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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

SPSB2 Gene

protein-coding   GIFtS: 50
GCID: GC12M006980

splA/ryanodine receptor domain and SOCS box containing 2

 Explore 1 disease affiliated with
SPSB2 via our new
 Human Malady Compendium 
Biological research products
for SPSB2
    

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section

Aliases
SplA/Ryanodine Receptor Domain And SOCS Box Containing 21 2     Gene-Rich Cluster Protein C92 3
GRCC91 2 3     SPRY Domain-Containing SOCS Box Protein 22
SSB22 3 5     SPRY Domain-Containing SOCS Box Protein SSB-22
SSB-21 3     

External Ids:    HGNC: 295221   Entrez Gene: 847272   Ensembl: ENSG000001116717   OMIM: 6116585   UniProtKB: Q996193   

Export aliases for SPSB2 gene to outside databases

Previous GC identifer: GC12M006851


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for SPSB2:
This gene encodes encodes a suppressor of cytokine signaling (SOCS) family member, and it belongs to the subfamily of
proteins containing a central SPRY (repeats in splA and RyR) domain and a C-terminal SOCS box. 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, Sep 2009)

UniProtKB/Swiss-Prot: SPSB2_HUMAN, Q99619
Function: Probable 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




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000012.11  NC_018923.1  NT_009759.16  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the SPSB2 gene promoter:
         E2F-1   E2F   AP-1   ATF-2   E2F-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidSPSB2 promoter sequence
   Search SABiosciences Chromatin IP Primers for SPSB2

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat SPSB2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12p13.31   Ensembl cytogenetic band:  12p13.31   HGNC cytogenetic band: 12p13.31

SPSB2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SPSB2 gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12M006980:  view genomic region     (about GC identifiers)

Start:
6,980,099 bp from pter      End:
6,998,522 bp from pter
Size:
18,424 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: SPSB2_HUMAN, Q99619 (See protein sequence)
Recommended Name: SPRY domain-containing SOCS box protein 2  
Size: 263 amino acids; 28630 Da
Subunit: Interacts with PARW (By similarity). Component of the probable ECS(SPSB2) E3 ubiquitin-protein ligase complex
which contains CUL5, RNF7/RBX2, Elongin BC complex and SPSB2. Interacts with CUL5, RNF7, TCEB1 and TCEB2. Interacts
with MET
Subcellular location: Cytoplasm (Probable)
1 PDB 3D structure from and Proteopedia for SPSB2:
3EMW (3D)    
Secondary accessions: D3DUT0

Explore the universe of human proteins at neXtProt for SPSB2: NX_Q99619

Post-translational modifications:

  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q99619

  • SPSB2 Protein expression data from MOPED and PaxDb: --
    REFSEQ proteins (2 alternative transcripts): 
    NP_001139788.1  NP_116030.1  

    ENSEMBL proteins: 
     ENSP00000430872   ENSP00000428338   ENSP00000431037   ENSP00000428458  
    Reactome Protein details: Q99619
    Human Recombinant Protein Products: 
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    Uscn Proteins for SPSB2

    Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005575cellular_component ND--
    GO:0005737cytoplasm IEA--


    SPSB2 for ontologies           About GeneDecksing



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    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    SPSB2 for domains           About GeneDecksing

    5 InterPro domains/families:
     IPR001496 SOCS_C
     IPR018355 SPla/RYanodine_receptor_subgr
     IPR001870 B30.2/SPRY
     IPR008985 ConA-like_lec_gl_sf
     IPR003877 SPRY_rcpt

    Graphical View of Domain Structure for InterPro Entry Q99619

    ProtoNet protein and cluster: Q99619

    1 Blocks protein family: IPB001496 SOCS protein

    UniProtKB/Swiss-Prot: SPSB2_HUMAN, Q99619
    Domain: The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3
    ubiquitin ligase complexes (By similarity)
    Similarity: Belongs to the SPSB family
    Similarity: Contains 1 B30.2/SPRY domain
    Similarity: Contains 1 SOCS box domain


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section

    Function Summary:

         UniProtKB/Swiss-Prot: SPSB2_HUMAN, Q99619
    Function: Probable 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

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    Gene Ontology (GO): 2 molecular function terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003674molecular_function ND--
    GO:0005515protein binding IPI19159283


