SIAL_HUMAN
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 03-AUG-2022, entry version 166.
DE RecName: Full=Bone sialoprotein 2;
DE AltName: Full=Bone sialoprotein II;
DE Short=BSP II;
DE AltName: Full=Cell-binding sialoprotein;
DE AltName: Full=Integrin-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, GLYCOSYLATION AT THR-119; THR-122; THR-227;
RP THR-228; THR-229; THR-238 AND THR-239, STRUCTURE OF CARBOHYDRATE, VARIANT
RP GLY-213, AND 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 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).
CC -!- FUNCTION: Binds tightly to hydroxyapatite. Appears to form an integral
CC part of the mineralized matrix. Probably important to cell-matrix
CC interaction. Promotes Arg-Gly-Asp-dependent cell attachment.
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.
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 -!- PTM: Sulfated on either Tyr-313 or Tyr-314.
CC {ECO:0000269|PubMed:11669636}.
CC -!- MISCELLANEOUS: It is possible that the segments of clustered carboxyl
CC groups mediate the strong binding to hydroxyapatite.
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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; 13.
DR IntAct; P21815; 2.
DR STRING; 9606.ENSP00000226284; -.
DR GlyGen; P21815; 11 sites.
DR iPTMnet; P21815; -.
DR PhosphoSitePlus; P21815; -.
DR BioMuta; IBSP; -.
DR DMDM; 317373545; -.
DR PaxDb; P21815; -.
DR PeptideAtlas; P21815; -.
DR PRIDE; P21815; -.
DR ProteomicsDB; 53929; -.
DR Antibodypedia; 14494; 390 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 CTD; 3381; -.
DR DisGeNET; 3381; -.
DR GeneCards; IBSP; -.
DR HGNC; HGNC:5341; IBSP.
DR HPA; ENSG00000029559; Tissue enhanced (brain, pituitary gland).
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; QDYYYHQ; -.
DR OrthoDB; 1565775at2759; -.
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 1064 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 tissues.
DR Genevisible; P21815; HS.
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: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; BSP_II.
DR PANTHER; PTHR10345; PTHR10345; 1.
DR Pfam; PF05432; BSP_II; 1.
PE 1: Evidence at protein level;
KW Biomineralization; Cell adhesion; Direct protein sequencing; Glycoprotein;
KW Phosphoprotein; Reference proteome; Secreted; Sialic acid; Signal;
KW Sulfation.
FT SIGNAL 1..16
FT CHAIN 17..317
FT /note="Bone sialoprotein 2"
FT /id="PRO_0000020330"
FT REGION 58..254
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 286..288
FT /note="Cell attachment site"
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 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
