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    RNF170 ring finger protein 170 [ Homo sapiens (human) ]

    Gene ID: 81790, updated on 2-Nov-2024

    Summary

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    Official Symbol
    RNF170provided by HGNC
    Official Full Name
    ring finger protein 170provided by HGNC
    Primary source
    HGNC:HGNC:25358
    See related
    Ensembl:ENSG00000120925 MIM:614649; AllianceGenome:HGNC:25358
    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
    ADSA; SNAX1; SPG85
    Summary
    This gene encodes a RING domain-containing protein that resides in the endoplasmic reticulum (ER) membrane. This protein functions as an E3 ubiquitin ligase and mediates ubiquitination and processing of inositol 1,4,5-trisphosphate (IP3) receptors via the ER-associated protein degradation pathway. It is recruited to the activated IP3 receptors by the ERLIN1/ERLIN2 complex to which it is constitutively bound. Mutations in this gene are associated with autosomal dominant sensory ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]
    Expression
    Ubiquitous expression in thyroid (RPKM 10.8), brain (RPKM 6.2) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See RNF170 in Genome Data Viewer
    Location:
    8p11.21
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (42849637..42897299, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (43117750..43166240, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (42704780..42751748, complement)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27315 Neighboring gene cholinergic receptor nicotinic alpha 6 subunit Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27316 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:42649154-42649988 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27317 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:42671563-42671730 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr8:42698061-42698851 Neighboring gene uncharacterized LOC124901940 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27319 Neighboring gene THAP domain containing 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:42750865-42751426 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19160 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19161 Neighboring gene RNA, 7SL, cytoplasmic 806, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:42774215-42774934 Neighboring gene microRNA 4469 Neighboring gene hook microtubule tethering protein 3 Neighboring gene MPRA-validated peak7007 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:42888473-42889024 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27320 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19162 Neighboring gene RNA, U1 small nuclear 124, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27321 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:42947622-42948528 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:42948529-42949434 Neighboring gene farnesyltransferase, CAAX box, subunit alpha Neighboring gene NANOG hESC enhancer GRCh37_chr8:42971985-42972543 Neighboring gene protein O-mannose kinase

    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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    Related articles in PubMed

    1. A novel neurodegenerative disease characterised by posterior column ataxia and pyramidal tract involvement maps to chromosome 8p12-8q12.1. Valdmanis PN, et al. J Med Genet, 2004 Aug. PMID 15286160, Free PMC Article
    2. RNF170-Related Hereditary Spastic Paraplegia: Confirmation by a Novel Mutation. de Sainte Agathe JM, et al. Mov Disord, 2021 Mar. PMID 33165979
    3. RNF170 mutation causes autosomal dominant sensory ataxia with variable pyramidal involvement. Van Daele SH, et al. Eur J Neurol, 2022 Jan. PMID 34469621, Free PMC Article
    4. Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia. Wagner M, et al. Nat Commun, 2019 Oct 21. PMID 31636353, Free PMC Article
    5. A mutation in the RNF170 gene causes autosomal dominant sensory ataxia. Valdmanis PN, et al. Brain, 2011 Feb. PMID 21115467

