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Protein

Alpha-2-HS-glycoprotein

Gene

AHSG

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Promotes endocytosis, possesses opsonic properties and influences the mineral phase of bone. Shows affinity for calcium and barium ions.

GO - Molecular functioni

GO - Biological processi

  • acute-phase response Source: UniProtKB
  • negative regulation of biomineral tissue development Source: GO_Central
  • negative regulation of bone mineralization Source: UniProtKB
  • negative regulation of insulin receptor signaling pathway Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • ossification Source: Ensembl
  • pinocytosis Source: UniProtKB
  • platelet degranulation Source: Reactome
  • positive regulation of phagocytosis Source: UniProtKB
  • regulation of bone mineralization Source: UniProtKB
  • regulation of inflammatory response Source: UniProtKB
  • skeletal system development Source: UniProtKB

Keywordsi

Biological processMineral balance

Enzyme and pathway databases

ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-HSA-6798695. Neutrophil degranulation.
R-HSA-8957275. Post-translational protein phosphorylation.

Protein family/group databases

MEROPSiI25.020.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-2-HS-glycoprotein
Alternative name(s):
Alpha-2-Z-globulin
Ba-alpha-2-glycoprotein
Fetuin-A
Cleaved into the following 2 chains:
Gene namesi
Name:AHSG
Synonyms:FETUA
ORF Names:PRO2743
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:349. AHSG.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular matrix Source: GO_Central
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • Golgi apparatus Source: HPA
  • platelet alpha granule lumen Source: Reactome
  • secretory granule lumen Source: Reactome

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi197.
PharmGKBiPA24642.

Polymorphism and mutation databases

BioMutaiAHSG.
DMDMi112910.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 182 PublicationsAdd BLAST18
ChainiPRO_000000888719 – 300Alpha-2-HS-glycoprotein chain A1 PublicationAdd BLAST282
PropeptideiPRO_0000008888301 – 340Connecting peptide1 PublicationAdd BLAST40
ChainiPRO_0000008889341 – 367Alpha-2-HS-glycoprotein chain BAdd BLAST27

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi32 ↔ 358Interchain (between A and B chains)
Disulfide bondi89 ↔ 100PROSITE-ProRule annotation1 Publication
Disulfide bondi114 ↔ 132PROSITE-ProRule annotation1 Publication
Modified residuei134PhosphoserineCombined sources1
Modified residuei135Phosphoserine; by FAM20C1 Publication1
Modified residuei138Phosphoserine; by FAM20CCombined sources2 Publications1
Disulfide bondi146 ↔ 149PROSITE-ProRule annotation1 Publication
GlycosylationiCAR_000064156N-linked (GlcNAc...) (complex) asparagine7 Publications1
GlycosylationiCAR_000065176N-linked (GlcNAc...) (complex) asparagine5 Publications1
Disulfide bondi208 ↔ 219PROSITE-ProRule annotation1 Publication
Disulfide bondi230 ↔ 247PROSITE-ProRule annotation1 Publication
GlycosylationiCAR_000066256O-linked (GalNAc...) threonine1
GlycosylationiCAR_000067270O-linked (GalNAc...) threonine1
Modified residuei319Phosphothreonine; by FAM20CCombined sources1 Publication1
Modified residuei325Phosphoserine; by FAM20C1 Publication1
Modified residuei328Phosphoserine; by FAM20C1 Publication1
Modified residuei330Phosphoserine; by FAM20CCombined sources2 Publications1
Glycosylationi339O-linked (GalNAc...) threonineBy similarity1
GlycosylationiCAR_000068346O-linked (GalNAc...) serine1 Publication1

Post-translational modificationi

Phosphorylated by FAM20C in the extracellular medium.2 Publications
O- and N-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. N-glycan at Asn-156: Hex5HexNAc4; N-glycan heterogeneity at Asn-176: Hex5HexNAc4 (major) and Hex6HexNAc5 (minor).8 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP02765.
PaxDbiP02765.
PeptideAtlasiP02765.
PRIDEiP02765.
TopDownProteomicsiP02765.

2D gel databases

DOSAC-COBS-2DPAGEiP02765.
SWISS-2DPAGEiP02765.

PTM databases

iPTMnetiP02765.
PhosphoSitePlusiP02765.
UniCarbKBiP02765.

Miscellaneous databases

PMAP-CutDBiP02765.

