ID SIAL_HUMAN Reviewed; 317 AA. AC P21815; DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 4. DT 27-NOV-2024, entry version 179. DE RecName: Full=Integrin-binding sialoprotein {ECO:0000303|PubMed:36261010}; DE AltName: Full=Bone sialoprotein 2 {ECO:0000305}; DE AltName: Full=Bone sialoprotein II; DE Short=BSP II; DE AltName: Full=Cell-binding sialoprotein; DE Flags: Precursor; GN Name=IBSP; Synonyms=BNSP; 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 GLY-213; GLY-219 AND VAL-268. RX PubMed=2404984; DOI=10.1016/s0021-9258(19)39982-x; RA Fisher L.W., McBride O.W., Termine J.D., Young M.F.; RT "Human bone sialoprotein. Deduced protein sequence and chromosomal RT localization."; RL J. Biol. Chem. 265:2347-2351(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-195; GLY-213; GLY-219 RP AND ASP-270. RX PubMed=8406493; DOI=10.1006/geno.1993.1340; RA Kerr J.M., Fisher L.W., Termine J.D., Wang M.G., McBride W., Young M.F.; RT "The human bone sialoprotein gene (IBSP): genomic localization and RT characterization."; RL Genomics 17:408-415(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-195; GLY-213 AND RP ASP-270. RX PubMed=8061918; DOI=10.1016/0945-053x(94)90027-2; RA Kim R.H., Shapiro H.S., Li J.J., Wrana J.L., Sodek J.; RT "Characterization of the human bone sialoprotein (BSP) gene and its RT promoter sequence."; RL Matrix Biol. 14:31-40(1994). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION. RX PubMed=3597437; DOI=10.1016/s0021-9258(18)47991-4; RA Fisher L.W., Hawkins G.R., Tuross N., Termine J.D.; RT "Purification and partial characterization of small proteoglycans I and II, RT bone sialoproteins I and II, and osteonectin from the mineral compartment RT of developing human bone."; RL J. Biol. Chem. 262:9702-9708(1987). RN [6] RP PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, GLYCOSYLATION AT THR-119; THR-122; THR-227; THR-228; THR-229; RP THR-238 AND THR-239, STRUCTURE OF CARBOHYDRATE, VARIANT GLY-213, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11459848; DOI=10.1074/jbc.m105689200; RA Wuttke M., Muller S., Nitsche D.P., Paulsson M., Hanisch F.G., Maurer P.; RT "Structural characterization of human recombinant and bone-derived bone RT sialoprotein. Functional implications for cell attachment and RT hydroxyapatite binding."; RL J. Biol. Chem. 276:36839-36848(2001). RN [7] RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=1818768; DOI=10.1007/bf02555854; RA Bianco P., Fisher L.W., Young M.F., Termine J.D., Robey P.G.; RT "Expression of bone sialoprotein (BSP) in developing human tissues."; RL Calcif. Tissue Int. 49:421-426(1991). RN [8] RP FUNCTION, AND DOMAIN. RX PubMed=10640428; DOI=10.1006/excr.1999.4765; RA Byzova T.V., Kim W., Midura R.J., Plow E.F.; RT "Activation of integrin alpha(V)beta(3) regulates cell adhesion and RT migration to bone sialoprotein."; RL Exp. Cell Res. 254:299-308(2000). RN [9] RP PHOSPHORYLATION AT SER-31, SULFATION AT TYR-313 AND TYR-314, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11669636; DOI=10.1021/bi010887r; RA Zaia J., Boynton R., Heinegard D., Barry F.; RT "Posttranslational modifications to human bone sialoprotein determined by RT mass spectrometry."; RL Biochemistry 40:12983-12991(2001). RN [10] RP FUNCTION, DOMAIN, AND MUTAGENESIS OF 286-ARG--ASP-288 AND ASP-288. RX PubMed=24103036; DOI=10.1111/eos.12081; RA Rapuano B.E., MacDonald D.E.; RT "Structure-activity relationship of human bone sialoprotein peptides."; RL Eur. J. Oral Sci. 121:600-609(2013). RN [11] RP TISSUE SPECIFICITY. RX PubMed=36261010; DOI=10.1016/j.celrep.2022.111511; RA Ghochani Y., Muthukrishnan S.D., Sohrabi A., Kawaguchi R., Condro M.C., RA Bastola S., Gao F., Qin Y., Mottahedeh J., Iruela-Arispe M.L., Rao N., RA Laks D.R., Liau L.M., Mathern G.W., Goldman S.A., Carmichael S.T., RA Nakano I., Coppola G., Seidlits S.K., Kornblum H.I.; RT "A molecular interactome of the glioblastoma perivascular niche reveals RT integrin binding sialoprotein as a mediator of tumor cell migration."; RL Cell Rep. 41:111511-111511(2022). CC -!