ID FETUA_HUMAN Reviewed; 367 AA. AC P02765; A8K9N6; B2R7G1; O14961; O14962; Q9P152; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 12-SEP-2018, sequence version 2. DT 27-MAR-2024, entry version 232. DE RecName: Full=Alpha-2-HS-glycoprotein; DE AltName: Full=Alpha-2-Z-globulin; DE AltName: Full=Ba-alpha-2-glycoprotein; DE AltName: Full=Fetuin-A; DE Contains: DE RecName: Full=Alpha-2-HS-glycoprotein chain A; DE Contains: DE RecName: Full=Alpha-2-HS-glycoprotein chain B; DE Flags: Precursor; GN Name=AHSG; Synonyms=FETUA; ORFNames=PRO2743; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS THR-248 AND THR-256. RX PubMed=3474608; DOI=10.1073/pnas.84.13.4403; RA Lee C.-C., Bowman B.H., Yang F.; RT "Human alpha 2-HS-glycoprotein: the A and B chains with a connecting RT sequence are encoded by a single mRNA transcript."; RL Proc. Natl. Acad. Sci. U.S.A. 84:4403-4407(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS THR-248 AND THR-256. RX PubMed=9322749; DOI=10.1016/s0378-1119(97)00216-3; RA Osawa M., Umetsu K., Sato M., Ohki T., Yukawa N., Suzuki T., Takeichi S.; RT "Structure of the gene encoding human alpha 2-HS glycoprotein (AHSG)."; RL Gene 196:121-125(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-248; THR-256; ASN-276 RP AND CYS-317. RX PubMed=11415520; DOI=10.1046/j.1469-1809.2001.6510027.x; RA Osawa M., Yuasa I., Kitano T., Henke J., Kaneko M., Udono T., Saitou N., RA Umetsu K.; RT "Haplotype analysis of the human alpha2-HS glycoprotein (fetuin) gene."; RL Ann. Hum. Genet. 65:27-34(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS THR-248 AND THR-256. RC TISSUE=Liver, and Mammary gland; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS THR-248 AND THR-256. RC TISSUE=Liver; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 19-300. RX PubMed=3944104; DOI=10.1016/s0021-9258(17)35992-6; RA Yoshioka Y., Gejyo F., Marti T., Rickli E.E., Burgi W., Offner G.D., RA Troxler R.F., Schmid K.; RT "The complete amino acid sequence of the A-chain of human plasma alpha 2HS- RT glycoprotein."; RL J. Biol. Chem. 261:1665-1676(1986). RN [9] RP PROTEIN SEQUENCE OF 19-28. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 34-367, VARIANTS THR-248 AND THR-256, AND RP POLYMORPHISM. RC TISSUE=Liver; RX PubMed=9003486; DOI=10.1007/s004390050302; RA Osawa M., Umetsu K., Ohki T., Nagasawa T., Suzuki T., Takeichi S.; RT "Molecular evidence for human alpha 2-HS glycoprotein (AHSG) RT polymorphism."; RL Hum. Genet. 99:18-21(1997). RN [11] RP PROTEIN SEQUENCE OF 107-120, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Vishwanath V.; RL Submitted (MAR-2007) to UniProtKB. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 150-367, AND VARIANTS THR-248 AND RP THR-256. RC TISSUE=Fetal liver; RA Zhang C., Yu Y., Zhang S., Wei H., Zhang Y., Zhou G., Bi J., Liu M., He F.; RT "Functional prediction of the coding sequences of 79 new genes deduced by RT analysis of cDNA clones from human fetal liver."; RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases. RN [13] RP PROTEIN SEQUENCE OF 341-367. RX PubMed=6833285; DOI=10.1016/s0021-9258(18)32522-5; RA Gejyo F., Chang J.-L., Burgi W., Schmid K., Offner G.D., Troxler R.F., RA van Halbeek H., Dorland L., Gerwig G.J., Vliegenthart J.F.G.; RT "Characterization of the B-chain of human plasma alpha 2HS-glycoprotein. RT The complete amino acid sequence and primary structure of its RT heteroglycan."; RL J. Biol. Chem. 258:4966-4971(1983). RN [14] RP DISULFIDE BONDS. RX PubMed=2645941; DOI=10.1016/0167-4838(89)90293-8; RA Araki T., Yoshioka Y., Schmid K.; RT "The position of the disulfide bonds in human plasma alpha 2 HS- RT glycoprotein and the repeating double disulfide bonds in the domain RT structure."; RL Biochim. Biophys. Acta 994:195-199(1989). RN [15] RP DISULFIDE BONDS. RX PubMed=2760061; DOI=10.1016/s0021-9258(18)71651-7; RA Kellerman J., Haupt H., Auerswald E.