ID   OSTP_HUMAN              Reviewed;         314 AA.
AC   P10451; Q15681; Q15682; Q15683; Q8NBK2; Q96IZ1;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   18-MAR-2008, entry version 100.
DE   Osteopontin precursor (Bone sialoprotein 1) (Secreted phosphoprotein
DE   1) (SPP-1) (Urinary stone protein) (Nephropontin) (Uropontin).
GN   Name=SPP1; Synonyms=BNSP, OPN; ORFNames=PSEC0156;
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] (ISOFORM A).
RX   MEDLINE=89263749; PubMed=2726470; DOI=10.1093/nar/17.8.3306;
RA   Kiefer M.C., Bauer D.M., Barr P.J.;
RT   "The cDNA and derived amino acid sequence for human osteopontin.";
RL   Nucleic Acids Res. 17:3306-3306(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RX   MEDLINE=90353945; PubMed=1974876; DOI=10.1016/0888-7543(90)90191-V;
RA   Young M.F., Kerr J.M., Termine J.D., Wewer U.M., Wang M.G.,
RA   McBride O.W., Fisher L.W.;
RT   "cDNA cloning, mRNA distribution and heterogeneity, chromosomal
RT   location, and RFLP analysis of human osteopontin (OPN).";
RL   Genomics 7:491-502(1990).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RX   MEDLINE=92108068; PubMed=1729712;
RA   Shiraga H., Min W., VanDusen W.J., Clayman M.D., Miner D.,
RA   Terrell C.H., Sherbotie J.R., Foreman J.W., Przysiecki C.,
RA   Neilson E.G., Hoyer J.R.;
RT   "Inhibition of calcium oxalate crystal growth in vitro by uropontin:
RT   another member of the aspartic acid-rich protein superfamily.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:426-430(1992).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A).
RX   MEDLINE=95394452; PubMed=7665163; DOI=10.1006/geno.1995.1018;
RA   Crosby A.H., Edwards S.J., Murray J.C., Dixon M.J.;
RT   "Genomic organization of the human osteopontin gene: exclusion of the
RT   locus from a causative role in the pathogenesis of dentinogenesis
RT   imperfecta type II.";
RL   Genomics 27:155-160(1995).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A).
RC   TISSUE=Liver;
RX   MEDLINE=95031968; PubMed=7945249;
RA   Hijiya N., Setoguchi M., Matsuura K., Higuchi Y., Akizuki S.,
RA   Yamamoto S.;
RT   "Cloning and characterization of the human osteopontin gene and its
RT   promoter.";
RL   Biochem. J. 303:255-262(1994).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C).
RX   MEDLINE=95139605; PubMed=7837791;
RA   Saitoh Y., Kuratsu J., Takeshima H., Yamamoto S., Ushio Y.;
RT   "Expression of osteopontin in human glioma. Its correlation with the
RT   malignancy.";
RL   Lab. Invest. 72:55-63(1995).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC   TISSUE=Brain;
RA   Yu W., Sarginson J., Gibbs R.A.;
RL   Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D).
RC   TISSUE=Placenta;
RA   Ota T., Nishikawa T., Suzuki Y., Kawai-Hio Y., Hayashi K., Ishii S.,
RA   Saito K., Yamamoto J., Wakamatsu A., Nagai T., Nakamura Y.,
RA   Nagahari K., Sugano S., Isogai T.;
RT   "HRI human cDNA sequencing project.";
RL   Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
RC   TISSUE=Brain, and Kidney;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 67-278.
RC   TISSUE=Kidney;
RX   MEDLINE=92246977; PubMed=1575754; DOI=10.1016/0006-291X(92)90669-C;
RA   Kohri K., Suzuki Y., Yoshida K., Yamamoto K., Amasaki N., Yamate T.,
RA   Umekawa T., Iguchi M., Sinohara H., Kurita T.;
RT   "Molecular cloning and sequencing of cDNA encoding urinary stone
RT   protein, which is identical to osteopontin.";
RL   Biochem. Biophys. Res. Commun. 184:859-864(1992).
RN   [11]
RP   PROTEIN SEQUENCE OF 17-23 AND 169-182.
RC   TISSUE=Milk;
RX   MEDLINE=89287357; PubMed=2736258; DOI=10.1016/0167-4838(89)90092-7;
RA   Senger D.R., Perruzzi C.A., Papadopoulos A., Tenen D.G.;
RT   "Purification of a human milk protein closely similar to tumor-
RT   secreted phosphoproteins and osteopontin.";
RL   Biochim. Biophys. Acta 996:43-48(1989).
