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    SPP2 secreted phosphoprotein 2 [ Homo sapiens (human) ]

    Gene ID: 6694, updated on 10-Dec-2024

    Summary

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    Official Symbol
    SPP2provided by HGNC
    Official Full Name
    secreted phosphoprotein 2provided by HGNC
    Primary source
    HGNC:HGNC:11256
    See related
    Ensembl:ENSG00000072080 MIM:602637; AllianceGenome:HGNC:11256
    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
    SPP24; SPP-24
    Summary
    This gene encodes a secreted phosphoprotein that is a member of the cystatin superfamily. [provided by RefSeq, Oct 2008]
    Expression
    Restricted expression toward liver (RPKM 29.9) See more
    Orthologs
    mouse all
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    Genomic context

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    See SPP2 in Genome Data Viewer
    Location:
    2q37.1
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (234050702..234077134)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (234539661..234566083)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (234959346..234985778)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene MSL complex subunit 3B Neighboring gene transient receptor potential cation channel subfamily M member 8 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:234882993-234884192 Neighboring gene Sharpr-MPRA regulatory region 7512 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17351 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:234920120-234920398 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:235066116-235066288 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:235072133-235073332 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:235077257-235077756 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:235079950-235080452 Neighboring gene uncharacterized LOC105373932 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:235121411-235121911 Neighboring gene uncharacterized LOC105373933 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17352

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. SPP2 plays a role in the tumorigenesis of hepatocellular carcinoma: A bioinformatic based analysis. Peng H, et al. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2023 Dec 28. PMID 38448371, Free PMC Article
    2. Secreted Phosphoprotein 24 is a Biomarker of Mineral Metabolism. Turner ME, et al. Calcif Tissue Int, 2021 Mar. PMID 33481052
    3. Assignment of secreted phosphoprotein 24 (SPP2) to human chromosome band 2q37-->qter by in situ hybridization. Swallow JE, et al. Cytogenet Cell Genet, 1997. PMID 9533032
    4. Spp24 derivatives stimulate a Gi-protein coupled receptor-Erk1/2 signaling pathway and modulate gene expressions in W-20-17 cells. Zhao KW, et al. J Cell Biochem, 2015 May. PMID 25501958
    5. A carboxy terminal BMP/TGF-β binding site in secreted phosphoprotein 24 kD independently affects BMP-2 activity. Tian H, et al. J Cell Biochem, 2015 Apr. PMID 25418420

    See all (22) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. SPP2 plays a role in the tumorigenesis of hepatocellular carcinoma: A bioinformatic based analysis.
      Title: SPP2 plays a role in the tumorigenesis of hepatocellular carcinoma: A bioinformatic based analysis.
    2. Secreted phosphoprotein 24 kD (Spp24) inhibits the growth of human osteosarcoma through the BMP-2/Smad signaling pathway.
      Title: Secreted phosphoprotein 24 kD (Spp24) inhibits the growth of human osteosarcoma through the BMP-2/Smad signaling pathway.
    3. Secreted Phosphoprotein 24 is a Biomarker of Mineral Metabolism.
      Title: Secreted Phosphoprotein 24 is a Biomarker of Mineral Metabolism.
    4. SPP2 expression was decreased in colorectal cancer, leukemia, liver cancer and pancreatic cancer.
      Title: Association between the expression of secreted phosphoprotein - related genes and prognosis of human cancer.
    5. Spp24 can inhibit the growth of prostate cancer and its bone metastasis induced by BMP2; spp24 may have great potential to be a therapeutic agent in clinical situations
      Title: Secreted Phosphoprotein 24 kD Inhibits Growth of Human Prostate Cancer Cells Stimulated by BMP-2.
    6. the two mutations of SPP2 have dominant negative effects and cellular accumulation of Spp-24 might be particularly toxic to photoreceptors and/or retinal pigment epithelium. SPP2 has a new role in retinal degeneration.
      Title: SPP2 Mutations Cause Autosomal Dominant Retinitis Pigmentosa.
    7. Report describes a C-terminal fragment within SPP24 that is distinct from the cystatin domain and which independently binds to BMP-2 and TGF-beta. This fragment inhibited BMP-2 activity in an ectopic bone forming assay.
      Title: A carboxy terminal BMP/TGF-β binding site in secreted phosphoprotein 24 kD independently affects BMP-2 activity.
    8. Spp24, or proteolytic products of Spp24, bind cytokines of the TGF-beta superfamily and also activate intracellular signaling pathways [review]
      Title: The bone matrix protein secreted phosphoprotein 24 kD (Spp24): bone metabolism regulator and starting material for biotherapeutic materials.
    9. Spp24 truncation products have effects on osteoblastic differentiation mediated by kinase pathways that are independent of exogenous BMP/TGF-beta cytokines.
      Title: Spp24 derivatives stimulate a Gi-protein coupled receptor-Erk1/2 signaling pathway and modulate gene expressions in W-20-17 cells.
    10. spp24 contains at least 2 single nucleotide polymorphisms. Given its mechanism of action and sequence variability, SPP24 may be an interesting candidate for future studies of the genetic regulation of bone mass.
      Title: Bone morphogenetic protein-2 activity is regulated by secreted phosphoprotein-24 kd, an extracellular pseudoreceptor, the gene for which maps to a region of the human genome important for bone quality.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    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

