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    RAP1GDS1 Rap1 GTPase-GDP dissociation stimulator 1 [ Homo sapiens (human) ]

    Gene ID: 5910, updated on 2-Nov-2024

    Summary

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    Official Symbol
    RAP1GDS1provided by HGNC
    Official Full Name
    Rap1 GTPase-GDP dissociation stimulator 1provided by HGNC
    Primary source
    HGNC:HGNC:9859
    See related
    Ensembl:ENSG00000138698 MIM:179502; AllianceGenome:HGNC:9859
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GDS1; SmgGDS
    Summary
    The smg GDP dissociation stimulator (smgGDS) protein is a stimulatory GDP/GTP exchange protein with GTPase activity (Riess et al., 1993 [PubMed 8262526]).[supplied by OMIM, Feb 2010]
    Expression
    Ubiquitous expression in brain (RPKM 27.0), testis (RPKM 10.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See RAP1GDS1 in Genome Data Viewer
    Location:
    4q23
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (98261384..98443858)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (101576339..101758825)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (99182535..99365009)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene sperm tail PG-rich repeat containing 2 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:99031922-99032747 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21732 Neighboring gene deoxyuridine triphosphatase pseudogene 8 Neighboring gene uncharacterized LOC105377340 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:99125201-99125922 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:99181827-99182389 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15576 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15577 Neighboring gene uncharacterized LOC124900919 Neighboring gene ribosomal protein L21 pseudogene 48 Neighboring gene Sharpr-MPRA regulatory region 12770 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21734 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:99457519-99458032 Neighboring gene tetraspanin 5 Neighboring gene Sharpr-MPRA regulatory region 11258 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:99518736-99519334 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21735 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr4:99574420-99575619 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:99579327-99579486 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15578 Neighboring gene uncharacterized LOC112267901 Neighboring gene TSPAN5 divergent transcript

    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. Silencing of SmgGDS, a Novel mTORC1 Inducer That Binds to RHEBs, Inhibits Malignant Mesothelioma Cell Proliferation.
      Title: Silencing of SmgGDS, a Novel mTORC1 Inducer That Binds to RHEBs, Inhibits Malignant Mesothelioma Cell Proliferation.
    2. Mutated RAP1GDS1 causes a new syndrome of dysmorphic feature, intellectual disability & speech delay.
      Title: Mutated RAP1GDS1 causes a new syndrome of dysmorphic feature, intellectual disability & speech delay.
    3. Targeting SmgGDS splicing to lower the protein isoform ratio is effective to inhibit the malignant phenotype generated by small GTPases.
      Title: Splice switching an oncogenic ratio of SmgGDS isoforms as a strategy to diminish malignancy.
    4. The competitive binding affinities of the small GTPase for SmgGDS-607 and FTase dictate the extent of this inhibition. SmgGDS-607 increases the rate of farnesylation of HRas by enhancing product release from FTase.
      Title: The chaperone SmgGDS-607 has a dual role, both activating and inhibiting farnesylation of small GTPases.
    5. SmgGDS-607 completely inhibits RhoA prenylation catalyzed by protein geranylgeranyltransferase I (GGTase-I) in an in vitro radiolabel incorporation assay. SmgGDS-607 inhibits prenylation by binding to and blocking access to the C-terminal tail of the small GTPase (substrate sequestration mechanism) rather than via inhibition of the prenyltransferase activity.
      Title: SmgGDS-607 Regulation of RhoA GTPase Prenylation Is Nucleotide-Dependent.
    6. Study reveals a cryptic pocket by which SmgGDS-558 accommodates RhoA prenylation, loosening the structure of Rho when it interacts with SmgGDS, which may enable drug development strategies for targeting SmgGDS and small GTPases.
      Title: GEF mechanism revealed by the structure of SmgGDS-558 and farnesylated RhoA complex and its implication for a chaperone mechanism.
    7. a novel nuclear role for SmgGDS in protecting malignant cells from nucleolar stress, thus promoting cell cycle progression and tumorigenesis.
      Title: SmgGDS is a transient nucleolar protein that protects cells from nucleolar stress and promotes the cell cycle by regulating DREAM complex gene expression.
    8. Data suggest that SmgGDS-558 splice variant exhibits a fold containing tandem copies of armadillo-repeat motifs not present in other guanine nucleotide exchange factors (GEFs); SmgGDS harbors distinct positively and negatively charged regions, both of which play critical roles in binding to RhoA and in GEF activity. (SmgGDS = smg p21 stimulatory GDP exchange protein; RhoA = ras homolog gene family, member A)
      Title: Structure-based analysis of the guanine nucleotide exchange factor SmgGDS reveals armadillo-repeat motifs and key regions for activity and GTPase binding.
    9. Unlike Rap1B, phosphorylation in the polybasic region of Rap1A does not detectably inhibit its prenylation or its binding to SmgGDS-607.
      Title: Differences in the Phosphorylation-Dependent Regulation of Prenylation of Rap1A and Rap1B.
    10. In addition, a PINK1 mutant, which induced mitochondrial enlargement and had been considered as a Drosophila model of Parkinson's disease (PD), caused fly muscle defects, and the loss of vimar could rescue these defects. Furthermore, we found that the mammalian homolog of Vimar, RAP1GDS1, played a similar role in regulating mitochondrial morphology, suggesting a functional conservation of this GEF member.
      Title: Vimar Is a Novel Regulator of Mitochondrial Fission through Miro.
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    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
    Alfadhel syndrome
    MedGen: C5882735 OMIM: 620655 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Genome-wide association study of biochemical traits in Korcula Island, Croatia.
    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)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of RAP1GDS1 PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat downregulates the expression of RAP1, GTP-GDP dissociation stimulator 1 (RAP1GDS1; GDS1) in human primary T cells 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

