Reviewed, UniProtKB/Swiss-Prot P02771 (FETA_HUMAN)

Names and origin

Protein names

Recommended name:
    Alpha-fetoprotein
Alternative name(s):
    Alpha-1-fetoprotein
    Alpha-fetoglobulin

Gene names

Name:	AFP
Synonyms:	HPAFP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	609 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties.
Subunit structure	Dimeric and trimeric forms have been found in addition to the monomeric form.
Subcellular location	Secreted.
Tissue specificity	Plasma. Synthesized by the fetal liver and yolk sac.
Developmental stage	Occurs in the plasma of fetuses more than 4 weeks old, reaches the highest levels during the 12th-16th week of gestation, and drops to trace amounts after birth. The serum level in adults is usually less than 40 ng/ml. AFP occurs also at high levels in the plasma and ascitic fluid of adults with hepatoma.
Post-translational modification	Independent studies suggest heterogeneity of the N-terminal sequence of the mature protein and of the cleavage site of the signal sequence. Sulfated.
Sequence similarities	Belongs to the ALB/AFP/VDB family. Contains 3 albumin domains.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
Ligand	Copper Metal-binding Nickel
PTM	Disulfide bond Glycoprotein Sulfation
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	transport Inferred from electronic annotation. Source: InterPro
Molecular function	copper ion binding Inferred from electronic annotation. Source: UniProtKB-KW nickel ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Ref.8 Ref.9 Ref.10 Ref.11
	Chain	19 – 609	591	Alpha-fetoprotein		PRO_0000001097
Regions
	Domain	19 – 210	192	Albumin 1
	Domain	211 – 402	192	Albumin 2
	Domain	403 – 601	199	Albumin 3
Sites
	Metal binding	22	1	Copper or nickel Ref.13
Amino acid modifications
	Glycosylation	251	1	N-linked (GlcNAc...)		CAR_000070
	Disulfide bond	99 ↔ 114
	Disulfide bond	113 ↔ 124
	Disulfide bond	148 ↔ 193
	Disulfide bond	192 ↔ 201
	Disulfide bond	224 ↔ 270
	Disulfide bond	269 ↔ 277
	Disulfide bond	289 ↔ 303
	Disulfide bond	302 ↔ 313
	Disulfide bond	384 ↔ 393
	Disulfide bond	416 ↔ 462
	Disulfide bond	461 ↔ 472
	Disulfide bond	485 ↔ 501
	Disulfide bond	500 ↔ 511
	Disulfide bond	538 ↔ 583
	Disulfide bond	582 ↔ 591
Natural variations
	Natural variant	187	1	K → Q: dbSNP rs35765619.		VAR_033928
	Natural variant	570	1	A → G: dbSNP rs7790. Ref.3		VAR_012049

