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    SPP1 secreted phosphoprotein 1 [ Homo sapiens (human) ]

    Gene ID: 6696, updated on 2-Nov-2024

    Summary

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    Official Symbol
    SPP1provided by HGNC
    Official Full Name
    secreted phosphoprotein 1provided by HGNC
    Primary source
    HGNC:HGNC:11255
    See related
    Ensembl:ENSG00000118785 MIM:166490; AllianceGenome:HGNC:11255
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    OPN; BNSP; BSPI; ETA-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 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]
    Expression
    Biased expression in placenta (RPKM 1043.5), gall bladder (RPKM 1025.4) and 3 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SPP1 in Genome Data Viewer
    Location:
    4q22.1
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (87975714..87983411)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (91302203..91309899)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (88896866..88904563)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr4:88813182-88814381 Neighboring gene heat shock protein 90 alpha family class B member 3, pseudogene Neighboring gene Sharpr-MPRA regulatory region 543 Neighboring gene Sharpr-MPRA regulatory region 601 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:88842859-88843386 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:88843387-88843913 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:88856983-88857804 Neighboring gene uncharacterized LOC124900730 Neighboring gene SPP1 5' regulatory region Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15559 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15560 Neighboring gene RNA, U1 small nuclear 36, pseudogene Neighboring gene polycystin 2, transient receptor potential cation channel Neighboring gene Sharpr-MPRA regulatory region 5607

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Osteopontin promotes inflammation in patients with acute coronary syndrome through its activity on IL-17 producing cells. Zheng Y, et al. Eur J Immunol, 2012 Oct. PMID 22711477
    2. The value of osteopontin in the assessment of bone mineral density status in postmenopausal women. Fodor D, et al. J Investig Med, 2013 Jan. PMID 23117696
    3. Osteopontin-enhanced hepatic metastasis of colorectal cancer cells. Huang J, et al. PLoS One, 2012. PMID 23112867, Free PMC Article
    4. Increased levels of osteopontin in sputum supernatant of smoking asthmatics. Hillas G, et al. Cytokine, 2013 Jan. PMID 23098767
    5. Soluble levels of osteopontin in patients with Behcet's disease: association with disease activity and vascular involvement. Bassyouni IH, et al. J Clin Immunol, 2013 Feb. PMID 23097037

    See all (1000) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Dynamics of osteopontin levels and correlation with parasitemia in acute malaria in Uganda and Sweden.
      Title: Dynamics of osteopontin levels and correlation with parasitemia in acute malaria in Uganda and Sweden.
    2. The resistance to anoikis, mediated by Spp1, and the evasion of immune surveillance facilitate the invasion and metastasis of hepatocellular carcinoma.
      Title: The resistance to anoikis, mediated by Spp1, and the evasion of immune surveillance facilitate the invasion and metastasis of hepatocellular carcinoma.
    3. Expression of Osteopontin and Gremlin 1 Proteins in Cardiomyocytes in Ischemic Heart Failure.
      Title: Expression of Osteopontin and Gremlin 1 Proteins in Cardiomyocytes in Ischemic Heart Failure.
    4. Osteopontin deficiency promotes cartilaginous endplate degeneration by enhancing the NF-kappaB signaling to recruit macrophages and activate the NLRP3 inflammasome.
      Title: Osteopontin deficiency promotes cartilaginous endplate degeneration by enhancing the NF-κB signaling to recruit macrophages and activate the NLRP3 inflammasome.
    5. Osteopontin deletion attenuates cyst growth but exacerbates fibrosis in mice with cystic kidney disease.
      Title: Osteopontin deletion attenuates cyst growth but exacerbates fibrosis in mice with cystic kidney disease.
    6. NOX4 and its association with myeloperoxidase and osteopontin in regulating endochondral ossification.
      Title: NOX4 and its association with myeloperoxidase and osteopontin in regulating endochondral ossification.
    7. Relationships between Interleukin 18 -607 C/A and -137 G/C, Osteopontin -9250 C/T Genetic Polymorphisms and Systemic Inflammatory Response Syndrome in Coronary Artery Bypass Graft Surgery.
      Title: Relationships between Interleukin 18 -607 C/A and -137 G/C, Osteopontin -9250 C/T Genetic Polymorphisms and Systemic Inflammatory Response Syndrome in Coronary Artery Bypass Graft Surgery.
    8. LINC01133 promotes pancreatic ductal adenocarcinoma epithelial-mesenchymal transition mediated by SPP1 through binding to Arp3.
      Title: LINC01133 promotes pancreatic ductal adenocarcinoma epithelial-mesenchymal transition mediated by SPP1 through binding to Arp3.
    9. Single-cell transcriptome sequencing reveals SPP1-CD44-mediated macrophage-tumor cell interactions drive chemoresistance in TNBC.
      Title: Single-cell transcriptome sequencing reveals SPP1-CD44-mediated macrophage-tumor cell interactions drive chemoresistance in TNBC.
    10. Osteopontin/SPP1: a potential mediator between immune cells and vascular calcification.
      Title: Osteopontin/SPP1: a potential mediator between immune cells and vascular calcification.
    Submit: New GeneRIF Correction See all GeneRIFs (1097)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    GWAS of dental caries patterns in the permanent dentition.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC110940

