P02771 (FETA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	SMAD protein signal transduction Inferred from electronic annotation. Source: Compara ovulation from ovarian follicle Inferred from electronic annotation. Source: Compara progesterone metabolic process Inferred from electronic annotation. Source: Compara transport Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: Compara
Molecular_function	metal 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.9 Ref.10 Ref.11 Ref.12
	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. Corresponds to variant rs35765619 [ dbSNP | Ensembl ].		VAR_033928
	Natural variant	570	1	A → G. Ref.3 Corresponds to variant rs7790 [ dbSNP | Ensembl ].		VAR_012049

Sequences

	Sequence		Length	Mass (Da)
	P02771 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28 AND 596-609, GENE STRUCTURE.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
[7]	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.
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 429-556.
[9]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-609.
[10]	"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] [Europe PMC] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 19-35.
[11]	"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] [Europe PMC] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 19-38.
[12]	"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] [Europe PMC] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 19-39.
[13]	"Copper(II)-binding ability of human alpha-fetoprotein." Aoyagi Y., Ikenaka T., Ichida F. Cancer Res. 38:3483-3486(1978) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: SULFATION.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

Wikipedia

Alpha-fetoprotein entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

V01514 mRNA. Translation: CAA24758.1.
M16110 Genomic DNA. Translation: AAB58754.1.
AK314817 mRNA. Translation: BAG37340.1.
BC027881 mRNA. Translation: AAH27881.1.
M10949 Genomic DNA. Translation: AAA51674.1.
M10950 Genomic DNA. Translation: AAA51675.1.
Z19532 Genomic DNA. Translation: CAA79592.1.

IPI

IPI00022443.

PIR

FPHU. A26624.

RefSeq

NP_001125.1. NM_001134.1.

UniGene

Hs.518808.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3MRK	X-ray	1.40	P	137-145	[»]

ProteinModelPortal

P02771.

ModBase

Search...

Protein-protein interaction databases

IntAct

P02771. 9 interactions.

MINT

MINT-1401527.

STRING

9606.ENSP00000226359.

PTM databases

GlycoSuiteDB

P02771.

PhosphoSite

P02771.

Polymorphism databases

DMDM

120042.

Proteomic databases

PaxDb

P02771.

PeptideAtlas

P02771.

PRIDE

P02771.

Protocols and materials databases

DNASU

174.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000395792; ENSP00000379138; ENSG00000081051.

GeneID

174.

KEGG

hsa:174.

UCSC

uc003hgz.1. human.

Organism-specific databases

CTD

174.

GeneCards

GC04P074298.

HGNC

HGNC:317. AFP.

HPA

CAB024283.
CAB025339.
HPA010607.
HPA023600.

MIM

104150. gene+phenotype.

neXtProt

NX_P02771.

Orphanet

168612. Congenital deficiency in alpha-fetoprotein.
168615. Hereditary persistence of alpha-fetoprotein.

PharmGKB

PA24614.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG45992.

HOGENOM

HOG000293137.

HOVERGEN

HBG004207.

InParanoid

P02771.

KO

K16144.

OrthoDB

EOG44F68N.

PhylomeDB

P02771.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.

Gene expression databases

Bgee

P02771.

CleanEx

HS_AFP.

Genevestigator

P02771.

GermOnline

ENSG00000081051. Homo sapiens.

Family and domain databases

InterPro

IPR000264. ALB/AFP/VDB.
IPR001703. Alpha-fetoprotein.
IPR020858. Serum_albumin-like.
IPR021177. Serum_albumin/AFP.
IPR020857. Serum_albumin_CS.
IPR014760. Serum_albumin_N.
[Graphical view]

Pfam

PF00273. Serum_albumin. 3 hits.
[Graphical view]

PIRSF

PIRSF002520. Serum_albumin_subgroup. 1 hit.

PRINTS

PR00803. AFETOPROTEIN.
PR00802. SERUMALBUMIN.

SMART

SM00103. ALBUMIN. 3 hits.
[Graphical view]

SUPFAM

SSF48552. Serum_albumin. 3 hits.

PROSITE

PS00212. ALBUMIN_1. 2 hits.
PS51438. ALBUMIN_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

AFP. human.

GenomeRNAi

174.

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:	May 29, 2013
This is version 142 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.