Human Gene SPP1 (ENST00000237623.11) Description and Page Index
  Description: Homo sapiens secreted phosphoprotein 1 (SPP1), transcript variant 2, mRNA. (from RefSeq NM_000582)
RefSeq Summary (NM_000582): The protein encoded by this gene is involved in the attachment of osteoclasts to the mineralized bone matrix. The encoded protein is secreted and binds hydroxyapatite with high affinity. The osteoclast vitronectin receptor is found in the cell membrane and may be involved in the binding to this protein. This protein is also a cytokine that upregulates expression of interferon-gamma and interleukin-12. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011].
Gencode Transcript: ENST00000237623.11
Gencode Gene: ENSG00000118785.14
Transcript (Including UTRs)
   Position: hg38 chr4:87,975,667-87,983,426 Size: 7,760 Total Exon Count: 6 Strand: +
Coding Region
   Position: hg38 chr4:87,976,896-87,982,896 Size: 6,001 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr4:87,975,667-87,983,426)mRNA (may differ from genome)Protein (300 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
Stanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Osteopontin; AltName: Full=Bone sialoprotein 1; AltName: Full=Nephropontin; AltName: Full=Secreted phosphoprotein 1; Short=SPP-1; AltName: Full=Urinary stone protein; AltName: Full=Uropontin; Flags: Precursor;
FUNCTION: Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction.
FUNCTION: Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity (By similarity).
SUBUNIT: Ligand for integrin alpha-V/beta-3.
TISSUE SPECIFICITY: Bone. Found in plasma.
PTM: Extensively phosphorylated by FAM20C in the extracellular medium at multiple sites within the S-x-E/pS motif.
PTM: N- and O-glycosylated.
SIMILARITY: Belongs to the osteopontin family.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="";
WEB RESOURCE: Name=Wikipedia; Note=Osteopontin entry; URL="";

-  MalaCards Disease Associations
  MalaCards Gene Search: SPP1
Diseases sorted by gene-association score: malignant pleural mesothelioma (32), bone giant cell tumor (19), dentin dysplasia (17), calcific tendinitis (17), dentinogenesis imperfecta (15), pediatric systemic lupus erythematosus* (14), osteofibrous dysplasia (13), tendinitis (12), calcinosis (12), dentin dysplasia, type ii (10), nephrogenic systemic fibrosis (10), papillary cystadenocarcinoma (10), leukomalacia (10), granulomatous gastritis (10), hemarthrosis (10), root resorption (10), autoimmune myocarditis (9), uremia (9), nephrolithiasis (9), pleural cancer (8), retroperitoneal fibrosis (8), atypical teratoid rhabdoid tumor (8), biliary atresia (8), carotid stenosis (7), nephrolithiasis, calcium oxalate (7), arteriosclerosis (7), mesothelioma, somatic (7), aortic atherosclerosis (7), osteosarcoma, somatic (6), pseudoxanthoma elasticum (6), tympanic membrane disease (6), osteoporosis (6), xanthinuria, type i (6), adenomyosis (6), hypophosphatasia, adult (5), aortic valve disease 2 (5), aortic valve disease 1 (5), dental pulp calcification (5), rhabdoid cancer (5), chylothorax, congenital (4), sialolithiasis (4), connective tissue disease (3), demyelinating disease (3), hepatocellular carcinoma (2), lung cancer (2), adamantinoma of long bones (2), autoimmune lymphoproliferative syndrome (2), breast cancer (2), prostate cancer (1), bone resorption disease (1), multiple sclerosis, disease progression, modifier of (1), pulmonary fibrosis, idiopathic (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 1610.08 RPKM in Kidney - Cortex
Total median expression: 3682.53 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -43.10148-0.291 Picture PostScript Text
3' UTR -102.80530-0.194 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002038 - Osteopontin
IPR019841 - Osteopontin_CS

Pfam Domains:
PF00865 - Osteopontin

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray

- X-ray

ModBase Predicted Comparative 3D Structure on P10451
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005125 cytokine activity
GO:0005515 protein binding
GO:0050840 extracellular matrix binding

