This gene encodes a member of a subfamily of proteins containing a central SPRY (repeats in splA and RyR) domain and a C-terminal suppressor of cytokine signaling (SOCS) box. This protein plays a role in cell signaling. This gene is present in a gene-rich cluster on chromosome 12p13 in the vicinity of the CD4 antigen and triosephosphate isomerase genes. Alternative splicing res... See more...

Aliases for SPSB2 Gene

Aliases for SPSB2 Gene

  • SplA/Ryanodine Receptor Domain And SOCS Box Containing 2 2 3 5
  • GRCC9 2 3 4
  • SPRY Domain-Containing SOCS Box Protein 2 3 4
  • Gene-Rich Cluster Protein C9 3 4
  • SSB-2 2 4
  • SSB2 3 4
  • SPRY Domain-Containing SOCS Box Protein SSB-2 3
  • SPSB2 5

External Ids for SPSB2 Gene

Previous GeneCards Identifiers for SPSB2 Gene

  • GC12M006980

Summaries for SPSB2 Gene

Entrez Gene Summary for SPSB2 Gene

  • This gene encodes a member of a subfamily of proteins containing a central SPRY (repeats in splA and RyR) domain and a C-terminal suppressor of cytokine signaling (SOCS) box. This protein plays a role in cell signaling. This gene is present in a gene-rich cluster on chromosome 12p13 in the vicinity of the CD4 antigen and triosephosphate isomerase genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

GeneCards Summary for SPSB2 Gene

SPSB2 (SplA/Ryanodine Receptor Domain And SOCS Box Containing 2) is a Protein Coding gene. Diseases associated with SPSB2 include Congenital Muscular Dystrophy-Dystroglycanopathy A7 and Acute Contagious Conjunctivitis. Among its related pathways are Innate Immune System and Class I MHC mediated antigen processing and presentation. An important paralog of this gene is SPSB4.

UniProtKB/Swiss-Prot Summary for SPSB2 Gene

  • Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15601820, PubMed:21199876). Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2 (PubMed:21199876). Acts as a bridge which links NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (PubMed:21199876).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SPSB2 Gene

Genomics for SPSB2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SPSB2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SPSB2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SPSB2

Top Transcription factor binding sites by QIAGEN in the SPSB2 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • E2F
  • E2F-1
  • E2F-2

Genomic Locations for SPSB2 Gene

Genomic Locations for SPSB2 Gene
chr12:6,870,935-6,889,358
(GRCh38/hg38)
Size:
18,424 bases
Orientation:
Minus strand
chr12:6,980,099-6,998,522
(GRCh37/hg19)
Size:
18,424 bases
Orientation:
Minus strand

Genomic View for SPSB2 Gene

Genes around SPSB2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SPSB2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SPSB2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SPSB2 Gene

Proteins for SPSB2 Gene

  • Protein details for SPSB2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99619-SPSB2_HUMAN
    Recommended name:
    SPRY domain-containing SOCS box protein 2
    Protein Accession:
    Q99619
    Secondary Accessions:
    • B7Z4W1
    • D3DUT0

    Protein attributes for SPSB2 Gene

    Size:
    263 amino acids
    Molecular mass:
    28630 Da
    Quaternary structure:
    • Component of the probable ECS(SPSB2) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SPSB2 (PubMed:15601820). Interacts with CUL5, RNF7, ELOB and ELOC (PubMed:15601820). Interacts with MET (PubMed:15713673). Interacts (via B30.2/SPRY domain) with PAWR; this interaction occurs in association with the Elongin BC complex (PubMed:16498413, PubMed:20561531). Interacts with NOS2 (PubMed:21199876).

    Three dimensional structures from OCA and Proteopedia for SPSB2 Gene

    Alternative splice isoforms for SPSB2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SPSB2 Gene

Post-translational modifications for SPSB2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SPSB2 Gene

No data available for DME Specific Peptides for SPSB2 Gene

Domains & Families for SPSB2 Gene

Gene Families for SPSB2 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for SPSB2 Gene

InterPro:
Blocks:
  • SOCS protein, C-terminal
ProtoNet:

Suggested Antigen Peptide Sequences for SPSB2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ55414, highly similar to SPRY domain-containing SOCS box protein 2 (B7Z4W1_HUMAN)
  • Gene-rich cluster protein C9 (SPSB2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q99619

UniProtKB/Swiss-Prot:

SPSB2_HUMAN :
  • The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes (By similarity). Essential for its ability to link NOS2 and the ECS E3 ubiquitin ligase complex components ELOC and CUL5.
  • Belongs to the SPSB family.
Domain:
  • The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes (By similarity). Essential for its ability to link NOS2 and the ECS E3 ubiquitin ligase complex components ELOC and CUL5.
Family:
  • Belongs to the SPSB family.
genes like me logo Genes that share domains with SPSB2: view

Function for SPSB2 Gene

Molecular function for SPSB2 Gene

UniProtKB/Swiss-Prot Function:
Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15601820, PubMed:21199876). Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2 (PubMed:21199876). Acts as a bridge which links NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (PubMed:21199876).

