ID   FETUA_BOVIN             Reviewed;         359 AA.
AC   P12763; A6QLF7;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 2.
DT   27-MAR-2024, entry version 164.
DE   RecName: Full=Alpha-2-HS-glycoprotein;
DE   AltName: Full=Asialofetuin;
DE   AltName: Full=Fetuin-A;
DE   Flags: Precursor;
GN   Name=AHSG; Synonyms=FETUA;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RX   PubMed=1689725; DOI=10.1016/s0021-9258(19)39571-7;
RA   Dziegielewska K.D., Brown W.M., Casey S.J., Christie D.L., Foreman R.C.,
RA   Hill R.M., Saunders N.R.;
RT   "The complete cDNA and amino acid sequence of bovine fetuin. Its homology
RT   with alpha 2HS glycoprotein and relation to other members of the cystatin
RT   superfamily.";
RL   J. Biol. Chem. 265:4354-4357(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Fetal liver;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   PROTEIN SEQUENCE OF 19-123 AND 188-243.
RX   PubMed=2436943; DOI=10.1016/0014-5793(87)80010-8;
RA   Christie D.L., Dziegielewska K.M., Hill R.M., Saunders N.R.;
RT   "Fetuin: the bovine homologue of human alpha 2HS glycoprotein.";
RL   FEBS Lett. 214:45-49(1987).
RN   [4]
RP   PROTEIN SEQUENCE OF 19-62.
RX   PubMed=6165360; DOI=10.1016/0006-291x(81)91708-3;
RA   Alcaraz G., Marti J., Moinier D., Fougereau M.;
RT   "NH2-terminal sequence of calf fetuin.";
RL   Biochem. Biophys. Res. Commun. 99:30-36(1981).
RN   [5]
RP   PROTEIN SEQUENCE OF 72-103 AND 144-187, AND GLYCOSYLATION AT ASN-99;
RP   ASN-156 AND ASN-176.
RX   PubMed=2447075; DOI=10.1016/s0021-9258(19)57364-1;
RA   Yet M.G., Chin C.C.Q., Wold F.;
RT   "The covalent structure of individual N-linked glycopeptides from ovomucoid
RT   and asialofetuin.";
RL   J. Biol. Chem. 263:111-117(1988).
RN   [6]
RP   GLYCOSYLATION AT SER-271; THR-280; SER-282 AND SER-341.
RA   Pisano A., Jardine D.R., Packer N.H., Farnsworth V., Carson W., Cartier P.,
RA   Redmond J.W., Williams K.L., Gooley A.A.;
RT   "Identifying sites of glycosylation in proteins.";
RL   (In) Townsend R.R., Hotchkiss A.T. Jr. (eds.);
RL   Techniques in glycobiology, pp.299-320, Marcel Dekker, New York (1996).
RN   [7]
RP   GLYCOSYLATION AT ASN-99; ASN-156 AND ASN-176, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=15253437; DOI=10.1021/pr034112b;
RA   Hagglund P., Bunkenborg J., Elortza F., Jensen O.N., Roepstorff P.;
RT   "A new strategy for identification of N-glycosylated proteins and
RT   unambiguous assignment of their glycosylation sites using HILIC enrichment
RT   and partial deglycosylation.";
RL   J. Proteome Res. 3:556-566(2004).
RN   [8]
RP   GLYCOSYLATION AT ASN-99; ASN-156 AND ASN-176.
RX   PubMed=19358553; DOI=10.1021/ac900231w;
RA   Thaysen-Andersen M., Mysling S., Hojrup P.;
RT   "Site-specific glycoprofiling of N-linked glycopeptides using MALDI-TOF MS:
RT   strong correlation between signal strength and glycoform quantities.";
RL   Anal. Chem. 81:3933-3943(2009).
RN   [9]
RP   GLYCOSYLATION AT SER-296; THR-334 AND SER-341, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=19674964; DOI=10.1074/mcp.m900211-mcp200;
RA   Darula Z., Medzihradszky K.F.;
RT   "Affinity enrichment and characterization of mucin core-1 type
RT   glycopeptides from bovine serum.";
RL   Mol. Cell. Proteomics 8:2515-2526(2009).
RN   [10]
RP   GLYCOSYLATION AT SER-271; THR-280; SER-282; SER-296 AND SER-341,
RP   PHOSPHORYLATION AT SER-138, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=25456591; DOI=10.1016/j.chroma.2014.10.046;
RA   Huang L.J., Lin J.H., Tsai J.H., Chu Y.Y., Chen Y.W., Chen S.L., Chen S.H.;
RT   "Identification of protein O-glycosylation site and corresponding glycans
RT   using liquid chromatography-tandem mass spectrometry via mapping accurate
RT   mass and retention time shift.";
RL   J. Chromatogr. A 1371:136-145(2014).
