Description: Homo sapiens timeless circadian clock (TIMELESS), mRNA. RefSeq Summary (NM_003920): The protein encoded by this gene is highly conserved and is involved in cell survival after damage or stress, increase in DNA polymerase epsilon activity, maintenance of telomere length, and epithelial cell morphogenesis. The encoded protein also plays a role in the circadian rhythm autoregulatory loop, interacting with the PERIOD genes (PER1, PER2, and PER3) and others to downregulate activation of PER1 by CLOCK/ARNTL. Changes in this gene or its expression may promote prostate cancer, lung cancer, breast cancer, and mental disorders. [provided by RefSeq, Feb 2014]. Transcript (Including UTRs) Position: hg19 chr12:56,810,157-56,843,200 Size: 33,044 Total Exon Count: 29 Strand: - Coding Region Position: hg19 chr12:56,811,500-56,827,954 Size: 16,455 Coding Exon Count: 28
ID:TIM_HUMAN DESCRIPTION: RecName: Full=Protein timeless homolog; Short=hTIM; FUNCTION: Required for normal progression of S-phase. Involved in the circadian rhythm autoregulatory loop. Negatively regulates CLOCK-NPAS2/BMAL1-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus. Promotes TIPIN nuclear localiZation. Involved in cell survival after DNA damage or replication stress. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light. May also play an important role in epithelial cell morphogenesis and formation of branching tubules. SUBUNIT: Homomultimer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSKN1D and/or CSNK1E, TIMELESS, and the PER proteins. Interacts directly with PER1, PER2 and PER3. Interacts with PER2 via its second PAS domain in vitro. Binds CRY1, CRY2, CHEK1, ATR and ATRIP (By similarity). Interacts with TIPIN and CLSPN. INTERACTION: O14757:CHEK1; NbExp=2; IntAct=EBI-2212315, EBI-974488; SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Expressed in all tissues examined including brain, heart, lung, liver, skeletal muscle, kidney, placenta, pancreas, spleen, thymus and testis. Highest levels of expression in placenta, pancreas, thymus and testis. INDUCTION: Regulated by the cell cycle. High levels in S, G(2) and M phases, with highest level in S phase. Low expression in G(0) and G(1) phases. SIMILARITY: Belongs to the timeless family. SEQUENCE CAUTION: Sequence=AAH39842.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/timeless/";
asthma; atopy Chae, S. C. et al. 2003, The association of the exon 4 variations of Tim-1 gene with allergic diseases in a Korean population., Biochemical and biophysical research communications. 2003 Dec;312(2):346-50.
[PubMed 14637143]
Our results strongly suggest that the 5383+AF8-5397del variation site of Tim-1 exon 4 might be associated with atopic dermatitis susceptibility.
rheumatoid arthritis Chae, S. C. et al. 2004, The exon 4 variations of Tim-1 gene are associated with rheumatoid arthritis in a Korean population., Biochemical and biophysical research communications. 2004 Mar;315(4):971-5.
[PubMed 14985107]
Our results strongly suggest that the variations of Tim-1 exon 4 might be associated with the susceptibility to RA.
rheumatoid arthritis Chae, S. C. et al. 2004, The polymorphisms of Tim-1 promoter region are associated with rheumatoid arthritis in a Korean population., Immunogenetics. 2005 Jan;56(10):696-701.