Sequences

	Sequence		Length	Mass (Da)
	P02771-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 4D4E45820E1C2D4F	FASTA	609	68,678
	10 20 30 40 50 60 MKWVESIFLI FLLNFTESRT LHRNEYGIAS ILDSYQCTAE ISLADLATIF FAQFVQEATY 70 80 90 100 110 120 KEVSKMVKDA LTAIEKPTGD EQSSGCLENQ LPAFLEELCH EKEILEKYGH SDCCSQSEEG 130 140 150 160 170 180 RHNCFLAHKK PTPASIPLFQ VPEPVTSCEA YEEDRETFMN KFIYEIARRH PFLYAPTILL 190 200 210 220 230 240 WAARYDKIIP SCCKAENAVE CFQTKAATVT KELRESSLLN QHACAVMKNF GTRTFQAITV 250 260 270 280 290 300 TKLSQKFTKV NFTEIQKLVL DVAHVHEHCC RGDVLDCLQD GEKIMSYICS QQDTLSNKIT 310 320 330 340 350 360 ECCKLTTLER GQCIIHAEND EKPEGLSPNL NRFLGDRDFN QFSSGEKNIF LASFVHEYSR 370 380 390 400 410 420 RHPQLAVSVI LRVAKGYQEL LEKCFQTENP LECQDKGEEE LQKYIQESQA LAKRSCGLFQ 430 440 450 460 470 480 KLGEYYLQNA FLVAYTKKAP QLTSSELMAI TRKMAATAAT CCQLSEDKLL ACGEGAADII 490 500 510 520 530 540 IGHLCIRHEM TPVNPGVGQC CTSSYANRRP CFSSLVVDET YVPPAFSDDK FIFHKDLCQA 550 560 570 580 590 600 QGVALQTMKQ EFLINLVKQK PQITEEQLEA VIADFSGLLE KCCQGQEQEV CFAEEGQKLI SKTRAALGV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structures of human alpha-fetoprotein and its mRNA." Morinaga T., Sakai M., Wegmann T.G., Tamaoki T. Proc. Natl. Acad. Sci. U.S.A. 80:4604-4608(1983) [PubMed: 6192439] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure, polymorphism, and novel repeated DNA elements revealed by a complete sequence of the human alpha-fetoprotein gene." Gibbs P.E.M., Zielinski R., Boyd C., Dugaiczyk A. Biochemistry 26:1332-1343(1987) [PubMed: 2436661] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-570. Tissue: Heart.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[5]	"A G-->A substitution in an HNF I binding site in the human alpha-fetoprotein gene is associated with hereditary persistence of alpha-fetoprotein (HPAFP)." McVey J.H., Michaelides K., Hansen L.P., Ferguson-Smith M., Tilghman S., Krumlauf R., Tuddenham E.G.D. Hum. Mol. Genet. 2:379-384(1993) [PubMed: 7684942] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
[6]	Lubec G., Vishwanath V. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 311-332; 348-372 AND 422-437, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[7]	"Structure and evolution of human alpha-fetoprotein deduced from partial sequence of cloned cDNA." Beattie W.G., Dugaiczyk A. Gene 20:415-422(1982) [PubMed: 6187626] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 429-556.
[8]	"Human alpha-fetoprotein primary structure: a mass spectrometric study." Pucci P., Siciliano R., Malorni A., Marino G., Tecce M.F., Ceccarini C., Terrana B. Biochemistry 30:5061-5066(1991) [PubMed: 1709810] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 19-609.
[9]	"Studies on human alpha-fetoprotein. Isolation and characterization of monomeric and polymeric forms and amino-terminal sequence analysis." Yachnin S., Hsu R., Heinrikson R.L., Miller J.B. Biochim. Biophys. Acta 493:418-428(1977) [PubMed: 70228] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 19-35.
[10]	"Comparative chemical structures of human alpha-fetoproteins from fetal serum and from ascites fluid of a patient with hepatoma." Aoyagi Y., Ikenaka T., Ichida F. Cancer Res. 37:3663-3667(1977) [PubMed: 71198] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 19-38.
[11]	"Alpha fetoprotein: structure and expression in man and inbred mouse strains under normal conditions and liver injury." Ruoslahti E., Pihko H., Vaheri A., Seppala M., Virolainen M., Konttinen A. Johns Hopkins Med. J. Suppl. 3:249-255(1974) [PubMed: 4138095] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 19-39.
[12]	"The human alpha-fetoprotein gene. Sequence organization and the 5' flanking region." Sakai M., Morinaga T., Urano Y., Watanabe K., Wegmann T.G., Tamaoki T. J. Biol. Chem. 260:5055-5060(1985) [PubMed: 2580830] [Abstract] Cited for: GENE STRUCTURE.
[13]	"Copper(II)-binding ability of human alpha-fetoprotein." Aoyagi Y., Ikenaka T., Ichida F. Cancer Res. 38:3483-3486(1978) [PubMed: 80265] [Abstract] Cited for: METAL-BINDING.
[14]	"Alpha-fetoprotein as a carrier protein in plasma and its bilirubin-binding ability." Aoyagi Y., Ikenaka T., Ichida F. Cancer Res. 39:3571-3574(1979) [PubMed: 89900] [Abstract] Cited for: BILIRUBIN-BINDING.
[15]	"Tyrosine sulfation of proteins from the human hepatoma cell line HepG2." Liu M.C., Yu S., Sy J., Redman C.M., Lipmann F. Proc. Natl. Acad. Sci. U.S.A. 82:7160-7164(1985) [PubMed: 2414772] [Abstract] Cited for: SULFATION.
+	Additional computationally mapped references.

Web resources

Wikipedia

Alpha-fetoprotein entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	M10949 Genomic DNA. Translation: AAA51674.1. M10950 Genomic DNA. Translation: AAA51675.1. V01514 mRNA. Translation: CAA24758.1. M16110 Genomic DNA. Translation: AAB58754.1. AK314817 mRNA. Translation: BAG37340.1. BC027881 mRNA. Translation: AAH27881.1. Z19532 Genomic DNA. Translation: CAA79592.1.
IPI	IPI00022443.
PIR	FPHU. A26624.
RefSeq	NP_001125.1.
UniGene	Hs.518808
3D structure databases
HSSP	HSSP built from PDB template 1E7B based on UniProtKB P02768.
ModBase	Search...
Protein-protein interaction databases
IntAct	P02771. 2 interactions.
PTM databases
GlycoSuiteDB	P02771.
PhosphoSite	P02771.
2-D gel databases
Siena-2DPAGE	P02771.
Proteomic databases
PeptideAtlas	P02771.
PRIDE	P02771.
Genome annotation databases
Ensembl	ENSG00000081051. Homo sapiens. [Contig view]
GeneID	174.
KEGG	hsa:174.
Organism-specific databases
GeneCards	GC04P074541.
H-InvDB	HIX0004279.
HGNC	HGNC:317. AFP.
HPA	HPA010607.
MIM	104150. gene+phenotype.
Orphanet	168612. Congenital deficiency in alpha-fetoprotein. 168615. Hereditary persistence of alpha-fetoprotein.
PharmGKB	PA24614.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P02771.
HOVERGEN	P02771.
OMA	P02771. FHKDLCQ.
Enzyme and pathway databases
Pathway_Interaction_DB	hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
Gene expression databases
ArrayExpress	P02771.
Bgee	P02771.
CleanEx	HS_AFP.
GermOnline	ENSG00000081051. Homo sapiens.
Family and domain databases
InterPro	IPR001703. Alpha-fetoprotein. IPR000264. Serum_albumin. IPR014760. Serum_albumin_N. [Graphical view]
Pfam	PF00273. Serum_albumin. 3 hits. [Graphical view]
PRINTS	PR00803. AFETOPROTEIN. PR00802. SERUMALBUMIN.
ProDom	PD002486. Serum_albumin. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00103. ALBUMIN. 3 hits. [Graphical view]
PROSITE	PS00212. ALBUMIN_1. 2 hits. PS51438. ALBUMIN_2. 3 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	698.
SOURCE	Search...

Entry information

Entry name

FETA_HUMAN

Accession

Primary (citable) accession number: P02771
Secondary accession number(s): B2RBU3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	June 16, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)