Reviewed, UniProtKB/Swiss-Prot P02765 (FETUA_HUMAN)

Names and origin

Protein names

Recommended name:
    Alpha-2-HS-glycoprotein
Alternative name(s):
    Ba-alpha-2-glycoprotein
    Alpha-2-Z-globulin
    Fetuin-A
Cleaved into the following 2 chains:
    1- Recommended name:
            Alpha-2-HS-glycoprotein chain A
    2- Recommended name:
            Alpha-2-HS-glycoprotein chain B

Gene names

Name:	AHSG
Synonyms:	FETUA
ORF Names:	PRO2743

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	367 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	Promotes endocytosis, possesses opsonic properties and influences the mineral phase of bone. Shows affinity for calcium and barium ions.
Subunit structure	Alpha-2-HS glycoprotein derives from this precursor, when the connecting peptide is cleaved off. The two chains A and B are held together by a single disulfide bond.
Subcellular location	Secreted.
Tissue specificity	Synthesized in liver and selectively concentrated in bone matrix. Secrete din plasma. It is also found in dentin in much higher quantities than other plasma proteins.
Polymorphism	There are two common alleles, AHSG*1 and AHSG*2. AHSG*1 has Thr-248/Thr-256; AHSG*2 has Met-248/Ser-256.
Sequence similarities	Belongs to the fetuin family. Contains 2 cystatin domains.

Ontologies

Keywords
Biological process	Mineral balance
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	acute-phase response Inferred from direct assay. Source: UniProtKB negative regulation of bone mineralization Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of insulin receptor signaling pathway Non-traceable author statement. Source: UniProtKB pinocytosis Non-traceable author statement. Source: UniProtKB positive regulation of phagocytosis Inferred from direct assay. Source: UniProtKB regulation of inflammatory response Inferred from mutant phenotype. Source: UniProtKB
Cellular component	extracellular space Non-traceable author statement. Source: UniProtKB
Molecular function	cysteine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-1223374,EBI-375543

