ID VTNC_HUMAN Reviewed; 478 AA. AC P04004; B2R7G0; P01141; Q9BSH7; DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot. DT 23-OCT-1986, sequence version 1. DT 27-NOV-2024, entry version 259. DE RecName: Full=Vitronectin; DE Short=VN; DE AltName: Full=S-protein; DE AltName: Full=Serum-spreading factor; DE AltName: Full=V75; DE Contains: DE RecName: Full=Vitronectin V65 subunit; DE Contains: DE RecName: Full=Vitronectin V10 subunit; DE Contains: DE RecName: Full=Somatomedin-B; DE Flags: Precursor; GN Name=VTN; 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]. RX PubMed=2414098; DOI=10.1002/j.1460-2075.1985.tb03965.x; RA Suzuki S., Oldberg A., Hayman E.G., Pierschbacher M.D., Ruoslahti E.; RT "Complete amino acid sequence of human vitronectin deduced from cDNA. RT Similarity of cell attachment sites in vitronectin and fibronectin."; RL EMBO J. 4:2519-2524(1985). RN [2] RP SEQUENCE REVISION. RA Suzuki S., Oldberg A., Hayman E.G., Pierschbacher M.D., Ruoslahti E.; RL Submitted (JUN-1986) to the PIR data bank. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3004934; DOI=10.1002/j.1460-2075.1985.tb04058.x; RA Jenne D.E., Stanley K.K.; RT "Molecular cloning of S-protein, a link between complement, coagulation and RT cell-substrate adhesion."; RL EMBO J. 4:3153-3157(1985). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2447940; DOI=10.1021/bi00395a024; RA Jenne D.E., Stanley K.K.; RT "Nucleotide sequence and organization of the human S-protein gene: RT repeating peptide motifs in the 'pexin' family and a model for their RT evolution."; RL Biochemistry 26:6735-6742(1987). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=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 [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-122; GLN-268 AND RP MET-400. RG SeattleSNPs variation discovery resource; RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-400. RC TISSUE=Lung; 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 20-63. RX PubMed=631332; DOI=10.1016/0014-5793(78)80132-x; RA Fryklund L., Sievertsson H.; RT "Primary structure of somatomedin B: a growth hormone-dependent serum RT factor with protease inhibiting activity."; RL FEBS Lett. 87:55-60(1978). RN [9] RP PROTEIN SEQUENCE OF 20-44, AND INTERACTION WITH SERPINE1/PAI1. RX PubMed=7522053; DOI=10.1016/0167-4838(94)90166-x; RA Sigurdardottir O., Wiman B.; RT "Identification of a PAI-1 binding site in vitronectin."; RL Biochim. Biophys. Acta 1208:104-110(1994). RN [10] RP PROTEIN SEQUENCE OF 360-368, AND INTERACTION WITH INSULIN. RX PubMed=1709100; DOI=10.1016/0014-4827(91)90351-t; RA Yaoi Y., Hashimoto K., Takahara K., Kato I.; RT "Insulin binds to type V collagen with retention of mitogenic activity."; RL Exp. Cell Res. 194:180-185(1991). RN [11] RP PROTEIN SEQUENCE OF 393-400, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP PHOSPHORYLATION AT SER-397. RX PubMed=2448300; DOI=10.1016/s0021-9258(19)77969-1; RA McGuire E.A., Peacock M.E., Inhorn R.C., Siegel N.R., Tollefsen D.M.; RT "Phosphorylation of vitronectin by a protein kinase in human plasma. RT Identification of a unique phosphorylation site in the heparin-binding RT domain."; RL J. Biol. Chem. 263:1942-1945(1988). RN [12] RP PROTEIN SEQUENCE OF 399-413. RC TISSUE=Plasma; RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., RA Appel R.D., Hughes G.J.; RL Submitted (JUN-1992) to UniProtKB. RN [13] RP SULFATION. RX PubMed=2479556; DOI=10.1111/j.1432-1033.1989.tb15127.x; RA Jenne D.E., Hille A., Stanley K.K., Huttner W.B.; RT "Sulfation of two tyrosine-residues in human complement S-protein RT (vitronectin)."; RL Eur. J. Biochem. 