Biological Process:
GO:0001503 ossification
GO:0001649 osteoblast differentiation
GO:0006710 androgen catabolic process
GO:0006954 inflammatory response
GO:0007155 cell adhesion
GO:0007566 embryo implantation
GO:0010033 response to organic substance
GO:0010469 regulation of receptor activity
GO:0030154 cell differentiation
GO:0030198 extracellular matrix organization
GO:0031214 biomineral tissue development
GO:0033280 response to vitamin D
GO:0043687 post-translational protein modification
GO:0044267 cellular protein metabolic process
GO:0045780 positive regulation of bone resorption
GO:0045893 positive regulation of transcription, DNA-templated
GO:0046697 decidualization
GO:0048545 response to steroid hormone
GO:0048685 negative regulation of collateral sprouting of intact axon in response to injury
GO:0071394 cellular response to testosterone stimulus
GO:2000866 positive regulation of estradiol secretion

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005788 endoplasmic reticulum lumen
GO:0005794 Golgi apparatus
GO:0031982 vesicle
GO:0042995 cell projection
GO:0048471 perinuclear region of cytoplasm
GO:0070062 extracellular exosome

-  Descriptions from all associated GenBank mRNAs
  HH837112 - Sequence 39 from Patent EP2231168.
HH837113 - Sequence 40 from Patent EP2231168.
HH837114 - Sequence 41 from Patent EP2231168.
HI214753 - Sequence 39 from Patent EP2076526.
HI214754 - Sequence 40 from Patent EP2076526.
HI214755 - Sequence 41 from Patent EP2076526.
HV601555 - JP 2011500003-A/39: Novel siRNA Structures.
HV601556 - JP 2011500003-A/40: Novel siRNA Structures.
HV601557 - JP 2011500003-A/41: Novel siRNA Structures.
HV708917 - JP 2012506450-A/15: Methods for treating eye disorders.
HV708918 - JP 2012506450-A/16: Methods for treating eye disorders.
HV708919 - JP 2012506450-A/17: Methods for treating eye disorders.
HV856628 - JP 2010507387-A/39: Novel siRNAs and Methods of Use Thereof.
HV856629 - JP 2010507387-A/40: Novel siRNAs and Methods of Use Thereof.
HV856630 - JP 2010507387-A/41: Novel siRNAs and Methods of Use Thereof.
HW165115 - JP 2013102767-A/39: Novel siRNA's and Use Thereof.
HW165116 - JP 2013102767-A/40: Novel siRNA's and Use Thereof.
HW165117 - JP 2013102767-A/41: Novel siRNA's and Use Thereof.
HW675623 - JP 2014210789-A/39: Novel siRNA Structures.
HW675624 - JP 2014210789-A/40: Novel siRNA Structures.
HW675625 - JP 2014210789-A/41: Novel siRNA Structures.
HW835311 - JP 2015051004-A/39: Novel siRNA's and Use Thereof.
HW835312 - JP 2015051004-A/40: Novel siRNA's and Use Thereof.
HW835313 - JP 2015051004-A/41: Novel siRNA's and Use Thereof.
JA538154 - Sequence 39 from Patent EP2371958.
JA538155 - Sequence 40 from Patent EP2371958.
JA538156 - Sequence 41 from Patent EP2371958.
JB251975 - Sequence 42 from Patent EP2440214.
JB251976 - Sequence 43 from Patent EP2440214.
JB251977 - Sequence 44 from Patent EP2440214.
LP764874 - Sequence 42 from Patent EP3276004.
LP764875 - Sequence 43 from Patent EP3276004.
LP764876 - Sequence 44 from Patent EP3276004.
JF412667 - Homo sapiens osteopontin-C mRNA, complete cds, alternatively spliced.
BC093033 - Homo sapiens secreted phosphoprotein 1, mRNA (cDNA clone MGC:110940 IMAGE:5288027), complete cds.
BX648003 - Homo sapiens mRNA; cDNA DKFZp686G0159 (from clone DKFZp686G0159).
LF206904 - JP 2014500723-A/14407: Polycomb-Associated Non-Coding RNAs.
MA442481 - JP 2018138019-A/14407: Polycomb-Associated Non-Coding RNAs.
LF213724 - JP 2014500723-A/21227: Polycomb-Associated Non-Coding RNAs.
MA449301 - JP 2018138019-A/21227: Polycomb-Associated Non-Coding RNAs.
J04765 - Human osteopontin mRNA, complete cds.
AK296035 - Homo sapiens cDNA FLJ52507 complete cds, highly similar to Osteopontin precursor.
AK290090 - Homo sapiens cDNA FLJ77801 complete cds.
BC017387 - Homo sapiens secreted phosphoprotein 1, mRNA (cDNA clone MGC:22826 IMAGE:3828885), complete cds.
AK057738 - Homo sapiens cDNA FLJ25009 fis, clone CBL01101, highly similar to OSTEOPONTIN PRECURSOR.
AK075463 - Homo sapiens cDNA PSEC0156 fis, clone PLACE1008107, highly similar to Human osteopontin gene.
BC007016 - Homo sapiens secreted phosphoprotein 1, mRNA (cDNA clone MGC:12351 IMAGE:4052438), complete cds.
BC022844 - Homo sapiens secreted phosphoprotein 1, mRNA (cDNA clone MGC:24777 IMAGE:4284921), complete cds.
AK295491 - Homo sapiens cDNA FLJ54682 complete cds, highly similar to Osteopontin precursor.
KR062183 - Homo sapiens secreted phosphoprotein 1 variant 6 (SPP1) mRNA, complete cds.
AK290104 - Homo sapiens cDNA FLJ78337 complete cds, highly similar to Homo sapiens secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1), transcript variant 1, mRNA.
M83248 - Homo sapiens nephropontin precursor, mRNA, complete cds.
