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   11-NOV-2015, entry version 128.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS GLY-213; GLY-219 AND VAL-268.
RX   PubMed=2404984;
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;
RP   GLY-219 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.,
RA   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.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   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.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   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.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [5]
RP   PARTIAL PROTEIN SEQUENCE, AND CHARACTERIZATION.
RX   PubMed=3597437;
RA   Fisher L.W., Hawkins G.R., Tuross N., Termine J.D.;
RT   "Purification and partial characterization of small proteoglycans I
RT   and II, bone sialoproteins I and II, and osteonectin from the mineral
RT   compartment 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,
RP   VARIANT 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.,
RA   Maurer P.;
RT   "Structural characterization of human recombinant and bone-derived
RT   bone 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
RT   by mass spectrometry.";
RL   Biochemistry 40:12983-12991(2001).
CC   -!- FUNCTION: Binds tightly to hydroxyapatite. Appears to form an
CC       integral part of the mineralized matrix. Probably important to
CC       cell-matrix interaction. Promotes Arg-Gly-Asp-dependent cell
CC       attachment.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- PTM: N-glycosylated; glycans consist of sialylated and core-
CC       fucosylated bi-, tri- and tetraantennary chains.
CC       {ECO:0000269|PubMed:11459848}.
CC   -!- PTM: O-glycosylated at eight sites; mucin-type glycans contain
CC       Gal, GlcNAc, GalNAc and terminal NeuAc.
CC       {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
CC       carboxyl 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   UniGene; Hs.518726; -.
DR   DisProt; DP00332; -.
DR   ProteinModelPortal; P21815; -.
DR   STRING; 9606.ENSP00000226284; -.
DR   PhosphoSite; P21815; -.
DR   BioMuta; IBSP; -.
DR   DMDM; 317373545; -.
DR   PaxDb; P21815; -.
DR   PRIDE; P21815; -.
DR   DNASU; 3381; -.
DR   Ensembl; ENST00000226284; ENSP00000226284; ENSG00000029559.
DR   GeneID; 3381; -.
DR   KEGG; hsa:3381; -.
DR   UCSC; uc003hqx.4; human.
DR   CTD; 3381; -.
DR   GeneCards; IBSP; -.
DR   H-InvDB; HIX0031506; -.
DR   HGNC; HGNC:5341; IBSP.
DR   MIM; 147563; gene.
DR   neXtProt; NX_P21815; -.
DR   PharmGKB; PA29590; -.
DR   eggNOG; KOG1181; Eukaryota.
DR   eggNOG; ENOG4111M3T; LUCA.
DR   GeneTree; ENSGT00390000002485; -.
DR   HOGENOM; HOG000234824; -.
DR   HOVERGEN; HBG007981; -.
DR   InParanoid; P21815; -.
DR   KO; K06253; -.
DR   OMA; AYEDEYS; -.
DR   OrthoDB; EOG7NW6BX; -.
DR   PhylomeDB; P21815; -.
DR   TreeFam; TF338678; -.
DR   Reactome; R-HSA-216083; Integrin cell surface interactions.
DR   Reactome; R-HSA-3000178; ECM proteoglycans.
DR   GeneWiki; Bone_sialoprotein; -.
DR   GenomeRNAi; 3381; -.
DR   NextBio; 13366; -.
DR   PRO; PR:P21815; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   Bgee; P21815; -.
DR   CleanEx; HS_IBSP; -.
DR   Genevisible; P21815; HS.
DR   GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0031988; C:membrane-bounded vesicle; ISS:UniProtKB.
DR   GO; GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
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; IDA:UniProtKB.
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; Complete proteome;
KW   Direct protein sequencing; Glycoprotein; Phosphoprotein; Polymorphism;
KW   Reference proteome; Secreted; Sialic acid; Signal; Sulfation.
FT   SIGNAL        1     16
FT   CHAIN        17    317       Bone sialoprotein 2.
FT                                /FTId=PRO_0000020330.
FT   MOTIF       286    288       Cell attachment site.
FT   COMPBIAS     65    173       Asp/Glu-rich (acidic).
FT   COMPBIAS     76     83       Poly-Glu.
FT   COMPBIAS    151    158       Poly-Glu.
FT   MOD_RES      31     31       Phosphoserine.
FT                                {ECO:0000269|PubMed:11669636}.
FT   MOD_RES      67     67       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q28862}.
FT   MOD_RES      74     74       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q28862}.
FT   MOD_RES      75     75       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q28862}.
FT   MOD_RES      94     94       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q28862}.
FT   MOD_RES     100    100       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q28862}.
FT   MOD_RES     149    149       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q28862}.
FT   MOD_RES     280    280       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q28862}.
FT   MOD_RES     313    313       Sulfotyrosine.
FT                                {ECO:0000269|PubMed:11669636}.
FT   MOD_RES     314    314       Sulfotyrosine.
FT                                {ECO:0000269|PubMed:11669636}.
FT   CARBOHYD    104    104       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    119    119       O-linked (GalNAc...).
FT                                {ECO:0000305|PubMed:11459848}.
FT   CARBOHYD    122    122       O-linked (GalNAc...).
FT                                {ECO:0000305|PubMed:11459848}.
FT   CARBOHYD    177    177       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    182    182       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    190    190       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    227    227       O-linked (GalNAc...).
FT                                {ECO:0000305|PubMed:11459848}.
FT   CARBOHYD    228    228       O-linked (GalNAc...).
FT                                {ECO:0000305|PubMed:11459848}.
FT   CARBOHYD    229    229       O-linked (GalNAc...).
FT                                {ECO:0000305|PubMed:11459848}.
FT   CARBOHYD    238    238       O-linked (GalNAc...).
FT                                {ECO:0000305|PubMed:11459848}.
FT   CARBOHYD    239    239       O-linked (GalNAc...).
FT                                {ECO:0000305|PubMed:11459848}.
FT   VARIANT     195    195       G -> E (in dbSNP:rs1054627).
FT                                {ECO:0000269|PubMed:8061918,
FT                                ECO:0000269|PubMed:8406493}.
FT                                /FTId=VAR_058014.
FT   VARIANT     213    213       D -> G (in dbSNP:rs13144371).
FT                                {ECO:0000269|PubMed:11459848,
FT                                ECO:0000269|PubMed:2404984,
FT                                ECO:0000269|PubMed:8061918,
FT                                ECO:0000269|PubMed:8406493}.
FT                                /FTId=VAR_058015.
FT   VARIANT     219    219       R -> G (in dbSNP:rs17013181).
FT                                {ECO:0000269|PubMed:2404984,
FT                                ECO:0000269|PubMed:8406493}.
FT                                /FTId=VAR_058016.
FT   VARIANT     256    256       T -> A (in dbSNP:rs17013182).
FT                                /FTId=VAR_056579.
FT   VARIANT     268    268       A -> V (in dbSNP:rs1054628).
FT                                {ECO:0000269|PubMed:2404984}.
FT                                /FTId=VAR_056580.
FT   VARIANT     270    270       E -> D (in dbSNP:rs1054629).
FT                                {ECO:0000269|PubMed:8061918,
FT                                ECO:0000269|PubMed:8406493}.
FT                                /FTId=VAR_058017.
FT   CONFLICT     94     94       S -> L (in Ref. 3; AAC37560).
FT                                {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
//