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UniProtKB/Swiss-Prot entry P02765


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name FETUA_HUMAN
Primary accession number P02765
Secondary accession numbers O14961 O14962 Q9P152
Integrated into Swiss-Prot on July 21, 1986
Sequence was last modified on April 1, 1988 (Sequence version 1)
Annotations were last modified on    September 2, 2008 (Entry version 108)
Name and origin of the protein
Protein name Alpha-2-HS-glycoprotein [Precursor]
Synonyms Ba-alpha-2-glycoprotein
Alpha-2-Z-globulin
Fetuin-A
Contains Alpha-2-HS-glycoprotein chain A
Alpha-2-HS-glycoprotein chain B
Gene name
Name: AHSG
Synonyms: FETUA
ORFNames: PRO2743
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=3474608 [NCBI, ExPASy, EBI, Israel, Japan]
Lee C.-C., Bowman B.H., Yang F.;
"Human alpha 2-HS-glycoprotein: the A and B chains with a connecting sequence are encoded by a single mRNA transcript.";
Proc. Natl. Acad. Sci. U.S.A. 84:4403-4407(1987).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
DOI=10.1016/S0378-1119(97)00216-3; PubMed=9322749 [NCBI, ExPASy, EBI, Israel, Japan]
Osawa M., Umetsu K., Sato M., Ohki T., Yukawa N., Suzuki T., Takeichi S.;
"Structure of the gene encoding human alpha 2-HS glycoprotein (AHSG).";
Gene 196:121-125(1997).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS AHSG*5 ASN-276 AND AHSG*3 CYS-317.
PubMed=11415520 [NCBI, ExPASy, EBI, Israel, Japan]
Osawa M., Yuasa I., Kitano T., Henke J., Kaneko M., Udono T., Saitou N., Umetsu K.;
"Haplotype analysis of the human alpha2-HS glycoprotein (fetuin) gene.";
Ann. Hum. Genet. 65:27-34(2001).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Liver;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
PROTEIN SEQUENCE OF 19-300.
PubMed=3944104 [NCBI, ExPASy, EBI, Israel, Japan]
Yoshioka Y., Gejyo F., Marti T., Rickli E.E., Burgi W., Offner G.D., Troxler R.F., Schmid K.;
"The complete amino acid sequence of the A-chain of human plasma alpha 2HS-glycoprotein.";
J. Biol. Chem. 261:1665-1676(1986).
[6]
PROTEIN SEQUENCE OF 19-28.
TISSUE=Platelet;
DOI=10.1038/nbt810; PubMed=12665801 [NCBI, ExPASy, EBI, Israel, Japan]
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.;
"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.";
Nat. Biotechnol. 21:566-569(2003).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 34-367, AND VARIANTS ALLELE AHSG*2 MET-248 AND SER-256.
TISSUE=Liver;
DOI=10.1007/s004390050302; PubMed=9003486 [NCBI, ExPASy, EBI, Israel, Japan]
Osawa M., Umetsu K., Ohki T., Nagasawa T., Suzuki T., Takeichi S.;
"Molecular evidence for human alpha 2-HS glycoprotein (AHSG) polymorphism.";
Hum. Genet. 99:18-21(1997).
[8]
PROTEIN SEQUENCE OF 107-120, AND MASS SPECTROMETRY.
TISSUE=Brain, and Cajal-Retzius cell;
Lubec G., Vishwanath V.;
Submitted (MAR-2007) to UniProtKB.
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 150-367.
TISSUE=Fetal liver;
Zhang C., Yu Y., Zhang S., Wei H., Zhang Y., Zhou G., Bi J., Liu M., He F.;
"Functional prediction of the coding sequences of 79 new genes deduced by analysis of cDNA clones from human fetal liver.";
Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
[10]
PROTEIN SEQUENCE OF 341-367.
PubMed=6833285 [NCBI, ExPASy, EBI, Israel, Japan]
Gejyo F., Chang J.-L., Burgi W., Schmid K., Offner G.D., Troxler R.F., van Halbeek H., Dorland L., Gerwig G.J., Vliegenthart F.G.;
"Characterization of the B-chain of human plasma alpha 2HS-glycoprotein. The complete amino acid sequence and primary structure of its heteroglycan.";
J. Biol. Chem. 258:4966-4971(1983).
[11]
DISULFIDE BONDS.
