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    TTC3 tetratricopeptide repeat domain 3 [ Homo sapiens (human) ]

    Gene ID: 7267, updated on 5-Mar-2024

    Summary

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    Official Symbol
    TTC3provided by HGNC
    Official Full Name
    tetratricopeptide repeat domain 3provided by HGNC
    Primary source
    HGNC:HGNC:12393
    See related
    Ensembl:ENSG00000182670 MIM:602259; AllianceGenome:HGNC:12393
    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
    DCRR1; RNF105; TPRDIII
    Summary
    Enables ubiquitin-protein transferase activity. Involved in protein K48-linked ubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in brain (RPKM 28.4), thyroid (RPKM 22.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TTC3 in Genome Data Viewer
    Location:
    21q22.13
    Exon count:
    48
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 21 NC_000021.9 (37073254..37203118)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 21 NC_060945.1 (35455436..35585344)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 21 NC_000021.8 (38445554..38575419)

    Chromosome 21 - NC_000021.9Genomic Context describing neighboring genes Neighboring gene RNA, U6 small nuclear 696, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13296 Neighboring gene Sharpr-MPRA regulatory region 5899 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13298 Neighboring gene phosphatidylinositol glycan anchor biosynthesis class P Neighboring gene GFI1 motif-containing MPRA enhancer 103 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:38519638-38520138 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18443 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr21:38567734-38568933 Neighboring gene TTC3 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:38579468-38580304 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18444 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18445 Neighboring gene RNA, 7SL, cytoplasmic 678, pseudogene Neighboring gene Down syndrome critical region 9 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18446 Neighboring gene VPS26 endosomal protein sorting factor C Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18447 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:38629775-38630367 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:38630368-38630960 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13299 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18449 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13300

    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. TTC3-Mediated Protein Quality Control, A Potential Mechanism for Cognitive Impairment. Zhou X, et al. Cell Mol Neurobiol, 2022 Aug. PMID 33638766, Free PMC Article
    2. Derivation of stem cell line UMi028-A-2 containing a CRISPR/Cas9 induced Alzheimer's disease risk variant p.S1038C in the TTC3 gene. Laverde-Paz MJ, et al. Stem Cell Res, 2021 Apr. PMID 33626494
    3. Overexpressed TTC3 Protein Tends to be Cleaved into Fragments and Form Aggregates in the Nucleus. Gong Y, et al. Neuromolecular Med, 2019 Mar. PMID 30203323
    4. Regional and cellular specificity of the expression of TPRD, the tetratricopeptide Down syndrome gene, during human embryonic development. Rachidi M, et al. Mech Dev, 2000 May. PMID 10781955
    5. Cloning and characterization of novel gene, DCRR1, expressed from Down's syndrome critical region of human chromosome 21q22.2. Eki T, et al. DNA Seq, 1997. PMID 9254009

    See all (48) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. An Alzheimer's disease risk variant in TTC3 modifies the actin cytoskeleton organization and the PI3K-Akt signaling pathway in iPSC-derived forebrain neurons.
      Title: An Alzheimer's disease risk variant in TTC3 modifies the actin cytoskeleton organization and the PI3K-Akt signaling pathway in iPSC-derived forebrain neurons.
    2. TTC3-Mediated Protein Quality Control, A Potential Mechanism for Cognitive Impairment.
      Title: TTC3-Mediated Protein Quality Control, A Potential Mechanism for Cognitive Impairment.
    3. Derivation of stem cell line UMi028-A-2 containing a CRISPR/Cas9 induced Alzheimer's disease risk variant p.S1038C in the TTC3 gene.
      Title: Derivation of stem cell line UMi028-A-2 containing a CRISPR/Cas9 induced Alzheimer's disease risk variant p.S1038C in the TTC3 gene.
    4. Overexpressed TTC3 Protein Tends to be Cleaved into Fragments and Form Aggregates in the Nucleus.
      Title: Overexpressed TTC3 Protein Tends to be Cleaved into Fragments and Form Aggregates in the Nucleus.
    5. Data suggest that TTC3 may contribute to TGF-beta1-induced EMT and myofibroblast differentiation, potentially through SMURF2 ubiquitylation/proteasomal degradation and subsequent inhibition of SMURF2-mediated suppression of SMAD2 and SMAD3, which in turn induces TTC3 expression.
      Title: TTC3 contributes to TGF-β(1)-induced epithelial-mesenchymal transition and myofibroblast differentiation, potentially through SMURF2 ubiquitylation and degradation.
    6. USP16 and TTC3 were dysregulated in all affected human cells and two mouse models of Down syndrome.
      Title: An Integrated Human/Murine Transcriptome and Pathway Approach To Identify Prenatal Treatments For Down Syndrome.
    7. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    8. Interaction between TTC3 and Akt may contribute to the clinical symptoms of Down syndrome.
      Title: The E3 ligase TTC3 facilitates ubiquitination and degradation of phosphorylated Akt.
    9. These results suggest that the TTC3-RhoA-CIT-K pathway could be a crucial determinant of in vivo neuronal development, whose hyperactivity may result in detrimental effects on the normal differentiation program.
      Title: The Down syndrome critical region protein TTC3 inhibits neuronal differentiation via RhoA and Citron kinase.
    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