RN   [11]
RP   GLYCOSYLATION AT ASN-99; ASN-156; ASN-176; SER-271; THR-280; SER-282;
RP   SER-296 AND SER-341, PHOSPHORYLATION AT SER-138; SER-320; SER-323 AND
RP   SER-325, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=24907489; DOI=10.1016/j.jprot.2014.05.022;
RA   Windwarder M., Altmann F.;
RT   "Site-specific analysis of the O-glycosylation of bovine fetuin by
RT   electron-transfer dissociation mass spectrometry.";
RL   J. Proteomics 108:258-268(2014).
CC   -!- FUNCTION: Promotes endocytosis, possesses opsonic properties and
CC       influences the mineral phase of bone. Suggested to have lymphocyte
CC       stimulating properties, lipid binding capability and to bind thyroid
CC       hormone.
CC   -!- INTERACTION:
CC       P12763; P17931: LGALS3; Xeno; NbExp=2; IntAct=EBI-9396660, EBI-1170392;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Liver and bone.
CC   -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC       {ECO:0000250|UniProtKB:P02765}.
CC   -!- SIMILARITY: Belongs to the fetuin family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00861}.
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DR   EMBL; X16577; CAA34596.1; -; mRNA.
DR   EMBL; BC147948; AAI47949.1; -; mRNA.
DR   PIR; A35714; A35714.
DR   RefSeq; NP_776409.1; NM_173984.3.
DR   AlphaFoldDB; P12763; -.
DR   SMR; P12763; -.
DR   IntAct; P12763; 2.
DR   STRING; 9913.ENSBTAP00000000673; -.
DR   MEROPS; I25.020; -.
DR   MEROPS; I25.021; -.
DR   GlyConnect; 22; 60 N-Linked glycans (3 sites), 13 O-Linked glycans (6 sites).
DR   GlyCosmos; P12763; 9 sites, 69 glycans.
DR   iPTMnet; P12763; -.
DR   PaxDb; 9913-ENSBTAP00000000673; -.
DR   PeptideAtlas; P12763; -.
DR   Ensembl; ENSBTAT00000000673.5; ENSBTAP00000000673.4; ENSBTAG00000000522.5.
DR   GeneID; 280988; -.
DR   KEGG; bta:280988; -.
DR   CTD; 197; -.
DR   VEuPathDB; HostDB:ENSBTAG00000000522; -.
DR   VGNC; VGNC:25756; AHSG.
DR   eggNOG; ENOG502RYRI; Eukaryota.
DR   GeneTree; ENSGT00950000182930; -.
DR   HOGENOM; CLU_052519_0_0_1; -.
DR   InParanoid; P12763; -.
DR   OMA; KVWPRQP; -.
DR   OrthoDB; 5312104at2759; -.
DR   TreeFam; TF333729; -.
DR   Reactome; R-BTA-114608; Platelet degranulation.
DR   Reactome; R-BTA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-BTA-6798695; Neutrophil degranulation.
DR   Reactome; R-BTA-8957275; Post-translational protein phosphorylation.
DR   Proteomes; UP000009136; Chromosome 1.
DR   Bgee; ENSBTAG00000000522; Expressed in liver and 64 other cell types or tissues.
DR   ExpressionAtlas; P12763; baseline.
DR   GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR   GO; GO:0065010; C:extracellular membrane-bounded organelle; IDA:AgBase.
DR   GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; TAS:AgBase.
DR   GO; GO:0031982; C:vesicle; IDA:AgBase.
DR   GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IEA:InterPro.
DR   GO; GO:0004866; F:endopeptidase inhibitor activity; IBA:GO_Central.
DR   GO; GO:0006953; P:acute-phase response; ISS:UniProtKB.
DR   GO; GO:0030502; P:negative regulation of bone mineralization; ISS:UniProtKB.
DR   GO; GO:0001503; P:ossification; IEA:Ensembl.
DR   GO; GO:0050766; P:positive regulation of phagocytosis; ISS:UniProtKB.
DR   GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR   CDD; cd00042; CY; 2.
DR   Gene3D; 3.10.450.10; -; 2.
DR   InterPro; IPR000010; Cystatin_dom.
DR   InterPro; IPR025760; Cystatin_Fetuin_A.
DR   InterPro; IPR046350; Cystatin_sf.
DR   InterPro; IPR001363; Prot_inh_fetuin_CS.
DR   PANTHER; PTHR13814:SF6; ALPHA-2-HS-GLYCOPROTEIN; 1.
DR   PANTHER; PTHR13814; FETUIN; 1.
DR   Pfam; PF00031; Cystatin; 1.
DR   SMART; SM00043; CY; 2.
