthors = Bansal V, Kumari K, Dixit A, Sahib MK | title = Interaction of human alpha fetoprotein with bilirubin | journal = Indian Journal of Experimental Biology | volume = 28 | issue = 7 | pages = 697–698 | date = Jul 1990 | pmid = 1703124 }} *{{cite journal | vauthors = Pucci P, Siciliano R, Malorni A, Marino G, Tecce MF, Ceccarini C, Terrana B | title = Human alpha-fetoprotein primary structure: a mass spectrometric study | journal = Biochemistry | volume = 30 | issue = 20 | pages = 5061–5066 | date = May 1991 | pmid = 1709810 | doi = 10.1021/bi00234a032 }} *{{cite journal | vauthors = Liu MC, Yu S, Sy J, Redman CM, Lipmann F | title = Tyrosine sulfation of proteins from the human hepatoma cell line HepG2 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 21 | pages = 7160–7164 | date = Nov 1985 | pmid = 2414772 | pmc = 390808 | doi = 10.1073/pnas.82.21.7160 | bibcode = 1985PNAS...82.7160L | doi-access = free }} *{{cite journal | vauthors = Gibbs PE, Zielinski R, Boyd C, Dugaiczyk A | title = Structure, polymorphism, and novel repeated DNA elements revealed by a complete sequence of the human alpha-fetoprotein gene | journal = Biochemistry | volume = 26 | issue = 5 | pages = 1332–1343 | date = Mar 1987 | pmid = 2436661 | doi = 10.1021/bi00379a020 }} *{{cite journal | vauthors = Sakai M, Morinaga T, Urano Y | title = The human alpha-fetoprotein gene. Sequence organization and the 5' flanking region | journal = The Journal of Biological Chemistry | volume = 260 | issue = 8 | pages = 5055–5060 | date = Apr 1985 | pmid = 2580830 | doi = 10.1016/S0021-9258(18)89178-5 | doi-access = free }} *{{cite journal | vauthors = Ruoslahti E, Pihko H, Vaheri A, Seppala M, Virolainen M, Konttinen A | title = Alpha fetoprotein: structure and expression in man and inbred mouse strains under normal conditions and liver injury | journal = Johns Hopkins Medical Journal. Supplement | volume = 3 | pages = 249–255 | year = 1975 | pmid = 4138095 }} *{{cite journal | vauthors = Urano Y, Sakai M, Watanabe K, Tamaoki T | title = Tandem arrangement of the albumin and alpha-fetoprotein genes in the human genome | journal = Gene | volume = 32 | issue = 3 | pages = 255–261 | date = Dec 1984 | pmid = 6085063 | doi = 10.1016/0378-1119(84)90001-5 }} *{{cite journal | vauthors = Beattie WG, Dugaiczyk A | title = Structure and evolution of human alpha-fetoprotein deduced from partial sequence of cloned cDNA | journal = Gene | volume = 20 | issue = 3 | pages = 415–422 | date = Dec 1982 | pmid = 6187626 | doi = 10.1016/0378-1119(82)90210-4 }} *{{cite journal | vauthors = Morinaga T, Sakai M, Wegmann TG, Tamaoki T | title = Primary structures of human alpha-fetoprotein and its mRNA | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 80 | issue = 15 | pages = 4604–4608 | date = Aug 1983 | pmid = 6192439 | pmc = 384092 | doi = 10.1073/pnas.80.15.4604 | bibcode = 1983PNAS...80.4604M | doi-access = free }} {{refend}}

==External links== * {{MeshName|alpha-Fetoproteins}} * {{PDBe-KB2|P02771|Alpha-fetoprotein}}

Category:Glycoproteins Category:Tumor markers Category:Obstetrics Category:Midwifery