    See all (35) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. RNF170 mutation causes autosomal dominant sensory ataxia with variable pyramidal involvement.
      Title: RNF170 mutation causes autosomal dominant sensory ataxia with variable pyramidal involvement.
    2. RNF170-Related Hereditary Spastic Paraplegia: Confirmation by a Novel Mutation.
      Title: RNF170-Related Hereditary Spastic Paraplegia: Confirmation by a Novel Mutation.
    3. mutations in the ubiquitin E3 ligase gene RNF170, which targets inositol 1,4,5-trisphosphate receptors for degradation, are the likely cause of autosomal recessive HSP in four unrelated families and functionally evaluate the consequences of mutations in patient fibroblasts and mutant SH-SY5Y cells. Our findings highlight inositol 1,4,5-trisphosphate signaling as a candidate key pathway for hereditary spastic paraplegias.
      Title: Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia.
    4. aberrant ubiquitination of substrates, or cellular adaptation to chronically reduced RNF170 levels likely accounts for the autosomal dominant sensory ataxia-associated Ca2+ signaling deficit
      Title: A Point Mutation in the Ubiquitin Ligase RNF170 That Causes Autosomal Dominant Sensory Ataxia Destabilizes the Protein and Impairs Inositol 1,4,5-Trisphosphate Receptor-mediated Ca2+ Signaling.
    5. RNF170 plays an essential role in IP(3) receptor processing via the ubiquitin-proteasome pathway.
      Title: RNF170 protein, an endoplasmic reticulum membrane ubiquitin ligase, mediates inositol 1,4,5-trisphosphate receptor ubiquitination and degradation.
    6. Together these results suggest that the mutation in RNF170 is causal for the sensory ataxia
      Title: A mutation in the RNF170 gene causes autosomal dominant sensory ataxia.
    Submit: New GeneRIF Correction

    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

    Associated conditions

    Description Tests
    Autosomal dominant sensory ataxia 1
    MedGen: C1837015 OMIM: 608984 GeneReviews: Not available
    		Compare labs
    Spastic paraplegia 85, autosomal recessive
    MedGen: C5562053 OMIM: 619686 GeneReviews: Not available
    		Compare labs

    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

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of ring finger protein 170 (RNF170) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ38306, DKFZp564A022

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in adult walking behavior IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in gene expression IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in innate immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein K48-linked ubiquitination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to temperature stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in toll-like receptor 3 signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase RNF170
    Names
    RING-type E3 ubiquitin transferase RNF170
    putative LAG1-interacting protein
    NP_001153695.1
    NP_001153696.1
    NP_001153697.1
    NP_112216.3
    XP_006716467.1
    XP_006716468.1
    XP_011542968.1
    XP_016869370.1
    XP_047278234.1
    XP_047278235.1
    XP_047278236.1
    XP_047278237.1
    XP_047278238.1
    XP_047278239.1
    XP_047278240.1
    XP_047278241.1
    XP_047278242.1
    XP_047278243.1
    XP_047278244.1
    XP_054217281.1
    XP_054217282.1
    XP_054217283.1
    XP_054217284.1
    XP_054217285.1
    XP_054217286.1
    XP_054217287.1
    XP_054217288.1
    XP_054217289.1
    XP_054217290.1
    XP_054217291.1
    XP_054217292.1
    XP_054217293.1
    XP_054217294.1

    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.

    Genomic

    1. NG_032868.1 RefSeqGene

      Range
      5119..48423
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001160223.2 → NP_001153695.1  E3 ubiquitin-protein ligase RNF170 isoform a

      See identical proteins and their annotated locations for NP_001153695.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Variants 1 and 2 encode the same isoform (a).
      Source sequence(s)
      AA973979, AC087533, BC039461, BG910500
      Consensus CDS
      CCDS6138.1
      UniProtKB/Swiss-Prot
      D3DSY6, E9PIL4, Q7Z483, Q86YC0, Q8IXR7, Q8N2B5, Q8N5G9, Q8NG30, Q96K19, Q9H0V6
      Related
      ENSP00000445725.1, ENST00000534961.5
      Conserved Domains (2) summary
      cd00162
      Location:87 → 133
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam06803
      Location:203 → 239
      DUF1232; Protein of unknown function (DUF1232)

    2. NM_001160224.2 → NP_001153696.1  E3 ubiquitin-protein ligase RNF170 isoform b

      See identical proteins and their annotated locations for NP_001153696.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' and 3' UTRs and has multiple coding region differences compared to variant 1. This results in a shorter isoform (b) with a distinct C-terminus, compared to isoform a.
      Source sequence(s)
      AC087533, BC032393, DA751961
      Consensus CDS
      CCDS55230.1
      UniProtKB/Swiss-Prot
      Q96K19
      Related
      ENSP00000326138.3, ENST00000319104.7
      Conserved Domains (1) summary
      cd00162
      Location:87 → 132
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...