    EBI GWAS Catalog

    Description
    Digital quantification of human eye color highlights genetic association of three new loci.
    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
    Knockdown of tetratricopeptide repeat domain 3 (TTC3) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 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

    • DKFZp686M0150

    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 transferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin-protein transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in protein K48-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Golgi apparatus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase TTC3
    Names
    RING finger protein 105
    RING-type E3 ubiquitin transferase TTC3
    TPR repeat protein 3
    TPR repeat protein D
    tetratricopeptide repeat protein 3
    NP_001001894.1
    NP_001307632.1
    NP_001307633.1
    NP_001317610.1
    NP_001317611.1
    NP_001317612.1
    NP_001340865.1
    NP_001340866.1
    NP_001340867.1
    NP_003307.3

    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_001001894.3 → NP_001001894.1  E3 ubiquitin-protein ligase TTC3 isoform 1

      See identical proteins and their annotated locations for NP_001001894.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2), as well as variants 1 and 7, encodes isoform 1.
      Source sequence(s)
      AP001429, AP001432, KF510554
      Consensus CDS
      CCDS13651.1
      UniProtKB/Swiss-Prot
      A8K7H7, B2RPA7, D3DSG9, D3DSH2, D3DSH3, O60767, P53804, P78476, P78477, Q569I2, Q6P578, Q9UEK4
      UniProtKB/TrEMBL
      A0A8Q3WLN3
      Related
      ENSP00000408456.2, ENST00000450533.6
      Conserved Domains (4) summary
      sd00006
      Location:232 → 259
      TPR; TPR repeat [structural motif]
      pfam12895
      Location:243 → 321
      ANAPC3; Anaphase-promoting complex, cyclosome, subunit 3
      pfam13414
      Location:540 → 605
      TPR_11; TPR repeat
      pfam13639
      Location:1956 → 1996
      zf-RING_2; Ring finger domain

    2. NM_001320703.2 → NP_001307632.1  E3 ubiquitin-protein ligase TTC3 isoform 3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) encodes the longest isoform (3).
      Source sequence(s)
      AI066542, AI745113, AL040434, AP001429, AP001432, AW510696, BE780449, BG029806, BP327196, BU179028, BU508034, CD244359, CD655107, CT002499, DB484247
      UniProtKB/TrEMBL
      A0A8Q3WLN3
      Conserved Domains (4) summary
      sd00006
      Location:254 → 281
      TPR; TPR repeat [structural motif]
      pfam12895
      Location:265 → 343
      ANAPC3; Anaphase-promoting complex, cyclosome, subunit 3
      pfam13414
      Location:562 → 627
      TPR_11; TPR repeat
      pfam13639
      Location:1996 → 2036
      zf-RING_2; Ring finger domain

    3. NM_001320704.2 → NP_001307633.1  E3 ubiquitin-protein ligase TTC3 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AA482675, AK291992, AL040434, AP001429, AP001432, AW510696, BP327196, BU508034, CN350112, CT002499, CX868913, D84294, DB484247
      Consensus CDS
      CCDS93095.1
      UniProtKB/TrEMBL
      A0A8Q3WLN3, H7BZ57
      Related
      ENSP00000387880.2, ENST00000411496.2
      Conserved Domains (4) summary
      sd00006
      Location:232 → 259
      TPR; TPR repeat [structural motif]
      pfam12895
      Location:243 → 321
      ANAPC3; Anaphase-promoting complex, cyclosome, subunit 3
      pfam13414
      Location:540 → 605
      TPR_11; TPR repeat
      pfam13639
      Location:1974 → 2014
      zf-RING_2; Ring finger domain

    4. NM_001330681.2 → NP_001317610.1  E3 ubiquitin-protein ligase TTC3 isoform 4

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5), as well as variants 6 and 8, encodes isoform 4.
      Source sequence(s)
      AP001429, AP001432, KF510554
      Consensus CDS
      CCDS93096.1
      UniProtKB/TrEMBL
      Q5CZA6
      Related
      ENSP00000512889.1, ENST00000492275.6
      Conserved Domains (3) summary
      sd00006
      Location:181 → 208
      TPR; TPR repeat [structural motif]
      cd16481
      Location:1646 → 1687
      RING-H2_TTC3; RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins
      cl25732
      Location:1176 → 1422
      SMC_N; RecF/RecN/SMC N terminal domain