185:391-395(1989). RN [14] RP PHOSPHORYLATION AT SER-397. RX PubMed=1696913; DOI=10.1016/0014-5793(90)81159-l; RA Chain D., Korc-Grodzicki B., Kreizman T., Shaltiel S.; RT "The phosphorylation of the two-chain form of vitronectin by protein kinase RT A is heparin dependent."; RL FEBS Lett. 269:221-225(1990). RN [15] RP INTERACTION WITH SERPINE1/PAI1. RX PubMed=1704366; DOI=10.1016/s0021-9258(18)49921-8; RA Seiffert D., Loskutoff D.J.; RT "Evidence that type 1 plasminogen activator inhibitor binds to the RT somatomedin B domain of vitronectin."; RL J. Biol. Chem. 266:2824-2830(1991). RN [16] RP INTERACTION WITH C1QBP. RX PubMed=8900153; DOI=10.1074/jbc.271.43.26739; RA Lim B.L., Reid K.B., Ghebrehiwet B., Peerschke E.I., Leigh L.A., RA Preissner K.T.; RT "The binding protein for globular heads of complement C1q, gC1qR. RT Functional expression and characterization as a novel vitronectin binding RT factor."; RL J. Biol. Chem. 271:26739-26744(1996). RN [17] RP PHOSPHORYLATION AT THR-69 AND THR-76, AND MUTAGENESIS OF THR-69 AND THR-76. RX PubMed=9733784; DOI=10.1074/jbc.273.38.24805; RA Seger D., Gechtman Z., Shaltiel S.; RT "Phosphorylation of vitronectin by casein kinase II. Identification of the RT sites and their promotion of cell adhesion and spreading."; RL J. Biol. Chem. 273:24805-24813(1998). RN [18] RP DISULFIDE BONDS IN SOMATOMEDIN-B. RX PubMed=12019263; DOI=10.1074/jbc.m200354200; RA Kamikubo Y., Okumura Y., Loskutoff D.J.; RT "Identification of the disulfide bonds in the recombinant somatomedin B RT domain of human vitronectin."; RL J. Biol. Chem. 277:27109-27119(2002). RN [19] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-169 AND ASN-242. 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 [20] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-169 AND ASN-242. 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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Pituitary; RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x; RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.; RT "Phosphoproteomic analysis of the human pituitary."; RL Pituitary 9:109-120(2006). RN [22] RP SULFATION AT TYR-75 AND TYR-78, PHOSPHORYLATION AT SER-312, GLYCOSYLATION RP AT ASN-86, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=17558413; DOI=10.1038/nmeth1056; RA Yu Y., Hoffhines A.J., Moore K.L., Leary J.A.; RT "Determination of the sites of tyrosine O-sulfation in peptides and RT proteins."; RL Nat. Methods 4:583-588(2007). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312, 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 [24] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-86; ASN-169 AND ASN-242. 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-86 AND ASN-242. 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 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 [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130; SER-137 AND SER-312, AND RP 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 [28] RP TISSUE SPECIFICITY, AND SULFATION. RX PubMed=25136834; DOI=10.1371/journal.pone.0105409; RA Kanan Y., Siefert J.C., Kinter M., Al-Ubaidi M.R.; RT "Complement factor H, vitronectin, and opticin are tyrosine-sulfated RT proteins of the retinal pigment epithelium."; RL PLoS ONE 9:E105409-E105409(2014). RN [29] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [30] RP INTERACTION WITH P.FALCIPARUM SERA5 (MICROBIAL INFECTION), SUBCELLULAR RP LOCATION (MICROBIAL INFECTION), AND TISSUE SPECIFICITY. RX PubMed=29567995; DOI=10.1038/s41598-018-23194-9; RA Tougan T., Edula J.R., Takashima E., Morita M., Shinohara M., Shinohara A., RA Tsuboi T., Horii T.; RT "Molecular Camouflage of Plasmodium falciparum Merozoites by Binding of RT Host Vitronectin to P47 Fragment of SERA5."; RL Sci. Rep. 8:5052-5052(2018). