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    TAFAZZIN tafazzin, phospholipid-lysophospholipid transacylase [ Homo sapiens (human) ]

    Gene ID: 6901, updated on 10-Dec-2024

    Summary

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    Official Symbol
    TAFAZZINprovided by HGNC
    Official Full Name
    tafazzin, phospholipid-lysophospholipid transacylaseprovided by HGNC
    Primary source
    HGNC:HGNC:11577
    See related
    Ensembl:ENSG00000102125 MIM:300394; AllianceGenome:HGNC:11577
    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
    EFE; TAZ; BTHS; EFE2; G4.5; Taz1; CMD3A; LVNCX
    Summary
    This gene encodes a protein that is expressed at high levels in cardiac and skeletal muscle. Mutations in this gene have been associated with a number of clinical disorders including Barth syndrome, dilated cardiomyopathy (DCM), hypertrophic DCM, endocardial fibroelastosis, and left ventricular noncompaction (LVNC). Multiple transcript variants encoding different isoforms have been described. A long form and a short form of each of these isoforms is produced; the short form lacks a hydrophobic leader sequence and may exist as a cytoplasmic protein rather than being membrane-bound. Other alternatively spliced transcripts have been described but the full-length nature of all these transcripts is not known. [provided by RefSeq, Jul 2008]
    Annotation information
    Note: TAZ (GeneID 6901) and WWTR1 (GeneID 25937) loci share the TAZ symbol/alias in common. TAZ is a widely used alternative name for the transcriptional coactivator with PDZ-binding motif (WWTR1) conflicting with the official symbol for tafazzin (TAZ). [19 Jun 2012]
    Expression
    Ubiquitous expression in bone marrow (RPKM 11.6), spleen (RPKM 10.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TAFAZZIN in Genome Data Viewer
    Location:
    Xq28
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (154411539..154421726)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (152648045..152658233)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (153639875..153650065)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene Xq28 distal FLNA-EMD recombination region Neighboring gene uncharacterized LOC124905228 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21099 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21100 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:153626083-153626628 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30060 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:153627173-153627718 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:153627719-153628262 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:153628263-153628808 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:153628809-153629352 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30061 Neighboring gene ribosomal protein L10 Neighboring gene small nucleolar RNA, H/ACA box 70 Neighboring gene deoxyribonuclease 1 like 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21101 Neighboring gene ReSE screen-validated silencer GRCh37_chrX:153641748-153641921 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:153647927-153648428 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:153648429-153648928 Neighboring gene ATP6AP1 divergent transcript Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:153656739-153657240 Neighboring gene ATPase H+ transporting accessory protein 1

    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
    • 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. NGS identifies TAZ mutation in a family with X-linked dilated cardiomyopathy. Man E, et al. BMJ Case Rep, 2013 Jan 22. PMID 23345479, Free PMC Article
    2. The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies. D'Adamo P, et al. Am J Hum Genet, 1997 Oct. PMID 9382096, Free PMC Article
    3. Clinical and Echocardiographic Impact of Tafazzin Variants on Dilated Cardiomyopathy Phenotype in Left Ventricular Non-Compaction Patients in Early Infancy. Hirono K, et al. Circ J, 2018 Sep 25. PMID 30122738
    4. BARTH SYNDROME IN MALE AND FEMALE SIBLINGS CAUSED BY A NOVEL MUTATION IN THE TAZ GENE. Avdjieva-Tzavella DM, et al. Genet Couns, 2016. PMID 30226969
    5. Familial occurrence of the contracted form of endocardial fibroelastosis. Fixler DE, et al. Am J Cardiol, 1970 Aug. PMID 5455540

