TIMELESS
Protein timeless homolog
Also known as: hTIM, TIM, TIM_HUMAN, TIM1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9UNS1
- Gene
- TIMELESS
- Ensembl
- ENSG00000111602
- Chromosome
- 12
- Canonical length
- 1208 aa
- Protein class
- Disease related genes, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm
- Quaternary structure
- Homodimer
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
1208 residues, UniProt reviewed canonical sequence.
>Q9UNS1|TIMELESS
1 MDLHMMNCEL LATCSALGYL EGDTYHKEPD CLESVKDLIR YLRHEDETRD VRQQLGAAQI
61 LQSDLLPILT QHHQDKPLFD AVIRLMVNLT QPALLCFGNL PKEPSFRHHF LQVLTYLQAY
121 KEAFASEKAF GVLSETLYEL LQLGWEERQE EDNLLIERIL LLVRNILHVP ADLDQEKKID
181 DDASAHDQLL WAIHLSGLDD LLLFLASSSA EEQWSLHVLE IVSLMFRDQN PEQLAGVGQG
241 RLAQERSADF AELEVLRQRE MAEKKTRALQ RGNRHSRFGG SYIVQGLKSI GERDLIFHKG
301 LHNLRNYSSD LGKQPKKVPK RRQAARELSI QRRSALNVRL FLRDFCSEFL ENCYNRLMGS
361 VKDHLLREKA QQHDETYYMW ALAFFMAFNR AASFRPGLVS ETLSVRTFHF IEQNLTNYYE
421 MMLTDRKEAA SWARRMHLAL KAYQELLATV NEMDISPDEA VRESSRIIKN NIFYVMEYRE
481 LFLALFRKFD ERCQPRSFLR DLVETTHLFL KMLERFCRSR GNLVVQNKQK KRRKKKKKVL
541 DQAIVSGNVP SSPEEVEAVW PALAEQLQCC AQNSELSMDS VVPFDAASEV PVEEQRAEAM
601 VRIQDCLLAG QAPQALTLLR SAREVWPEGD VFGSQDISPE EEIQLLKQIL SAPLPRQQGP
661 EERGAEEEEE EEEEEEEELQ VVQVSEKEFN FLDYLKRFAC STVVRAYVLL LRSYQQNSAH
721 TNHCIVKMLH RLAHDLKMEA LLFQLSVFCL FNRLLSDPAA GAYKELVTFA KYILGKFFAL
781 AAVNQKAFVE LLFWKNTAVV REMTEGYGSL DDRSSSRRAP TWSPEEEAHL RELYLANKDV
841 EGQDVVEAIL AHLNTVPRTR KQIIHHLVQM GLADSVKDFQ RKGTHIVLWT GDQELELQRL
901 FEEFRDSDDV LGHIMKNITA KRSRARIVDK LLALGLVAER RELYKKRQKK LASSILPNGA
961 ESLKDFCQED LEEEENLPEE DSEEEEEGGS EAEQVQGSLV LSNENLGQSL HQEGFSIPLL
1021 WLQNCLIRAA DDREEDGCSQ AVPLVPLTEE NEEAMENEQF QQLLRKLGVR PPASGQETFW
1081 RIPAKLSPTQ LRRAAASLSQ PEEEQKLQPE LQPKVPGEQG SDEEHCKEHR AQALRALLLA
1141 HKKKAGLASP EEEDAVGKEP LKAAPKKRQL LDSDEEQEED EGRNRAPELG APGIQKKKRY
1201 QIEDDEDDLocalizationUniProt · AlphaFold · HPA
Whether an antibody against TIMELESS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.37
- Highest tissue expression
- 21 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 21 nTPM
- thymus: 18 nTPM
- tonsil: 17 nTPM
- lymph node: 14 nTPM
- retina: 13 nTPM
- appendix: 10 nTPM
Single-cell type
- retinal bipolar cells: 55 nCPM
- monocyte progenitors: 44 nCPM
- erythrocyte progenitors: 44 nCPM
- megakaryocyte progenitors: 40 nCPM
- differentiating spermatogonia: 34 nCPM
- gonadotrophs: 32 nCPM
Immune cell
- naive B-cell: 4.9 nTPM
- memory B-cell: 3.3 nTPM
- gdT-cell: 1.8 nTPM
- intermediate monocyte: 1.5 nTPM
- NK-cell: 1.5 nTPM
- T-reg: 1.5 nTPM
Brain region
- choroid plexus: 5.3 nTPM
- thalamus: 5.2 nTPM
- pons: 4.8 nTPM
- medulla oblongata: 4.7 nTPM
- white matter: 4.7 nTPM
- midbrain: 4.5 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about TIMELESS.
Disease | AllUniProt
Conditions TIMELESS is implicated in, by any mechanism.
- Advanced sleep phase syndrome, familial, 4 (FASPS4) MIM:620015
Disease | GeneticClinVar
1 pathogenic / likely-pathogenic of 238 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Advance sleep phase syndrome, familial, 4
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.98
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.07
- DepMap mean gene effect
- -1.38
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- branching morphogenesis of an epithelial tube
- cell cycle phase transition
- cell division
- cellular response to bleomycin
- cellular response to cisplatin
- cellular response to hydroxyurea
- circadian rhythm
- detection of abiotic stimulus
- DNA damage response
- DNA repair
- DNA replication checkpoint signaling
- lung development
- morphogenesis of an epithelium
- negative regulation of DNA-templated transcription
- positive regulation of double-strand break repair
- positive regulation of double-strand break repair via homologous recombination
- regulation of circadian rhythm
- replication fork arrest
- replication fork processing
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Timeless, N-terminal
- Timeless, PAB domain
- Timeless
- Timeless protein
- Timeless-like, PAB domain
- TIMELESS, tri-helical helix-turn-helix domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of TIMELESS in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads TIMELESS as an antibody target. Whether an autoantibody or antibody against TIMELESS could matter depends on whether native TIMELESS is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
TIMELESS is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label TIMELESS as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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