AFP

Protein identityUniProt · HPA

UniProt accession

P02771

Gene

AFP

Ensembl

ENSG00000081051

Chromosome

4

Canonical length

609 aa

Protein class

Cancer-related genes, Disease related genes, Plasma proteins, Predicted secreted proteins

Subcellular location

Golgi apparatus

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes alpha-fetoprotein, a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatocarcinoma and with teratoma, and has prognostic value for managing advanced gastric cancer. However, hereditary persistance of alpha-fetoprotein may also be found in individuals with no obvious pathology. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. Alpha-fetoprotein is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty acids and bilirubin. The level of alpha-fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly. [provided by RefSeq, Oct 2019]

Canonical amino-acid sequenceUniProt

609 residues, UniProt reviewed canonical sequence.

>P02771|AFP
     1  MKWVESIFLI FLLNFTESRT LHRNEYGIAS ILDSYQCTAE ISLADLATIF FAQFVQEATY
    61  KEVSKMVKDA LTAIEKPTGD EQSSGCLENQ LPAFLEELCH EKEILEKYGH SDCCSQSEEG
   121  RHNCFLAHKK PTPASIPLFQ VPEPVTSCEA YEEDRETFMN KFIYEIARRH PFLYAPTILL
   181  WAARYDKIIP SCCKAENAVE CFQTKAATVT KELRESSLLN QHACAVMKNF GTRTFQAITV
   241  TKLSQKFTKV NFTEIQKLVL DVAHVHEHCC RGDVLDCLQD GEKIMSYICS QQDTLSNKIT
   301  ECCKLTTLER GQCIIHAEND EKPEGLSPNL NRFLGDRDFN QFSSGEKNIF LASFVHEYSR
   361  RHPQLAVSVI LRVAKGYQEL LEKCFQTENP LECQDKGEEE LQKYIQESQA LAKRSCGLFQ
   421  KLGEYYLQNA FLVAYTKKAP QLTSSELMAI TRKMAATAAT CCQLSEDKLL ACGEGAADII
   481  IGHLCIRHEM TPVNPGVGQC CTSSYANRRP CFSSLVVDET YVPPAFSDDK FIFHKDLCQA
   541  QGVALQTMKQ EFLINLVKQK PQITEEQLEA VIADFSGLLE KCCQGQEQEV CFAEEGQKLI
   601  SKTRAALGV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AFP can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

3.4 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AFP.

Disease | AllUniProt

Conditions AFP is implicated in, by any mechanism.

• Alpha-fetoprotein deficiency (AFPD) MIM:615969
• Alpha-fetoprotein, hereditary persistence (HPAFP) MIM:615970

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 104 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Alpha-fetoprotein deficiency
• Premature ovarian failure

Disease | ImmuneIEDB

Conditions an epitope on AFP was assayed in.

• hepatocellular carcinoma T cell
• invasive ductal carcinoma T cell
• hepatitis C T cell

ReferencesPubMed · IEDB

Publications for AFP from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.91

gnomAD pLI

0

gnomAD missense Z

0.19

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic process
• homeostasis of number of cells
• immune response
• ovulation from ovarian follicle
• progesterone metabolic process
• response to nutrient levels

Molecular functions

• metal ion binding
• small molecule binding

Cellular components

• endoplasmic reticulum lumen
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• ALB/AFP/VDB
• Serum albumin, N-terminal
• Serum albumin, conserved site
• Serum albumin-like
• Serum albumin/Alpha-fetoprotein/Afamin
• Serum albumin family

KeywordsUniProt

• Copper
• Disulfide bond
• Glycoprotein
• Metal-binding
• Nickel
• Phosphoprotein
• Repeat
• Secreted
• Signal
• Sulfation