Expressioni

Tissue specificityi

Synthesized in liver and selectively concentrated in bone matrix. Secreted in plasma. It is also found in dentin in much higher quantities than other plasma proteins.

Gene expression databases

BgeeiENSG00000145192.
CleanExiHS_AHSG.
ExpressionAtlasiP02765. baseline and differential.
GenevisibleiP02765. HS.

Organism-specific databases

HPAiCAB026209.
HPA001524.
HPA001525.

Interactioni

Subunit structurei

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.

Protein-protein interaction databases

BioGridi106700. 20 interactors.
IntActiP02765. 10 interactors.
MINTiMINT-5004009.
STRINGi9606.ENSP00000393887.

Structurei

3D structure databases

ProteinModelPortaliP02765.
SMRiP02765.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 133Cystatin fetuin-A-type 1PROSITE-ProRule annotationAdd BLAST107
Domaini144 – 255Cystatin fetuin-A-type 2PROSITE-ProRule annotationAdd BLAST112

Sequence similaritiesi

Belongs to the fetuin family.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IK8F. Eukaryota.
ENOG4111RIP. LUCA.
HOVERGENiHBG051607.
InParanoidiP02765.
PhylomeDBiP02765.
TreeFamiTF333729.

Family and domain databases

CDDicd00042. CY. 2 hits.
InterProiView protein in InterPro
IPR000010. Cystatin_dom.
IPR025760. Cystatin_Fetuin_A.
IPR001363. Prot_inh_fetuin_CS.
PfamiView protein in Pfam
PF00031. Cystatin. 1 hit.
SMARTiView protein in SMART
SM00043. CY. 2 hits.
PROSITEiView protein in PROSITE
PS51529. CYSTATIN_FETUIN_A. 2 hits.
PS01254. FETUIN_1. 1 hit.
PS01255. FETUIN_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P02765-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKSLVLLLCL AQLWGCHSAP HGPGLIYRQP NCDDPETEEA ALVAIDYINQ
60 70 80 90 100
NLPWGYKHTL NQIDEVKVWP QQPSGELFEI EIDTLETTCH VLDPTPVARC
110 120 130 140 150
SVRQLKEHAV EGDCDFQLLK LDGKFSVVYA KCDSSPDSAE DVRKVCQDCP
160 170 180 190 200
LLAPLNDTRV VHAAKAALAA FNAQNNGSNF QLEEISRAQL VPLPPSTYVE
210 220 230 240 250
FTVSGTDCVA KEATEAAKCN LLAEKQYGFC KATLSEKLGG AEVAVTCTVF
260 270 280 290 300
QTQPVTSQPQ PEGANEAVPT PVVDPDAPPS PPLGAPGLPP AGSPPDSHVL
310 320 330 340 350
LAAPPGHQLH RAHYDLRHTF MGVVSLGSPS GEVSHPRKTR TVVQPSVGAA
360
AGPVVPPCPG RIRHFKV
Length:367
Mass (Da):39,325
Last modified:April 1, 1988 - v1
Checksum:i1AAF0C8D6B7E2789
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti16C → W in BAA22652 (PubMed:9322749).Curated1
Sequence conflicti54W → K AA sequence (PubMed:3944104).Curated1
Sequence conflicti125F → S in BAA22651 (PubMed:9003486).Curated1
Sequence conflicti150 – 182PLLAP…SNFQL → MVGWQEGANHKNGAGRSQKQ EMAEKMVPEVASG in AAF69649 (Ref. 12) CuratedAdd BLAST33
Sequence conflicti204S → C in BAA22652 (PubMed:9322749).Curated1

Polymorphismi

There are two common alleles, AHSG*1 and AHSG*2. AHSG*1 has Thr-248/Thr-256; AHSG*2 has Met-248/Ser-256.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_055802142V → L. Corresponds to variant dbSNP:rs7633550Ensembl.1
Natural variantiVAR_002388248T → M in allele AHSG*2. 1 PublicationCorresponds to variant dbSNP:rs4917Ensembl.1
Natural variantiVAR_002389256T → S in allele AHSG*2. 2 PublicationsCorresponds to variant dbSNP:rs4918Ensembl.1
Natural variantiVAR_012474276D → N in allele AHSG*5. 1 PublicationCorresponds to variant dbSNP:rs70961709Ensembl.1
Natural variantiVAR_012475317R → C in allele AHSG*3. 1 PublicationCorresponds to variant dbSNP:rs35457250Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M16961 mRNA. Translation: AAA51683.1.
D67013 Genomic DNA. Translation: BAA22652.1.
AB038689 Genomic DNA. Translation: BAA92189.1.
AK292751 mRNA. Translation: BAF85440.1.
AK312969 mRNA. Translation: BAG35808.1.
AC068631 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78189.1.
BC048198 mRNA. Translation: AAH48198.1.
BC052590 mRNA. Translation: AAH52590.1.
D67012 mRNA. Translation: BAA22651.1.
AF119895 mRNA. Translation: AAF69649.1.
CCDSiCCDS3278.1.
PIRiA29081. WOHU.
RefSeqiNP_001613.2. NM_001622.2.
UniGeneiHs.324746.

