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TIPIN TIMELESS interacting protein [ Homo sapiens (human) ]

Gene ID: 54962, updated on 2-Nov-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
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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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Review eQTL and phenotype association data in this region using PheGenI

Variation

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See Variation Viewer (GRCh37.p13)

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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