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 22-58 IN COMPLEX WITH RP SERPINE1/PAI1. RX PubMed=12808446; DOI=10.1038/nsb943; RA Zhou A., Huntington J.A., Pannu N.S., Carrell R.W., Read R.J.; RT "How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration."; RL Nat. Struct. Biol. 10:541-544(2003). CC -!- FUNCTION: Vitronectin is a cell adhesion and spreading factor found in CC serum and tissues. Vitronectin interact with glycosaminoglycans and CC proteoglycans. Is recognized by certain members of the integrin family CC and serves as a cell-to-substrate adhesion molecule. Inhibitor of the CC membrane-damaging effect of the terminal cytolytic complement pathway. CC -!- FUNCTION: Somatomedin-B is a growth hormone-dependent serum factor with CC protease-inhibiting activity. CC -!- SUBUNIT: Exists in two forms: a single chain 75 kDa form (V75) and a CC clipped form composed of two chains (65 kDa and 10 kDa) (V65+V10) which CC are held together by a disulfide bond. Interacts with SERPINE1/PAI1, CC insulin and C1QBP. {ECO:0000269|PubMed:12808446, CC ECO:0000269|PubMed:1704366, ECO:0000269|PubMed:1709100, CC ECO:0000269|PubMed:7522053, ECO:0000269|PubMed:8900153}. CC -!- SUBUNIT: (Microbial infection) Interacts (via hemopexin repeat 2) with CC P.falciparum (isolate CDC / Honduras) SERA5 P47 (via C-terminus); may CC form heterotetramers of two VTN and SERA5 P47 heterodimers; the CC interaction may protect merozoites from phagocytosis by host monocytes; CC VTN glycosylation appears to be dispensable for the interaction. CC {ECO:0000269|PubMed:29567995}. CC -!- INTERACTION: CC P04004; Q07021: C1QBP; NbExp=10; IntAct=EBI-1036653, EBI-347528; CC P04004; Q15700: DLG2; NbExp=3; IntAct=EBI-1036653, EBI-80426; CC P04004; Q92796: DLG3; NbExp=3; IntAct=EBI-1036653, EBI-80440; CC P04004; Q9HD26: GOPC; NbExp=4; IntAct=EBI-1036653, EBI-349832; CC P04004; Q9HD26-2: GOPC; NbExp=3; IntAct=EBI-1036653, EBI-11102276; CC P04004; Q9NSN8: SNTG1; NbExp=3; IntAct=EBI-1036653, EBI-19763427; CC P04004; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-1036653, EBI-947187; CC P04004; P75358: gapA; Xeno; NbExp=3; IntAct=EBI-1036653, EBI-2259469; CC P04004; P75167: gpmI; Xeno; NbExp=2; IntAct=EBI-1036653, EBI-2259565; CC P04004; P78007: ldh; Xeno; NbExp=3; IntAct=EBI-1036653, EBI-2260877; CC P04004; A0A024A2C9: lph; Xeno; NbExp=7; IntAct=EBI-1036653, EBI-12498321; CC P04004; P75390: pdhA; Xeno; NbExp=3; IntAct=EBI-1036653, EBI-2259629; CC P04004; P75391: pdhB; Xeno; NbExp=3; IntAct=EBI-1036653, EBI-2259621; CC P04004; P78031: pyk; Xeno; NbExp=3; IntAct=EBI-1036653, EBI-2259473; CC P04004; P75611: tkt; Xeno; NbExp=3; IntAct=EBI-1036653, EBI-12654979; CC P04004; Q4KTX9; Xeno; NbExp=12; IntAct=EBI-1036653, EBI-12501515; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space CC {ECO:0000269|PubMed:2448300, ECO:0000269|PubMed:29567995}. CC -!- SUBCELLULAR LOCATION: Parasitophorous vacuole CC {ECO:0000269|PubMed:29567995}. Note=(Microbial infection) In CC P.falciparum-infected red blood cells, VTN internalization is detected CC at the early trophozoite stage (PubMed:29567995). Colocalizes with CC SERA5 at the schizont stage and with SERA5 P47 at the merozoite surface CC (PubMed:29567995). {ECO:0000269|PubMed:29567995}. CC -!- TISSUE SPECIFICITY: Expressed in the retina pigment epithelium (at CC protein level) (PubMed:25136834). Expressed in plasma (at protein CC level) (PubMed:2448300). Expressed in serum (at protein level) CC (PubMed:29567995). {ECO:0000269|PubMed:2448300, CC ECO:0000269|PubMed:25136834, ECO:0000269|PubMed:29567995}. CC -!