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    RNF7 ring finger protein 7 [ Homo sapiens (human) ]

    Gene ID: 9616, updated on 2-Nov-2024

    Summary

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    Official Symbol
    RNF7provided by HGNC
    Official Full Name
    ring finger protein 7provided by HGNC
    Primary source
    HGNC:HGNC:10070
    See related
    Ensembl:ENSG00000114125 MIM:603863; AllianceGenome:HGNC:10070
    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
    SAG; ROC2; rbx2; CKBBP1
    Summary
    The protein encoded by this gene is a highly conserved ring finger protein. It is an essential subunit of SKP1-cullin/CDC53-F box protein ubiquitin ligases, which are a part of the protein degradation machinery important for cell cycle progression and signal transduction. This protein interacts with, and is a substrate of, casein kinase II (CSNK2A1/CKII). The phosphorylation of this protein by CSNK2A1 has been shown to promote the degradation of IkappaBalpha (CHUK/IKK-alpha/IKBKA) and p27Kip1(CDKN1B). Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
    Annotation information
    Note: SAG (Gene ID: 6295) and RNF7 (Gene ID: 9616) share the SAG symbol/alias in common. SAG is a widely used alternative name for ring finger protein 7 (RNF7), which can be confused with the official symbol for SAG (S-antigen visual arrestin, GeneID 6295). [01 Jun 2018]
    Expression
    Ubiquitous expression in testis (RPKM 15.8), adrenal (RPKM 15.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See RNF7 in Genome Data Viewer
    Location:
    3q23
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (141738298..141747560)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (144485514..144494774)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (141457140..141466402)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene RAS p21 protein activator 2 Neighboring gene YWHAQ pseudogene 6 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:141382574-141383094 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:141383095-141383614 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20633 Neighboring gene leucine rich repeat containing 78, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20634 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20635 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:141456933-141457612 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:141457613-141458291 Neighboring gene TPT1 pseudogene 3 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:141481495-141481669 Neighboring gene G protein-coupled receptor kinase 7 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20637 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20638 Neighboring gene CRISPRi-validated cis-regulatory element chr3.4237 Neighboring gene CRISPRi-validated cis-regulatory element chr3.4238 Neighboring gene uncharacterized LOC105374134 Neighboring gene VISTA enhancer hs2041

    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 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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. RNF7 Facilitated the Tumorigenesis of Pancreatic Cancer by Activating PI3K/Akt Signaling Pathway.
      Title: RNF7 Facilitated the Tumorigenesis of Pancreatic Cancer by Activating PI3K/Akt Signaling Pathway.
    2. RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop.
      Title: RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop.
    3. We demonstrated that RNF7 knockdown induced growth suppression of prostate cancer cells and inactivated ERK1/2 pathway, which suggested RNF7 might be a potential novel therapeutic target for CRPC.
      Title: RNF7 knockdown inhibits prostate cancer tumorigenesis by inactivation of ERK1/2 pathway.
    4. Results identified RNF7 to interact with CARMA2 regulating its NF-kappaB-activating capacity. Mechanistically, RNF7 influences CARMA2 signaling by regulating the ubiquitination state of MALT1 and the NF-kappaB-regulatory molecule NEMO.
      Title: The E3 Ubiquitin Ligase RNF7 Negatively Regulates CARD14/CARMA2sh Signaling.
    5. This is the first report on a diagnostic test for simultaneous genotyping of IFNL3, ABCB11, and RNF7 in Chronic hepatitis C (CHC) patients. Reliable and inexpensive, the assay should provide useful information for the clinical management of CHC, like identification of patients at risk of rapid disease progression or with high chances of response to classic therapy.
      Title: Triplex High-Resolution Melting Assay for the Simultaneous Assessment of IFNL3 rs12979860, ABCB11 rs2287622, and RNF7 rs16851720 Genotypes in Chronic Hepatitis C Patients.
    6. Sag is a Kras-cooperating oncogene that promotes lung tumorigenesis
      Title: Inactivation of SAG/RBX2 E3 ubiquitin ligase suppresses KrasG12D-driven lung tumorigenesis.
    7. NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function.
      Title: SAG/RBX2 is a novel substrate of NEDD4-1 E3 ubiquitin ligase and mediates NEDD4-1 induced chemosensitization.
    8. SAG/RBX2 E3 ligase complexes with UBCH10 and UBE2S ubiquitin-conjugating enzymes to ubiquitylate beta-TrCP1 via K11-linkage for degradation.
      Title: SAG/RBX2 E3 ligase complexes with UBCH10 and UBE2S E2s to ubiquitylate β-TrCP1 via K11-linkage for degradation.
    9. RNF7 gene variant is associated with the risk of developing liver fibrosis and cirrhosis in an Eastern European population.
      Title: PNPLA3 and RNF7 Gene Variants are Associated with the Risk of Developing Liver Fibrosis and Cirrhosis in an Eastern European Population.
    10. MAF1, RNF7 and SETD3 are identified as PCNA-associated proteins in human cells and given this interaction with PCNA, Maf1, RNF7, and SetD3 are potentially involved in DNA replication, DNA repair, or associated processes.
      Title: A fluorescent bimolecular complementation screen reveals MAF1, RNF7 and SETD3 as PCNA-associated proteins in human cells.
    Submit: New GeneRIF Correction See all GeneRIFs (23)

