TIPIN TIMELESS interacting protein [Homo sapiens (human)] - Gene

Summary

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

Location:: 15q22.31

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (66336191..66386717, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (64157927..64208168, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (66628529..66679055, complement)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

RH48847 (e-PCR)
- UniSTS:4423

D1S1423 (e-PCR)
- UniSTS:149619

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
part_of 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)

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
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
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
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
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
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
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
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
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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

66336191..66386717 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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