- DOMAIN: The SMB domain mediates interaction with SERPINE1/PAI1. The CC heparin-binding domain mediates interaction with insulin. CC -!- PTM: Sulfated on tyrosine residues. {ECO:0000269|PubMed:17558413, CC ECO:0000269|PubMed:2479556, ECO:0000269|PubMed:25136834}. CC -!- PTM: N- and O-glycosylated. {ECO:0000250}. CC -!- PTM: Phosphorylation on Thr-69 and Thr-76 favors cell adhesion and CC spreading. {ECO:0000269|PubMed:9733784}. CC -!- PTM: It has been suggested that the active SMB domain may be permitted CC considerable disulfide bond heterogeneity or variability, thus two CC alternate disulfide patterns based on 3D structures are described with CC 1 disulfide bond conserved in both. CC -!- PTM: Phosphorylation sites are present in the extracellular medium. 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; X03168; CAA26933.1; ALT_SEQ; mRNA. DR EMBL; X05006; CAA28659.1; ALT_SEQ; Genomic_DNA. DR EMBL; AK312968; BAG35807.1; -; mRNA. DR EMBL; AF382388; AAK60270.1; -; Genomic_DNA. DR EMBL; BC005046; AAH05046.1; -; mRNA. DR CCDS; CCDS11229.1; -. DR PIR; A29744; SGHU1V. DR RefSeq; NP_000629.3; NM_000638.3. DR PDB; 1OC0; X-ray; 2.28 A; B=20-70. DR PDB; 1S4G; NMR; -; A=20-70. DR PDB; 1SSU; NMR; -; A=20-70. DR PDB; 2JQ8; NMR; -; A=20-66. DR PDB; 3BT1; X-ray; 2.80 A; B=21-60. DR PDB; 3BT2; X-ray; 2.50 A; B=21-60. DR PDB; 4K24; X-ray; 4.50 A; B=21-60. DR PDB; 6O5E; X-ray; 1.90 A; A/B=154-474. DR PDB; 7RJ9; X-ray; 1.70 A; A/B=154-474. DR PDBsum; 1OC0; -. DR PDBsum; 1S4G; -. DR PDBsum; 1SSU; -. DR PDBsum; 2JQ8; -. DR PDBsum; 3BT1; -. DR PDBsum; 3BT2; -. DR PDBsum; 4K24; -. DR PDBsum; 6O5E; -. DR PDBsum; 7RJ9; -. DR AlphaFoldDB; P04004; -. DR BMRB; P04004; -. DR SMR; P04004; -. DR BioGRID; 113287; 182. DR ComplexPortal; CPX-475; Vitronectin-PAI-1 complex. DR ComplexPortal; CPX-501; uPA-uPAR-vitronectin complex. DR CORUM; P04004; -. DR DIP; DIP-36566N; -. DR ELM; P04004; -. DR IntAct; P04004; 133. DR MINT; P04004; -. DR STRING; 9606.ENSP00000226218; -. DR ChEMBL; CHEMBL1075314; -. DR DrugBank; DB00054; Abciximab. 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 TCDB; 8.B.14.2.5; the sea anemone peptide toxin, class 1 (bgk) family. DR GlyConnect; 625; 78 N-Linked glycans (3 sites). DR GlyCosmos; P04004; 9 sites, 101 glycans. DR GlyGen; P04004; 16 sites, 163 N-linked glycans (4 sites), 5 O-linked glycans (13 sites). DR iPTMnet; P04004; -. DR PhosphoSitePlus; P04004; -. DR SwissPalm; P04004; -. DR BioMuta; VTN; -. DR DMDM; 139653; -. DR CPTAC; CPTAC-690; -. DR jPOST; P04004; -. DR MassIVE; P04004; -. DR PaxDb; 9606-ENSP00000226218; -. DR PeptideAtlas; P04004; -. DR PRIDE; P04004; -. DR ProteomicsDB; 51633; -. DR Pumba; P04004; -. DR Antibodypedia; 79506; 1033 antibodies from 43 providers. DR DNASU; 7448; -. DR Ensembl; ENST00000226218.9; ENSP00000226218.4; ENSG00000109072.14. DR GeneID; 7448; -. DR KEGG; hsa:7448; -. DR MANE-Select; ENST00000226218.9; ENSP00000226218.4; NM_000638.4; NP_000629.3. DR UCSC; uc002hbc.4; human. DR AGR; HGNC:12724; -. DR CTD; 7448; -. DR DisGeNET; 7448; -. DR GeneCards; VTN; -. DR GeneReviews; VTN; -. DR HGNC; HGNC:12724; VTN. DR HPA; ENSG00000109072; Tissue enriched (liver). DR MIM; 193190; gene. DR neXtProt; NX_P04004; -. DR OpenTargets; ENSG00000109072; -. DR PharmGKB; PA37335; -. DR VEuPathDB; HostDB:ENSG00000109072; -. DR eggNOG; KOG1565; Eukaryota. DR GeneTree; ENSGT00530000063751; -. DR HOGENOM; CLU_046227_0_0_1; -. DR InParanoid; P04004; -. DR OMA; LGTYNYD; -. DR OrthoDB; 5310951at2759; -. DR PhylomeDB; P04004; -. DR TreeFam; TF332780; -. DR PathwayCommons; P04004; -. DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres. DR Reactome; R-HSA-216083; Integrin cell surface interactions. DR Reactome; R-HSA-3000170; Syndecan interactions. DR Reactome; R-HSA-3000178; ECM proteoglycans. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR SignaLink; P04004; -. DR SIGNOR; P04004; -. DR BioGRID-ORCS; 7448; 20 hits in 1118 CRISPR screens. DR ChiTaRS; VTN; human. DR EvolutionaryTrace; P04004; -. DR GeneWiki; Vitronectin; -. DR GenomeRNAi; 7448; -. DR Pharos; P04004; Tbio. DR PRO; PR:P04004; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P04004; protein. DR Bgee; ENSG00000109072; Expressed in right lobe of liver and 93 other cell types or tissues. DR ExpressionAtlas; P04004; baseline and differential. DR GO; GO:0071062; C:alphav-beta3 integrin-vitronectin complex; TAS:BHF-UCL. DR GO; GO:0005604; C:basement membrane; IEA:Ensembl. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:BHF-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005796; C:Golgi lumen; IEA:Ensembl. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:1904090; C:peptidase inhibitor complex; IPI:ComplexPortal. DR GO; GO:0098637; C:protein complex involved in cell-matrix adhesion; IPI:ComplexPortal. DR GO; GO:0048237; C:rough endoplasmic reticulum lumen; IEA:Ensembl. DR GO; GO:0005518; F:collagen binding; IEA:Ensembl. DR GO; GO:0050840; F:extracellular matrix binding; IBA:GO_Central. DR GO; GO:0005201; F:extracellular matrix structural constituent; ISS:BHF-UCL. DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB. DR GO; GO:0030247; F:polysaccharide binding; IEA:InterPro. DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0033627; P:cell adhesion mediated by integrin; IDA:BHF-UCL. DR GO; GO:0016477; P:cell migration; IGI:UniProtKB. DR GO; GO:0007160; P:cell-matrix adhesion; IDA:BHF-UCL. DR GO; GO:0035987; P:endodermal cell differentiation; IDA:UniProtKB. DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl. DR GO; GO:0030195; P:negative regulation of blood coagulation; IC:BHF-UCL. DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IDA:BHF-UCL. DR GO; GO:0051918; P:negative regulation of fibrinolysis; NAS:ComplexPortal. DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl. DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IEA:Ensembl. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL. DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL. DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IDA:BHF-UCL. DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IDA:BHF-UCL. DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; TAS:BHF-UCL. DR GO; GO:0090303; P:positive regulation of wound healing; IC:BHF-UCL. DR GO; GO:0051258; P:protein polymerization; IEA:Ensembl. DR GO; GO:0030155; P:regulation of cell adhesion; IDA:ComplexPortal. DR GO; GO:0061302; P:smooth muscle cell-matrix adhesion; IDA:BHF-UCL. DR CDD; cd00094; HX; 1. DR DisProt; DP02913; -. DR FunFam; 4.10.410.20:FF:000002; Ectonucleotide pyrophosphatase/phosphodiesterase family member 2; 1. DR FunFam; 2.110.10.10:FF:000025; Vitronectin; 1. DR FunFam; 2.110.10.10:FF:000010; vitronectin; 1. DR Gene3D; 4.10.410.20; -; 1. DR Gene3D; 2.110.10.10; Hemopexin-like domain; 2. DR InterPro; IPR051298; Heme_transport/Cell_adhesion. DR InterPro; IPR000585; Hemopexin-like_dom. DR InterPro; IPR036375; Hemopexin-like_dom_sf. DR InterPro; IPR018487; Hemopexin-like_repeat. DR InterPro; IPR018486; Hemopexin_CS. DR InterPro; IPR020436; SMB_chordata. DR InterPro; IPR036024; Somatomedin_B-like_dom_sf. DR InterPro; IPR001212; Somatomedin_B_dom. DR