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    Spsb2 splA/ryanodine receptor domain and SOCS box containing 2 [ Mus musculus (house mouse) ]

    Gene ID: 14794, updated on 11-Apr-2024

    Summary

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    Official Symbol
    Spsb2provided by MGI
    Official Full Name
    splA/ryanodine receptor domain and SOCS box containing 2provided by MGI
    Primary source
    MGI:MGI:1315199
    See related
    Ensembl:ENSMUSG00000038451 AllianceGenome:MGI:1315199
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    C9; SSB2; Grcc9
    Summary
    This gene encodes a member of the SSB family of proteins that contain a central SPRY (repeats in splA and ryanodine receptors) domain and a C-terminal SOCS (suppressor of cytokine signaling) box. The encoded protein is an adaptor protein in the E3 ubiquitin ligase complex that ubiquitinates inducible nitric oxide synthase and targets it for proteasomal degradation. Mice lacking the encoded protein exhibit lower blood urea nitrogen levels and mild thrombocytopenia due to reduced platelet production. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
    Expression
    Ubiquitous expression in testis adult (RPKM 25.4), adrenal adult (RPKM 14.6) and 25 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    6 F2; 6 59.17 cM
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 6 NC_000072.7 (124785640..124787582)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 6 NC_000072.6 (124808604..124810619)

    Chromosome 6 - NC_000072.7Genomic Context describing neighboring genes Neighboring gene leucine rich repeat containing 23 Neighboring gene predicted gene, 38895 Neighboring gene STARR-seq mESC enhancer starr_17308 Neighboring gene predicted gene, 38894 Neighboring gene STARR-positive B cell enhancer ABC_E2803 Neighboring gene STARR-positive B cell enhancer mm9_chr6:124764120-124764420 Neighboring gene triosephosphate isomerase 1 Neighboring gene ubiquitin specific peptidase 5 (isopeptidase T) Neighboring gene CapStarr-seq enhancer MGSCv37_chr6:124778211-124778394 Neighboring gene cell division cycle associated 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. A potent cyclic peptide targeting SPSB2 protein as a potential anti-infective agent. Yap BK, et al. J Med Chem, 2014 Aug 28. PMID 25068993
    2. SPRY domain-containing SOCS box protein 2: crystal structure and residues critical for protein binding. Kuang Z, et al. J Mol Biol, 2009 Feb 27. PMID 19154741
    3. Dynamics of the SPRY domain-containing SOCS box protein 2: flexibility of key functional loops. Yao S, et al. Protein Sci, 2006 Dec. PMID 17088318, Free PMC Article
    4. Genetic deletion of murine SPRY domain-containing SOCS box protein 2 (SSB-2) results in very mild thrombocytopenia. Masters SL, et al. Mol Cell Biol, 2005 Jul. PMID 15964819, Free PMC Article
    5. TLR regulation of SPSB1 controls inducible nitric oxide synthase induction. Lewis RS, et al. J Immunol, 2011 Oct 1. PMID 21876038

    See all (28) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Structural basis for the regulation of inducible nitric oxide synthase by the SPRY domain-containing SOCS box protein SPSB2, an E3 ubiquitin ligase.
      Title: Structural basis for the regulation of inducible nitric oxide synthase by the SPRY domain-containing SOCS box protein SPSB2, an E3 ubiquitin ligase.
    2. these results establish SSB1/2 as safeguards of B cell development and unveil their differential requirement in immature and mature B lymphocytes
      Title: SSB1/SSB2 Proteins Safeguard B Cell Development by Protecting the Genomes of B Cell Precursors.
    3. Collectively, Ssb1 and Ssb2 control crucial aspects of Hematopoietic stem and progenitor cells function, including proliferation and survival in vivo by resolving replicative stress to maintain genomic stability.
      Title: Ssb1 and Ssb2 cooperate to regulate mouse hematopoietic stem and progenitor cells by resolving replicative stress.
    4. structural changes limit high-affinity interactions for SPSB2 to aspartate-containing sequences
      Title: Structural basis for Par-4 recognition by the SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4.
    5. The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for proteasomal degradation.
      Title: The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for proteasomal degradation.
    6. Determined the first SPRY-domain structure of SSB-2 that adopts a novel fold and contains conserved structural determinants for binding to prostate apoptosis response protein-4 (PAR-4).
      Title: The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-4-binding residues.
    7. The binding site on SSB-2 for the prostate apoptosis response-4 (Par-4) protein has been mapped in finer detail using mutational analyses.
      Title: SPRY domain-containing SOCS box protein 2: crystal structure and residues critical for protein binding.
    8. Genetic deletion of SOCS Box Protein 2 results in a very mild thrombocytopenia.
      Title: Genetic deletion of murine SPRY domain-containing SOCS box protein 2 (SSB-2) results in very mild thrombocytopenia.
    9. Backbone dynamics of SSB-2 by means of Modelfree analysis.
      Title: Dynamics of the SPRY domain-containing SOCS box protein 2: flexibility of key functional loops.
    Submit: New GeneRIF Correction