- FUNCTION: Binds tightly to hydroxyapatite (PubMed:11459848). Appears to CC form an integral part of the mineralized matrix (PubMed:1818768). CC Probably important to cell-matrix interaction (PubMed:1818768). CC Promotes adhesion and migration of various cells via the alpha-V/beta-3 CC integrin receptor (ITGAV:ITGB3) (PubMed:10640428, PubMed:11459848, CC PubMed:24103036). {ECO:0000269|PubMed:10640428, CC ECO:0000269|PubMed:11459848, ECO:0000269|PubMed:1818768, CC ECO:0000269|PubMed:24103036}. CC -!- SUBUNIT: Monomer (PubMed:11459848). Interacts with integrins; the CC interaction promotes cell adhesion (By similarity). CC {ECO:0000250|UniProtKB:Q28862, ECO:0000269|PubMed:11459848}. CC -!- INTERACTION: CC P21815; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-18400392, EBI-10175124; CC P21815; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-18400392, EBI-12175685; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11459848}. CC -!- TISSUE SPECIFICITY: Expressed in bone (at protein level) CC (PubMed:11459848). Expressed in trophoblast cells of placenta (at CC protein level) (PubMed:1818768). Expressed in brain (PubMed:36261010). CC {ECO:0000269|PubMed:11459848, ECO:0000269|PubMed:1818768, CC ECO:0000269|PubMed:36261010}. CC -!- DEVELOPMENTAL STAGE: In fetal developing bone of gestational age of 14- CC 17 weeks, expressed in mature osteoblasts, young osteocytes and CC osteoclasts (at protein level) (PubMed:1818768). Expressed in bone CC matrix (at protein level) (PubMed:1818768). Expressed in osteoid at the CC borderline with mature mineralized matrix (at protein level) CC (PubMed:1818768). Expressed in chondrocytes in the growth plate (at CC protein level) (PubMed:1818768). Not detected in preosteogenic cells in CC the inner layer of the periosteum and in the fibroblastic cells in the CC outer layer (at protein level) (PubMed:1818768). Not detected in CC cartilage matrix (at protein level) (PubMed:1818768). Not detected in CC ocular tissues, skin, tendon, muscle and kidney of gestational age of CC 14-17 weeks (at protein level) (PubMed:1818768). CC {ECO:0000269|PubMed:1818768}. CC -!- DOMAIN: The Arg-Gly-Asp (RGD) sequence serves as an integrin-binding CC motif and is required for integrin-mediated cell attachment. CC {ECO:0000269|PubMed:10640428, ECO:0000269|PubMed:24103036}. CC -!- PTM: N-glycosylated; glycans consist of sialylated and core-fucosylated CC bi-, tri- and tetraantennary chains. {ECO:0000269|PubMed:11459848}. CC -!- PTM: O-glycosylated at eight sites; mucin-type glycans contain Gal, CC GlcNAc, GalNAc and terminal NeuAc. {ECO:0000269|PubMed:11459848}. CC -!- MISCELLANEOUS: It is possible that the segments of clustered carboxyl CC groups mediate the strong binding to hydroxyapatite. Highly expressed CC in glioblastoma samples, especially in microvascular-enriched regions CC (PubMed:36261010). Elevated expression correlates with poor survival in CC patients with proneural glioblastomas (PubMed:36261010). Promotes up- CC regulation of genes associated with mesenchymal phenotype in proneural CC glioblastoma cultures (PubMed:36261010). Promotes migration and CC proliferation of glioblastoma, breast carcinoma and melanoma cells CC (PubMed:10640428, PubMed:36261010). ITGAV, ITGAV:ITGB3 or ITGAV:ITGB5 CC act as integrin receptors for IBSP in glioblastoma, breast carcinoma CC and melanoma cells (PubMed:10640428, PubMed:36261010). CC {ECO:0000269|PubMed:10640428, ECO:0000269|PubMed:36261010}. 