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cytokine activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables extracellular matrix binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables integrin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables small molecule binding EXP
    Inferred from Experiment
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in androgen catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in biomineral tissue development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell adhesion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cell adhesion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to testosterone stimulus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in decidualization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in embryo implantation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in negative regulation of collateral sprouting of intact axon in response to injury IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in osteoblast differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of bone resorption IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of estradiol secretion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to 2,3,7,8-tetrachlorodibenzodioxine IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to macrophage colony-stimulating factor IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to steroid hormone IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to vitamin D IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cell projection IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular space HDA PubMed 
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    osteopontin
    Names
    SPP1/CALPHA1 fusion
    early T-lymphocyte activation 1
    lnc-PKD2-2-3
    nephropontin
    osteopontin/immunoglobulin alpha 1 heavy chain constant region fusion protein
    secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1)
    urinary stone protein
    uropontin

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_030362.1 RefSeqGene

      Range
      5065..12762
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000582.3 → NP_000573.1  osteopontin isoform OPN-b precursor

      See identical proteins and their annotated locations for NP_000573.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence and lacks an alternate in-frame exon compared to variant 5. The resulting isoform (OPN-b, as described in PubMed: 7837791) has a shorter and distinct N-terminus and lacks an alternate internal segment compared to isoform e.
      Source sequence(s)
      AF052124, BX648003
      Consensus CDS
      CCDS3626.1
      UniProtKB/TrEMBL
      A6XMV6
      Related
      ENSP00000237623.7, ENST00000237623.11
      Conserved Domains (1) summary
      pfam00865
      Location:21 → 300
      Osteopontin; Osteopontin

    2. NM_001040058.2 → NP_001035147.1  osteopontin isoform OPN-a precursor

      See identical proteins and their annotated locations for NP_001035147.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR and coding sequence compared to variant 5. The resulting isoform (OPN-a, as described in PubMed: 7837791) has a shorter and distinct N-terminus compared to isoform e.
      Source sequence(s)
      AA665210, BC017387, CB117856
      Consensus CDS
      CCDS43250.1
      UniProtKB/Swiss-Prot
      B2RDA1, P10451, Q15681, Q15682, Q15683, Q4W597, Q567T5, Q8NBK2, Q96IZ1
      UniProtKB/TrEMBL
      A6XMV6
      Related
      ENSP00000378517.3, ENST00000395080.8
      Conserved Domains (1) summary
      pfam00865
      Location:21 → 314
      Osteopontin

    3. NM_001040060.2 → NP_001035149.1  osteopontin isoform OPN-c precursor

      See identical proteins and their annotated locations for NP_001035149.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence and lacks an alternate in-frame exon compared to variant 5. The resulting isoform (OPN-c, as described in PubMed: 7837791) has a shorter and distinct N-terminus and lacks an alternate internal segment compared to isoform e.
      Source sequence(s)
      AA665210, AC131944, BC093033
      Consensus CDS
      CCDS34027.1
      UniProtKB/TrEMBL
      C4B6Q2
      Related
      ENSP00000354042.4, ENST00000360804.4
      Conserved Domains (1) summary
      pfam00865
      Location:21 → 287
      Osteopontin; Osteopontin

    4. NM_001251829.2 → NP_001238758.1  osteopontin isoform 4 precursor

      See identical proteins and their annotated locations for NP_001238758.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence and lacks two alternate in-frame exons compared to variant 5. The resulting isoform (4) has a shorter and distinct N-terminus and lacks an alternate internal segment compared to isoform e.
      Source sequence(s)
      AB209987, AC131944, CB117856, JF412667
      Consensus CDS
      CCDS93558.1
      UniProtKB/TrEMBL
      C4B6Q2, D6R9C5, Q3LGB0
      Related
      ENSP00000422973.2, ENST00000508233.6
      Conserved Domains (1) summary
      pfam00865
      Location:26 → 273
      Osteopontin; Osteopontin

    5. NM_001251830.2 → NP_001238759.1  osteopontin isoform 5

      See identical proteins and their annotated locations for NP_001238759.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) represents the longest transcript and encodes the longest isoform (5).
      Source sequence(s)
      AC131944, AK295491, CB117856, JF412667
      UniProtKB/TrEMBL
      A6XMV6, B7Z351
      Related
      ENST00000509659.5
      Conserved Domains (1) summary
      pfam00865
      Location:43 → 327
      Osteopontin; Osteopontin

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      87975714..87983411
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      91302203..91309899
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P10451.1 GenPept UniProtKB/Swiss-Prot:P10451

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Other Literature Sources
    Chemical Information
    Molecular Biology Databases
    Research Materials
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