DOI=10.1016/0167-4838(89)90293-8; PubMed=2645941 [NCBI, ExPASy, EBI, Israel, Japan]
Araki T., Yoshioka Y., Schmid K.;
"The position of the disulfide bonds in human plasma alpha 2 HS-glycoprotein and the repeating double disulfide bonds in the domain structure.";
Biochim. Biophys. Acta 994:195-199(1989).
[12]
DISULFIDE BONDS.
PubMed=2760061 [NCBI, ExPASy, EBI, Israel, Japan]
Kellerman J., Haupt H., Auerswald E.-A., Mueller-Esterl W.;
"The arrangement of disulfide loops in human alpha 2-HS glycoprotein. Similarity to the disulfide bridge structures of cystatins and kininogens.";
J. Biol. Chem. 264:14121-14128(1989).
[13]
PARTIAL PROTEIN SEQUENCE, AND PHOSPHORYLATION AT SER-138 AND SER-330.
TISSUE=Plasma;
DOI=10.1042/0264-6021:3570437; PubMed=11439093 [NCBI, ExPASy, EBI, Israel, Japan]
Haglund A.C., Ek B., Ek P.;
"Phosphorylation of human plasma alpha2-Heremans-Schmid glycoprotein (human fetuin) in vivo.";
Biochem. J. 357:437-445(2001).
[14]
GLYCOSYLATION AT ASN-176.
DOI=10.1038/nbt827; PubMed=12754519 [NCBI, ExPASy, EBI, Israel, Japan]
Zhang H., Li X.-J., Martin D.B., Aebersold R.;
"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry.";
Nat. Biotechnol. 21:660-666(2003).
[15]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156, AND MASS SPECTROMETRY.
TISSUE=Plasma;
DOI=10.1002/pmic.200300556; PubMed=14760718 [NCBI, ExPASy, EBI, Israel, Japan]
Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry.";
Proteomics 4:454-465(2004).
[16]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156 AND ASN-176, AND MASS SPECTROMETRY.
TISSUE=Plasma;
DOI=10.1021/pr0502065; PubMed=16335952 [NCBI, ExPASy, EBI, Israel, Japan]
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.;
"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.";
J. Proteome Res. 4:2070-2080(2005).
[17]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156 AND ASN-176, AND MASS SPECTROMETRY.
TISSUE=Saliva;
DOI=10.1021/pr050492k; PubMed=16740002 [NCBI, ExPASy, EBI, Israel, Japan]
Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.;
"Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry.";
J. Proteome Res. 5:1493-1503(2006).
[18]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, AND MASS SPECTROMETRY.
TISSUE=Platelet;
DOI=10.1021/pr0704130; PubMed=18088087 [NCBI, ExPASy, EBI, Israel, Japan]
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.;
"Phosphoproteome of resting human platelets.";
J. Proteome Res. 7:526-534(2008).
[19]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, AND MASS SPECTROMETRY.
TISSUE=Liver;
DOI=10.1002/pmic.200700884; PubMed=18318008 [NCBI, ExPASy, EBI, Israel, Japan]
Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J.;
"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography.";
Proteomics 8:1346-1361(2008).
Comments
  • FUNCTION: Promotes endocytosis, possesses opsonic properties and influences the mineral phase of bone. Shows affinity for calcium and barium ions.
  • SUBUNIT: 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.
  • SIMILARITY: Belongs to the fetuin family.
  • SIMILARITY: Contains 2 cystatin domains.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M16961; AAA51683.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
D67013; BAA22652.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB038689; BAA92189.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC048198; AAH48198.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC052590; AAH52590.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
D67012; BAA22651.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF119895; AAF69649.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A29081; WOHU.
RefSeq NP_001613.2; -.
UniGene Hs.324746
3D structure databases
ModBase P02765.
Protein-protein interaction databases
IntAct P02765; -.
Protein family/group databases
MEROPS I25.020; -.
I25.021; -.
PTM databases
GlycoSuiteDB P02765; -.
PhosphoSite P02765; -.
2D gel databases
SWISS-2DPAGE P02765; -.
DOSAC-COBS-2DPAGE P02765; -.
Siena-2DPAGE P02765; -.
Organism-specific databases
H-InvDB HIX0024338; -.
HGNC HGNC:349; AHSG.
GenAtlas AHSG.
HPA HPA001524; -.
HPA001525; -.
MIM 138680; gene. [NCBI / EBI]
PharmGKB PA24642; -.
GeneCards P02765.
Gene expression databases
ArrayExpress P02765; -.
CleanEx HS_AHSG; -.
GermOnline ENSG00000145192; Homo sapiens.