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; J05213; AAC95490.1; -; mRNA. DR EMBL; L09558; AAA60549.1; -; Genomic_DNA. DR EMBL; L09554; AAA60549.1; JOINED; Genomic_DNA. DR EMBL; L09555; AAA60549.1; JOINED; Genomic_DNA. DR EMBL; L09556; AAA60549.1; JOINED; Genomic_DNA. DR EMBL; L09557; AAA60549.1; JOINED; Genomic_DNA. DR EMBL; L24759; AAC37560.1; -; Genomic_DNA. DR EMBL; L24757; AAC37560.1; JOINED; Genomic_DNA. DR EMBL; AC093768; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS3624.1; -. DR PIR; A35043; GEHUS. DR RefSeq; NP_004958.2; NM_004967.3. DR AlphaFoldDB; P21815; -. DR BioGRID; 109608; 14. DR IntAct; P21815; 12. DR STRING; 9606.ENSP00000226284; -. DR GlyCosmos; P21815; 11 sites, No reported glycans. DR GlyGen; P21815; 11 sites. DR iPTMnet; P21815; -. DR PhosphoSitePlus; P21815; -. DR BioMuta; IBSP; -. DR DMDM; 317373545; -. DR MassIVE; P21815; -. DR PaxDb; 9606-ENSP00000226284; -. DR PeptideAtlas; P21815; -. DR ProteomicsDB; 53929; -. DR Antibodypedia; 14494; 369 antibodies from 32 providers. DR DNASU; 3381; -. DR Ensembl; ENST00000226284.7; ENSP00000226284.5; ENSG00000029559.7. DR GeneID; 3381; -. DR KEGG; hsa:3381; -. DR MANE-Select; ENST00000226284.7; ENSP00000226284.5; NM_004967.4; NP_004958.2. DR UCSC; uc003hqx.5; human. DR AGR; HGNC:5341; -. DR CTD; 3381; -. DR DisGeNET; 3381; -. DR GeneCards; IBSP; -. DR HGNC; HGNC:5341; IBSP. DR HPA; ENSG00000029559; Tissue enhanced (pituitary). DR MIM; 147563; gene. DR neXtProt; NX_P21815; -. DR OpenTargets; ENSG00000029559; -. DR PharmGKB; PA29590; -. DR VEuPathDB; HostDB:ENSG00000029559; -. DR eggNOG; KOG1181; Eukaryota. DR GeneTree; ENSGT00390000002485; -. DR HOGENOM; CLU_076119_0_0_1; -. DR InParanoid; P21815; -. DR OMA; HAYFYPH; -. DR OrthoDB; 4616590at2759; -. DR PhylomeDB; P21815; -. DR TreeFam; TF338678; -. DR PathwayCommons; P21815; -. DR Reactome; R-HSA-216083; Integrin cell surface interactions. DR Reactome; R-HSA-3000178; ECM proteoglycans. DR SignaLink; P21815; -. DR SIGNOR; P21815; -. DR BioGRID-ORCS; 3381; 9 hits in 1142 CRISPR screens. DR ChiTaRS; IBSP; human. DR GeneWiki; Bone_sialoprotein; -. DR GenomeRNAi; 3381; -. DR Pharos; P21815; Tbio. DR PRO; PR:P21815; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P21815; protein. DR Bgee; ENSG00000029559; Expressed in tibia and 105 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0031982; C:vesicle; ISS:UniProtKB. DR GO; GO:0005178; F:integrin binding; IMP:CAFA. DR GO; GO:0036094; F:small molecule binding; IPI:DisProt. DR GO; GO:0030282; P:bone mineralization; IBA:GO_Central. DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB. DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISS:UniProtKB. DR GO; GO:0030198; P:extracellular matrix organization; ISS:UniProtKB. DR GO; GO:0001649; P:osteoblast differentiation; HDA:UniProtKB. DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:CAFA. DR DisProt; DP00332; -. DR InterPro; IPR008412; IBSP. DR PANTHER; PTHR10345; BONE SIALOPROTEIN 2; 1. DR PANTHER; PTHR10345:SF0; BONE SIALOPROTEIN 2; 1. DR Pfam; PF05432; BSP_II; 1. PE 1: Evidence at protein level; KW Biomineralization; Cell adhesion; Direct protein sequencing; Glycoprotein; KW Phosphoprotein; Proteomics identification; Reference proteome; Secreted; KW Sialic acid; Signal; Sulfation. FT SIGNAL 1..16 FT /evidence="ECO:0000255" FT CHAIN 17..317 FT /note="Integrin-binding sialoprotein" FT /id="PRO_0000020330" FT REGION 58..254 