Phenotypes From GWAS Catalog for SPSB2 Gene

Gene Ontology (GO) - Molecular Function for SPSB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003674 molecular_function ND --
GO:0005515 protein binding IPI 15601820
GO:1990756 protein binding, bridging involved in substrate recognition for ubiquitination IPI 21199876
genes like me logo Genes that share ontologies with SPSB2: view
genes like me logo Genes that share phenotypes with SPSB2: view

Animal Models for SPSB2 Gene

MGI Knock Outs for SPSB2:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPSB2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for SPSB2 Gene

Localization for SPSB2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPSB2 Gene

Cytoplasm. Cytoplasm, cytosol. Note=Exhibits a diffuse cytosolic localization. {ECO:0000269 PubMed:21199876}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SPSB2 gene
Compartment Confidence
cytosol 5
plasma membrane 1
extracellular 1
nucleus 1
endoplasmic reticulum 1
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for SPSB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0019005 SCF ubiquitin ligase complex IBA 21873635
genes like me logo Genes that share ontologies with SPSB2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for SPSB2 Gene

Pathways & Interactions for SPSB2 Gene

genes like me logo Genes that share pathways with SPSB2: view

UniProtKB/Swiss-Prot Q99619-SPSB2_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for SPSB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006511 ubiquitin-dependent protein catabolic process IBA,IDA 21199876
GO:0016567 protein ubiquitination IEA --
GO:0035556 intracellular signal transduction IEA --
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process IBA 21873635
GO:0043687 post-translational protein modification TAS --
genes like me logo Genes that share ontologies with SPSB2: view

No data available for SIGNOR curated interactions for SPSB2 Gene

Drugs & Compounds for SPSB2 Gene

(1) Drugs for SPSB2 Gene - From: PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Methylphenidate Approved, Investigational Pharma 431
genes like me logo Genes that share compounds with SPSB2: view

Transcripts for SPSB2 Gene

mRNA/cDNA for SPSB2 Gene

4 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPSB2

Alternative Splicing Database (ASD) splice patterns (SP) for SPSB2 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3
SP1: -
SP2: -

Relevant External Links for SPSB2 Gene

GeneLoc Exon Structure for
SPSB2

Expression for SPSB2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SPSB2 Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for SPSB2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SPSB2

SOURCE GeneReport for Unigene cluster for SPSB2 Gene:

Hs.479856

Evidence on tissue expression from TISSUES for SPSB2 Gene

  • Spleen(4)
genes like me logo Genes that share expression patterns with SPSB2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for SPSB2 Gene

Orthologs for SPSB2 Gene

This gene was present in the common ancestor of animals.

Orthologs for SPSB2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SPSB2 30
  • 98.99 (n)
Dog
(Canis familiaris)
Mammalia SPSB2 30 31
  • 93.41 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SPSB2 30 31
  • 91.18 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Spsb2 30 17 31
  • 87.2 (n)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii SPSB2 31
  • 39 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta gus 31
  • 47 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea spsb-2 31
  • 44 (a)
ManyToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.8004 31
  • 40 (a)
OneToMany
Species where no ortholog for SPSB2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for SPSB2 Gene

ENSEMBL:
Gene Tree for SPSB2 (if available)
TreeFam:
Gene Tree for SPSB2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SPSB2: view image

Paralogs for SPSB2 Gene

Paralogs for SPSB2 Gene

(3) SIMAP similar genes for SPSB2 Gene using alignment to 3 proteins:

  • SPSB2_HUMAN
  • B7Z4W1_HUMAN
  • E5RIC2_HUMAN
genes like me logo Genes that share paralogs with SPSB2: view

Variants for SPSB2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SPSB2 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
781241 Benign: not provided 6,871,328(-) GAGA/G INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for SPSB2 Gene

Structural Variations from Database of Genomic Variants (DGV) for SPSB2 Gene

Variant ID Type Subtype PubMed ID
esv3580405 CNV gain 25503493
nsv557261 CNV loss 21841781
nsv832324 CNV loss 17160897

Variation tolerance for SPSB2 Gene

Residual Variation Intolerance Score: 37.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.33; 81.50% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SPSB2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SPSB2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SPSB2 Gene

Disorders for SPSB2 Gene

MalaCards: The human disease database

(3) MalaCards diseases for SPSB2 Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search SPSB2 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with SPSB2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SPSB2 Gene

Publications for SPSB2 Gene

  1. The SPRY domain-containing SOCS box protein 1 (SSB-1) interacts with MET and enhances the hepatocyte growth factor-induced Erk-Elk-1-serum response element pathway. (PMID: 15713673) Wang D … Wu G (The Journal of biological chemistry 2005) 3 4 23
  2. Regulation of inducible nitric-oxide synthase by the SPRY domain- and SOCS box-containing proteins. (PMID: 21199876) Nishiya T … Miwa S (The Journal of biological chemistry 2011) 3 4
  3. Structural basis for Par-4 recognition by the SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4. (PMID: 20561531) Filippakopoulos P … Bullock AN (Journal of molecular biology 2010) 3 4
  4. Structural and functional insights into the B30.2/SPRY domain. (PMID: 16498413) Woo JS … Oh BH (The EMBO journal 2006) 3 4
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4

Products for SPSB2 Gene

  • Signalway Proteins for SPSB2

Sources for SPSB2 Gene