RN   [12]
RP   PHOSPHORYLATION AT SER-24; SER-26; SER-27; SER-62; SER-63; THR-66;
RP   SER-76; SER-81; SER-99; SER-102; SER-108; SER-117; SER-120; SER-123;
RP   SER-129; THR-185; SER-191; SER-195; SER-215; SER-219; SER-224;
RP   SER-228; SER-234; SER-254; SER-263; SER-267; SER-275; SER-280;
RP   SER-303; SER-308; SER-310; SER-105 AND SER-126, AND GLYCOSYLATION AT
RP   ASN-79; ASN-106; THR-134; THR-138; THR-143; THR-147 AND THR-152.
RC   TISSUE=Milk;
RX   PubMed=15869464; DOI=10.1042/BJ20050341;
RA   Christensen B., Nielsen M.S., Haselmann K.F., Petersen T.E.,
RA   Sorensen E.S.;
RT   "Post-translationally modified residues of native human osteopontin
RT   are located in clusters: identification of 36 phosphorylation and five
RT   O-glycosylation sites and their biological implications.";
RL   Biochem. J. 390:285-292(2005).
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-81, AND MASS
RP   SPECTROMETRY.
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).
CC   -!- FUNCTION: Binds tightly to hydroxyapatite. Appears to form an
CC       integral part of the mineralized matrix. Probably important to
CC       cell-matrix interaction.
CC   -!- FUNCTION: Acts as a cytokine involved in enhancing production of
CC       interferon-gamma and interleukin-12 and reducing production of
CC       interleukin-10 and is essential in the pathway that leads to type
CC       I immunity (By similarity).
CC   -!- SUBUNIT: Ligand for integrin alpha-V/beta-3.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=A; Synonyms=OPN-a, OP1B;
CC         IsoId=P10451-1; Sequence=Displayed;
CC       Name=B; Synonyms=OPN-b, OP1A;
CC         IsoId=P10451-2; Sequence=VSP_003778;
CC       Name=C; Synonyms=OPN-c;
CC         IsoId=P10451-3; Sequence=VSP_003777;
CC       Name=D;
CC         IsoId=P10451-4; Sequence=VSP_011639;
CC   -!- PTM: Extensively phosphorylated on clustered serine residues.
CC   -!- PTM: N- and O-glycosylated.
CC   -!- DISEASE: This protein plays a principal role in urinary stone
CC       formation as the stone matrix.
CC   -!- SIMILARITY: Belongs to the osteopontin family.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Osteopontin entry;
CC       URL="http://en.wikipedia.org/wiki/Osteopontin";
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DR   EMBL; X13694; CAA31984.1; -; mRNA.
DR   EMBL; J04765; AAA59974.1; -; mRNA.
DR   EMBL; M83248; AAA17675.1; -; mRNA.
DR   EMBL; U20758; AAA86886.1; -; Genomic_DNA.
DR   EMBL; D14813; BAA03554.1; -; Genomic_DNA.
DR   EMBL; D28759; BAA05949.1; -; mRNA.
DR   EMBL; D28760; BAA05950.1; -; mRNA.
DR   EMBL; D28761; BAA05951.1; -; mRNA.
DR   EMBL; AF052124; AAC28619.1; -; mRNA.
DR   EMBL; AK075463; BAC11635.1; -; mRNA.
DR   EMBL; BC007016; AAH07016.1; -; mRNA.
DR   EMBL; BC017387; AAH17387.1; -; mRNA.
DR   EMBL; BC022844; AAH22844.1; -; mRNA.
DR   PIR; S50028; S09575.
DR   RefSeq; NP_000573.1; -.
DR   RefSeq; NP_001035147.1; -.
DR   UniGene; Hs.313; -.
DR   DisProt; DP00214; -.
DR   IntAct; P10451; -.
DR   GlycoSuiteDB; P10451; -.
DR   PhosphoSite; P10451; -.
DR   Ensembl; ENSG00000118785; Homo sapiens.
DR   GeneID; 6696; -.
DR   KEGG; hsa:6696; -.
DR   H-InvDB; HIX0004361; -.
DR   HGNC; HGNC:11255; SPP1.
DR   HPA; CAB002212; -.
DR   MIM; 166490; gene.
DR   PharmGKB; PA142672066; -.
DR   ArrayExpress; P10451; -.
DR   CleanEx; HS_SPP1; -.
DR   GermOnline; ENSG00000118785; Homo sapiens.
DR   InterPro; IPR002038; Osteopontin.
DR   PANTHER; PTHR10607; Osteopontin; 1.
DR   Pfam; PF00865; Osteopontin; 1.