DR   SUPFAM; SSF54403; Cystatin/monellin; 2.
DR   PROSITE; PS51529; CYSTATIN_FETUIN_A; 2.
DR   PROSITE; PS01254; FETUIN_1; 1.
DR   PROSITE; PS01255; FETUIN_2; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Mineral balance;
KW   Phosphoprotein; Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000269|PubMed:2436943,
FT                   ECO:0000269|PubMed:6165360"
FT   CHAIN           19..359
FT                   /note="Alpha-2-HS-glycoprotein"
FT                   /id="PRO_0000008885"
FT   DOMAIN          27..133
FT                   /note="Cystatin fetuin-A-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00861"
FT   DOMAIN          144..256
FT                   /note="Cystatin fetuin-A-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00861"
FT   REGION          257..285
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            143..144
FT                   /note="Cleavage; by trypsin"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         134
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P02765"
FT   MOD_RES         135
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P02765"
FT   MOD_RES         138
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:24907489,
FT                   ECO:0000269|PubMed:25456591"
FT   MOD_RES         314
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P02765"
FT   MOD_RES         316
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P24090"
FT   MOD_RES         320
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:24907489"
FT   MOD_RES         323
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:24907489"
FT   MOD_RES         325
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:24907489"
FT   CARBOHYD        99
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:15253437,
FT                   ECO:0000269|PubMed:19358553, ECO:0000269|PubMed:2447075,
FT                   ECO:0000269|PubMed:24907489"
FT                   /id="CAR_000061"
FT   CARBOHYD        156
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:15253437,
FT                   ECO:0000269|PubMed:19358553, ECO:0000269|PubMed:2447075,
FT                   ECO:0000269|PubMed:24907489"
FT                   /id="CAR_000062"
FT   CARBOHYD        176
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:15253437,
FT                   ECO:0000269|PubMed:19358553, ECO:0000269|PubMed:2447075,
FT                   ECO:0000269|PubMed:24907489"
FT                   /id="CAR_000063"
FT   CARBOHYD        271
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:24907489,
FT                   ECO:0000269|PubMed:25456591, ECO:0000269|Ref.6"
FT   CARBOHYD        280
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:24907489,
FT                   ECO:0000269|PubMed:25456591, ECO:0000269|Ref.6"
FT   CARBOHYD        282
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:24907489,
FT                   ECO:0000269|PubMed:25456591, ECO:0000269|Ref.6"
FT   CARBOHYD        296
FT                   /note="O-linked (GalNAc...) serine"
FT                   /evidence="ECO:0000269|PubMed:19674964,
FT                   ECO:0000269|PubMed:24907489, ECO:0000269|PubMed:25456591"
FT   CARBOHYD        334
FT                   /note="O-linked (GalNAc...) threonine"
FT                   /evidence="ECO:0000269|PubMed:19674964"
FT   CARBOHYD        341
FT                   /note="O-linked (GalNAc...) serine; partial"
FT                   /evidence="ECO:0000269|PubMed:19674964,
FT                   ECO:0000269|PubMed:24907489, ECO:0000269|PubMed:25456591,
FT                   ECO:0000269|Ref.6"
FT   DISULFID        32..350
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00861"
FT   DISULFID        89..100
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00861"
FT   DISULFID        114..132
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00861"
FT   DISULFID        146..149
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00861"
FT   DISULFID        208..219
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00861"
FT   DISULFID        230..248
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00861"
FT   CONFLICT        57..58
FT                   /note="KH -> VK (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        72
FT                   /note="R -> Q (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        106
FT                   /note="T -> H (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        116..121
FT                   /note="IHVLKQ -> FSVVKL (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        186
FT                   /note="S -> R (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        195
FT                   /note="V -> P (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   359 AA;  38419 MW;  ED8F685C44CCE49B CRC64;
     MKSFVLLFCL AQLWGCHSIP LDPVAGYKEP ACDDPDTEQA ALAAVDYINK HLPRGYKHTL
     NQIDSVKVWP RRPTGEVYDI EIDTLETTCH VLDPTPLANC SVRQQTQHAV EGDCDIHVLK
     QDGQFSVLFT KCDSSPDSAE DVRKLCPDCP LLAPLNDSRV VHAVEVALAT FNAESNGSYL
     QLVEISRAQF VPLPVSVSVE FAVAATDCIA KEVVDPTKCN LLAEKQYGFC KGSVIQKALG
     GEDVRVTCTL FQTQPVIPQP QPDGAEAEAP SAVPDAAGPT PSAAGPPVAS VVVGPSVVAV
     PLPLHRAHYD LRHTFSGVAS VESSSGEAFH VGKTPIVGQP SIPGGPVRLC PGRIRYFKI
//