FETA_HUMAN
ID FETA_HUMAN Reviewed; 609 AA.
AC P02771; B2RBU3;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Alpha-fetoprotein;
DE AltName: Full=Alpha-1-fetoprotein;
DE AltName: Full=Alpha-fetoglobulin;
DE Flags: Precursor;
GN Name=AFP; Synonyms=HPAFP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6192439; DOI=10.1073/pnas.80.15.4604;
RA Morinaga T., Sakai M., Wegmann T.G., Tamaoki T.;
RT "Primary structures of human alpha-fetoprotein and its mRNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:4604-4608(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2436661; DOI=10.1021/bi00379a020;
RA Gibbs P.E.M., Zielinski R., Boyd C., Dugaiczyk A.;
RT "Structure, polymorphism, and novel repeated DNA elements revealed by a
RT complete sequence of the human alpha-fetoprotein gene.";
RL Biochemistry 26:1332-1343(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-570.
RC TISSUE=Heart;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28 AND 596-609, AND GENE STRUCTURE.
RX PubMed=2580830; DOI=10.1016/s0021-9258(18)89178-5;
RA Sakai M., Morinaga T., Urano Y., Watanabe K., Wegmann T.G., Tamaoki T.;
RT "The human alpha-fetoprotein gene. Sequence organization and the 5'
RT flanking region.";
RL J. Biol. Chem. 260:5055-5060(1985).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28, AND INVOLVEMENT IN HPAFP.
RX PubMed=7684942; DOI=10.1093/hmg/2.4.379;
RA McVey J.H., Michaelides K., Hansen L.P., Ferguson-Smith M., Tilghman S.,
RA Krumlauf R., Tuddenham E.G.D.;
RT "A G-->A substitution in an HNF I binding site in the human alpha-
RT fetoprotein gene is associated with hereditary persistence of alpha-
RT fetoprotein (HPAFP).";
RL Hum. Mol. Genet. 2:379-384(1993).
RN [7]
RP PROTEIN SEQUENCE OF 311-332; 348-372 AND 422-437, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 429-556.
RX PubMed=6187626; DOI=10.1016/0378-1119(82)90210-4;
RA Beattie W.G., Dugaiczyk A.;
RT "Structure and evolution of human alpha-fetoprotein deduced from partial
RT sequence of cloned cDNA.";
RL Gene 20:415-422(1982).
RN [9]
RP PROTEIN SEQUENCE OF 19-609.
RX PubMed=1709810; DOI=10.1021/bi00234a032;
RA Pucci P., Siciliano R., Malorni A., Marino G., Tecce M.F., Ceccarini C.,
RA Terrana B.;
RT "Human alpha-fetoprotein primary structure: a mass spectrometric study.";
RL Biochemistry 30:5061-5066(1991).
RN [10]
RP PRELIMINARY PROTEIN SEQUENCE OF 19-35.
RX PubMed=70228; DOI=10.1016/0005-2795(77)90198-2;
RA Yachnin S., Hsu R., Heinrikson R.L., Miller J.B.;
RT "Studies on human alpha-fetoprotein. Isolation and characterization of
RT monomeric and polymeric forms and amino-terminal sequence analysis.";
RL Biochim. Biophys. Acta 493:418-428(1977).
RN [11]
RP PRELIMINARY PROTEIN SEQUENCE OF 19-38.
RX PubMed=71198;
RA Aoyagi Y., Ikenaka T., Ichida F.;
RT "Comparative chemical structures of human alpha-fetoproteins from fetal
RT serum and from ascites fluid of a patient with hepatoma.";
RL Cancer Res. 37:3663-3667(1977).
RN [12]
RP PRELIMINARY PROTEIN SEQUENCE OF 19-39.
RX PubMed=4138095;
RA Ruoslahti E., Pihko H., Vaheri A., Seppala M., Virolainen M., Konttinen A.;
RT "Alpha fetoprotein: structure and expression in man and inbred mouse
RT strains under normal conditions and liver injury.";
RL Johns Hopkins Med. J. Suppl. 3:249-255(1974).
