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    TIPIN TIMELESS interacting protein [ Homo sapiens (human) ]

    Gene ID: 54962, updated on 28-Oct-2024

    Summary

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    Official Symbol
    TIPINprovided by HGNC
    Official Full Name
    TIMELESS interacting proteinprovided by HGNC
    Primary source
    HGNC:HGNC:30750
    See related
    Ensembl:ENSG00000075131 MIM:610716; AllianceGenome:HGNC:30750
    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
    Summary
    The protein encoded by this gene is part of the replisome complex, a group of proteins that support DNA replication. It binds TIM, which is involved in circadian rhythm regulation, and aids in protecting cells against DNA damage and stress. Two pseudogenes and two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]
    Expression
    Broad expression in testis (RPKM 3.8), lymph node (RPKM 1.8) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TIPIN in Genome Data Viewer
    Location:
    15q22.31
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (66336191..66386717, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (64157927..64208168, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (66628529..66679055, complement)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene multiple EGF like domains 11 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:66340493-66341368 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:66349054-66349554 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:66357857-66358057 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:66358200-66358762 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:66365553-66366053 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:66371850-66372818 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:66372819-66373785 Neighboring gene microRNA 4311 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:66388655-66389435 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:66408056-66408295 Neighboring gene Sharpr-MPRA regulatory region 9514 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:66435333-66436223 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:66460026-66460820 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:66461585-66462085 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr15:66472833-66473489 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6562 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:66591355-66591855 Neighboring gene DIS3L antisense RNA 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:66630872-66631107 Neighboring gene DIS3 like exosome 3'-5' exoribonuclease Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9611 Neighboring gene small Cajal body-specific RNA 14 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9612 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6563 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6564 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:66681899-66682075 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6565 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr15:66696135-66696928 Neighboring gene ribosomal protein L9 pseudogene 25 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:66720755-66721254 Neighboring gene mitogen-activated protein kinase kinase 1 Neighboring gene ATP synthase membrane subunit f pseudogene 6 Neighboring gene ribosomal protein L35a pseudogene 32

    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. TIPIN depletion leads to apoptosis in breast cancer cells. Baldeyron C, et al. Mol Oncol, 2015 Oct. PMID 26004086, Free PMC Article
    2. Human Tim-Tipin complex affects the biochemical properties of the replicative DNA helicase and DNA polymerases. Cho WH, et al. Proc Natl Acad Sci U S A, 2013 Feb 12. PMID 23359676, Free PMC Article
    3. Tipin and Timeless form a mutually protective complex required for genotoxic stress resistance and checkpoint function. Chou DM, et al. Proc Natl Acad Sci U S A, 2006 Nov 28. PMID 17116885, Free PMC Article
    4. Crystal structure of the N-terminal domain of human Timeless and its interaction with Tipin. Holzer S, et al. Nucleic Acids Res, 2017 May 19. PMID 28334766, Free PMC Article
    5. The replisome pausing factor Timeless is required for episomal maintenance of latent Epstein-Barr virus. Dheekollu J, et al. J Virol, 2011 Jun. PMID 21490103, Free PMC Article

    See all (45) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Germline polymorphisms in genes maintaining the replication fork predict the efficacy of oxaliplatin and irinotecan in patients with metastatic colorectal cancer.
      Title: Germline polymorphisms in genes maintaining the replication fork predict the efficacy of oxaliplatin and irinotecan in patients with metastatic colorectal cancer.
    2. the 1.85 A crystal structure of a large N-terminal segment of human Timeless, spanning amino acids 1-463, is presented and this region of human Timeless harbours a partial binding site for Tipin.
      Title: Crystal structure of the N-terminal domain of human Timeless and its interaction with Tipin.
    3. TIPIN is important for the maintenance of DNA replication and represents a potential treatment target for the worst prognosis associated breast cancers, such as Triple-negative breast cancer.
      Title: TIPIN depletion leads to apoptosis in breast cancer cells.
    4. Tim-Tipin complex (or Tim alone) is able to associate with DNA polymerase epsilon bound to a 40-/80-mer DNA ligand.
      Title: The human Tim-Tipin complex interacts directly with DNA polymerase epsilon and stimulates its synthetic activity.
    5. Tim-Tipin complex might play a role in coupling DNA unwinding and DNA synthesis by directly affecting the catalytic activities of replication fork proteins.
      Title: Human Tim-Tipin complex affects the biochemical properties of the replicative DNA helicase and DNA polymerases.
    6. We now show that cellular DNA replication fork pausing and protection factors Timeless (Tim) and Tipin (Timeless-interacting protein) accumulate at OriP during S phase of the cell cycle.
      Title: The replisome pausing factor Timeless is required for episomal maintenance of latent Epstein-Barr virus.
    7. RPA-covered ssDNA not only supports recruitment and activation of ATR but also, through Tipin and Claspin, it plays an important role in the action of ATR on its critical downstream target Chk1
      Title: Tipin-replication protein A interaction mediates Chk1 phosphorylation by ATR in response to genotoxic stress.
    8. The results suggest that Timeless-Tipin functions as a replication fork stabilizer that couples DNA replication with sister chromatid cohesion established at replication forks.
      Title: Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion.
    9. Observational study of gene-disease association. (HuGE Navigator)
      Title: Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance.
    10. observation explains the similar checkpoint phenotypes observed in both Tipin- and Timeless-depleted cells
      Title: Tipin and Timeless form a mutually protective complex required for genotoxic stress resistance and checkpoint function.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    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)

    Genotypes

    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

    • FLJ20516

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA replication checkpoint signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA replication checkpoint signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cell cycle phase transition IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cell division IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitotic intra-S DNA damage checkpoint signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of cell population proliferation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of nuclear cell cycle DNA replication TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in replication fork arrest IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in replication fork processing IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to UV IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of replication fork protection complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    TIMELESS-interacting protein
    Names
    CSM3 homolog

    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_001289986.2 → NP_001276915.1  TIMELESS-interacting protein isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC055855
      UniProtKB/TrEMBL
      B4DRF3
      Conserved Domains (1) summary
      pfam07962
      Location:2 → 47
      Swi3; Replication Fork Protection Component Swi3

    2. NM_001398281.1 → NP_001385210.1  TIMELESS-interacting protein isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC055855
      Consensus CDS
      CCDS10215.1
      UniProtKB/Swiss-Prot
      B2CW64, Q9BVW5, Q9NWZ6
      Conserved Domains (1) summary
      pfam07962
      Location:66 → 148
      Swi3; Replication Fork Protection Component Swi3

    3. NM_001398282.1 → NP_001385211.1  TIMELESS-interacting protein isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC055855
      Consensus CDS
      CCDS10215.1
      UniProtKB/Swiss-Prot
      B2CW64, Q9BVW5, Q9NWZ6
      Conserved Domains (1) summary
      pfam07962
      Location:66 → 148
      Swi3; Replication Fork Protection Component Swi3

    4. NM_001398283.1 → NP_001385212.1  TIMELESS-interacting protein isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC055855
      Consensus CDS
      CCDS10215.1
      UniProtKB/Swiss-Prot
      B2CW64, Q9BVW5, Q9NWZ6
      Related
      ENSP00000457406.1, ENST00000562124.5
      Conserved Domains (1) summary
      pfam07962
      Location:66 → 148
      Swi3; Replication Fork Protection Component Swi3

    5. NM_001398284.1 → NP_001385213.1  TIMELESS-interacting protein isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC055855
      Consensus CDS
      CCDS10215.1
      UniProtKB/Swiss-Prot
      B2CW64, Q9BVW5, Q9NWZ6
      Conserved Domains (1) summary
      pfam07962
      Location:66 → 148
      Swi3; Replication Fork Protection Component Swi3

    6. NM_001398285.1 → NP_001385214.1  TIMELESS-interacting protein isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC055855
      Conserved Domains (1) summary
      pfam07962
      Location:2 → 47
      Swi3; Replication Fork Protection Component Swi3

    7. NM_001398286.1 → NP_001385215.1  TIMELESS-interacting protein isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC055855
      Conserved Domains (1) summary
      pfam07962
      Location:2 → 47
      Swi3; Replication Fork Protection Component Swi3

    8. NM_001398287.1 → NP_001385216.1  TIMELESS-interacting protein isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC055855
      Conserved Domains (1) summary
      pfam07962
      Location:2 → 47
      Swi3; Replication Fork Protection Component Swi3

    9. NM_017858.3 → NP_060328.3  TIMELESS-interacting protein isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC055855
      Consensus CDS
      CCDS10215.1
      UniProtKB/Swiss-Prot
      B2CW64, Q9BVW5, Q9NWZ6
      UniProtKB/TrEMBL
      H3BU04
      Related
      ENSP00000261881.4, ENST00000261881.9
      Conserved Domains (1) summary
      pfam07962
      Location:66 → 148
      Swi3; Replication Fork Protection Component Swi3

    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_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      66336191..66386717 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017022390.2 → XP_016877879.1  TIMELESS-interacting protein isoform X1

      UniProtKB/Swiss-Prot
      B2CW64, Q9BVW5, Q9NWZ6
      UniProtKB/TrEMBL
      H3BU04
      Conserved Domains (1) summary
      pfam07962
      Location:66 → 148
      Swi3; Replication Fork Protection Component Swi3

    2. XM_024449971.2 → XP_024305739.1  TIMELESS-interacting protein isoform X1

      UniProtKB/Swiss-Prot
      B2CW64, Q9BVW5, Q9NWZ6
      UniProtKB/TrEMBL
      H3BU04
      Conserved Domains (1) summary
      pfam07962
      Location:66 → 148
      Swi3; Replication Fork Protection Component Swi3

    3. XM_047432779.1 → XP_047288735.1  TIMELESS-interacting protein isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      64157927..64208168 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054378343.1 → XP_054234318.1  TIMELESS-interacting protein isoform X1

    2. XM_054378344.1 → XP_054234319.1  TIMELESS-interacting protein isoform X1

    3. XM_054378345.1 → XP_054234320.1  TIMELESS-interacting protein isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BVW5.2 GenPept UniProtKB/Swiss-Prot:Q9BVW5

    Gene LinkOut

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

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