SPP1
Osteopontin
Also known as: BNSP, BSPI, ETA-1, OPN, OSTP_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P10451
- Gene
- SPP1
- Ensembl
- ENSG00000118785
- Chromosome
- 4
- Canonical length
- 314 aa
- Protein class
- Cancer-related genes, Plasma proteins, Predicted secreted proteins
- Subcellular location
- Golgi apparatus
- Secretome location
- Secreted to blood
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
314 residues, UniProt reviewed canonical sequence.
>P10451|SPP1
1 MRIAVICFCL LGITCAIPVK QADSGSSEEK QLYNKYPDAV ATWLNPDPSQ KQNLLAPQNA
61 VSSEETNDFK QETLPSKSNE SHDHMDDMDD EDDDDHVDSQ DSIDSNDSDD VDDTDDSHQS
121 DESHHSDESD ELVTDFPTDL PATEVFTPVV PTVDTYDGRG DSVVYGLRSK SKKFRRPDIQ
181 YPDATDEDIT SHMESEELNG AYKAIPVAQD LNAPSDWDSR GKDSYETSQL DDQSAETHSH
241 KQSRLYKRKA NDESNEHSDV IDSQELSKVS REFHSHEFHS HEDMLVVDPK SKEEDKHLKF
301 RISHELDSAS SEVNLocalizationUniProt · AlphaFold · HPA
Whether an antibody against SPP1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.7
- Highest tissue expression
- 3,271 nTPM
Expression across tissuesHPA
Tissue
- kidney: 3,271 nTPM
- placenta: 2,626 nTPM
- gallbladder: 2,284 nTPM
- spinal cord: 1,840 nTPM
- midbrain: 771 nTPM
- retina: 767 nTPM
Single-cell type
- hofbauer cells: 104,895 nCPM
- breast lactating cells: 18,829 nCPM
- müller glia: 3,622 nCPM
- pancreatic duct cells: 2,306 nCPM
- cholangiocytes: 1,434 nCPM
- distal convoluted tubule cells: 1,382 nCPM
Immune cell
- neutrophil: 27 nTPM
- basophil: 2.3 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
Brain region
- pons: 1,537 nTPM
- white matter: 1,496 nTPM
- medulla oblongata: 1,455 nTPM
- thalamus: 1,112 nTPM
- cerebellum: 1,087 nTPM
- midbrain: 891 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about SPP1.
Disease | AutoantibodyPubMed
Conditions in which antibodies against SPP1 are reported. Each links to that disease's full target list.
ReferencesPubMed · IEDB
Publications for SPP1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
14 publications
- Osteopontin Promotes Left Ventricular Diastolic Dysfunction Through a Mitochondrial Pathway.
2019 · J Am Coll Cardiol · RCR 2.1 · 50 citations - Osteopontin expression in cardiomyocytes induces dilated cardiomyopathy.
2010 · Circ Heart Fail · RCR 1.4 · 50 citations - Treatment of collagen-induced arthritis with an anti-osteopontin monoclonal antibody through promotion of apoptosis of both murine and human activated T cells.
2008 · Arthritis Rheum · RCR 1.3 · 53 citations - Role of Anti-Osteopontin Antibodies in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.
2017 · Front Immunol · RCR 1.3 · 35 citations - Autoantibodies to osteopontin in patients with osteoarthritis and rheumatoid arthritis.
2001 · J Rheumatol · RCR 1.2 · 49 citations
Show 9 more
- Increased serum osteopontin levels in autistic children: relation to the disease severity.
2011 · Brain Behav Immun · RCR 1 · 29 citations - Identification of anti-citrullinated osteopontin antibodies and increased inflammatory response by enhancement of osteopontin binding to fibroblast-like synoviocytes in rheumatoid arthritis.
2023 · Arthritis Res Ther · RCR 0.7 · 7 citations - Osteopontin is an autoantigen of the somatostatin cells in human islets: identification by screening random peptide libraries with sera of patients with insulin-dependent diabetes mellitus.
1999 · Vaccine · RCR 0.5 · 23 citations - Serum anti-osteopontin autoantibody as a novel diagnostic and prognostic biomarker in patients with hepatocellular carcinoma.
2014 · Oncol Rep · RCR 0.5 · 15 citations - Serum anti-SPP1 autoantibody as a potential novel biomarker in detection of esophageal squamous cell carcinoma.
2022 · BMC Cancer · RCR 0.4 · 5 citations - The role of osteopontin in the induction of the CD40 ligand in Graves' disease.
2014 · Clin Endocrinol (Oxf) · RCR 0.3 · 10 citations - Osteopontin is a tumor autoantigen in prostate cancer patients.
2011 · Oncol Lett · RCR 0.2 · 8 citations - Anti‑osteopontin autoantibodies in various types of cancer.
2018 · Oncol Rep · RCR 0.1 · 3 citations - Tubular osteopontin expression in patients with ANCA-associated glomerulonephritis.
2001 · Clin Nephrol · RCR 0.1 · 2 citations
Reference: B cellIEDB
1 publication
- Peptide microarray-based characterization of antibody responses to host proteins after bacille Calmette-Guérin vaccination.
2017 · Int J Infect Dis · RCR 0.7 · 19 citations
Reference: T cellIEDB
1 publication
- Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides.
2021 · Cell Rep · RCR 0.9 · 19 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.6
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.28
- DepMap mean gene effect
- 0.06
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- androgen catabolic process
- biomineral tissue development
- cell adhesion
- cellular response to testosterone stimulus
- decidualization
- embryo implantation
- osteoblast differentiation
- positive regulation of bone resorption
- positive regulation of DNA-templated transcription
- positive regulation of estradiol secretion
- response to 2,3,7,8-tetrachlorodibenzodioxine
- response to macrophage colony-stimulating factor
- response to steroid hormone
- response to vitamin D
- negative regulation of collateral sprouting of intact axon in response to injury
Molecular functions
- calcium ion binding
- cytokine activity
- extracellular matrix binding
- integrin binding
- small molecule binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Osteopontin
- Osteopontin, conserved site
- Osteopontin
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of SPP1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads SPP1 as an antibody target. Whether an autoantibody or antibody against SPP1 could matter depends on whether native SPP1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
SPP1 is annotated as secreted, so native SPP1 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Annotation status
The present source text does not explicitly label SPP1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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