RN [13]
RP METAL-BINDING.
RX PubMed=80265;
RA Aoyagi Y., Ikenaka T., Ichida F.;
RT "Copper(II)-binding ability of human alpha-fetoprotein.";
RL Cancer Res. 38:3483-3486(1978).
RN [14]
RP BILIRUBIN-BINDING.
RX PubMed=89900;
RA Aoyagi Y., Ikenaka T., Ichida F.;
RT "Alpha-fetoprotein as a carrier protein in plasma and its bilirubin-binding
RT ability.";
RL Cancer Res. 39:3571-3574(1979).
RN [15]
RP SULFATION.
RX PubMed=2414772; DOI=10.1073/pnas.82.21.7160;
RA Liu M.C., Yu S., Sy J., Redman C.M., Lipmann F.;
RT "Tyrosine sulfation of proteins from the human hepatoma cell line HepG2.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:7160-7164(1985).
RN [16]
RP INVOLVEMENT IN AFPD.
RX PubMed=15280901; DOI=10.1038/sj.ejhg.5201246;
RA Sharony R., Zadik I., Parvari R.;
RT "Congenital deficiency of alpha feto-protein.";
RL Eur. J. Hum. Genet. 12:871-874(2004).
RN [17]
RP INVOLVEMENT IN AFPD.
RX PubMed=18854864; DOI=10.1038/ejhg.2008.186;
RA Petit F.M., Hebert M., Picone O., Brisset S., Maurin M.L., Parisot F.,
RA Capel L., Benattar C., Senat M.V., Tachdjian G., Labrune P.;
RT "A new mutation in the AFP gene responsible for a total absence of alpha
RT feto-protein on second trimester maternal serum screening for Down
RT syndrome.";
RL Eur. J. Hum. Genet. 17:387-390(2009).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION AT SER-111; SER-115; SER-117; SER-344; SER-444 AND SER-445.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
CC -!- FUNCTION: Binds copper, nickel, and fatty acids as well as, and
CC bilirubin less well than, serum albumin. Only a small percentage (less
CC than 2%) of the human AFP shows estrogen-binding properties.
CC -!- SUBUNIT: Dimeric and trimeric forms have been found in addition to the
CC monomeric form.
CC -!- INTERACTION:
CC P02771; PRO_0000045596 [Q99IB8]; Xeno; NbExp=2; IntAct=EBI-722498, EBI-6901449;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Plasma. Synthesized by the fetal liver and yolk
CC sac.
CC -!- DEVELOPMENTAL STAGE: Occurs in the plasma of fetuses more than 4 weeks
CC old, reaches the highest levels during the 12th-16th week of gestation,
CC and drops to trace amounts after birth. The serum level in adults is
CC usually less than 40 ng/ml. AFP occurs also at high levels in the
CC plasma and ascitic fluid of adults with hepatoma.
CC -!- PTM: Independent studies suggest heterogeneity of the N-terminal
CC sequence of the mature protein and of the cleavage site of the signal
CC sequence.
CC -!- PTM: Sulfated. {ECO:0000269|PubMed:2414772}.
CC -!- DISEASE: Alpha-fetoprotein deficiency (AFPD) [MIM:615969]: A benign
CC condition characterized by undetectable AFP levels in the amniotic
CC fluid. Affected individuals are asymptomatic and present normal
CC development. {ECO:0000269|PubMed:15280901,
CC ECO:0000269|PubMed:18854864}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Alpha-fetoprotein, hereditary persistence (HPAFP)
CC [MIM:615970]: A benign autosomal dominant condition characterized by
CC continued expression of alpha-fetoprotein in adult life.
CC {ECO:0000269|PubMed:7684942}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ALB/AFP/VDB family. {ECO:0000255|PROSITE-
CC ProRule:PRU00769}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Alpha-fetoprotein entry;
CC URL="https://en.wikipedia.org/wiki/Alpha-fetoprotein";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AFPID44248ch4q13.html";
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DR EMBL; V01514; CAA24758.1; -; mRNA.