    See all (133) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. TAZ upregulates MIR-224 to inhibit oxidative stress response in multiple myeloma.
      Title: TAZ upregulates MIR-224 to inhibit oxidative stress response in multiple myeloma.
    2. Analysis of tafazzin and deoxyribonuclease 1 like 1 transcripts and X chromosome sequencing in the evaluation of the effect of mosaicism in the TAZ gene on phenotypes in a family affected by Barth syndrome.
      Title: Analysis of tafazzin and deoxyribonuclease 1 like 1 transcripts and X chromosome sequencing in the evaluation of the effect of mosaicism in the TAZ gene on phenotypes in a family affected by Barth syndrome.
    3. N-oleoylethanolamide treatment of lymphoblasts deficient in Tafazzin improves cell growth and mitochondrial morphology and dynamics.
      Title: N-oleoylethanolamide treatment of lymphoblasts deficient in Tafazzin improves cell growth and mitochondrial morphology and dynamics.
    4. miR125a5p reverses epithelialmesenchymal transition and restores drug sensitivity by negatively regulating TAFAZZIN signaling in breast cancer.
      Title: miR‑125a‑5p reverses epithelial‑mesenchymal transition and restores drug sensitivity by negatively regulating TAFAZZIN signaling in breast cancer.
    5. Diverse mitochondrial abnormalities in a new cellular model of TAFFAZZIN deficiency are remediated by cardiolipin-interacting small molecules.
      Title: Diverse mitochondrial abnormalities in a new cellular model of TAFFAZZIN deficiency are remediated by cardiolipin-interacting small molecules.
    6. Tafazzin Mutation Affecting Cardiolipin Leads to Increased Mitochondrial Superoxide Anions and Mitophagy Inhibition in Barth Syndrome.
      Title: Tafazzin Mutation Affecting Cardiolipin Leads to Increased Mitochondrial Superoxide Anions and Mitophagy Inhibition in Barth Syndrome.
    7. The Function of Tafazzin, a Mitochondrial Phospholipid-Lysophospholipid Acyltransferase.
      Title: The Function of Tafazzin, a Mitochondrial Phospholipid-Lysophospholipid Acyltransferase.
    8. Delayed appearance of 3-methylglutaconic aciduria in neonates with early onset metabolic cardiomyopathies: A potential pitfall for the diagnosis.
      Title: Delayed appearance of 3-methylglutaconic aciduria in neonates with early onset metabolic cardiomyopathies: A potential pitfall for the diagnosis.
    9. Truncated TEAD-binding protein of TAZ inhibits glioma survival through the induction of apoptosis and repression of epithelial-mesenchymal transition.
      Title: Truncated TEAD-binding protein of TAZ inhibits glioma survival through the induction of apoptosis and repression of epithelial-mesenchymal transition.
    10. This study demonstrated that overexpression of TAZ caused by downregulation of miR-125b promoted resistance of glioma cells to TRAIL. MiR-125b/TAZ axis may represent a potential strategy to reverse the TRAIL in glioma.
      Title: Downregulation of miR-125b promotes resistance of glioma cells to TRAIL through overexpression of Tafazzin which is a mitochondrial protein.
    Submit: New GeneRIF Correction See all GeneRIFs (47)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    • FLJ27390

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 1-acylglycerol-3-phosphate O-acyltransferase activity TAS
    Traceable Author Statement
    more info
    		  
    enables 1-acylglycerophosphocholine O-acyltransferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 1-acylglycerophosphocholine O-acyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables 1-acylglycerophosphocholine O-acyltransferase activity TAS
    Traceable Author Statement
    more info
    		  
    enables O-acyltransferase activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in cardiac muscle contraction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cardiac muscle tissue development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cardiolipin acyl-chain remodeling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cardiolipin acyl-chain remodeling TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cardiolipin biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cardiolipin metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cardiolipin metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cristae formation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in heart development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in heart morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in hemopoiesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in inner mitochondrial membrane organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitochondrial ATP synthesis coupled electron transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitochondrial respiratory chain complex I assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitochondrion organization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in mitophagy IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitophagy ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in muscle contraction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of ATP biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of cardiolipin metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in skeletal muscle tissue development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in spermatocyte division ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in mitochondrial inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		  
    is_active_in mitochondrial membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial outer membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IC
    Inferred by Curator
    more info
    		 PubMed 
    is_active_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    tafazzin
    Names
    protein G4.5

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_009634.2 RefSeqGene

      Range
      5005..15192
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_131

    mRNA and Protein(s)

