FETUA_RAT
ID FETUA_RAT Reviewed; 352 AA.
AC P24090; Q5BKD2;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Alpha-2-HS-glycoprotein;
DE AltName: Full=59 kDa bone sialic acid-containing protein;
DE Short=BSP;
DE AltName: Full=Fetuin-A;
DE AltName: Full=Glycoprotein PP63;
DE Flags: Precursor;
GN Name=Ahsg; Synonyms=Fetua;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1371750; DOI=10.1111/j.1432-1033.1992.tb16663.x;
RA Rauth G., Poeschke O., Fink E., Eulitz M., Tippmer S., Kellerer M.,
RA Haering H., Nawratil P., Haasemann M., Jahnen-Dechent W.,
RA Mueller-Esterl W.;
RT "The nucleotide and partial amino acid sequences of rat fetuin. Identity
RT with the natural tyrosine kinase inhibitor of the rat insulin receptor.";
RL Eur. J. Biochem. 204:523-529(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2766355; DOI=10.1016/0092-8674(89)90098-6;
RA Auberger P., Falquerho L., Contreres J.O., Pages G., le Cam G., Rossi B.,
RA le Cam A.;
RT "Characterization of a natural inhibitor of the insulin receptor tyrosine
RT kinase: cDNA cloning, purification, and anti-mitogenic activity.";
RL Cell 58:631-640(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SEQUENCE REVISION.
RX PubMed=1849862; DOI=10.1016/0378-1119(91)90175-b;
RA Falquerho L., Patey G., Paqureau L., Rossi V., Lahuna O., Szpirer J.,
RA Szpirer C., Levan G., le Cam A.;
RT "Primary structure of the rat gene encoding an inhibitor of the insulin
RT receptor tyrosine kinase.";
RL Gene 98:209-216(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7681247; DOI=10.1002/jbmr.5650080314;
RA Ohnishi T., Nakamura O., Ozawa M., Arakaki N., Muramatsu T., Daikuhara Y.;
RT "Molecular cloning and sequence analysis of cDNA for a 59 kD bone
RT sialoprotein of the rat: demonstration that it is a counterpart of human
RT alpha 2-HS glycoprotein and bovine fetuin.";
RL J. Bone Miner. Res. 8:367-377(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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 [6]
RP PROTEIN SEQUENCE OF 19-35; 51-64; 165-180; 231-247 AND 327-348.
RC TISSUE=Mandible;
RX PubMed=1860865; DOI=10.1016/s0021-9258(18)98733-8;
RA Ohnishi T., Arakaki N., Nakamura O., Hirono S., Daikuhara Y.;
RT "Purification, characterization, and studies on biosynthesis of a 59-kDa
RT bone sialic acid-containing protein (BSP) from rat mandible using a
RT monoclonal antibody. Evidence that 59-kDa BSP may be the rat counterpart of
RT human alpha 2-HS glycoprotein and is synthesized by both hepatocytes and
RT osteoblasts.";
RL J. Biol. Chem. 266:14636-14645(1991).
RN [7]
RP IDENTITY OF PP63 WITH FETUIN.
RX PubMed=1707273; DOI=10.1042/bj2740899;
RA Haasemann M., Nawratil P., Mueller-Esterl W.;
RT "Rat tyrosine kinase inhibitor shows sequence similarity to human alpha 2-
RT HS glycoprotein and bovine fetuin.";
RL Biochem. J. 274:899-902(1991).
RN [8]
RP IDENTITY OF PP63 WITH FETUIN.
RX PubMed=1370655; DOI=10.1016/0092-8674(92)90200-v;
RA Brown W.M., Christie D.L., Dziegielewska K.M., Saunders N.R., Yang F.;
RT "The rat protein encoded by clone pp63 is a fetuin/alpha 2-HS glycoprotein-
RT like molecule, but is it the tyrosine kinase inhibitor pp63?";
RL Cell 68:7-8(1992).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-138; SER-309; SER-313;
RP SER-316 AND SER-318, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Could inhibit both insulin-receptor tyrosine kinase activity
CC and insulin-stimulated receptor autophosphorylation and, concomitantly,
CC antagonize the mitogenic effect of the hormone in cultured rat hepatoma
CC cells.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Synthesized in liver and secreted by the
CC hepatocytes in the blood.