DR EMBL; M16110; AAB58754.1; -; Genomic_DNA.
DR EMBL; AK314817; BAG37340.1; -; mRNA.
DR EMBL; BC027881; AAH27881.1; -; mRNA.
DR EMBL; M10949; AAA51674.1; -; Genomic_DNA.
DR EMBL; M10950; AAA51675.1; -; Genomic_DNA.
DR EMBL; Z19532; CAA79592.1; -; Genomic_DNA.
DR CCDS; CCDS3556.1; -.
DR PIR; A26624; FPHU.
DR RefSeq; NP_001125.1; NM_001134.2.
DR PDB; 3MRK; X-ray; 1.40 A; P=137-145.
DR PDBsum; 3MRK; -.
DR AlphaFoldDB; P02771; -.
DR SMR; P02771; -.
DR BioGRID; 106682; 19.
DR IntAct; P02771; 10.
DR STRING; 9606.ENSP00000379138; -.
DR ChEMBL; CHEMBL3712864; -.
DR GlyConnect; 41; 31 N-Linked glycans (2 sites).
DR GlyGen; P02771; 3 sites, 48 N-linked glycans (3 sites).
DR iPTMnet; P02771; -.
DR PhosphoSitePlus; P02771; -.
DR BioMuta; AFP; -.
DR DMDM; 120042; -.
DR jPOST; P02771; -.
DR MassIVE; P02771; -.
DR MaxQB; P02771; -.
DR PaxDb; P02771; -.
DR PeptideAtlas; P02771; -.
DR PRIDE; P02771; -.
DR ProteomicsDB; 51589; -.
DR TopDownProteomics; P02771; -.
DR ABCD; P02771; 16 sequenced antibodies.
DR Antibodypedia; 1359; 3533 antibodies from 57 providers.
DR DNASU; 174; -.
DR Ensembl; ENST00000395792.7; ENSP00000379138.2; ENSG00000081051.8.
DR GeneID; 174; -.
DR KEGG; hsa:174; -.
DR MANE-Select; ENST00000395792.7; ENSP00000379138.2; NM_001134.3; NP_001125.1.
DR UCSC; uc003hgz.3; human.
DR CTD; 174; -.
DR DisGeNET; 174; -.
DR GeneCards; AFP; -.
DR HGNC; HGNC:317; AFP.
DR HPA; ENSG00000081051; Tissue enriched (liver).
DR MalaCards; AFP; -.
DR MIM; 104150; gene.
DR MIM; 615969; phenotype.
DR MIM; 615970; phenotype.
DR neXtProt; NX_P02771; -.
DR OpenTargets; ENSG00000081051; -.
DR Orphanet; 168612; Congenital deficiency in alpha-fetoprotein.
DR Orphanet; 168615; Hereditary persistence of alpha-fetoprotein.
DR PharmGKB; PA24614; -.
DR VEuPathDB; HostDB:ENSG00000081051; -.
DR eggNOG; ENOG502R7EA; Eukaryota.
DR GeneTree; ENSGT00390000000113; -.
DR HOGENOM; CLU_030161_1_0_1; -.
DR InParanoid; P02771; -.
DR OMA; HEECCRG; -.
DR OrthoDB; 906547at2759; -.
DR PhylomeDB; P02771; -.
DR TreeFam; TF335561; -.
DR PathwayCommons; P02771; -.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; P02771; -.
DR SIGNOR; P02771; -.
DR BioGRID-ORCS; 174; 14 hits in 1075 CRISPR screens.
DR ChiTaRS; AFP; human.
DR GeneWiki; Alpha-fetoprotein; -.
DR GenomeRNAi; 174; -.
DR Pharos; P02771; Tbio.
DR PRO; PR:P02771; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P02771; protein.
DR Bgee; ENSG00000081051; Expressed in right lobe of liver and 110 other tissues.
DR ExpressionAtlas; P02771; baseline and differential.
DR Genevisible; P02771; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0005504; F:fatty acid binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0001542; P:ovulation from ovarian follicle; IEA:Ensembl.