    5. NM_001330682.2 → NP_001317611.1  E3 ubiquitin-protein ligase TTC3 isoform 4

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6), as well as variants 5 and 8, encodes isoform 4.
      Source sequence(s)
      AP001429, AP001432, KF510554
      Consensus CDS
      CCDS93096.1
      UniProtKB/TrEMBL
      Q5CZA6
      Related
      ENSP00000512893.1, ENST00000463216.6
      Conserved Domains (3) summary
      sd00006
      Location:181 → 208
      TPR; TPR repeat [structural motif]
      cd16481
      Location:1646 → 1687
      RING-H2_TTC3; RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins
      cl25732
      Location:1176 → 1422
      SMC_N; RecF/RecN/SMC N terminal domain

    6. NM_001330683.2 → NP_001317612.1  E3 ubiquitin-protein ligase TTC3 isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (7), as well as variants 1 and 2, encodes isoform 1.
      Source sequence(s)
      AP001429, AP001432, KF510554
      Consensus CDS
      CCDS13651.1
      UniProtKB/Swiss-Prot
      A8K7H7, B2RPA7, D3DSG9, D3DSH2, D3DSH3, O60767, P53804, P78476, P78477, Q569I2, Q6P578, Q9UEK4
      UniProtKB/TrEMBL
      A0A8Q3WLN3
      Related
      ENSP00000403943.2, ENST00000418766.6

    7. NM_001353936.2 → NP_001340865.1  E3 ubiquitin-protein ligase TTC3 isoform 4

      Status: VALIDATED

      Description
      Transcript Variant: This variant (8), as well as variants 5 and 6, encodes isoform 4.
      Source sequence(s)
      AP001429, AP001432, KF510554
      Consensus CDS
      CCDS93096.1
      UniProtKB/TrEMBL
      Q5CZA6
      Conserved Domains (3) summary
      sd00006
      Location:181 → 208
      TPR; TPR repeat [structural motif]
      cd16481
      Location:1646 → 1687
      RING-H2_TTC3; RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins
      cl25732
      Location:1176 → 1422
      SMC_N; RecF/RecN/SMC N terminal domain

    8. NM_001353937.2 → NP_001340866.1  E3 ubiquitin-protein ligase TTC3 isoform 5

      Status: VALIDATED

      Description
      Transcript Variant: This variant (9), as well as variant 10, encodes isoform 5.
      Source sequence(s)
      AP001429, AP001432, KF510554
      UniProtKB/TrEMBL
      Q5CZA6
      Conserved Domains (2) summary
      cd16481
      Location:1234 → 1275
      RING-H2_TTC3; RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins
      cl25732
      Location:764 → 1010
      SMC_N; RecF/RecN/SMC N terminal domain

    9. NM_001353938.2 → NP_001340867.1  E3 ubiquitin-protein ligase TTC3 isoform 5

      Status: VALIDATED

      Description
      Transcript Variant: This variant (10), as well as variant 9, encodes isoform 5.
      Source sequence(s)
      AP001429, AP001432, KF510554
      UniProtKB/TrEMBL
      Q5CZA6
      Conserved Domains (2) summary
      cd16481
      Location:1234 → 1275
      RING-H2_TTC3; RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins
      cl25732
      Location:764 → 1010
      SMC_N; RecF/RecN/SMC N terminal domain

    10. NM_003316.4 → NP_003307.3  E3 ubiquitin-protein ligase TTC3 isoform 1

      See identical proteins and their annotated locations for NP_003307.3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR and has multiple coding region differences compared to variant 3. These differences cause translation initiation at a downstream AUG and result in an isoform (1) with a shorter N-terminus compared to isoform 3. Variants 1, 2, and 7 all encode the same isoform (1).
      Source sequence(s)
      AP001429, AP001432, KF510554
      Consensus CDS
      CCDS13651.1
      UniProtKB/Swiss-Prot
      A8K7H7, B2RPA7, D3DSG9, D3DSH2, D3DSH3, O60767, P53804, P78476, P78477, Q569I2, Q6P578, Q9UEK4
      UniProtKB/TrEMBL
      A0A8Q3WLN3
      Related
      ENSP00000381981.2, ENST00000399017.6
      Conserved Domains (4) summary
      sd00006
      Location:232 → 259
      TPR; TPR repeat [structural motif]
      pfam12895
      Location:243 → 321
      ANAPC3; Anaphase-promoting complex, cyclosome, subunit 3
      pfam13414
      Location:540 → 605
      TPR_11; TPR repeat
      pfam13639
      Location:1956 → 1996
      zf-RING_2; Ring finger domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000021.9 Reference GRCh38.p14 Primary Assembly

      Range
      37073254..37203118
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060945.1 Alternate T2T-CHM13v2.0

      Range
      35455436..35585344
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P53804.2 GenPept UniProtKB/Swiss-Prot:P53804

    Gene LinkOut

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