Genome annotation databases

EnsembliENST00000411641; ENSP00000393887; ENSG00000145192.
GeneIDi197.
KEGGihsa:197.
UCSCiuc003fqk.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M16961 mRNA. Translation: AAA51683.1.
D67013 Genomic DNA. Translation: BAA22652.1.
AB038689 Genomic DNA. Translation: BAA92189.1.
AK292751 mRNA. Translation: BAF85440.1.
AK312969 mRNA. Translation: BAG35808.1.
AC068631 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78189.1.
BC048198 mRNA. Translation: AAH48198.1.
BC052590 mRNA. Translation: AAH52590.1.
D67012 mRNA. Translation: BAA22651.1.
AF119895 mRNA. Translation: AAF69649.1.
CCDSiCCDS3278.1.
PIRiA29081. WOHU.
RefSeqiNP_001613.2. NM_001622.2.
UniGeneiHs.324746.

3D structure databases

ProteinModelPortaliP02765.
SMRiP02765.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106700. 20 interactors.
IntActiP02765. 10 interactors.
MINTiMINT-5004009.
STRINGi9606.ENSP00000393887.

Protein family/group databases

MEROPSiI25.020.

PTM databases

iPTMnetiP02765.
PhosphoSitePlusiP02765.
UniCarbKBiP02765.

Polymorphism and mutation databases

BioMutaiAHSG.
DMDMi112910.

2D gel databases

DOSAC-COBS-2DPAGEiP02765.
SWISS-2DPAGEiP02765.

Proteomic databases

MaxQBiP02765.
PaxDbiP02765.
PeptideAtlasiP02765.
PRIDEiP02765.
TopDownProteomicsiP02765.

Protocols and materials databases

DNASUi197.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000411641; ENSP00000393887; ENSG00000145192.
GeneIDi197.
KEGGihsa:197.
UCSCiuc003fqk.5. human.

Organism-specific databases

CTDi197.
DisGeNETi197.
GeneCardsiAHSG.
H-InvDBiHIX0024338.
HGNCiHGNC:349. AHSG.
HPAiCAB026209.
HPA001524.
HPA001525.
MIMi138680. gene.
neXtProtiNX_P02765.
PharmGKBiPA24642.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IK8F. Eukaryota.
ENOG4111RIP. LUCA.
HOVERGENiHBG051607.
InParanoidiP02765.
PhylomeDBiP02765.
TreeFamiTF333729.

Enzyme and pathway databases

ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-HSA-6798695. Neutrophil degranulation.
R-HSA-8957275. Post-translational protein phosphorylation.

Miscellaneous databases

ChiTaRSiAHSG. human.
GeneWikiiAlpha-2-HS-glycoprotein.
GenomeRNAii197.
PMAP-CutDBiP02765.
PROiPR:P02765.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145192.
CleanExiHS_AHSG.
ExpressionAtlasiP02765. baseline and differential.
GenevisibleiP02765. HS.

Family and domain databases

CDDicd00042. CY. 2 hits.
InterProiView protein in InterPro
IPR000010. Cystatin_dom.
IPR025760. Cystatin_Fetuin_A.
IPR001363. Prot_inh_fetuin_CS.
PfamiView protein in Pfam
PF00031. Cystatin. 1 hit.
SMARTiView protein in SMART
SM00043. CY. 2 hits.
PROSITEiView protein in PROSITE
PS51529. CYSTATIN_FETUIN_A. 2 hits.
PS01254. FETUIN_1. 1 hit.
PS01255. FETUIN_2. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiFETUA_HUMAN
AccessioniPrimary (citable) accession number: P02765
Secondary accession number(s): A8K9N6
, B2R7G1, O14961, O14962, Q9P152
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: April 1, 1988
Last modified: June 7, 2017
This is version 189 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.