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Targeted (1)  1 citation
    • Endonuclease-mediated (1) 

    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 MGI

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin-like ligase-substrate adaptor activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    Process Evidence Code Pubs
    involved_in intracellular signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in ubiquitin-dependent protein catabolic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    part_of SCF ubiquitin ligase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    SPRY domain-containing SOCS box protein 2
    Names
    gene-rich cluster protein C9

    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.

    mRNA and Protein(s)

    1. NM_001306050.2 → NP_001292979.1  SPRY domain-containing SOCS box protein 2 isoform 1

      See identical proteins and their annotated locations for NP_001292979.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1-4 and 6-7 all encode the same isoform (1).
      Source sequence(s)
      AC142254
      Consensus CDS
      CCDS20529.1
      UniProtKB/Swiss-Prot
      O88838, Q8CBA5, Q91Z15
      UniProtKB/TrEMBL
      D3YX10
      Conserved Domains (2) summary
      cd03719
      Location:223 → 264
      SOCS_SSB2; SOCS (suppressors of cytokine signaling) box of SSB2 (SPRY domain-containing SOCS box proteins)-like proteins. SSB proteins contain a central SPRY domain and a C-terminal SOCS. SSB2 has been shown to bind to MET, the receptor protein-tyrosine kinase for ...
      cd12906
      Location:46 → 217
      SPRY_SOCS1-2-4; SPRY domain in the suppressor of cytokine signaling 1, 2, 4 families (SOCS1, SOCS2, SOCS4)

    2. NM_001306051.2 → NP_001292980.1  SPRY domain-containing SOCS box protein 2 isoform 1

      See identical proteins and their annotated locations for NP_001292980.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1-4 and 6-7 all encode the same isoform (1).
      Source sequence(s)
      AC142254
      Consensus CDS
      CCDS20529.1
      UniProtKB/Swiss-Prot
      O88838, Q8CBA5, Q91Z15
      UniProtKB/TrEMBL
      D3YX10
      Related
      ENSMUSP00000041585.4, ENSMUST00000047760.10
      Conserved Domains (2) summary
      cd03719
      Location:223 → 264
      SOCS_SSB2; SOCS (suppressors of cytokine signaling) box of SSB2 (SPRY domain-containing SOCS box proteins)-like proteins. SSB proteins contain a central SPRY domain and a C-terminal SOCS. SSB2 has been shown to bind to MET, the receptor protein-tyrosine kinase for ...
      cd12906
      Location:46 → 217
      SPRY_SOCS1-2-4; SPRY domain in the suppressor of cytokine signaling 1, 2, 4 families (SOCS1, SOCS2, SOCS4)