-A., Mueller-Esterl W.; RT "The arrangement of disulfide loops in human alpha 2-HS glycoprotein. RT Similarity to the disulfide bridge structures of cystatins and RT kininogens."; RL J. Biol. Chem. 264:14121-14128(1989). RN [16] RP PARTIAL PROTEIN SEQUENCE, AND PHOSPHORYLATION AT SER-138 AND SER-330. RC TISSUE=Plasma; RX PubMed=11439093; DOI=10.1042/0264-6021:3570437; RA Haglund A.C., Ek B., Ek P.; RT "Phosphorylation of human plasma alpha2-Heremans-Schmid glycoprotein (human RT fetuin) in vivo."; RL Biochem. J. 357:437-445(2001). RN [17] RP GLYCOSYLATION AT ASN-176. RX PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [18] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156. RC TISSUE=Plasma; RX PubMed=14760718; DOI=10.1002/pmic.200300556; RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.; RT "Screening for N-glycosylated proteins by liquid chromatography mass RT spectrometry."; RL Proteomics 4:454-465(2004). RN [19] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156 AND ASN-176. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [20] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156 AND ASN-176. RC TISSUE=Saliva; RX PubMed=16740002; DOI=10.1021/pr050492k; RA Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A.; RT "Identification of N-linked glycoproteins in human saliva by glycoprotein RT capture and mass spectrometry."; RL J. Proteome Res. 5:1493-1503(2006). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [24] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [25] RP GLYCOSYLATION AT ASN-156. RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200; RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., RA Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core fucosylated RT glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [26] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156 AND ASN-176, AND STRUCTURE RP OF CARBOHYDRATES. RC TISSUE=Cerebrospinal fluid; RX PubMed=19838169; DOI=10.1038/nmeth.1392; RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., RA Larson G.; RT "Enrichment of glycopeptides for glycan structure and attachment site RT identification."; RL Nat. Methods 6:809-811(2009). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [28] RP GLYCOSYLATION AT ASN-156; ASN-176 AND SER-346, STRUCTURE OF CARBOHYDRATES, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=22171320; DOI=10.1074/mcp.m111.013649; RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.; RT "Human urinary glycoproteomics; attachment site specific analysis of N- and RT O-linked glycosylations by CID and ECD."; RL Mol. Cell. Proteomics 11:1-17(2012). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134; SER-138; THR-319 AND RP SER-330, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [31] RP PHOSPHORYLATION AT SER-135; SER-138; THR-319; SER-325 AND SER-328 AND RP SER-330. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted phosphoproteome."; RL Cell 161:1619-1632(2015). RN [32] RP INVOLVEMENT IN APMR1, AND VARIANT APMR1 HIS-317. RX PubMed=28054173; DOI=10.1007/s00439-016-1756-5; RA Reza Sailani M., Jahanbani F., Nasiri J., Behnam M., Salehi M., Sedghi M., RA Hoseinzadeh M., Takahashi S., Zia A., Gruber J., Lynch J.L., Lam D., RA Winkelmann J., Amirkiai S., Pang B., Rego S., Mazroui S., Bernstein J.A., RA Snyder M.P.; RT "Association of AHSG with alopecia and mental retardation (APMR) RT syndrome."; RL Hum. Genet. 