    SPSB2 for ontologies           About GeneDecksing


    1 GenomeRNAi human phenotype for SPSB2:
     Increased cell death HMECs cel 

    Animal Models:
         2 MGI mutant phenotypes (inferred from 1 allele(MGI details for Spsb2):
     hematopoietic system  homeostasis/metabolism 

    SPSB2 for phenotypes           About GeneDecksing


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways  About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Antigen processing: Ubiquitination & Proteasome degradation
    Antigen processing: Ubiquitination & Proteasome degradation1.00
    Polyubiquitination of substrate0.75
    Class I MHC mediated antigen processing & presentation0.83
    2Immune System
    Immune System1.00
    Adaptive Immune System0.59

    Pathway sources
    See GeneCards unified pathways
    Show all pathways


    5        Reactome Pathways for SPSB2
        Antigen processing: Ubiquitination & Proteasome degradation
    Polyubiquitination of substrate
    Adaptive Immune System
    Class I MHC mediated antigen processing & presentation
    Immune System


    UniProtKB/Swiss-Prot: SPSB2_HUMAN, Q99619
    Pathway: Protein modification; protein ubiquitination


    SPSB2 for pathways           About GeneDecksing

    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for SPSB2

    5 Interacting proteins for SPSB2 (Q996191, 3) via UniProtKB, MINT, STRING, and/or I2D

    InteractantInteraction Details
    GeneCardExternal ID(s)
    TCEB1Q153691, 3EBI-2323209,EBI-301231 I2D: score=2 
    CUL5Q930343I2D: score=1 
    NOS2P352283I2D: score=1 
    RNF7Q9UBF63I2D: score=1 
    TCEB2Q153703I2D: score=1 
    About this table

    Gene Ontology (GO): 3 biological process terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0008150biological_process ND--
    GO:0016567protein ubiquitination IEA--
    GO:0035556intracellular signal transduction IEA--


    SPSB2 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section
    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for SPSB2
    Search CenterWatch for drugs/clinical trials and news about SPSB2 

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
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    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for SPSB2 gene (3 alternative transcripts): 
    NM_001146316.1  NM_032641.3  NM_001146317.1  

    Unigene Cluster for SPSB2:

    SplA/ryanodine receptor domain and SOCS box containing 2
    Hs.479856  [show with all ESTs]
    Unigene Representative Sequence: AK297963
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000523102(uc001qrl.3) ENST00000524270(uc001qrm.3) ENST00000519357
    ENST00000432205 ENST00000437851

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    Additional cDNA sequence: 

    AF403027.1 AK297963.1 BC002983.1 BC071933.1 

    6 DOTS entries:

    DT.65284346  DT.91933271  DT.91947326  DT.87016189  DT.97784464  DT.91684584 

    24/69 AceView cDNA sequences (see all 69):

    BU632072 AW043762 CA426909 NM_032641 AI341418 AF403027 AW779948 BX331561 
    AI377783 CD366415 BC071933 AI635626 CB852191 BF684271 BU500968 BE222853 
    AI241963 BM969281 BQ710545 BC002983 AI359227 AI674052 BG757073 BI458291 

    GeneLoc Exon Structure

    2 Alternative Splicing Database (ASD) splice patterns (SP) for SPSB2    About this scheme

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


    ECgene alternative splicing isoforms for SPSB2

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    SPSB2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: AAGCGCTACC

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)

    About this image
    Genevestigator expression for SPSB2

    SOURCE GeneReport for Unigene cluster: Hs.479856
        SABiosciences Expression via Pathway-Focused PCR Array including SPSB2: 
              Ubiquitin Ligases in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of animals.

    Orthologs for SPSB2 gene from 4/14 species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Spsb21 , 5 splA/ryanodine receptor domain and SOCS box containing more1, 5 87.2(n)1
    90.87(a)1
      6 (59.17 cM)5
    147941  NM_013539.11  NP_038567.11 
     1248086615 
    zebrafish
    (Danio rerio)
    Actinopterygii si:ch1073-228j22.26
    si:ch1073-228j22.2
    37(a)
    1 ↔ 1
    23(44581024-44582288)
    fruit fly
    (Drosophila melanogaster)
    Insecta gus6
    gustavus
    47(a)
    1 → many
    2R(1004495-1015816)
    worm
    (Caenorhabditis elegans)
    Secernentea spsb-26
    spsb-16
    Protein SPSB-1
    44(a)
    22(a)
    many ↔ many
    many ↔ many
    II(15230286-15232726)
    II(15207367-15226652)