    3. NM_001306052.2 → NP_001292981.1  SPRY domain-containing SOCS box protein 2 isoform 1

      See identical proteins and their annotated locations for NP_001292981.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1-4 and 6-7 all encode the same isoform (1).
      Source sequence(s)
      AC142254
      Consensus CDS
      CCDS20529.1
      UniProtKB/Swiss-Prot
      O88838, Q8CBA5, Q91Z15
      UniProtKB/TrEMBL
      D3YX10
      Related
      ENSMUSP00000118347.2, ENSMUST00000143040.8
      Conserved Domains (2) summary
      cd03719
      Location:223 → 264
      SOCS_SSB2; SOCS (suppressors of cytokine signaling) box of SSB2 (SPRY domain-containing SOCS box proteins)-like proteins. SSB proteins contain a central SPRY domain and a C-terminal SOCS. SSB2 has been shown to bind to MET, the receptor protein-tyrosine kinase for ...
      cd12906
      Location:46 → 217
      SPRY_SOCS1-2-4; SPRY domain in the suppressor of cytokine signaling 1, 2, 4 families (SOCS1, SOCS2, SOCS4)

    4. NM_001306053.2 → NP_001292982.1  SPRY domain-containing SOCS box protein 2 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) uses an alternate splice site in the coding region, which results in a frameshift and an early stop codon, compared to variant 1. It encodes isoform 2, which has a shorter and distinct C-terminus, compared to isoform 1. Variants 5 and 8-10 all encode the same isoform (2).
      Source sequence(s)
      AC142254
      UniProtKB/TrEMBL
      D3Z7N7
      Conserved Domains (1) summary
      cd12906
      Location:46 → 201
      SPRY_SOCS1-2-4; SPRY domain in the suppressor of cytokine signaling 1, 2, 4 families (SOCS1, SOCS2, SOCS4)

    5. NM_001409886.1 → NP_001396815.1  SPRY domain-containing SOCS box protein 2 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC142254
      UniProtKB/Swiss-Prot
      O88838, Q8CBA5, Q91Z15

    6. NM_001409887.1 → NP_001396816.1  SPRY domain-containing SOCS box protein 2 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC142254
      UniProtKB/Swiss-Prot
      O88838, Q8CBA5, Q91Z15

    7. NM_001409888.1 → NP_001396817.1  SPRY domain-containing SOCS box protein 2 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC142254

    8. NM_001409889.1 → NP_001396818.1  SPRY domain-containing SOCS box protein 2 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC142254

    9. NM_001409890.1 → NP_001396819.1  SPRY domain-containing SOCS box protein 2 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC142254

    10. NM_013539.3 → NP_038567.1  SPRY domain-containing SOCS box protein 2 isoform 1

      See identical proteins and their annotated locations for NP_038567.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1). Variants 1-4 and 6-7 all encode the same isoform (1).
      Source sequence(s)
      AC142254
      Consensus CDS
      CCDS20529.1
      UniProtKB/Swiss-Prot
      O88838, Q8CBA5, Q91Z15
      UniProtKB/TrEMBL
      D3YX10
      Related
      ENSMUSP00000060124.5, ENSMUST00000052727.5
      Conserved Domains (2) summary
      cd03719
      Location:223 → 264
      SOCS_SSB2; SOCS (suppressors of cytokine signaling) box of SSB2 (SPRY domain-containing SOCS box proteins)-like proteins. SSB proteins contain a central SPRY domain and a C-terminal SOCS. SSB2 has been shown to bind to MET, the receptor protein-tyrosine kinase for ...
      cd12906
      Location:46 → 217
      SPRY_SOCS1-2-4; SPRY domain in the suppressor of cytokine signaling 1, 2, 4 families (SOCS1, SOCS2, SOCS4)

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000072.7 Reference GRCm39 C57BL/6J

      Range
      124785640..124787582
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_036165855.1 → XP_036021748.1  SPRY domain-containing SOCS box protein 2 isoform X1

      UniProtKB/TrEMBL
      D3Z7N7
      Conserved Domains (1) summary
      cd12906
      Location:46 → 201
      SPRY_SOCS1-2-4; SPRY domain in the suppressor of cytokine signaling 1, 2, 4 families (SOCS1, SOCS2, SOCS4)
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O88838.1 GenPept UniProtKB/Swiss-Prot:O88838

    Gene LinkOut

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

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