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 286..288 FT /note="Integrin-binding motif" FT /evidence="ECO:0000305|PubMed:10640428, FT ECO:0000305|PubMed:24103036" FT COMPBIAS 69..103 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 149..171 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 172..195 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 210..254 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 31 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11669636" FT MOD_RES 67 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q28862" FT MOD_RES 74 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q28862" FT MOD_RES 75 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q28862" FT MOD_RES 94 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q28862" FT MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q28862" FT MOD_RES 149 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q28862" FT MOD_RES 280 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q28862" FT MOD_RES 313 FT /note="Sulfotyrosine" FT /evidence="ECO:0000269|PubMed:11669636" FT MOD_RES 314 FT /note="Sulfotyrosine" FT /evidence="ECO:0000269|PubMed:11669636" FT CARBOHYD 104 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 119 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000305|PubMed:11459848" FT CARBOHYD 122 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000305|PubMed:11459848" FT CARBOHYD 177 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 182 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 190 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 227 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000305|PubMed:11459848" FT CARBOHYD 228 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000305|PubMed:11459848" FT CARBOHYD 229 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000305|PubMed:11459848" FT CARBOHYD 238 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000305|PubMed:11459848" FT CARBOHYD 239 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000305|PubMed:11459848" FT VARIANT 195 FT /note="G -> E (in dbSNP:rs1054627)" FT /evidence="ECO:0000269|PubMed:8061918, FT ECO:0000269|PubMed:8406493" FT /id="VAR_058014" FT VARIANT 213 FT /note="D -> G (in dbSNP:rs13144371)" FT /evidence="ECO:0000269|PubMed:11459848, FT ECO:0000269|PubMed:2404984, ECO:0000269|PubMed:8061918, FT ECO:0000269|PubMed:8406493" FT /id="VAR_058015" FT VARIANT 219 FT /note="R -> G (in dbSNP:rs17013181)" FT /evidence="ECO:0000269|PubMed:2404984, FT ECO:0000269|PubMed:8406493" FT /id="VAR_058016" FT VARIANT 256 FT /note="T -> A (in dbSNP:rs17013182)" FT /id="VAR_056579" FT VARIANT 268 FT /note="A -> V (in dbSNP:rs1054628)" FT /evidence="ECO:0000269|PubMed:2404984" FT /id="VAR_056580" FT VARIANT 270 FT /note="E -> D (in dbSNP:rs1054629)" FT /evidence="ECO:0000269|PubMed:8061918, FT ECO:0000269|PubMed:8406493" FT /id="VAR_058017" FT MUTAGEN 286..288 FT /note="RGD->KAE: Significantly reduces cell attachment FT activity." FT /evidence="ECO:0000269|PubMed:24103036" FT MUTAGEN 288 FT /note="D->E: Modestly reduces cell attachment activity." FT /evidence="ECO:0000269|PubMed:24103036" FT CONFLICT 94 FT /note="S -> L (in Ref. 3; AAC37560)" FT /evidence="ECO:0000305" SQ SEQUENCE 317 AA; 35148 MW; 736CB6B8C3716FE7 CRC64; MKTALILLSI LGMACAFSMK NLHRRVKIED SEENGVFKYR PRYYLYKHAY FYPHLKRFPV QGSSDSSEEN GDDSSEEEEE EEETSNEGEN NEESNEDEDS EAENTTLSAT TLGYGEDATP GTGYTGLAAI QLPKKAGDIT NKATKEKESD EEEEEEEEGN ENEESEAEVD ENEQGINGTS TNSTEAENGN GSSGGDNGEE GEEESVTGAN AEDTTETGRQ GKGTSKTTTS PNGGFEPTTP PQVYRTTSPP FGKTTTVEYE GEYEYTGANE YDNGYEIYES ENGEPRGDNY RAYEDEYSYF KGQGYDGYDG QNYYHHQ //