RTEL1

Protein identityUniProt · HPA

UniProt accession

Q9NZ71

Gene

RTEL1

Ensembl

ENSG00000258366

Chromosome

20

Canonical length

1219 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Nuclear membrane,Nuclear speckles

OverviewNCBI Gene

This gene encodes a DNA helicase which functions in the stability, protection and elongation of telomeres and interacts with proteins in the shelterin complex known to protect telomeres during DNA replication. Mutations in this gene have been associated with dyskeratosis congenita and Hoyerall-Hreidarsson syndrome. Read-through transcription of this gene into the neighboring downstream gene, which encodes tumor necrosis factor receptor superfamily, member 6b, generates a non-coding transcript. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

Canonical amino-acid sequenceUniProt

1219 residues, UniProt reviewed canonical sequence.

>Q9NZ71|RTEL1
     1  MPKIVLNGVT VDFPFQPYKC QQEYMTKVLE CLQQKVNGIL ESPTGTGKTL CLLCTTLAWR
    61  EHLRDGISAR KIAERAQGEL FPDRALSSWG NAAAAAGDPI ACYTDIPKII YASRTHSQLT
   121  QVINELRNTS YRPKVCVLGS REQLCIHPEV KKQESNHLQI HLCRKKVASR SCHFYNNVEE
   181  KSLEQELASP ILDIEDLVKS GSKHRVCPYY LSRNLKQQAD IIFMPYNYLL DAKSRRAHNI
   241  DLKGTVVIFD EAHNVEKMCE ESASFDLTPH DLASGLDVID QVLEEQTKAA QQGEPHPEFS
   301  ADSPSPGLNM ELEDIAKLKM ILLRLEGAID AVELPGDDSG VTKPGSYIFE LFAEAQITFQ
   361  TKGCILDSLD QIIQHLAGRA GVFTNTAGLQ KLADIIQIVF SVDPSEGSPG SPAGLGALQS
   421  YKVHIHPDAG HRRTAQRSDA WSTTAARKRG KVLSYWCFSP GHSMHELVRQ GVRSLILTSG
   481  TLAPVSSFAL EMQIPFPVCL ENPHIIDKHQ IWVGVVPRGP DGAQLSSAFD RRFSEECLSS
   541  LGKALGNIAR VVPYGLLIFF PSYPVMEKSL EFWRARDLAR KMEALKPLFV EPRSKGSFSE
   601  TISAYYARVA APGSTGATFL AVCRGKASEG LDFSDTNGRG VIVTGLPYPP RMDPRVVLKM
   661  QFLDEMKGQG GAGGQFLSGQ EWYRQQASRA VNQAIGRVIR HRQDYGAVFL CDHRFAFADA
   721  RAQLPSWVRP HVRVYDNFGH VIRDVAQFFR VAERTMPAPA PRATAPSVRG EDAVSEAKSP
   781  GPFFSTRKAK SLDLHVPSLK QRSSGSPAAG DPESSLCVEY EQEPVPARQR PRGLLAALEH
   841  SEQRAGSPGE EQAHSCSTLS LLSEKRPAEE PRGGRKKIRL VSHPEEPVAG AQTDRAKLFM
   901  VAVKQELSQA NFATFTQALQ DYKGSDDFAA LAACLGPLFA EDPKKHNLLQ GFYQFVRPHH
   961  KQQFEEVCIQ LTGRGCGYRP EHSIPRRQRA QPVLDPTGRT APDPKLTVST AAAQQLDPQE
  1021  HLNQGRPHLS PRPPPTGDPG SQPQWGSGVP RAGKQGQHAV SAYLADARRA LGSAGCSQLL
  1081  AALTAYKQDD DLDKVLAVLA ALTTAKPEDF PLLHRFSMFV RPHHKQRFSQ TCTDLTGRPY
  1141  PGMEPPGPQE ERLAVPPVLT HRAPQPGPSR SEKTGKTQSK ISSFLRQRPA GTVGAGGEDA
  1201  GPSQSSGPPH GPAASEWGL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RTEL1 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

13 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RTEL1.

Disease | AllUniProt

Conditions RTEL1 is implicated in, by any mechanism.

• Dyskeratosis congenita, autosomal recessive, 5 (DKCB5) MIM:615190
• Dyskeratosis congenita, autosomal dominant, 4 (DKCA4) MIM:615190
• Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 3 (PFBMFT3) MIM:616373

Disease | GeneticClinVar

287 pathogenic / likely-pathogenic of 4,691 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Dyskeratosis congenita, autosomal recessive 5
• Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3
• Dyskeratosis congenita
• Pulmonary fibrosis
• Interstitial lung disease 2

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)

0.54

gnomAD pLI

0

gnomAD missense Z

-1.15

DepMap mean gene effect

-0.57

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA repair
• mitotic telomere maintenance via semi-conservative replication
• negative regulation of DNA recombination
• negative regulation of t-circle formation
• positive regulation of telomere capping
• positive regulation of telomere maintenance
• positive regulation of telomere maintenance via telomere lengthening
• regulation of double-strand break repair via homologous recombination
• replication fork processing
• telomere maintenance
• telomere maintenance in response to DNA damage
• telomeric loop disassembly
• DNA strand displacement
• negative regulation of telomere maintenance in response to DNA damage
• positive regulation of telomeric loop disassembly

Molecular functions

• 4 iron, 4 sulfur cluster binding
• ATP binding
• ATP hydrolysis activity
• DNA binding
• DNA helicase activity
• DNA polymerase binding
• metal ion binding

Cellular components

• chromosome, telomeric region
• nuclear membrane
• nuclear speck
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Helicase-like, DEXD box c2 type
• ATP-dependent helicase, C-terminal
• RAD3-like helicase, DEAD
• ATP-dependent helicase Rad3/Chl1-like
• Helicase superfamily 1/2, ATP-binding domain, DinG/Rad3-type
• P-loop containing nucleoside triphosphate hydrolase
• Helicase superfamily 1/2, DinG/Rad3-like
• DEAD_2
• Helicase C-terminal domain
• Regulator of telomere elongation helicase 1
• Rtel1, harmonin homology domain
• Rtel1 helicase, ARCH domain
• RTEL1 helicase, ARCH domain
• RTEL1, HHD domain

KeywordsUniProt

• 4Fe-4S
• ATP-binding
• DNA damage
• DNA repair
• DNA-binding
• Dyskeratosis congenita
• Helicase
• Hydrolase
• Iron
• Iron-sulfur
• Isomerase
• Metal-binding
• Nucleotide-binding
• Nucleus

InteractionsUniProt · HPA

Protein binding partners of RTEL1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MMS19
• TERF1
• PCNA