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Ref.7 Ref.8
	Chain	19 – 300	282	Alpha-2-HS-glycoprotein chain A Ref.7		PRO_0000008887
	Propeptide	301 – 340	40	Connecting peptide Ref.12		PRO_0000008888
	Chain	341 – 367	27	Alpha-2-HS-glycoprotein chain B		PRO_0000008889
Regions
	Domain	27 – 144	118	Cystatin 1
	Domain	145 – 260	116	Cystatin 2
Amino acid modifications
	Modified residue	138	1	Phosphoserine Ref.15 Ref.20 Ref.21 Ref.22
	Modified residue	325	1	Phosphoserine By similarity
	Modified residue	328	1	Phosphoserine By similarity
	Modified residue	330	1	Phosphoserine Ref.15
	Glycosylation	156	1	N-linked (GlcNAc...) Ref.17 Ref.18 Ref.19		CAR_000064
	Glycosylation	176	1	N-linked (GlcNAc...) Ref.18 Ref.19 Ref.16		CAR_000065
	Glycosylation	256	1	O-linked (GalNAc...)		CAR_000066
	Glycosylation	270	1	O-linked (GalNAc...)		CAR_000067
	Glycosylation	346	1	O-linked (GalNAc...)		CAR_000068
	Disulfide bond	32 ↔ 358		Interchain (between A and B chains) Ref.13 Ref.14
	Disulfide bond	89 ↔ 100		Ref.13 Ref.14
	Disulfide bond	114 ↔ 132		Ref.13 Ref.14
	Disulfide bond	146 ↔ 149		Ref.13 Ref.14
	Disulfide bond	208 ↔ 219		Ref.13 Ref.14
	Disulfide bond	230 ↔ 247		Ref.13 Ref.14
Natural variations
	Natural variant	142	1	V → L: dbSNP rs7633550.		VAR_055802
	Natural variant	248	1	T → M in allele AHSG*2. dbSNP rs4917. Ref.9		VAR_002388
	Natural variant	256	1	T → S in allele AHSG*2. dbSNP rs4918. Ref.9 Ref.4		VAR_002389
	Natural variant	276	1	D → N in allele AHSG*5. Ref.3		VAR_012474
	Natural variant	317	1	R → C in allele AHSG*3. Ref.3		VAR_012475
Experimental info
	Sequence conflict	16	1	C → W in BAA22652. Ref.2
	Sequence conflict	54	1	W → K AA sequence Ref.7
	Sequence conflict	125	1	F → S in BAA22651. Ref.9
	Sequence conflict	150 – 182	33	PLLAP…SNFQL → MVGWQEGANHKNGAGRSQKQ EMAEKMVPEVASG in AAF69649. Ref.11
	Sequence conflict	204	1	S → C in BAA22652. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P02765-1 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: 1AAF0C8D6B7E2789	FASTA	367	39,325
	10 20 30 40 50 60 MKSLVLLLCL AQLWGCHSAP HGPGLIYRQP NCDDPETEEA ALVAIDYINQ NLPWGYKHTL 70 80 90 100 110 120 NQIDEVKVWP QQPSGELFEI EIDTLETTCH VLDPTPVARC SVRQLKEHAV EGDCDFQLLK 130 140 150 160 170 180 LDGKFSVVYA KCDSSPDSAE DVRKVCQDCP LLAPLNDTRV VHAAKAALAA FNAQNNGSNF 190 200 210 220 230 240 QLEEISRAQL VPLPPSTYVE FTVSGTDCVA KEATEAAKCN LLAEKQYGFC KATLSEKLGG 250 260 270 280 290 300 AEVAVTCTVF QTQPVTSQPQ PEGANEAVPT PVVDPDAPPS PPLGAPGLPP AGSPPDSHVL 310 320 330 340 350 360 LAAPPGHQLH RAHYDLRHTF MGVVSLGSPS GEVSHPRKTR TVVQPSVGAA AGPVVPPCPG RIRHFKV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human alpha 2-HS-glycoprotein: the A and B chains with a connecting sequence are encoded by a single mRNA transcript." Lee C.-C., Bowman B.H., Yang F. Proc. Natl. Acad. Sci. U.S.A. 84:4403-4407(1987) [PubMed: 3474608] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure of the gene encoding human alpha 2-HS glycoprotein (AHSG)." Osawa M., Umetsu K., Sato M., Ohki T., Yukawa N., Suzuki T., Takeichi S. Gene 196:121-125(1997) [PubMed: 9322749] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"Haplotype analysis of the human alpha2-HS glycoprotein (fetuin) gene." Osawa M., Yuasa I., Kitano T., Henke J., Kaneko M., Udono T., Saitou N., Umetsu K. Ann. Hum. Genet. 65:27-34(2001) [PubMed: 11415520] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS AHSG*5 ASN-276 AND AHSG*3 CYS-317.
[4]	"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 SER-256. Tissue: Liver.
[5]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Liver.
[7]	"The complete amino acid sequence of the A-chain of human plasma alpha 2HS-glycoprotein." Yoshioka Y., Gejyo F., Marti T., Rickli E.E., Burgi W., Offner G.D., Troxler R.F., Schmid K. J. Biol. Chem. 261:1665-1676(1986) [PubMed: 3944104] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-300.
[8]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-28. Tissue: Platelet.
[9]	"Molecular evidence for human alpha 2-HS glycoprotein (AHSG) polymorphism." Osawa M., Umetsu K., Ohki T., Nagasawa T., Suzuki T., Takeichi S. Hum. Genet. 99:18-21(1997) [PubMed: 9003486] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 34-367, VARIANTS ALLELE AHSG*2 MET-248 AND SER-256. Tissue: Liver.
[10]	Lubec G., Vishwanath V. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 107-120, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[11]	"Functional prediction of the coding sequences of 79 new genes deduced by analysis of cDNA clones from human fetal liver." Zhang C., Yu Y., Zhang S., Wei H., Zhang Y., Zhou G., Bi J., Liu M., He F. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 150-367. Tissue: Fetal liver.