PANTHER; PTHR22917; HEMOPEXIN DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR22917:SF3; VITRONECTIN; 1. DR Pfam; PF00045; Hemopexin; 4. DR Pfam; PF01033; Somatomedin_B; 1. DR PRINTS; PR00022; SOMATOMEDINB. DR SMART; SM00120; HX; 4. DR SMART; SM00201; SO; 1. DR SUPFAM; SSF50923; Hemopexin-like domain; 1. DR SUPFAM; SSF90188; Somatomedin B domain; 1. DR PROSITE; PS00024; HEMOPEXIN; 2. DR PROSITE; PS51642; HEMOPEXIN_2; 4. DR PROSITE; PS00524; SMB_1; 1. DR PROSITE; PS50958; SMB_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell adhesion; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Heparin-binding; Phosphoprotein; Proteomics identification; KW Reference proteome; Repeat; Secreted; Signal; Sulfation. FT SIGNAL 1..19 FT /evidence="ECO:0000269|PubMed:631332, FT ECO:0000269|PubMed:7522053" FT CHAIN 20..478 FT /note="Vitronectin" FT /id="PRO_0000036394" FT CHAIN 20..398 FT /note="Vitronectin V65 subunit" FT /id="PRO_0000036395" FT PEPTIDE 20..63 FT /note="Somatomedin-B" FT /id="PRO_0000036396" FT CHAIN 399..478 FT /note="Vitronectin V10 subunit" FT /id="PRO_0000036397" FT DOMAIN 20..63 FT /note="SMB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350" FT REPEAT 158..202 FT /note="Hemopexin 1" FT REPEAT 203..250 FT /note="Hemopexin 2" FT REPEAT 251..305 FT /note="Hemopexin 3" FT REPEAT 419..472 FT /note="Hemopexin 4" FT REGION 91..158 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 362..395 FT /note="Heparin-binding" FT REGION 364..398 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 64..66 FT /note="Cell attachment site" FT COMPBIAS 91..112 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 366..392 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 398..399 FT /note="Cleavage" FT MOD_RES 69 FT /note="Phosphothreonine; by CK2; in vitro" FT /evidence="ECO:0000269|PubMed:9733784" FT MOD_RES 75 FT /note="Sulfotyrosine" FT /evidence="ECO:0000269|PubMed:17558413" FT MOD_RES 76 FT /note="Phosphothreonine; by CK2; in vitro" FT /evidence="ECO:0000269|PubMed:9733784" FT MOD_RES 78 FT /note="Sulfotyrosine" FT /evidence="ECO:0000269|PubMed:17558413" FT MOD_RES 130 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 137 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 282 FT /note="Sulfotyrosine" FT /evidence="ECO:0000255" FT MOD_RES 312 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:17558413, FT ECO:0007744|PubMed:16807684, ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:24275569" FT MOD_RES 397 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:1696913, FT ECO:0000269|PubMed:2448300" FT MOD_RES 417 FT /note="Sulfotyrosine" FT /evidence="ECO:0000255" FT MOD_RES 420 FT /note="Sulfotyrosine" FT /evidence="ECO:0000255" FT CARBOHYD 86 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:17558413, FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218" FT CARBOHYD 169 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218" FT CARBOHYD 242 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:14760718, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19159218" FT DISULFID 24..40 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350" FT DISULFID 24..28 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:12019263" FT DISULFID 28..58 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350" FT DISULFID 38..51 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350" FT DISULFID 38..40 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:12019263" FT DISULFID 44..50 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:12019263" FT DISULFID 51..58 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:12019263" FT DISULFID 