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SPP2 secreted phosphoprotein 2 [ Homo sapiens (human) ]

Gene ID: 6694, updated on 17-Mar-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
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Genomic context

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Location:
2q37.1
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (234050702..234077134)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (234539661..234566083)
105.20220307 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: 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. Secreted Phosphoprotein 24 is a Biomarker of Mineral Metabolism. Turner ME, et al. Calcif Tissue Int, 2021 Mar. PMID 33481052
  2. 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
  3. 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
  4. The bone matrix protein secreted phosphoprotein 24 kD (Spp24): bone metabolism regulator and starting material for biotherapeutic materials. Murray SS, et al. Histol Histopathol, 2015 May. PMID 25339413
  5. 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

See all (20) 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)

Genotypes

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_2023_10

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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