    1. NM_000116.5 → NP_000107.1  tafazzin isoform 1

      See identical proteins and their annotated locations for NP_000107.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the major isoform (1).
      Source sequence(s)
      AL531401, BC005062, X92762
      Consensus CDS
      CCDS14748.1
      UniProtKB/TrEMBL
      A0A0S2Z4K0, A0A494C004
      Related
      ENSP00000469981.1, ENST00000601016.6
      Conserved Domains (1) summary
      cd07989
      Location:34 → 271
      LPLAT_AGPAT-like; Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-like

    2. NM_001303465.2 → NP_001290394.1  tafazzin isoform 5

      See identical proteins and their annotated locations for NP_001290394.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate in-frame splice junction in the 5' coding region and lacks an alternate in-frame exon in the 3' coding region compared to variant 1. The resulting isoform (5) contains an alternate segment near the N-terminus and lacks an alternate segment near the C-terminus compared to isoform 1.
      Source sequence(s)
      AL531401, BC005062, DB192394, DQ884408, X92762
      Consensus CDS
      CCDS94701.1
      UniProtKB/TrEMBL
      A0A087X0T0, A0A494C004, A6XNE1
      Related
      ENSP00000483636.2, ENST00000616020.5
      Conserved Domains (1) summary
      cd07989
      Location:56 → 275
      LPLAT_AGPAT-like; Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-like

    3. NM_001410698.1 → NP_001397627.1  tafazzin isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC244090, AC245140
      Consensus CDS
      CCDS94702.1
      UniProtKB/TrEMBL
      A0A494C004, A0A499FJ53
      Related
      ENSP00000419854.3, ENST00000475699.6

    4. NM_181311.4 → NP_851828.1  tafazzin isoform 2

      See identical proteins and their annotated locations for NP_851828.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame coding exon compared to variant 1, resulting in a shorter isoform (2) compared to isoform 1.
      Source sequence(s)
      AL531401, AY231461, BC005062, DB192394, X92762
      Consensus CDS
      CCDS14749.1
      UniProtKB/Swiss-Prot
      A3KQT2, D3DWX2, Q16635, Q5HY43, Q5HY44, Q5HY45, Q5HY48, Q86XQ6, Q86XQ7, Q86XQ8, Q86XQ9, Q86XR0
      UniProtKB/TrEMBL
      A0A0S2Z4E6, A0A494C004
      Related
      ENSP00000481037.1, ENST00000612460.5
      Conserved Domains (1) summary
      cd07989
      Location:34 → 241
      LPLAT_AGPAT-like; Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-like

    5. NM_181312.4 → NP_851829.1  tafazzin isoform 3

      See identical proteins and their annotated locations for NP_851829.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an in-frame coding exon compared to variant 1, resulting in a shorter isoform (3) compared to isoform 1.
      Source sequence(s)
      AL531401, AY231462, BC005062, DB192394, X92762
      Consensus CDS
      CCDS14750.1
      UniProtKB/TrEMBL
      A0A0S2Z4K9, A0A494C004
      Related
      ENSP00000482070.2, ENST00000612012.5
      Conserved Domains (1) summary
      cd07989
      Location:34 → 257
      LPLAT_AGPAT-like; Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-like

    6. NM_181313.4 → NP_851830.1  tafazzin isoform 4

      See identical proteins and their annotated locations for NP_851830.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks two in-frame coding exons compared to variant 1, resulting in a shorter isoform (4) compared to isoform 1.
      Source sequence(s)
      AL531401, AY231463, BC005062, DB192394, X92762
      Consensus CDS
      CCDS35450.1
      UniProtKB/TrEMBL
      A0A0S2Z4F4, F6Y2X3
      Related
      ENSP00000478154.1, ENST00000613002.4
      Conserved Domains (1) summary
      cd07989
      Location:34 → 227
      LPLAT_AGPAT-like; Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-like

    RNA

    1. NR_024048.3 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) uses an alternate donor splice site at one of the coding exons, and is also lacking an internal coding exon compared to variant 1. This results in premature translation termination rendering this transcript susceptible to NMD. This variant has transcript support, but is not expected to encode a viable protein product.
      Source sequence(s)
      AL531401, BC005062
      Related
      ENST00000615986.4

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      154411539..154421726
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006724836.2 → XP_006724899.1  tafazzin isoform X1