    3. NM_001160225.2 → NP_001153697.1  E3 ubiquitin-protein ligase RNF170 isoform c

      See identical proteins and their annotated locations for NP_001153697.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The resulting isoform (c) has a shorter N-terminus compared to isoform a.
      Source sequence(s)
      AA973979, AC087533, BC058289
      Consensus CDS
      CCDS55229.1
      UniProtKB/Swiss-Prot
      Q96K19
      Related
      ENSP00000435782.1, ENST00000526349.5
      Conserved Domains (2) summary
      pfam06803
      Location:119 → 153
      DUF1232; Protein of unknown function (DUF1232)
      cd16553
      Location:3 → 46
      RING-HC_RNF170; RING finger, HC subclass, found in RING finger protein 170 (RNF170) and similar proteins

    4. NM_030954.4 → NP_112216.3  E3 ubiquitin-protein ligase RNF170 isoform a

      See identical proteins and their annotated locations for NP_112216.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (a).
      Source sequence(s)
      AA973979, AC087533, AK225568
      Consensus CDS
      CCDS6138.1
      UniProtKB/Swiss-Prot
      D3DSY6, E9PIL4, Q7Z483, Q86YC0, Q8IXR7, Q8N2B5, Q8N5G9, Q8NG30, Q96K19, Q9H0V6
      Related
      ENSP00000434797.1, ENST00000527424.6
      Conserved Domains (2) summary
      cd00162
      Location:87 → 133
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam06803
      Location:203 → 239
      DUF1232; Protein of unknown function (DUF1232)

    RNA

    1. NR_027668.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AA973979, AC087533, AK090864

    2. NR_027669.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) uses an alternate 5' exon and lacks an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AA973979, AC087533, BC013422, DA751961

    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_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      42849637..42897299 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047422281.1 → XP_047278237.1  E3 ubiquitin-protein ligase RNF170 isoform X4

    2. XM_011544666.4 → XP_011542968.1  E3 ubiquitin-protein ligase RNF170 isoform X2

      See identical proteins and their annotated locations for XP_011542968.1

      UniProtKB/Swiss-Prot
      D3DSY6, E9PIL4, Q7Z483, Q86YC0, Q8IXR7, Q8N2B5, Q8N5G9, Q8NG30, Q96K19, Q9H0V6
      Conserved Domains (2) summary
      cd00162
      Location:87 → 133
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam06803
      Location:203 → 239
      DUF1232; Protein of unknown function (DUF1232)

    3. XM_047422279.1 → XP_047278235.1  E3 ubiquitin-protein ligase RNF170 isoform X2

      UniProtKB/Swiss-Prot
      D3DSY6, E9PIL4, Q7Z483, Q86YC0, Q8IXR7, Q8N2B5, Q8N5G9, Q8NG30, Q96K19, Q9H0V6

    4. XM_006716405.4 → XP_006716468.1  E3 ubiquitin-protein ligase RNF170 isoform X4

      Conserved Domains (1) summary
      pfam06803
      Location:153 → 189
      DUF1232; Protein of unknown function (DUF1232)

    5. XM_006716404.3 → XP_006716467.1  E3 ubiquitin-protein ligase RNF170 isoform X2

      See identical proteins and their annotated locations for XP_006716467.1

      UniProtKB/Swiss-Prot
      D3DSY6, E9PIL4, Q7Z483, Q86YC0, Q8IXR7, Q8N2B5, Q8N5G9, Q8NG30, Q96K19, Q9H0V6
      Conserved Domains (2) summary
      cd00162
      Location:87 → 133
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam06803
      Location:203 → 239
      DUF1232; Protein of unknown function (DUF1232)

    6. XM_017013881.2 → XP_016869370.1  E3 ubiquitin-protein ligase RNF170 isoform X2

      UniProtKB/Swiss-Prot
      D3DSY6, E9PIL4, Q7Z483, Q86YC0, Q8IXR7, Q8N2B5, Q8N5G9, Q8NG30, Q96K19, Q9H0V6
      Conserved Domains (2) summary
      cd00162
      Location:87 → 133
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam06803
      Location:203 → 239
      DUF1232; Protein of unknown function (DUF1232)