    Clone Names

    • MGC118859, MGC118861

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables guanyl-nucleotide exchange factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in CAAX-box protein maturation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in angiotensin-activated signaling pathway involved in heart process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cardiac muscle hypertrophy IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in myosin filament assembly IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of endoplasmic reticulum calcium ion concentration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of GTPase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of mitochondrial calcium ion concentration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein localization to nucleus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of ERK5 cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of matrix metallopeptidase secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of mitochondrion organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in vascular associated smooth muscle contraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular exosome HDA PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    rap1 GTPase-GDP dissociation stimulator 1
    Names
    RAP1, GTP-GDP dissociation stimulator 1
    SMG GDS protein
    SMG P21 stimulatory GDP/GTP exchange protein
    exchange factor smgGDS

    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_001100426.2 → NP_001093896.1  rap1 GTPase-GDP dissociation stimulator 1 isoform 1

      See identical proteins and their annotated locations for NP_001093896.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC058823, AF215923, AI800264, BC098269, DC367998
      Consensus CDS
      CCDS47105.1
      UniProtKB/TrEMBL
      B3KNU0
      Related
      ENSP00000340454.5, ENST00000339360.9
      Conserved Domains (2) summary
      cd00020
      Location:318 → 431
      ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
      sd00043
      Location:92 → 117
      ARM; armadillo repeat [structural motif]

    2. NM_001100427.2 → NP_001093897.1  rap1 GTPase-GDP dissociation stimulator 1 isoform 3

      See identical proteins and their annotated locations for NP_001093897.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, resulting in a shorter protein (isoform 3), compared to isoform 1.
      Source sequence(s)
      AC058823, AI800264, AK055032, BC098269, DC367998
      Consensus CDS
      CCDS43253.1
      UniProtKB/Swiss-Prot
      E9PH06, G5E9P9, P52306, Q499L7, Q4KMV2, Q4QQI8, Q9BUW9, Q9BUX6, Q9NYM2, Q9NZA8
      UniProtKB/TrEMBL
      B3KNU0
      Related
      ENSP00000386153.4, ENST00000408927.8
      Conserved Domains (2) summary
      cd00020
      Location:317 → 430
      ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
      sd00043
      Location:91 → 116
      ARM; armadillo repeat [structural motif]

    3. NM_001100428.2 → NP_001093898.1  rap1 GTPase-GDP dissociation stimulator 1 isoform 4

      See identical proteins and their annotated locations for NP_001093898.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) lacks an alternate in-frame exon in the mid-coding region, compared to variant 1, resulting in a shorter protein (isoform 4), compared to isoform 1.
      Source sequence(s)
      AC058823, AI800264, BC001851, BC099845, DC367998
      Consensus CDS
      CCDS47107.1
      UniProtKB/TrEMBL
      B7Z2V8
      Related
      ENSP00000369503.4, ENST00000380158.8
      Conserved Domains (3) summary
      cd00020
      Location:44 → 163
      ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
      sd00043
      Location:45 → 76
      ARM; armadillo repeat [structural motif]
      cl22454
      Location:391 → 459
      ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...

    4. NM_001100429.2 → NP_001093899.1  rap1 GTPase-GDP dissociation stimulator 1 isoform 5

      See identical proteins and their annotated locations for NP_001093899.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) uses an alternate in-frame splice site in the 5' coding region and lacks an alternate in-frame exon in the mid-coding region, compared to variant 1, resulting in a shorter protein (isoform 5), compared to isoform 1.
      Source sequence(s)
      AC058823, AI800264, BC098334, DC367998
      Consensus CDS
      CCDS43254.1
      UniProtKB/TrEMBL
      B7Z2V8
      Related
      ENSP00000386223.3, ENST00000408900.7
      Conserved Domains (3) summary
      cd00020
      Location:43 → 162
      ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
      sd00043
      Location:44 → 75
      ARM; armadillo repeat [structural motif]
      cl22454
      Location:390 → 458
      ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...