CC -!- PTM: Undergoes complex post-translational modification involving N-
CC glycosylation, and addition of fucose and sialic acid residues.
CC Phosphorylation occurs at a serine residue.
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; X63446; CAA45042.1; -; mRNA.
DR EMBL; M29758; AAA75502.1; -; mRNA.
DR EMBL; D10261; BAA01101.1; -; mRNA.
DR EMBL; BC091118; AAH91118.1; -; mRNA.
DR PIR; A32827; A32827.
DR RefSeq; NP_037030.1; NM_012898.4.
DR AlphaFoldDB; P24090; -.
DR SMR; P24090; -.
DR BioGRID; 247412; 1.
DR IntAct; P24090; 2.
DR STRING; 10116.ENSRNOP00000055223; -.
DR MEROPS; I25.020; -.
DR MEROPS; I25.021; -.
DR GlyGen; P24090; 3 sites.
DR iPTMnet; P24090; -.
DR PhosphoSitePlus; P24090; -.
DR SwissPalm; P24090; -.
DR PRIDE; P24090; -.
DR Ensembl; ENSRNOT00000058422; ENSRNOP00000055223; ENSRNOG00000038370.
DR GeneID; 25373; -.
DR KEGG; rno:25373; -.
DR UCSC; RGD:2075; rat.
DR CTD; 197; -.
DR RGD; 2075; Ahsg.
DR eggNOG; ENOG502RYRI; Eukaryota.
DR GeneTree; ENSGT00950000182930; -.
DR InParanoid; P24090; -.
DR OrthoDB; 913381at2759; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:P24090; -.
DR Proteomes; UP000002494; Chromosome 11.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:RGD.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
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:0030294; F:receptor signaling protein tyrosine kinase inhibitor activity; IDA:RGD.
DR GO; GO:0006953; P:acute-phase response; ISS:UniProtKB.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR GO; GO:0008584; P:male gonad development; IMP:RGD.
DR GO; GO:0030502; P:negative regulation of bone mineralization; IMP:RGD.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0001503; P:ossification; ISO:RGD.
DR GO; GO:0045780; P:positive regulation of bone resorption; IMP:RGD.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IPI:RGD.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS: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; Disulfide bond; Glycoprotein; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:1860865"
FT CHAIN 19..352
FT /note="Alpha-2-HS-glycoprotein"
FT /id="PRO_0000008897"
FT DOMAIN 19..133
FT /note="Cystatin fetuin-A-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00861"
FT DOMAIN 144..250
FT /note="Cystatin fetuin-A-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00861"
FT REGION 256..280
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 319..338
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="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P29699"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 316
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 32..343
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..247
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00861"
FT CONFLICT 21
FT /note="Q -> E (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 29
FT /note="E -> Q (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 33..34
FT /note="DD -> NN (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 46
FT /note="D -> H (in Ref. 3; AAA75502)"
FT /evidence="ECO:0000305"
FT CONFLICT 76
FT /note="E -> Q (in Ref. 3; AAA75502)"
FT /evidence="ECO:0000305"
FT CONFLICT 236..237
FT /note="HR -> QF (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 241..242
FT /note="EE -> QQ (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="Q -> E (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 352 AA; 37982 MW; 43564F60F3C7C90A CRC64;
MKSLVLLLCF AQLWSCQSAP QGAGLGFREL ACDDPETEHV ALIAVDYLNK HLLQGFRQIL
NQIDKVKVWS RRPFGEVYEL EIDTLETTCH ALDPTPLANC SVRQQAEHAV EGDCDFHILK
QDGQFRVLHA QCHSTPDSAE DVRKFCPRCP ILIRFNDTNV VHTVKTALAA FNAQNNGTYF
KLVEISRAQN VPFPVSTLVE FVIAATDCTG QEVTDPAKCN LLAEKQYGFC KATLIHRLGG
EEVSVACKLF QTQPQPANAN PAGPAPTVGQ AAPVAPPAGP PESVVVGPVA VPLGLPDHRT
HHDLRHAFSP VASVESASGE VLHSPKVGQP GDAGAAGPVA PLCPGRVRYF KI