DR   PRINTS; PR00216; OSTEOPONTIN.
DR   SMART; SM00017; OSTEO; 1.
DR   PROSITE; PS00884; OSTEOPONTIN; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Biomineralization; Cell adhesion; Cytokine;
KW   Direct protein sequencing; Glycoprotein; Phosphoprotein; Polymorphism;
KW   Secreted; Sialic acid; Signal.
FT   SIGNAL        1     16       Potential.
FT   CHAIN        17    314       Osteopontin.
FT                                /FTId=PRO_0000020321.
FT   MOTIF       159    161       Cell attachment site.
FT   MOD_RES      24     24       Phosphoserine.
FT   MOD_RES      26     26       Phosphoserine.
FT   MOD_RES      27     27       Phosphoserine.
FT   MOD_RES      62     62       Phosphoserine.
FT   MOD_RES      63     63       Phosphoserine.
FT   MOD_RES      66     66       Phosphothreonine.
FT   MOD_RES      76     76       Phosphoserine.
FT   MOD_RES      81     81       Phosphoserine.
FT   MOD_RES      99     99       Phosphoserine.
FT   MOD_RES     102    102       Phosphoserine.
FT   MOD_RES     105    105       Phosphoserine.
FT   MOD_RES     108    108       Phosphoserine.
FT   MOD_RES     117    117       Phosphoserine.
FT   MOD_RES     120    120       Phosphoserine.
FT   MOD_RES     123    123       Phosphoserine.
FT   MOD_RES     126    126       Phosphoserine.
FT   MOD_RES     129    129       Phosphoserine.
FT   MOD_RES     185    185       Phosphothreonine.
FT   MOD_RES     191    191       Phosphoserine.
FT   MOD_RES     195    195       Phosphoserine.
FT   MOD_RES     215    215       Phosphoserine.
FT   MOD_RES     219    219       Phosphoserine.
FT   MOD_RES     224    224       Phosphoserine.
FT   MOD_RES     228    228       Phosphoserine.
FT   MOD_RES     234    234       Phosphoserine.
FT   MOD_RES     254    254       Phosphoserine.
FT   MOD_RES     263    263       Phosphoserine.
FT   MOD_RES     267    267       Phosphoserine.
FT   MOD_RES     275    275       Phosphoserine.
FT   MOD_RES     280    280       Phosphoserine.
FT   MOD_RES     303    303       Phosphoserine.
FT   MOD_RES     308    308       Phosphoserine.
FT   MOD_RES     310    310       Phosphoserine.
FT   CARBOHYD     79     79       N-linked (GlcNAc...).
FT   CARBOHYD    106    106       N-linked (GlcNAc...).
FT   CARBOHYD    134    134       O-linked (GalNAc...).
FT   CARBOHYD    138    138       O-linked (GalNAc...).
FT   CARBOHYD    143    143       O-linked (GalNAc...).
FT   CARBOHYD    147    147       O-linked (GalNAc...).
FT   CARBOHYD    152    152       O-linked (GalNAc...).
FT   VAR_SEQ      31     57       Missing (in isoform C).
FT                                /FTId=VSP_003777.
FT   VAR_SEQ      58     71       Missing (in isoform B).
FT                                /FTId=VSP_003778.
FT   VAR_SEQ      95    116       Missing (in isoform D).
FT                                /FTId=VSP_011639.
FT   VARIANT     301    301       R -> H (in dbSNP:rs4660).
FT                                /FTId=VAR_014717.
FT   CONFLICT    188    188       D -> H (in Ref. 6).
FT   CONFLICT    237    237       T -> A (in Ref. 6).
FT   CONFLICT    275    278       SHEF -> GNSL (in Ref. 2).
SQ   SEQUENCE   314 AA;  35423 MW;  4996429EC4752B86 CRC64;
     MRIAVICFCL LGITCAIPVK QADSGSSEEK QLYNKYPDAV ATWLNPDPSQ KQNLLAPQNA
     VSSEETNDFK QETLPSKSNE SHDHMDDMDD EDDDDHVDSQ DSIDSNDSDD VDDTDDSHQS
     DESHHSDESD ELVTDFPTDL PATEVFTPVV PTVDTYDGRG DSVVYGLRSK SKKFRRPDIQ
     YPDATDEDIT SHMESEELNG AYKAIPVAQD LNAPSDWDSR GKDSYETSQL DDQSAETHSH
     KQSRLYKRKA NDESNEHSDV IDSQELSKVS REFHSHEFHS HEDMLVVDPK SKEEDKHLKF
     RISHELDSAS SEVN
//