SPP1 (secreted phosphoprotein 1)

Gene

• Entrez ID: 6696
• Gene name: Secreted phosphoprotein 1
• Gene symbol: SPP1
• Synonyms (NCBI Gene): BNSP, BSPI, ETA-1, OPN
• Chromosome: 4
• Chromosome location: 4q22.1
• Summary: 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 an

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004565	hsa-miR-299-5p	immunoblot	19538464
MIRT004565	hsa-miR-299-5p	qRT-PCR	19538464
MIRT004565	hsa-miR-299-5p	Luciferase reporter assay	19538464
MIRT004565	hsa-miR-299-5p	Luciferase reporter assay	19538464
MIRT004565	hsa-miR-299-5p	immunoblot, Luciferase reporter assay, Microarray, qRT-PCR	19538464
MIRT016866	hsa-miR-335-5p	Microarray	18185580
MIRT021279	hsa-miR-146a-5p	qRT-PCR	20110513
MIRT732307	hsa-miR-181b-5p	Luciferase reporter assay, qRT-PCR, Western blot	27192552
MIRT732307	hsa-miR-181b-5p	Luciferase reporter assay, qRT-PCR, Western blot	27192552
MIRT021279	hsa-miR-146a-5p	qRT-PCR	32921164
MIRT755688	hsa-miR-26a-5p	Western blotting, qRT-PCR, Flow cytometry	35246197
MIRT2433518	hsa-miR-181a	CLIP-seq
MIRT2433519	hsa-miR-181b	CLIP-seq
MIRT2433520	hsa-miR-181c	CLIP-seq
MIRT2433521	hsa-miR-181d	CLIP-seq
MIRT2433522	hsa-miR-577	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
CEBPA	Activation	14712233
ERG	Activation	21669963
FOXD3	Activation	11891324
HDAC1	Repression	20609221;22422937
HTATIP2	Repression	18537194;19349353
ING4	Repression	17848618
NR3C1	Unknown	11126367
POU2F1	Unknown	11126367
POU2F2	Unknown	11126367
POU5F1	Activation	11891324
SP1	Unknown	11126367
TFCP2	Activation	20404171;21703197

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001503	Process	Ossification	IEA
GO:0001649	Process	Osteoblast differentiation	IBA
GO:0001649	Process	Osteoblast differentiation	IEA
GO:0005125	Function	Cytokine activity	IEA
GO:0005178	Function	Integrin binding	IPI	25839998
GO:0005515	Function	Protein binding	IPI	8560266, 10747989, 11162539, 16189514, 21988832, 22582013, 25416956, 25789606, 25910212, 26091039, 32296183, 32814053
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	HDA	16502470
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	15516325
GO:0005615	Component	Extracellular space	IEA
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005794	Component	Golgi apparatus	IDA
GO:0006710	Process	Androgen catabolic process	IDA	26482249
GO:0007155	Process	Cell adhesion	IBA
GO:0007155	Process	Cell adhesion	IDA	25839998
GO:0007155	Process	Cell adhesion	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007566	Process	Embryo implantation	TAS	16720713
GO:0030154	Process	Cell differentiation	IEA
GO:0031214	Process	Biomineral tissue development	IEA
GO:0031982	Component	Vesicle	IEA
GO:0033280	Process	Response to vitamin D	IDA	16720713
GO:0036005	Process	Response to macrophage colony-stimulating factor	IEA
GO:0036094	Function	Small molecule binding	EXP	33914399
GO:0042995	Component	Cell projection	IEA
GO:0045780	Process	Positive regulation of bone resorption	IBA
GO:0045780	Process	Positive regulation of bone resorption	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	IDA	26482249
GO:0046697	Process	Decidualization	TAS	16720713
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0048545	Process	Response to steroid hormone	IEA
GO:0048685	Process	Negative regulation of collateral sprouting of intact axon in response to injury	IEA
GO:0050840	Function	Extracellular matrix binding	IBA
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0071394	Process	Cellular response to testosterone stimulus	IDA	26482249
GO:1904612	Process	Response to 2,3,7,8-tetrachlorodibenzodioxine	IEA
GO:2000866	Process	Positive regulation of estradiol secretion	IDA	26482249

Other IDs

• MIM: 166490
• HGNC: 11255
• e!Ensembl: ENSG00000118785

Protein

• UniProt ID: P10451
• Protein name: Osteopontin (Bone sialoprotein 1) (Nephropontin) (Secreted phosphoprotein 1) (SPP-1) (Urinary stone protein) (Uropontin)
• Protein function: Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. ; Acts as a cytokine inv
• PDB: 3CXD, 3DSF, 9EOU
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00865	Osteopontin	21 → 314	Osteopontin	Family

• Tissue specificity: TISSUE SPECIFICITY: Detected in cerebrospinal fluid and urine (at protein level) (PubMed:25326458, PubMed:36213313, PubMed:37453717). Bone. Found in plasma. {ECO:0000269|PubMed:25326458, ECO:0000269|PubMed:36213313, ECO:0000269|PubMed:37453717}.
• Sequence:

  MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQKQNLLAPQNA
  VSSEETNDFKQETLPSKSNESHDHMDDMDDEDDDDHVDSQDSIDSNDSDDVDDTDDSHQS
  DESHHSDESDELVTDFPTDLPATEVFTPVVPTVDTYDGRGDSVVYGLRSKSKKFRRPDIQ
  YPDATDEDITSHMESEELNGAYKAIPVAQDLNAPSDWDSRGKDSYETSQLDDQSAETHSH
  KQSRLYKRKANDESNEHSDVIDSQELSKVSREFHSHEFHSHEDMLVVDPKSKEEDKHLKF
  RISHELDSASSEVN

• Sequence length: 314

Pathways

KEGG:

PI3K-Akt signaling pathway
Apelin signaling pathway
Focal adhesion
ECM-receptor interaction
Toll-like receptor signaling pathway
GnRH secretion
Human papillomavirus infection

Reactome:

Degradation of the extracellular matrix
Signaling by PDGF
Integrin cell surface interactions
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
RUNX3 Regulates Immune Response and Cell Migration
Post-translational protein phosphorylation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASBESTOSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BILIARY ATRESIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BRAIN NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CALCINOSIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CAROTID STENOSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CEREBRAL HEMORRHAGE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC PERSISTENT HEPATITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY RESTENOSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DERMATITIS, ALLERGIC CONTACT	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC CARDIOMYOPATHIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FOCAL GLOMERULOSCLEROSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART VALVE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART VALVE DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART VALVE PROLAPSE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPATITIS, CHRONIC	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERSENSITIVITY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY FAILURE, ACUTE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER DISEASES, ALCOHOLIC	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER NEOPLASMS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUPUS ERYTHEMATOSUS, SYSTEMIC	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MESOTHELIOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTIPLE SCLEROSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOLYSIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOPOROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OTOSCLEROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANCREATIC DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROTEINURIA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PULMONARY FIBROSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RHEUMATOID ARTHRITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYSTEMIC LUPUS ERYTHEMATOSUS	—	GenCC, Orphanet GenCC, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TUBERCULOMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UREMIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VASCULAR SYSTEM INJURIES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations