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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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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.
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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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