FETUA_HUMAN
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 03-AUG-2022, entry version 223.
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}.
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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; 76.
DR IntAct; P02765; 41.
DR MINT; P02765; -.
DR STRING; 9606.ENSP00000393887; -.
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 GlyGen; P02765; 15 sites, 81 N-linked glycans (2 sites), 15 O-linked glycans (11 sites).
DR iPTMnet; P02765; -.
DR PhosphoSitePlus; P02765; -.
DR BioMuta; AHSG; -.
DR DMDM; 112910; -.
DR DOSAC-COBS-2DPAGE; P02765; -.
DR SWISS-2DPAGE; P02765; -.
DR CPTAC; non-CPTAC-1066; -.
DR CPTAC; non-CPTAC-1067; -.
DR jPOST; P02765; -.
DR MassIVE; P02765; -.
DR MaxQB; P02765; -.
DR PaxDb; P02765; -.
DR PeptideAtlas; P02765; -.
DR PRIDE; P02765; -.
DR ProteomicsDB; 51585; -.
DR TopDownProteomics; P02765; -.
DR Antibodypedia; 870; 673 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 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; 913381at2759; -.
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 BioGRID-ORCS; 197; 10 hits in 1068 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 113 other tissues.
DR ExpressionAtlas; P02765; baseline and differential.
DR Genevisible; P02765; HS.
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:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
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 InterPro; IPR000010; Cystatin_dom.
DR InterPro; IPR025760; Cystatin_Fetuin_A.
DR InterPro; IPR046350; Cystatin_sf.
DR InterPro; IPR001363; Prot_inh_fetuin_CS.
DR Pfam; PF00031; Cystatin; 1.
DR SMART; SM00043; CY; 2.
DR SUPFAM; SSF54403; SSF54403; 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; 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; unknown pathological 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