    7. XM_047422280.1 → XP_047278236.1  E3 ubiquitin-protein ligase RNF170 isoform X3

    8. XM_047422278.1 → XP_047278234.1  E3 ubiquitin-protein ligase RNF170 isoform X1

    9. XM_047422282.1 → XP_047278238.1  E3 ubiquitin-protein ligase RNF170 isoform X5

    10. XM_047422285.1 → XP_047278241.1  E3 ubiquitin-protein ligase RNF170 isoform X8

      Related
      ENSP00000325969.5, ENST00000319073.5

    11. XM_047422288.1 → XP_047278244.1  E3 ubiquitin-protein ligase RNF170 isoform X11

    12. XM_047422287.1 → XP_047278243.1  E3 ubiquitin-protein ligase RNF170 isoform X10

    13. XM_047422284.1 → XP_047278240.1  E3 ubiquitin-protein ligase RNF170 isoform X7

      Related
      ENSP00000436416.1, ENST00000531440.5

    14. XM_047422283.1 → XP_047278239.1  E3 ubiquitin-protein ligase RNF170 isoform X6

    15. XM_047422286.1 → XP_047278242.1  E3 ubiquitin-protein ligase RNF170 isoform X9

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      43117750..43166240 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054361308.1 → XP_054217283.1  E3 ubiquitin-protein ligase RNF170 isoform X2

      UniProtKB/Swiss-Prot
      D3DSY6, E9PIL4, Q7Z483, Q86YC0, Q8IXR7, Q8N2B5, Q8N5G9, Q8NG30, Q96K19, Q9H0V6

    2. XM_054361312.1 → XP_054217287.1  E3 ubiquitin-protein ligase RNF170 isoform X4

    3. XM_054361311.1 → XP_054217286.1  E3 ubiquitin-protein ligase RNF170 isoform X4

    4. XM_054361307.1 → XP_054217282.1  E3 ubiquitin-protein ligase RNF170 isoform X2

      UniProtKB/Swiss-Prot
      D3DSY6, E9PIL4, Q7Z483, Q86YC0, Q8IXR7, Q8N2B5, Q8N5G9, Q8NG30, Q96K19, Q9H0V6

    5. XM_054361309.1 → XP_054217284.1  E3 ubiquitin-protein ligase RNF170 isoform X2

      UniProtKB/Swiss-Prot
      D3DSY6, E9PIL4, Q7Z483, Q86YC0, Q8IXR7, Q8N2B5, Q8N5G9, Q8NG30, Q96K19, Q9H0V6

    6. XM_054361310.1 → XP_054217285.1  E3 ubiquitin-protein ligase RNF170 isoform X3

    7. XM_054361306.1 → XP_054217281.1  E3 ubiquitin-protein ligase RNF170 isoform X1

    8. XM_054361313.1 → XP_054217288.1  E3 ubiquitin-protein ligase RNF170 isoform X5

    9. XM_054361316.1 → XP_054217291.1  E3 ubiquitin-protein ligase RNF170 isoform X8

    10. XM_054361319.1 → XP_054217294.1  E3 ubiquitin-protein ligase RNF170 isoform X11

    11. XM_054361318.1 → XP_054217293.1  E3 ubiquitin-protein ligase RNF170 isoform X10

    12. XM_054361315.1 → XP_054217290.1  E3 ubiquitin-protein ligase RNF170 isoform X7

    13. XM_054361314.1 → XP_054217289.1  E3 ubiquitin-protein ligase RNF170 isoform X6

    14. XM_054361317.1 → XP_054217292.1  E3 ubiquitin-protein ligase RNF170 isoform X9

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96K19.2 GenPept UniProtKB/Swiss-Prot:Q96K19

    Gene LinkOut

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

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