    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

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection.
    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)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif Rbx1 I44A and Rbx2 I52A mutants disrupt the level of HIV-1 Vif-mediated APOBEC3G degradation in cells PubMed
    vif CUL5/RBX2/ELOB/ELOC/Vif/CBF-beta complex catalyzes polyubiquitin chain formation on A3G in the presence of ubiquitin E2 UBE2R1 (CDC34) or UBCH5b (UBE2D2) PubMed
    vif UBE2F and RBX2 are required for activation of the polyubiquitin synthesis activity of Vif/CBF-beta/CUL5, leading to HIV-1 Vif-mediated degradation of A3G in cells PubMed
    vif HIV-1 Vif can assemble into the Cul5-containing E3 ligase, the CUL5-RBX2-CBF-beta-ELOB-ELOC complex, in the presence of CBF-beta PubMed
    vif HIV-1 Vif is identified to have a physical interaction with ring finger protein 7 (RNF7; RBX2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    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 NEDD8 ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables NEDD8 transferase activity TAS
    Traceable Author Statement
    more info
    		  
    enables copper ion binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables cullin family protein binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cullin family protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin protein ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in endoplasmic reticulum unfolded protein response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in post-translational protein modification TAS
    Traceable Author Statement
    more info
    		  
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein K11-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein neddylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_negative_effect reelin-mediated signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of neuron migration ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in response to redox state TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    part_of Cul5-RING ubiquitin ligase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of Cul5-RING ubiquitin ligase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    RING-box protein 2
    Names
    CKII beta-binding protein 1
    regulator of cullins 2
    sensitive to apoptosis gene protein
    sensitive to apoptosis zinc RING finger protein SAG
    sensitive to apoptosis, zinc RING finger protein SAG, regulator of cullins 2
    zinc RING finger protein SAG
    NP_001188299.1
    NP_055060.1
    NP_899060.1

    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_001201370.2 → NP_001188299.1  RING-box protein 2 isoform 4

      See identical proteins and their annotated locations for NP_001188299.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC112771, AW150174, BG742338, DB272382
      Consensus CDS
      CCDS56283.1
      UniProtKB/TrEMBL
      B2R4X4
      Related
      ENSP00000419084.1, ENST00000480908.1
      Conserved Domains (1) summary
      cl17238
      Location:47 → 90
      RING_Ubox; The superfamily of RING finger (Really Interesting New Gene) domain and U-box domain

    2. NM_014245.5 → NP_055060.1  RING-box protein 2 isoform 1

      See identical proteins and their annotated locations for NP_055060.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC112771, AW150174, BG742338
      Consensus CDS
      CCDS3118.1
      UniProtKB/Swiss-Prot
      A8K1H9, A8MTB5, C9JYL3, D3DNF7, D3DNF8, Q9BXN8, Q9UBF6, Q9Y5M7
      UniProtKB/TrEMBL
      B2R4X4
      Related
      ENSP00000273480.3, ENST00000273480.4
      Conserved Domains (1) summary
      cd16466
      Location:47 → 106
      RING-H2_RBX2; RING finger, H2 subclass, found in RING-box protein 2 (RBX2) and similar proteins

    3. NM_183237.3 → NP_899060.1  RING-box protein 2 isoform 3

      See identical proteins and their annotated locations for NP_899060.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in the coding region compared to variant 1, which causes a frameshift. The resulting shorter isoform (3) has a distinct C-terminus, as compared to isoform 1.
      Source sequence(s)
      AC112771, AW150174, BG716023, BG742338
      Consensus CDS
      CCDS43158.1
      UniProtKB/Swiss-Prot
      Q9UBF6
      Related
      ENSP00000376725.3, ENST00000393000.3
      Conserved Domains (1) summary
      cl17238
      Location:28 → 55
      RING_Ubox; The superfamily of RING finger (Really Interesting New Gene) domain and U-box domain

    RNA

    1. NR_037702.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) contains an alternate exon compared to variant 1, that causes a frameshift. The resulting transcript is a nonsense-mediated mRNA decay candidate and is not thought to be protein-coding.
      Source sequence(s)
      AC112771, AF312226, AW150174, BG742338

    2. NR_037703.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) uses an alternate splice junction and contains an alternate exon compared to variant 1, that causes a frameshift. The resulting transcript is a nonsense-mediated mRNA decay candidate and is not thought to be protein-coding.
      Source sequence(s)
      AC112771, AW150174, BG720797, BG742338

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      141738298..141747560
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    RNA

    1. XR_007095770.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      144485514..144494774
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    RNA

    1. XR_008486859.1 RNA Sequence

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_183063.1: Suppressed sequence

      Description
      NM_183063.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UBF6.1 GenPept UniProtKB/Swiss-Prot:Q9UBF6

    Gene LinkOut

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

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