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   08-MAR-2011, entry version 122.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=83273664; 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   MEDLINE=87185438; 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
RT   a 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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
RT   project: 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
RP   STRUCTURE.
RX   MEDLINE=85182629; PubMed=2580830;
RA   Sakai M., Morinaga T., Urano Y., Watanabe K., Wegmann T.G.,
RA   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.
RX   MEDLINE=93278385; PubMed=7684942; DOI=10.1093/hmg/2.4.379;
RA   McVey J.H., Michaelides K., Hansen L.P., Ferguson-Smith M.,
RA   Tilghman S., 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 MASS
RP   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   MEDLINE=83158778; 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
RT   partial sequence of cloned cDNA.";
RL   Gene 20:415-422(1982).
RN   [9]
RP   PARTIAL PROTEIN SEQUENCE OF 19-609.
RX   MEDLINE=91242409; PubMed=1709810; DOI=10.1021/bi00234a032;
RA   Pucci P., Siciliano R., Malorni A., Marino G., Tecce M.F.,
RA   Ceccarini C., Terrana B.;
RT   "Human alpha-fetoprotein primary structure: a mass spectrometric
RT   study.";
RL   Biochemistry 30:5061-5066(1991).
RN   [10]
RP   PRELIMINARY PROTEIN SEQUENCE OF 19-35.
RX   MEDLINE=77242506; 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   MEDLINE=78001760; PubMed=71198;
RA   Aoyagi Y., Ikenaka T., Ichida F.;
RT   "Comparative chemical structures of human alpha-fetoproteins from
RT   fetal 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   MEDLINE=75018719; PubMed=4138095;
RA   Ruoslahti E., Pihko H., Vaheri A., Seppala M., Virolainen M.,
RA   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   MEDLINE=79001617; 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   MEDLINE=80001710; PubMed=89900;
RA   Aoyagi Y., Ikenaka T., Ichida F.;
RT   "Alpha-fetoprotein as a carrier protein in plasma and its bilirubin-
RT   binding ability.";
RL   Cancer Res. 39:3571-3574(1979).
RN   [15]
RP   SULFATION.
RX   MEDLINE=86042625; 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
RT   HepG2.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:7160-7164(1985).
CC   -!- FUNCTION: Binds copper, nickel, and fatty acids as well as, and
CC       bilirubin less well than, serum albumin. Only a small percentage
CC       (less than 2%) of the human AFP shows estrogen-binding properties.
CC   -!- SUBUNIT: Dimeric and trimeric forms have been found in addition to
CC       the monomeric form.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Plasma. Synthesized by the fetal liver and
CC       yolk sac.
CC   -!- DEVELOPMENTAL STAGE: Occurs in the plasma of fetuses more than 4
CC       weeks old, reaches the highest levels during the 12th-16th week of
CC       gestation, and drops to trace amounts after birth. The serum level
CC       in adults is usually less than 40 ng/ml. AFP occurs also at high
CC       levels in the 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
CC       signal sequence.
CC   -!- PTM: Sulfated.
CC   -!- SIMILARITY: Belongs to the ALB/AFP/VDB family.
CC   -!- SIMILARITY: Contains 3 albumin domains.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Alpha-fetoprotein entry;
CC       URL="http://en.wikipedia.org/wiki/Alpha-fetoprotein";
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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   IPI; IPI00022443; -.
DR   PIR; A26624; FPHU.
DR   RefSeq; NP_001125.1; NM_001134.1.
DR   UniGene; Hs.518808; -.
DR   ProteinModelPortal; P02771; -.
DR   SMR; P02771; 26-608.
DR   IntAct; P02771; 3.
DR   MINT; MINT-1401527; -.
DR   STRING; P02771; -.
DR   GlycoSuiteDB; P02771; -.
DR   PhosphoSite; P02771; -.
DR   Siena-2DPAGE; P02771; -.
DR   PeptideAtlas; P02771; -.
DR   PRIDE; P02771; -.
DR   Ensembl; ENST00000226359; ENSP00000226359; ENSG00000081051.
DR   Ensembl; ENST00000395792; ENSP00000379138; ENSG00000081051.
DR   GeneID; 174; -.
DR   KEGG; hsa:174; -.
DR   UCSC; uc003hgz.1; human.
DR   CTD; 174; -.
DR   GeneCards; GC04P074291; -.
DR   H-InvDB; HIX0200653; -.
DR   HGNC; HGNC:317; AFP.
DR   HPA; CAB024283; -.
DR   HPA; CAB025339; -.
DR   HPA; HPA010607; -.
DR   HPA; HPA023600; -.
DR   MIM; 104150; gene+phenotype.
DR   neXtProt; NX_P02771; -.
DR   Orphanet; 168612; Congenital deficiency in alpha-fetoprotein.
DR   Orphanet; 168615; Hereditary persistence of alpha-fetoprotein.
DR   PharmGKB; PA24614; -.
DR   eggNOG; prNOG05991; -.
DR   GeneTree; ENSGT00390000000113; -.
DR   HOGENOM; HBG283181; -.
DR   HOVERGEN; HBG004207; -.
DR   InParanoid; P02771; -.
DR   OMA; FHKDLCQ; -.
DR   OrthoDB; EOG44F68N; -.
DR   PhylomeDB; P02771; -.
DR   Pathway_Interaction_DB; hnf3bpathway; FOXA2 and FOXA3 transcription factor networks.
DR   NextBio; 698; -.
DR   ArrayExpress; P02771; -.
DR   Bgee; P02771; -.
DR   CleanEx; HS_AFP; -.
DR   Genevestigator; P02771; -.
DR   GermOnline; ENSG00000081051; Homo sapiens.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006810; P:transport; IEA:InterPro.
DR   InterPro; IPR001703; Alpha-fetoprotein.
DR   InterPro; IPR000264; Serum_albumin.
DR   InterPro; IPR020858; Serum_albumin-like.
DR   InterPro; IPR020857; Serum_albumin_CS.
DR   InterPro; IPR014760; Serum_albumin_N.
DR   InterPro; IPR021177; Serum_albumin_subgroup.
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; Serum_albumin; 3.
DR   PROSITE; PS00212; ALBUMIN_1; 2.
DR   PROSITE; PS51438; ALBUMIN_2; 3.
PE   1: Evidence at protein level;
KW   Complete proteome; Copper; Direct protein sequencing; Disulfide bond;
KW   Glycoprotein; Metal-binding; Nickel; Polymorphism; Repeat; Secreted;
KW   Signal; Sulfation.
FT   SIGNAL        1     18
FT   CHAIN        19    609       Alpha-fetoprotein.
FT                                /FTId=PRO_0000001097.
FT   DOMAIN       19    210       Albumin 1.
FT   DOMAIN      211    402       Albumin 2.
FT   DOMAIN      403    601       Albumin 3.
FT   METAL        22     22       Copper or nickel.
FT   CARBOHYD    251    251       N-linked (GlcNAc...).
FT                                /FTId=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    187       K -> Q (in dbSNP:rs35765619).
FT                                /FTId=VAR_033928.
FT   VARIANT     570    570       A -> G (in dbSNP:rs7790).
FT                                /FTId=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
//