      UniProtKB/TrEMBL
      A0A494C004
      Related
      ENSP00000498858.1, ENST00000652390.1
      Conserved Domains (1) summary
      cd07989
      Location:56 → 289
      LPLAT_AGPAT-like; Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-like

    2. XM_006724837.2 → XP_006724900.1  tafazzin isoform X2

      UniProtKB/TrEMBL
      F6Y2X3
      Related
      ENSP00000358791.4, ENST00000369776.8
      Conserved Domains (2) summary
      COG0204
      Location:60 → 294
      PlsC; 1-acyl-sn-glycerol-3-phosphate acyltransferase [Lipid transport and metabolism]
      pfam01553
      Location:59 → 169
      Acyltransferase; Acyltransferase

    3. XM_006724839.2 → XP_006724902.1  tafazzin isoform X4

      UniProtKB/TrEMBL
      F6Y2X3
      Conserved Domains (1) summary
      cd07989
      Location:56 → 245
      LPLAT_AGPAT-like; Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-like

    4. XM_011531189.2 → XP_011529491.1  tafazzin isoform X5

      Conserved Domains (1) summary
      cl17185
      Location:59 → 142
      LPLAT; Lysophospholipid acyltransferases (LPLATs) of glycerophospholipid biosynthesis

    5. XM_017029761.2 → XP_016885250.1  tafazzin isoform X3

      UniProtKB/TrEMBL
      F6Y2X3

    6. XM_017029763.2 → XP_016885252.1  tafazzin isoform X7

    7. XM_047442407.1 → XP_047298363.1  tafazzin isoform X6

      UniProtKB/TrEMBL
      A0A494C0C5, A0A494C0V5
      Related
      ENSP00000498464.1, ENST00000652358.1

    8. XM_047442408.1 → XP_047298364.1  tafazzin isoform X10

      UniProtKB/TrEMBL
      A0A494C0V5

    9. XM_011531191.3 → XP_011529493.1  tafazzin isoform X8

      UniProtKB/TrEMBL
      A0A494C0V5
      Related
      ENSP00000498734.1, ENST00000652354.1
      Conserved Domains (1) summary
      cd07989
      Location:58 → 179
      LPLAT_AGPAT-like; Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-like

    10. XM_017029764.2 → XP_016885253.1  tafazzin isoform X9

      UniProtKB/TrEMBL
      A0A494C0V5
      Conserved Domains (1) summary
      cd07989
      Location:57 → 178
      LPLAT_AGPAT-like; Lysophospholipid Acyltransferases (LPLATs) of Glycerophospholipid Biosynthesis: AGPAT-like

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      152648045..152658233
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054327646.1 → XP_054183621.1  tafazzin isoform X1

      UniProtKB/TrEMBL
      A0A494C004

    2. XM_054327647.1 → XP_054183622.1  tafazzin isoform X2

      UniProtKB/TrEMBL
      F6Y2X3

    3. XM_054327649.1 → XP_054183624.1  tafazzin isoform X4

      UniProtKB/TrEMBL
      F6Y2X3

    4. XM_054327650.1 → XP_054183625.1  tafazzin isoform X5

    5. XM_054327648.1 → XP_054183623.1  tafazzin isoform X3

      UniProtKB/TrEMBL
      F6Y2X3

    6. XM_054327652.1 → XP_054183627.1  tafazzin isoform X7

    7. XM_054327651.1 → XP_054183626.1  tafazzin isoform X6

      UniProtKB/TrEMBL
      A0A494C0C5, A0A494C0V5

    8. XM_054327655.1 → XP_054183630.1  tafazzin isoform X10

      UniProtKB/TrEMBL
      A0A494C0V5

    9. XM_054327653.1 → XP_054183628.1  tafazzin isoform X8

      UniProtKB/TrEMBL
      A0A494C0V5

    10. XM_054327654.1 → XP_054183629.1  tafazzin isoform X9

      UniProtKB/TrEMBL
      A0A494C0V5

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_181314.1: Suppressed sequence

      Description
      NM_181314.1: 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
    Q16635.2 GenPept UniProtKB/Swiss-Prot:Q16635

    Gene LinkOut

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

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