136:287-296(2017). CC -!- FUNCTION: Promotes endocytosis, possesses opsonic properties and CC influences the mineral phase of bone. Shows affinity for calcium and CC barium ions. CC -!- SUBUNIT: Alpha-2-HS glycoprotein derives from this precursor, when the CC connecting peptide is cleaved off. The two chains A and B are held CC together by a single disulfide bond. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Synthesized in liver and selectively concentrated CC in bone matrix. Secreted in plasma. It is also found in dentin in much CC higher quantities than other plasma proteins. CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium. CC {ECO:0000269|PubMed:11439093, ECO:0000269|PubMed:26091039}. CC -!- PTM: O- and N-glycosylated. O-glycosylated with core 1 or possibly core CC 8 glycans. N-glycan at Asn-156: Hex5HexNAc4; N-glycan heterogeneity at CC Asn-176: Hex5HexNAc4 (major) and Hex6HexNAc5 (minor). CC {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718, CC ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16740002, CC ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, CC ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320}. CC -!- POLYMORPHISM: There are two common alleles, AHSG*1 and AHSG*2. AHSG*1 CC has Thr-248/Thr-256; AHSG*2 has Met-248/Ser-256. CC {ECO:0000269|PubMed:9003486}. CC -!- DISEASE: Alopecia-intellectual disability syndrome 1 (APMR1) CC [MIM:203650]: A rare autosomal recessive form of alopecia. APMR1 CC patients show loss of hair on the scalp, absence of eyebrows, CC eyelashes, axillary and pubic hair, and mild to severe intellectual CC disability. {ECO:0000269|PubMed:28054173}. Note=The disease may be CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the fetuin family. {ECO:0000255|PROSITE- CC ProRule:PRU00861}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M16961; AAA51683.1; -; mRNA. DR EMBL; D67013; BAA22652.1; -; Genomic_DNA. DR EMBL; AB038689; BAA92189.1; -; Genomic_DNA. DR EMBL; AK292751; BAF85440.1; -; mRNA. DR EMBL; AK312969; BAG35808.1; -; mRNA. DR EMBL; AC068631; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW78189.1; -; Genomic_DNA. DR EMBL; BC048198; AAH48198.1; -; mRNA. DR EMBL; BC052590; AAH52590.1; -; mRNA. DR EMBL; D67012; BAA22651.1; -; mRNA. DR EMBL; AF119895; AAF69649.1; -; mRNA. DR CCDS; CCDS3278.1; -. DR PIR; A29081; WOHU. DR RefSeq; NP_001613.2; NM_001622.2. DR AlphaFoldDB; P02765; -. DR SMR; P02765; -. DR BioGRID; 106700; 103. DR IntAct; P02765; 47. DR MINT; P02765; -. DR STRING; 9606.ENSP00000273784; -. DR ChEMBL; CHEMBL4295694; -. DR DrugBank; DB09130; Copper. DR DrugBank; DB01593; Zinc. DR DrugBank; DB14487; Zinc acetate. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR MEROPS; I25.020; -. DR MEROPS; I25.021; -. DR CarbonylDB; P02765; -. DR GlyConnect; 23; 59 N-Linked glycans (2 sites), 4 O-Linked glycans (2 sites). DR GlyCosmos; P02765; 14 sites, 80 glycans. DR GlyGen; P02765; 15 sites, 85 N-linked glycans (2 sites), 16 O-linked glycans (11 sites). DR iPTMnet; P02765; -. DR PhosphoSitePlus; P02765; -. DR SwissPalm; P02765; -. DR BioMuta; AHSG; -. DR DMDM; 112910; -. DR DOSAC-COBS-2DPAGE; P02765; -. DR CPTAC; non-CPTAC-1066; -. DR CPTAC; non-CPTAC-1067; -. DR jPOST; P02765; -. DR MassIVE; P02765; -. DR MaxQB; P02765; -. DR PaxDb; 9606-ENSP00000393887; -. DR PeptideAtlas; P02765; -. DR PRIDE; P02765; -. DR ProteomicsDB; 51585; -. DR