DR GO; GO:0042448; P:progesterone metabolic process; IEA:Ensembl.
DR GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl.
DR CDD; cd00015; ALBUMIN; 3.
DR InterPro; IPR000264; ALB/AFP/VDB.
DR InterPro; IPR020858; Serum_albumin-like.
DR InterPro; IPR021177; Serum_albumin/AFP/Afamin.
DR InterPro; IPR020857; Serum_albumin_CS.
DR InterPro; IPR014760; Serum_albumin_N.
DR PANTHER; PTHR11385; PTHR11385; 1.
DR Pfam; PF00273; Serum_albumin; 3.
DR PIRSF; PIRSF002520; Serum_albumin_subgroup; 1.
DR PRINTS; PR00803; AFETOPROTEIN.
DR PRINTS; PR00802; SERUMALBUMIN.
DR SMART; SM00103; ALBUMIN; 3.
DR SUPFAM; SSF48552; SSF48552; 3.
DR PROSITE; PS00212; ALBUMIN_1; 2.
DR PROSITE; PS51438; ALBUMIN_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Copper; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Metal-binding; Nickel; Phosphoprotein; Reference proteome;
KW Repeat; Secreted; Signal; Sulfation.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:1709810"
FT CHAIN 19..609
FT /note="Alpha-fetoprotein"
FT /id="PRO_0000001097"
FT DOMAIN 19..210
FT /note="Albumin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00769"
FT DOMAIN 211..402
FT /note="Albumin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00769"
FT DOMAIN 403..601
FT /note="Albumin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00769"
FT BINDING 22
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /evidence="ECO:0000269|PubMed:80265"
FT MOD_RES 111
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 115
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 117
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 344
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 444
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 445
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 251
FT /note="N-linked (GlcNAc...) asparagine"
FT /id="CAR_000070"
FT DISULFID 99..114
FT DISULFID 113..124
FT DISULFID 148..193
FT DISULFID 192..201
FT DISULFID 224..270
FT DISULFID 269..277
FT DISULFID 289..303
FT DISULFID 302..313
FT DISULFID 384..393
FT DISULFID 416..462
FT DISULFID 461..472
FT DISULFID 485..501
FT DISULFID 500..511
FT DISULFID 538..583
FT DISULFID 582..591
FT VARIANT 187
FT /note="K -> Q (in dbSNP:rs35765619)"
FT /id="VAR_033928"
FT VARIANT 570
FT /note="A -> G (in dbSNP:rs7790)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_012049"
SQ SEQUENCE 609 AA; 68678 MW; 4D4E45820E1C2D4F CRC64;
MKWVESIFLI FLLNFTESRT LHRNEYGIAS ILDSYQCTAE ISLADLATIF FAQFVQEATY
KEVSKMVKDA LTAIEKPTGD EQSSGCLENQ LPAFLEELCH EKEILEKYGH SDCCSQSEEG
RHNCFLAHKK PTPASIPLFQ VPEPVTSCEA YEEDRETFMN KFIYEIARRH PFLYAPTILL
WAARYDKIIP SCCKAENAVE CFQTKAATVT KELRESSLLN QHACAVMKNF GTRTFQAITV
TKLSQKFTKV NFTEIQKLVL DVAHVHEHCC RGDVLDCLQD GEKIMSYICS QQDTLSNKIT
ECCKLTTLER GQCIIHAEND EKPEGLSPNL NRFLGDRDFN QFSSGEKNIF LASFVHEYSR
RHPQLAVSVI LRVAKGYQEL LEKCFQTENP LECQDKGEEE LQKYIQESQA LAKRSCGLFQ
KLGEYYLQNA FLVAYTKKAP QLTSSELMAI TRKMAATAAT CCQLSEDKLL ACGEGAADII
IGHLCIRHEM TPVNPGVGQC CTSSYANRRP CFSSLVVDET YVPPAFSDDK FIFHKDLCQA
QGVALQTMKQ EFLINLVKQK PQITEEQLEA VIADFSGLLE KCCQGQEQEV CFAEEGQKLI
SKTRAALGV