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AFP
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesAFP, AFPD, FETA, HPalpha fetoprotein
External IDsOMIM: 104150; MGI: 87951; HomoloGene: 36278; GeneCards: AFP; OMA:AFP - orthologs
Orthologs
SpeciesHumanMouse
Entrez

174

11576

Ensembl

ENSG00000081051

ENSMUSG00000054932

UniProt

P02771

P02772

RefSeq (mRNA)

NM_001134
NM_001354717

NM_007423

RefSeq (protein)

NP_001125
NP_001341646

NP_031449

Location (UCSC)Chr 4: 73.43 – 73.46 MbChr 5: 90.64 – 90.66 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein[5][6] that in humans is encoded by the AFP gene.[7][8] The AFP gene is located on the q arm of chromosome 4 (4q13.3).[9] Maternal AFP serum level is used to screen for Down syndrome, neural tube defects, and other chromosomal abnormalities.[10]

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[8] and is found in monomeric, dimeric and trimeric forms.

Structure

AFP is a glycoprotein of 591 amino acids[11] and a carbohydrate moiety.[12]

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.[13] Maternal plasma levels peak near the end of the first trimester, and begin decreasing prenatally at that time, then 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.[14] In human liver cancer, AFP is found to bind glypican-3 (GPC3), another oncofetal antigen.[15]

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.[16][17] 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.[18][19] 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 article: Elevated alpha-fetoprotein

Maternal

In pregnant women, fetal AFP levels can be monitored in the urine of the pregnant woman. 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.[20] 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.[21][22] 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.[23][24][25][26][27][28]

During this time, the normal range of AFP levels spans approximately two orders of magnitude.[25] Correct evaluation of abnormal AFP levels in infants must take into account these normal patterns.[25]

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.[29] 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 article: 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:

A peptide derived from AFP that is referred to as AFPep is claimed to possess anti-cancer properties.[36]

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, if the AFP is elevated, the tumor is treated as a nonseminomatous tumor because it contains yolk sac (nonseminomatous) components.[37]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000081051 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000054932 – 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. ^ Tomasi TB (1977). "Structure and function of alpha-fetoprotein". Annual Review of Medicine. 28: 453–65. doi:10.1146/annurev.me.28.020177.002321. PMID 67821.
  6. ^ Mizejewski GJ (May 2001). "Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants". Experimental Biology and Medicine. 226 (5): 377–408. doi:10.1177/153537020122600503. PMID 11393167. S2CID 23763069.
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  9. ^ "Entry - *104150 - ALPHA-FETOPROTEIN; AFP - OMIM". omim.org. Retrieved 2023-06-12.
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  19. ^ Harding CF (2004). "Hormonal modulation of singing: hormonal modulation of the songbird brain and singing behavior". Annals of the New York Academy of Sciences. 1016 (1): 524–39. Bibcode:2004NYASA1016..524H. doi:10.1196/annals.1298.030. PMID 15313793. S2CID 12457330.
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  21. ^ Ball D, Rose E, Alpert E (March 1992). "Alpha-fetoprotein levels in normal adults". The American Journal of the Medical Sciences. 303 (3): 157–9. doi:10.1097/00000441-199203000-00004. PMID 1375809.
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  23. ^ Blohm ME, Vesterling-Hörner D, Calaminus G, Göbel U (1998). "Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age". Pediatric Hematology and Oncology. 15 (2): 135–42. doi:10.3109/08880019809167228. PMID 9592840.
  24. ^ Ohama K, Nagase H, Ogino K, Tsuchida K, Tanaka M, Kubo M, Horita S, Kawakami K, Ohmori M (October 1997). "Alpha-fetoprotein (AFP) levels in normal children". European Journal of Pediatric Surgery. 7 (5): 267–9. doi:10.1055/s-2008-1071168. PMID 9402482. S2CID 260137699.
  25. ^ a b c Lee PI, Chang MH, Chen DS, Lee CY (January 1989). "Serum alpha-fetoprotein levels in normal infants: a reappraisal of regression analysis and sex difference". Journal of Pediatric Gastroenterology and Nutrition. 8 (1): 19–25. doi:10.1097/00005176-198901000-00005. PMID 2471821. S2CID 21104946.
  26. ^ Blair JI, Carachi R, Gupta R, Sim FG, McAllister EJ, Weston R (April 1987). "Plasma alpha fetoprotein reference ranges in infancy: effect of prematurity". Archives of Disease in Childhood. 62 (4): 362–9. doi:10.1136/adc.62.4.362. PMC 1778344. PMID 2439023.
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  29. ^ Jassam N, Jones CM, Briscoe T, Horner JH (July 2006). "The hook effect: a need for constant vigilance". Annals of Clinical Biochemistry. 43 (Pt 4): 314–7. doi:10.1258/000456306777695726. PMID 16824284.
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Further reading

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

source: https://en.wikipedia.org/wiki/Alpha-fetoprotein

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