TopDownProteomics; P02765; -. DR Antibodypedia; 870; 723 antibodies from 41 providers. DR DNASU; 197; -. DR Ensembl; ENST00000411641.7; ENSP00000393887.2; ENSG00000145192.13. DR GeneID; 197; -. DR KEGG; hsa:197; -. DR MANE-Select; ENST00000411641.7; ENSP00000393887.2; NM_001622.4; NP_001613.2. DR UCSC; uc003fqk.5; human. DR AGR; HGNC:349; -. DR CTD; 197; -. DR DisGeNET; 197; -. DR GeneCards; AHSG; -. DR HGNC; HGNC:349; AHSG. DR HPA; ENSG00000145192; Tissue enriched (liver). DR MalaCards; AHSG; -. DR MIM; 138680; gene. DR MIM; 203650; phenotype. DR neXtProt; NX_P02765; -. DR OpenTargets; ENSG00000145192; -. DR Orphanet; 2850; Alopecia-intellectual disability syndrome. DR PharmGKB; PA24642; -. DR VEuPathDB; HostDB:ENSG00000145192; -. DR eggNOG; ENOG502RYRI; Eukaryota. DR GeneTree; ENSGT00950000182930; -. DR HOGENOM; CLU_052519_0_0_1; -. DR InParanoid; P02765; -. DR OrthoDB; 5312104at2759; -. DR PhylomeDB; P02765; -. DR TreeFam; TF333729; -. DR PathwayCommons; P02765; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR SignaLink; P02765; -. DR SIGNOR; P02765; -. DR BioGRID-ORCS; 197; 12 hits in 1148 CRISPR screens. DR ChiTaRS; AHSG; human. DR GeneWiki; Alpha-2-HS-glycoprotein; -. DR GenomeRNAi; 197; -. DR Pharos; P02765; Tbio. DR PRO; PR:P02765; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P02765; Protein. DR Bgee; ENSG00000145192; Expressed in liver and 114 other cell types or tissues. DR ExpressionAtlas; P02765; baseline and differential. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. 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:0019210; F:kinase inhibitor activity; NAS:UniProtKB. DR GO; GO:0006953; P:acute-phase response; IDA:UniProtKB. DR GO; GO:0030502; P:negative regulation of bone mineralization; ISS:UniProtKB. DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; NAS:UniProtKB. DR GO; GO:0001503; P:ossification; IEA:Ensembl. DR GO; GO:0006907; P:pinocytosis; NAS:UniProtKB. DR GO; GO:0050766; P:positive regulation of phagocytosis; IDA:UniProtKB. DR GO; GO:0030500; P:regulation of bone mineralization; NAS:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; IMP:UniProtKB. DR GO; GO:0001501; P:skeletal system development; NAS: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. DR SWISS-2DPAGE; P02765; -. DR Genevisible; P02765; HS. PE 1: Evidence at protein level; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Hypotrichosis; Intellectual disability; Mineral balance; Phosphoprotein; KW Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..18 FT /evidence="ECO:0000269|PubMed:12665801, FT ECO:0000269|PubMed:3944104" FT CHAIN 19..300 FT /note="Alpha-2-HS-glycoprotein chain A" FT /evidence="ECO:0000269|PubMed:3944104" FT /id="PRO_0000008887" FT PROPEP 301..340 FT /note="Connecting peptide" FT /evidence="ECO:0000269|PubMed:6833285" FT /id="PRO_0000008888" FT CHAIN 341..367 FT /note="Alpha-2-HS-glycoprotein chain B" FT /id="PRO_0000008889" FT DOMAIN 27..133 FT /note="Cystatin fetuin-A-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00861" FT DOMAIN 144..255 FT /note="Cystatin fetuin-A-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00861" FT REGION 255..298 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 272..293 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 134 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 135 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" FT MOD_RES 138 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:11439093, FT ECO:0000269|PubMed:26091039, ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 319 FT /note="Phosphothreonine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039, FT ECO:0007744|PubMed:24275569" FT MOD_RES 325 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" FT MOD_RES 328 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" FT MOD_RES 330 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:11439093, FT ECO:0000269|PubMed:26091039, ECO:0007744|PubMed:24275569" FT CARBOHYD 156 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16740002, FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320" FT /id="CAR_000064" FT CARBOHYD 176 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16740002, FT ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320" FT /id="CAR_000065" FT CARBOHYD 270 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT /id="CAR_000067" FT CARBOHYD 280 FT /note="O-linked (GalNAc...) serine" FT /evidence="ECO:0000255" FT CARBOHYD 293 FT /note="O-linked (GalNAc...) serine" FT /evidence="ECO:0000255" FT CARBOHYD 339 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000250|UniProtKB:P12763" FT CARBOHYD 341 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000255" FT CARBOHYD 346 FT /note="O-linked (GalNAc...) serine" FT /evidence="ECO:0000269|PubMed:22171320" FT /id="CAR_000068" FT DISULFID 32..358 FT /note="Interchain (between A and B chains)" FT DISULFID 89..100 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00861, FT ECO:0000269|PubMed:2760061" FT DISULFID 114..132 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00861, FT ECO:0000269|PubMed:2760061" FT DISULFID 146..149 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00861, FT ECO:0000269|PubMed:2760061" FT DISULFID 208..219 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00861, FT ECO:0000269|PubMed:2760061" FT DISULFID 230..247 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00861, FT ECO:0000269|PubMed:2760061" FT VARIANT 142 FT /note="V -> L (in dbSNP:rs7633550)" FT /id="VAR_055802" FT VARIANT 248 FT /note="M -> T (in allele AHSG*1; dbSNP:rs4917)" FT /evidence="ECO:0000269|PubMed:9003486" FT /id="VAR_002388" FT VARIANT 256 FT /note="S -> T (in allele AHSG*1; dbSNP:rs4918)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:9003486" FT /id="VAR_002389" FT VARIANT 276 FT /note="D -> N (in allele AHSG*5; dbSNP:rs70961709)" FT /evidence="ECO:0000269|PubMed:11415520" FT /id="VAR_012474" FT VARIANT 317 FT /note="R -> C (in allele AHSG*3; dbSNP:rs35457250)" FT /evidence="ECO:0000269|PubMed:11415520" FT /id="VAR_012475" FT VARIANT 317 FT /note="R -> H (in APMR1; uncertain significance; FT dbSNP:rs201849460)" FT /evidence="ECO:0000269|PubMed:28054173" FT /id="VAR_080645" FT CONFLICT 16 FT /note="C -> W (in Ref. 2; BAA22652)" FT /evidence="ECO:0000305" FT CONFLICT 54 FT /note="W -> K (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 125 FT /note="F -> S (in Ref. 10; BAA22651)" FT /evidence="ECO:0000305" FT CONFLICT 150..182 FT /note="PLLAPLNDTRVVHAAKAALAAFNAQNNGSNFQL -> MVGWQEGANHKNGAG FT RSQKQEMAEKMVPEVASG (in Ref. 12; AAF69649)" FT /evidence="ECO:0000305" FT CONFLICT 204 FT /note="S -> C (in Ref. 2; BAA22652)" FT /evidence="ECO:0000305" SQ SEQUENCE 367 AA; 39341 MW; 3FE60C8D6B6272D5 CRC64; MKSLVLLLCL AQLWGCHSAP HGPGLIYRQP NCDDPETEEA ALVAIDYINQ NLPWGYKHTL NQIDEVKVWP QQPSGELFEI EIDTLETTCH VLDPTPVARC SVRQLKEHAV EGDCDFQLLK LDGKFSVVYA KCDSSPDSAE DVRKVCQDCP LLAPLNDTRV VHAAKAALAA FNAQNNGSNF QLEEISRAQL VPLPPSTYVE FTVSGTDCVA KEATEAAKCN LLAEKQYGFC KATLSEKLGG AEVAVTCMVF QTQPVSSQPQ PEGANEAVPT PVVDPDAPPS PPLGAPGLPP AGSPPDSHVL LAAPPGHQLH RAHYDLRHTF MGVVSLGSPS GEVSHPRKTR TVVQPSVGAA AGPVVPPCPG RIRHFKV //