Ontologies
GO
GO:0005615; Cellular component: extracellular space (non-traceable author statement from UniProtKB).
GO:0019210; Molecular function: kinase inhibitor activity (non-traceable author statement from UniProtKB).
GO:0006953; Biological process: acute-phase response (inferred from direct assay from UniProtKB).
GO:0030502; Biological process: negative regulation of bone mineralization (inferred from sequence or structural similarity from UniProtKB).
GO:0046627; Biological process: negative regulation of insulin receptor signaling pathway (non-traceable author statement from UniProtKB).
GO:0006907; Biological process: pinocytosis (non-traceable author statement from UniProtKB).
GO:0050766; Biological process: positive regulation of phagocytosis (inferred from direct assay from UniProtKB).
GO:0050727; Biological process: regulation of inflammatory response (inferred from mutant phenotype from UniProtKB).
GO:0001501; Biological process: skeletal development (non-traceable author statement from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR000010; Prot_inh_cystat.
IPR001363; Prot_inh_fetuin_CS.
Graphical view of domain structure.
Pfam PF00031; Cystatin; 2.
Pfam graphical view of domain structure.
SMART SM00043; CY; 2.
SMART graphical view of domain structure.
PROSITE PS01254; FETUIN_1; 1.
PS01255; FETUIN_2; 1.
BLOCKS P02765.
Genome annotation databases
Ensembl ENSG00000145192; Homo sapiens. [Contig view]
GeneID 197; -.
KEGG hsa:197; -.
Phylogenomic databases
HOGENOM P02765; -.
HOVERGEN P02765; -.
Other
SOURCE AHSG; Homo sapiens.
ProtoNet P02765.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Direct protein sequencing; Glycoprotein; Mineral balance; Phosphoprotein; Polymorphism; Repeat; Secreted; Signal.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    18  18      
CHAIN   19   300  282     Alpha-2-HS-glycoprotein chain A. PRO_0000008887
PROPEP   301   340  40     Connecting peptide. PRO_0000008888
CHAIN   341   367  27     Alpha-2-HS-glycoprotein chain B. PRO_0000008889
DOMAIN   27   144  118     Cystatin 1. 
DOMAIN   145   260  116     Cystatin 2. 
MOD_RES   138   138        Phosphoserine. 
MOD_RES   325   325        Phosphoserine (By similarity). 
MOD_RES   328   328        Phosphoserine (By similarity). 
MOD_RES   330   330        Phosphoserine. 
CARBOHYD   156   156        N-linked (GlcNAc...) [GlycoSuiteDB]. CAR_000064
CARBOHYD   176   176        N-linked (GlcNAc...) [GlycoSuiteDB]. CAR_000065
CARBOHYD   256   256        O-linked (GalNAc...) [GlycoSuiteDB]. CAR_000066
CARBOHYD   270   270        O-linked (GalNAc...) [GlycoSuiteDB]. CAR_000067
CARBOHYD   346   346        O-linked (GalNAc...) [GlycoSuiteDB]. CAR_000068
DISULFID   32   358        Interchain (between A and B chains). 
DISULFID   89   100         
DISULFID   114   132         
DISULFID   146   149         
DISULFID   208   219         
DISULFID   230   247         
VARIANT   248   248  1     T -> M (in allele AHSG*2; dbSNP:rs4917 [NCBI]). VAR_002388 
VARIANT   256   256  1     T -> S (in allele AHSG*2; dbSNP:rs4918 [NCBI]). VAR_002389 
VARIANT   276   276  1     D -> N (in allele AHSG*5). VAR_012474 
VARIANT   317   317  1     R -> C (in allele AHSG*3). VAR_012475 
CONFLICT   16    16        C -> W (in Ref. 2; BAA22652). 
CONFLICT   54    54        W -> K (in Ref. 5; AA sequence). 
CONFLICT   125   125        F -> S (in Ref. 7; BAA22651). 
CONFLICT   150   182        PLLAPLNDTRVVHAAKAALAAFNAQNNGSNFQL -> MVGWQEGANHKNGAGRSQKQEMAEKMVPEVASG (in Ref. 9; AAF69649). 
CONFLICT   204   204        S -> C (in Ref. 2; BAA22652). 
Sequence information
Length: 367 AA [This is the length of the unprocessed precursor] Molecular weight: 39325 Da [This is the MW of the unprocessed precursor] CRC64: 1AAF0C8D6B7E2789 [This is a checksum on the sequence]
        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 

P02765 in FASTA format

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