293..430 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350, FT ECO:0000269|PubMed:12019263" FT VARIANT 122 FT /note="A -> S (in dbSNP:rs2227741)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_012983" FT VARIANT 268 FT /note="R -> Q (in dbSNP:rs2227723)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_012984" FT VARIANT 400 FT /note="T -> M (in dbSNP:rs704)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.6" FT /id="VAR_012985" FT MUTAGEN 69 FT /note="T->A: Abolishes phosphorylation by CK2 and inhibits FT adhesion and spreading; when associated with A-76." FT /evidence="ECO:0000269|PubMed:9733784" FT MUTAGEN 69 FT /note="T->E: Abolishes phosphorylation by CK2 and enhances FT adhesion and spreading; when associated with E-76." FT /evidence="ECO:0000269|PubMed:9733784" FT MUTAGEN 76 FT /note="T->A: Abolishes phosphorylation by CK2 and inhibits FT adhesion and spreading; when associated with A-69." FT /evidence="ECO:0000269|PubMed:9733784" FT MUTAGEN 76 FT /note="T->E: Abolishes phosphorylation by CK2 and enhances FT adhesion and spreading; when associated with E-69." FT /evidence="ECO:0000269|PubMed:9733784" FT CONFLICT 50 FT /note="C -> N (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 225 FT /note="S -> N (in Ref. 3 and 4)" FT /evidence="ECO:0000305" FT CONFLICT 366 FT /note="A -> T (in Ref. 3; CAA26933)" FT /evidence="ECO:0000305" FT STRAND 22..24 FT /evidence="ECO:0007829|PDB:1S4G" FT TURN 25..29 FT /evidence="ECO:0007829|PDB:1SSU" FT STRAND 32..34 FT /evidence="ECO:0007829|PDB:1S4G" FT STRAND 36..39 FT /evidence="ECO:0007829|PDB:1OC0" FT HELIX 44..47 FT /evidence="ECO:0007829|PDB:1OC0" FT TURN 51..53 FT /evidence="ECO:0007829|PDB:1S4G" FT HELIX 54..57 FT /evidence="ECO:0007829|PDB:1OC0" FT STRAND 65..68 FT /evidence="ECO:0007829|PDB:1S4G" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 171..176 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 179..183 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 193..195 FT /evidence="ECO:0007829|PDB:6O5E" FT HELIX 196..199 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 208..211 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 214..216 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 219..223 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 226..231 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:7RJ9" FT HELIX 243..246 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 255..260 FT /evidence="ECO:0007829|PDB:7RJ9" FT TURN 264..266 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 270..275 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 278..283 FT /evidence="ECO:0007829|PDB:7RJ9" FT HELIX 335..338 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 347..351 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 435..440 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 443..448 FT /evidence="ECO:0007829|PDB:7RJ9" FT TURN 449..451 FT /evidence="ECO:0007829|PDB:7RJ9" FT STRAND 461..464 FT /evidence="ECO:0007829|PDB:7RJ9" FT HELIX 465..468 FT /evidence="ECO:0007829|PDB:7RJ9" SQ SEQUENCE 478 AA; 54306 MW; 0D6DB5591CBFEF45 CRC64; MAPLRPLLIL ALLAWVALAD QESCKGRCTE GFNVDKKCQC DELCSYYQSC CTDYTAECKP QVTRGDVFTM PEDEYTVYDD GEEKNNATVH EQVGGPSLTS DLQAQSKGNP EQTPVLKPEE EAPAPEVGAS KPEGIDSRPE TLHPGRPQPP AEEELCSGKP FDAFTDLKNG SLFAFRGQYC YELDEKAVRP GYPKLIRDVW GIEGPIDAAF TRINCQGKTY LFKGSQYWRF EDGVLDPDYP RNISDGFDGI PDNVDAALAL PAHSYSGRER VYFFKGKQYW EYQFQHQPSQ EECEGSSLSA VFEHFAMMQR DSWEDIFELL FWGRTSAGTR QPQFISRDWH GVPGQVDAAM AGRIYISGMA PRPSLAKKQR FRHRNRKGYR SQRGHSRGRN QNSRRPSRAT WLSLFSSEES NLGANNYDDY RMDWLVPATC EPIQSVFFFS GDKYYRVNLR TRRVDTVDPP YPRSIAQYWL GCPAPGHL //