[12]	"Characterization of the B-chain of human plasma alpha 2HS-glycoprotein. The complete amino acid sequence and primary structure of its heteroglycan." Gejyo F., Chang J.-L., Burgi W., Schmid K., Offner G.D., Troxler R.F., van Halbeek H., Dorland L., Gerwig G.J., Vliegenthart J.F.G. J. Biol. Chem. 258:4966-4971(1983) [PubMed: 6833285] [Abstract] Cited for: PROTEIN SEQUENCE OF 341-367.
[13]	"The position of the disulfide bonds in human plasma alpha 2 HS-glycoprotein and the repeating double disulfide bonds in the domain structure." Araki T., Yoshioka Y., Schmid K. Biochim. Biophys. Acta 994:195-199(1989) [PubMed: 2645941] [Abstract] Cited for: DISULFIDE BONDS.
[14]	"The arrangement of disulfide loops in human alpha 2-HS glycoprotein. Similarity to the disulfide bridge structures of cystatins and kininogens." Kellerman J., Haupt H., Auerswald E.-A., Mueller-Esterl W. J. Biol. Chem. 264:14121-14128(1989) [PubMed: 2760061] [Abstract] Cited for: DISULFIDE BONDS.
[15]	"Phosphorylation of human plasma alpha2-Heremans-Schmid glycoprotein (human fetuin) in vivo." Haglund A.C., Ek B., Ek P. Biochem. J. 357:437-445(2001) [PubMed: 11439093] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, PHOSPHORYLATION AT SER-138 AND SER-330. Tissue: Plasma.
[16]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed: 12754519] [Abstract] Cited for: GLYCOSYLATION AT ASN-176.
[17]	"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry." Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R. Proteomics 4:454-465(2004) [PubMed: 14760718] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156, MASS SPECTROMETRY. Tissue: Plasma.
[18]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156 AND ASN-176, MASS SPECTROMETRY. Tissue: Plasma.
[19]	"Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry." Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A. J. Proteome Res. 5:1493-1503(2006) [PubMed: 16740002] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156 AND ASN-176, MASS SPECTROMETRY. Tissue: Saliva.
[20]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, MASS SPECTROMETRY. Tissue: Platelet.
[21]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, MASS SPECTROMETRY.
[22]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, MASS SPECTROMETRY. Tissue: Liver.
[23]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[24]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M16961 mRNA. Translation: AAA51683.1. D67013 Genomic DNA. Translation: BAA22652.1. AB038689 Genomic DNA. Translation: BAA92189.1. AK292751 mRNA. Translation: BAF85440.1. AC068631 Genomic DNA. No translation available. BC048198 mRNA. Translation: AAH48198.1. BC052590 mRNA. Translation: AAH52590.1. D67012 mRNA. Translation: BAA22651.1. AF119895 mRNA. Translation: AAF69649.1.
IPI	IPI00022431.
PIR	WOHU. A29081.
RefSeq	NP_001613.2.
UniGene	Hs.324746
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P02765. 5 interactions.
Protein family/group databases
MEROPS	I25.020. I25.021.
PTM databases
GlycoSuiteDB	P02765.
PhosphoSite	P02765.
2-D gel databases
SWISS-2DPAGE	P02765.
DOSAC-COBS-2DPAGE	P02765.
Siena-2DPAGE	P02765.
Proteomic databases
PRIDE	P02765.
Genome annotation databases
Ensembl	ENSG00000145192. Homo sapiens. [Contig view]
GeneID	197.
KEGG	hsa:197.
Organism-specific databases
GeneCards	GC03P187813.
H-InvDB	HIX0024338.
HGNC	HGNC:349. AHSG.
HPA	HPA001524. HPA001525.
MIM	138680. gene.
PharmGKB	PA24642.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P02765.
HOVERGEN	P02765.
Enzyme and pathway databases
Pathway_Interaction_DB	bmppathway. BMP receptor signaling.
Gene expression databases
ArrayExpress	P02765.
Bgee	P02765.
CleanEx	HS_AHSG.
GermOnline	ENSG00000145192. Homo sapiens.
Family and domain databases
InterPro	IPR000010. Prot_inh_cystat. IPR001363. Prot_inh_fetuin_CS. [Graphical view]
Pfam	PF00031. Cystatin. 1 hit. [Graphical view]
SMART	SM00043. CY. 2 hits. [Graphical view]
PROSITE	PS01254. FETUIN_1. 1 hit. PS01255. FETUIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	790.
PMAP-CutDB	P02765.
SOURCE	Search...

Entry information

Entry name

FETUA_HUMAN

Accession

Primary (citable) accession number: P02765
Secondary accession number(s): A8K9N6 , O14961, O14962, Q9P152

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	April 1, 1988
Last modified:	May 26, 2009
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)