[PubMed 15565336]
Our results strongly suggest that polymorphism in the Tim-1 promoter region might be associated with susceptibility to RA.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF04821 - Timeless protein PF05029 - Timeless protein C terminal region
ModBase Predicted Comparative 3D Structure on Q9UNS1
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK000721 - Homo sapiens cDNA FLJ20714 fis, clone HUV00275, highly similar to AF098162 Homo sapiens timeless homolog mRNA. LF384696 - JP 2014500723-A/192199: Polycomb-Associated Non-Coding RNAs. JD063471 - Sequence 44495 from Patent EP1572962. JD275495 - Sequence 256519 from Patent EP1572962. JD275494 - Sequence 256518 from Patent EP1572962. JD497140 - Sequence 478164 from Patent EP1572962. JD275493 - Sequence 256517 from Patent EP1572962. JD497139 - Sequence 478163 from Patent EP1572962. JD089470 - Sequence 70494 from Patent EP1572962. BC031514 - Homo sapiens timeless homolog (Drosophila), mRNA (cDNA clone IMAGE:3874072). AF098162 - Homo sapiens timeless homolog mRNA, complete cds. AK022702 - Homo sapiens cDNA FLJ12640 fis, clone NT2RM4001940, highly similar to Timeless homolog. BC050557 - Homo sapiens timeless homolog (Drosophila), mRNA (cDNA clone MGC:57696 IMAGE:5574624), complete cds. BX640990 - Homo sapiens mRNA; cDNA DKFZp686H09231 (from clone DKFZp686H09231). JD521159 - Sequence 502183 from Patent EP1572962. JD527668 - Sequence 508692 from Patent EP1572962. JD062326 - Sequence 43350 from Patent EP1572962. JD565964 - Sequence 546988 from Patent EP1572962. JD296591 - Sequence 277615 from Patent EP1572962. JD184900 - Sequence 165924 from Patent EP1572962. AK296869 - Homo sapiens cDNA FLJ58786 complete cds, highly similar to Timeless homolog. JD419671 - Sequence 400695 from Patent EP1572962. JD326711 - Sequence 307735 from Patent EP1572962. JD244935 - Sequence 225959 from Patent EP1572962. JD119227 - Sequence 100251 from Patent EP1572962. JD113231 - Sequence 94255 from Patent EP1572962. AB015597 - Homo sapiens hTIM1 mRNA, complete cds, similar to Droshophila timeless gene sequence. LF324468 - JP 2014500723-A/131971: Polycomb-Associated Non-Coding RNAs. LF324467 - JP 2014500723-A/131970: Polycomb-Associated Non-Coding RNAs. LF324466 - JP 2014500723-A/131969: Polycomb-Associated Non-Coding RNAs. AY207390 - Homo sapiens timeless protein TIM1-like mRNA, partial sequence. LF324465 - JP 2014500723-A/131968: Polycomb-Associated Non-Coding RNAs. BC039842 - Homo sapiens, Similar to timeless homolog (Drosophila), clone IMAGE:6063535, mRNA, partial cds. LF324464 - JP 2014500723-A/131967: Polycomb-Associated Non-Coding RNAs. LF324463 - JP 2014500723-A/131966: Polycomb-Associated Non-Coding RNAs. LF324462 - JP 2014500723-A/131965: Polycomb-Associated Non-Coding RNAs. LF324461 - JP 2014500723-A/131964: Polycomb-Associated Non-Coding RNAs. JD378784 - Sequence 359808 from Patent EP1572962. JD142582 - Sequence 123606 from Patent EP1572962. MA620273 - JP 2018138019-A/192199: Polycomb-Associated Non-Coding RNAs. MA560045 - JP 2018138019-A/131971: Polycomb-Associated Non-Coding RNAs. MA560044 - JP 2018138019-A/131970: Polycomb-Associated Non-Coding RNAs. MA560043 - JP 2018138019-A/131969: Polycomb-Associated Non-Coding RNAs. MA560042 - JP 2018138019-A/131968: Polycomb-Associated Non-Coding RNAs. MA560041 - JP 2018138019-A/131967: Polycomb-Associated Non-Coding RNAs. MA560040 - JP 2018138019-A/131966: Polycomb-Associated Non-Coding RNAs. MA560039 - JP 2018138019-A/131965: Polycomb-Associated Non-Coding RNAs. MA560038 - JP 2018138019-A/131964: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q9UNS1 (Reactome details) participates in the following event(s):
R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693538 Homology Directed Repair R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-73894 DNA Repair