    ENSEMBL Gene Tree for SPSB2 (if available)
    TreeFam Gene Tree for SPSB2 (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for SPSB2 gene
    FBXO452  SPSB12  SPSB42  
    3 SIMAP similar genes for SPSB2 using alignment to 3 protein entries:     SPSB2_HUMAN (see all proteins):
    SPSB4    FBXO45    SPSB1

    SPSB2 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/69 NCBI SNPs in SPSB2 are shown (see all 69    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1122250891,2
    C,--6836251(+) CCTCCC/GTTGGG 2 -- us2k12Minor allele frequency- G:0.20NA 122
    rs1132085931,2
    --6836563(+) GCCCAG/TCTCAG 2 -- us2k11Minor allele frequency- T:0.50CSA 2
    rs1134890451,2
    C,--6836855(+) NNNNCC/TCTGCT 2 -- us2k12Minor allele frequency- T:0.04CSA WA 120
    rs73004111,2
    C,H,--6836896(+) TTACTG/TAGCCG 2 -- us2k17Minor allele frequency- T:0.00NS EA NA 650
    rs1125934401,2
    --6837769(+) TGTGGG/AACCAG 2 -- us2k12Minor allele frequency- A:0.02CSA WA 120
    rs1850072741,2
    --6980724(+) GGCTCA/TGACAG 2 -- int10--------
    rs1905574441,2
    --6980832(+) GAGCAA/GCTCCA 2 -- int10--------
    rs20710701,2
    C,F,--6980932(+) CCCAGG/AGCCCC 2 -- int17Minor allele frequency- A:0.19EA NA WA CSA 1509
    rs73082521,2
    C,H,--6980951(+) CATCCT/AGAGGT 2 -- int110Minor allele frequency- A:0.15WA NA CSA 251
    rs355357721,2
    C,F,--6980973(+) NNNNAG/ATAGGT 2 -- int15Minor allele frequency- A:0.22NA 128

    HapMap Linkage Disequilibrium report for SPSB2 (6980099 - 6998522 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for SPSB2: --

    SABiosciences Cancer Mutation PCR Assays
    Search QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing SPSB2
    DNA2.0 Custom Variant and Variant Library Synthesis for SPSB2

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

    SPSB2 for disorders           About GeneDecksing

    OMIM gene information: 611658    OMIM disorders: --

    1 disease for SPSB2:    About MalaCards
    parkinson's disease


    Export disorders for SPSB2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for SPSB2 gene, integrated from 9 sources (see all 15):
    (articles sorted by number of sources associating them with SPSB2)
        Utopia: connect your pdf to the dynamic
    world of online information

    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. (PubMed id 15713673)1, 2, 9 Wang D....Wu G. (2005)
    2. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S....Malek J. (2004)
    3. VHL-box and SOCS-box domains determine binding specificity for Cul2- Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. (PubMed id 15601820)1, 2 Kamura T.... Nakayama K.I. (2004)
    4. The SOCS box: a tale of destruction and degradation. (PubMed id 12076535)1, 3 Kile B.T....Hilton D.J. (2002)
    5. Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination. (PubMed id 9074930)1, 2 Ansari-Lari M.A....Gibbs R.A. (1997)
    6. A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13. (PubMed id 8723724)1, 3 Ansari-Lari M.A....Gibbs R.A. (1996)
    7. Regulation of inducible nitric-oxide synthase by the SPRY domain- and SOCS box-containing proteins. (PubMed id 21199876)1 Nishiya T....Miwa S. (2011)
    8. The ECS(SPSB) E3 ubiquitin ligase is the master regul ator of the lifetime of inducible nitric-oxide synthase. (PubMed id 21549100)1 Matsumoto K....Miwa S. (2011)
    9. Interactions of pathological hallmark proteins: tubul in polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. (PubMed id 21832049)1 OlA!h J....OvA!di J. (2011)
    10. The SPRY domain-containing SOCS box protein SPSB2 tar gets iNOS for proteasomal degradation. (PubMed id 20603330)1 Kuang Z....Nicholson S.E. (2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 84727 HGNC: 29522 AceView: GRCC9 Ensembl:ENSG00000111671 euGenes: HUgn84727
    ECgene: SPSB2 H-InvDB: SPSB2

    (According to HUGE)
    About This Section
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    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for SPSB2 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
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    Patent Information for SPSB2 gene:
    Search GeneIP for patents involving SPSB2

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