AK315461 - Homo sapiens cDNA, FLJ96520, Homo sapiens secreted phosphoprotein 1 (osteopontin, bonesialoprotein I, early T-lymphocyte activation 1) (SPP1), mRNA.
AF052124 - Homo sapiens clone 23810 osteopontin mRNA, complete cds.
AY956318 - Homo sapiens osteopontin/immunoglobulin alpha 1 heavy chain constant region fusion protein (SPP1/CALPHA1 fusion) mRNA, partial cds.
X13694 - Human mRNA for osteopontin.
DQ892544 - Synthetic construct clone IMAGE:100005174; FLH187345.01X; RZPDo839G0472D secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) (SPP1) gene, encodes complete protein.
AM392768 - Synthetic construct Homo sapiens clone IMAGE:100002166 for hypothetical protein (SPP1 gene).
AM392898 - Synthetic construct Homo sapiens clone IMAGE:100002165 for hypothetical protein (SPP1 gene).
DQ895755 - Synthetic construct Homo sapiens clone IMAGE:100010215; FLH187341.01L; RZPDo839G0462D secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) (SPP1) gene, encodes complete protein.
EU832035 - Synthetic construct Homo sapiens clone HAIB:100067064; DKFZo004D0524 secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) protein (SPP1) gene, encodes complete protein.
EU831940 - Synthetic construct Homo sapiens clone HAIB:100066969; DKFZo008D0523 secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) protein (SPP1) gene, encodes complete protein.
AB527274 - Synthetic construct DNA, clone: pF1KB3641, Homo sapiens SPP1 gene for secreted phosphoprotein 1, without stop codon, in Flexi system.
JF412666 - Homo sapiens osteopontin-D mRNA, complete cds, alternatively spliced.
CU675497 - Synthetic construct Homo sapiens gateway clone IMAGE:100023325 5' read SPP1 mRNA.
KJ905927 - Synthetic construct Homo sapiens clone ccsbBroadEn_15597 SPP1 gene, encodes complete protein.
KJ892194 - Synthetic construct Homo sapiens clone ccsbBroadEn_01588 SPP1 gene, encodes complete protein.
KR710494 - Synthetic construct Homo sapiens clone CCSBHm_00013424 SPP1 (SPP1) mRNA, encodes complete protein.
AB209987 - Homo sapiens opn mRNA for osteopontin, partial cds.
AB469789 - Homo sapiens opn mRNA for osteopontin, partial cds.
D28759 - Homo sapiens mRNA for OPN-a, partial cds.
D28760 - Homo sapiens mRNA for OPN-b, partial cds.
D28761 - Homo sapiens mRNA for OPN-c, partial cds.
DQ839491 - Homo sapiens clone BFC06011 secreted phosphoprotein 1 mRNA, complete cds.
DQ846870 - Homo sapiens clone BFC06119 secreted phosphoprotein 1 mRNA, complete cds.
DQ846871 - Homo sapiens clone BFC06121 secreted phosphoprotein 1 mRNA, complete cds.
LF359159 - JP 2014500723-A/166662: Polycomb-Associated Non-Coding RNAs.
MA594736 - JP 2018138019-A/166662: Polycomb-Associated Non-Coding RNAs.
LF359163 - JP 2014500723-A/166666: Polycomb-Associated Non-Coding RNAs.
MA594740 - JP 2018138019-A/166666: Polycomb-Associated Non-Coding RNAs.
HQ874461 - Homo sapiens osteopontin-D mRNA, partial cds, alternatively spliced.
HQ874460 - Homo sapiens osteopontin-C mRNA, partial cds, alternatively spliced.
LF359167 - JP 2014500723-A/166670: Polycomb-Associated Non-Coding RNAs.
MA594744 - JP 2018138019-A/166670: Polycomb-Associated Non-Coding RNAs.
LF359168 - JP 2014500723-A/166671: Polycomb-Associated Non-Coding RNAs.
MA594745 - JP 2018138019-A/166671: Polycomb-Associated Non-Coding RNAs.
LF359170 - JP 2014500723-A/166673: Polycomb-Associated Non-Coding RNAs.
MA594747 - JP 2018138019-A/166673: Polycomb-Associated Non-Coding RNAs.
JD024054 - Sequence 5078 from Patent EP1572962.
LF359171 - JP 2014500723-A/166674: Polycomb-Associated Non-Coding RNAs.
MA594748 - JP 2018138019-A/166674: Polycomb-Associated Non-Coding RNAs.
LF359174 - JP 2014500723-A/166677: Polycomb-Associated Non-Coding RNAs.
MA594751 - JP 2018138019-A/166677: Polycomb-Associated Non-Coding RNAs.
LF359175 - JP 2014500723-A/166678: Polycomb-Associated Non-Coding RNAs.
MA594752 - JP 2018138019-A/166678: Polycomb-Associated Non-Coding RNAs.
LF359176 - JP 2014500723-A/166679: Polycomb-Associated Non-Coding RNAs.
MA594753 - JP 2018138019-A/166679: Polycomb-Associated Non-Coding RNAs.
JD296592 - Sequence 277616 from Patent EP1572962.
LF359177 - JP 2014500723-A/166680: Polycomb-Associated Non-Coding RNAs.
MA594754 - JP 2018138019-A/166680: Polycomb-Associated Non-Coding RNAs.
LF359178 - JP 2014500723-A/166681: Polycomb-Associated Non-Coding RNAs.
MA594755 - JP 2018138019-A/166681: Polycomb-Associated Non-Coding RNAs.
JD263205 - Sequence 244229 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04510 - Focal adhesion
hsa04512 - ECM-receptor interaction
hsa04620 - Toll-like receptor signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein P10451 (Reactome details) participates in the following event(s):