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2019-02-27)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2019-02-27)

    ClinGen Genome Curation Page

    EBI GWAS Catalog

    Description
    An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility Loci for osteoporosis-related traits.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables endopeptidase inhibitor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in bone remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in skeletal system development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in collagen-containing extracellular matrix HDA PubMed 
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in platelet dense granule lumen TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    secreted phosphoprotein 24
    Names
    secreted phosphoprotein 2, 24kD
    secreted phosphoprotein 2, 24kDa

    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_008668.1 RefSeqGene

      Range
      5001..31433
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_006944.3 → NP_008875.1  secreted phosphoprotein 24 precursor

      See identical proteins and their annotated locations for NP_008875.1

      Status: REVIEWED

      Source sequence(s)
      AC006037, AJ308099
      Consensus CDS
      CCDS2511.1
      UniProtKB/Swiss-Prot
      A4QMV3, Q13103, Q3B892, Q546M5
      Related
      ENSP00000168148.3, ENST00000168148.8
      Conserved Domains (1) summary
      pfam07448
      Location:73 → 211
      Spp-24; Secreted phosphoprotein 24 (Spp-24)

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      234050702..234077134
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011511699.4 → XP_011510001.1  secreted phosphoprotein 24 isoform X1

      See identical proteins and their annotated locations for XP_011510001.1

      UniProtKB/Swiss-Prot
      A4QMV3, Q13103, Q3B892, Q546M5
      Related
      ENSP00000362466.1, ENST00000373368.5
      Conserved Domains (1) summary
      pfam07448
      Location:73 → 211
      Spp-24; Secreted phosphoprotein 24 (Spp-24)

    2. XM_011511698.3 → XP_011510000.1  secreted phosphoprotein 24 isoform X1

      See identical proteins and their annotated locations for XP_011510000.1

      UniProtKB/Swiss-Prot
      A4QMV3, Q13103, Q3B892, Q546M5
      Conserved Domains (1) summary
      pfam07448
      Location:73 → 211
      Spp-24; Secreted phosphoprotein 24 (Spp-24)

    3. XM_011511700.4 → XP_011510002.1  secreted phosphoprotein 24 isoform X1

      See identical proteins and their annotated locations for XP_011510002.1

      UniProtKB/Swiss-Prot
      A4QMV3, Q13103, Q3B892, Q546M5
      Conserved Domains (1) summary
      pfam07448
      Location:73 → 211
      Spp-24; Secreted phosphoprotein 24 (Spp-24)

    4. XM_005246102.5 → XP_005246159.1  secreted phosphoprotein 24 isoform X1

      See identical proteins and their annotated locations for XP_005246159.1

      UniProtKB/Swiss-Prot
      A4QMV3, Q13103, Q3B892, Q546M5
      Conserved Domains (1) summary
      pfam07448
      Location:73 → 211
      Spp-24; Secreted phosphoprotein 24 (Spp-24)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      234539661..234566083
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054343535.1 → XP_054199510.1  secreted phosphoprotein 24 isoform X1

      UniProtKB/Swiss-Prot
      A4QMV3, Q13103, Q3B892, Q546M5

    2. XM_054343537.1 → XP_054199512.1  secreted phosphoprotein 24 isoform X1

      UniProtKB/Swiss-Prot
      A4QMV3, Q13103, Q3B892, Q546M5

    3. XM_054343534.1 → XP_054199509.1  secreted phosphoprotein 24 isoform X1

      UniProtKB/Swiss-Prot
      A4QMV3, Q13103, Q3B892, Q546M5

    4. XM_054343536.1 → XP_054199511.1  secreted phosphoprotein 24 isoform X1

      UniProtKB/Swiss-Prot
      A4QMV3, Q13103, Q3B892, Q546M5
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13103.1 GenPept UniProtKB/Swiss-Prot:Q13103

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