    5. NM_001100430.2 → NP_001093900.1  rap1 GTPase-GDP dissociation stimulator 1 isoform 6

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6) lacks two alternate in-frame exons in the mid-coding region, compared to variant 1, resulting in a shorter protein (isoform 6), compared to isoform 1.
      Source sequence(s)
      AC058823, AI800264, AY376900, BC098334, BC099845, DC367998
      Consensus CDS
      CCDS47108.1
      UniProtKB/TrEMBL
      Q6U7G8
      Related
      ENSP00000264572.7, ENST00000264572.11
      Conserved Domains (2) summary
      cd00020
      Location:226 → 339
      ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
      sd00043
      Location:45 → 76
      ARM; armadillo repeat [structural motif]

    6. NM_021159.5 → NP_066982.3  rap1 GTPase-GDP dissociation stimulator 1 isoform 2

      See identical proteins and their annotated locations for NP_066982.3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      AC058823, AI800264, BC001851, BC098269, DC367998
      Consensus CDS
      CCDS47106.1
      UniProtKB/TrEMBL
      B3KNU0
      Related
      ENSP00000407157.2, ENST00000453712.6
      Conserved Domains (2) summary
      cd00020
      Location:318 → 431
      ARM; Armadillo/beta-catenin-like repeats. An approximately 40 amino acid long tandemly repeated sequence motif first identified in the Drosophila segment polarity gene armadillo; these repeats were also found in the mammalian armadillo homolog beta-catenin, ...
      sd00043
      Location:92 → 117
      ARM; armadillo repeat [structural motif]

    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_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      98261384..98443858
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024454165.2 → XP_024309933.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X2

      UniProtKB/TrEMBL
      B7Z2V8
      Conserved Domains (5) summary
      smart00185
      Location:298 → 341
      ARM; Armadillo/beta-catenin-like repeats
      pfam00514
      Location:87 → 118
      Arm; Armadillo/beta-catenin-like repeat
      sd00043
      Location:45 → 76
      ARM; armadillo repeat [structural motif]
      cl26969
      Location:178 → 343
      Vitellogenin_N; Lipoprotein amino terminal region
      cl27106
      Location:31 → 216
      PLN03200; cellulose synthase-interactive protein; Provisional

    2. XM_024454164.2 → XP_024309932.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X1

      UniProtKB/TrEMBL
      B3KNU0
      Conserved Domains (3) summary
      sd00043
      Location:91 → 116
      ARM; armadillo repeat [structural motif]
      cl26969
      Location:226 → 391
      Vitellogenin_N; Lipoprotein amino terminal region
      cl27106
      Location:18 → 264
      PLN03200; cellulose synthase-interactive protein; Provisional

    3. XM_024454166.2 → XP_024309934.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X3

      UniProtKB/TrEMBL
      B7Z2V8
      Conserved Domains (5) summary
      smart00185
      Location:297 → 340
      ARM; Armadillo/beta-catenin-like repeats
      pfam00514
      Location:86 → 117
      Arm; Armadillo/beta-catenin-like repeat
      sd00043
      Location:44 → 75
      ARM; armadillo repeat [structural motif]
      cl26969
      Location:177 → 342
      Vitellogenin_N; Lipoprotein amino terminal region
      cl27106
      Location:30 → 215
      PLN03200; cellulose synthase-interactive protein; Provisional

    4. XM_047416051.1 → XP_047272007.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X4

    5. XM_024454168.2 → XP_024309936.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X4

      UniProtKB/TrEMBL
      B7Z4M5
      Conserved Domains (4) summary
      smart00185
      Location:266 → 309
      ARM; Armadillo/beta-catenin-like repeats
      pfam00514
      Location:6 → 37
      Arm; Armadillo/beta-catenin-like repeat
      sd00043
      Location:11 → 36
      ARM; armadillo repeat [structural motif]
      cl27106
      Location:6 → 184
      PLN03200; cellulose synthase-interactive protein; Provisional

    6. XM_047416052.1 → XP_047272008.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      101576339..101758825
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054350661.1 → XP_054206636.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X2

    2. XM_054350660.1 → XP_054206635.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X1

    3. XM_054350662.1 → XP_054206637.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X3

    4. XM_054350663.1 → XP_054206638.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X4

    5. XM_054350664.1 → XP_054206639.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X4

    6. XM_054350665.1 → XP_054206640.1  rap1 GTPase-GDP dissociation stimulator 1 isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P52306.3 GenPept UniProtKB/Swiss-Prot:P52306

    Gene LinkOut

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

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