R-HSA-216061 SPP1 (osteopontin) binds integrin alpha8beta1
R-HSA-265424 SPP1 (osteopontin) binds integrin alpha5beta1, alpha9beta1
R-HSA-2752115 SPP1 (osteopontin) binds CD44
R-HSA-2752118 SPP1 (osteopontin) binds Integrin alpha4beta1
R-NUL-2752124 Osteopontin binds Integrins alphaVbeta1, 3, 5
R-HSA-2752125 SPP1 (osteopontin) binds integrins alphaVbeta1, alphaVbeta3, alphaVbeta5
R-NUL-4085131 Osteopontin binds integrin alpha8beta1
R-HSA-4086205 OPN (osteopontin) degradation by MMP3, MMP7
R-HSA-382054 PDGF binds to extracellular matrix proteins
R-HSA-8952289 FAM20C phosphorylates FAM20C substrates
R-HSA-216083 Integrin cell surface interactions
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-8949275 RUNX3 Regulates Immune Response and Cell Migration
R-HSA-186797 Signaling by PDGF
R-HSA-1474244 Extracellular matrix organization
R-HSA-8878159 Transcriptional regulation by RUNX3
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-212436 Generic Transcription Pathway
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-162582 Signal Transduction
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-392499 Metabolism of proteins
R-HSA-597592 Post-translational protein modification
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: B2RDA1, BNSP, NM_000582, OPN, OSTP_HUMAN, P10451, PSEC0156, Q15681, Q15682, Q15683, Q4W597, Q567T5, Q8NBK2, Q96IZ1, uc003hrc.1, uc003hrc.2, uc003hrc.3, uc003hrc.4
UCSC ID: uc003hrc.4
RefSeq Accession: NM_000582
Protein: P10451 (aka OSTP_HUMAN)
CCDS: CCDS3626.1, CCDS43250.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.