ERCC5

Protein identityUniProt · HPA

UniProt accession

P28715

Gene

ERCC5

Ensembl

ENSG00000134899

Chromosome

13

Canonical length

1186 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a single-strand specific DNA endonuclease that makes the 3' incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene. [provided by RefSeq, Feb 2011]

Canonical amino-acid sequenceUniProt

1186 residues, UniProt reviewed canonical sequence.

>P28715|ERCC5
     1  MGVQGLWKLL ECSGRQVSPE ALEGKILAVD ISIWLNQALK GVRDRHGNSI ENPHLLTLFH
    61  RLCKLLFFRI RPIFVFDGDA PLLKKQTLVK RRQRKDLASS DSRKTTEKLL KTFLKRQAIK
   121  TAFRSKRDEA LPSLTQVRRE NDLYVLPPLQ EEEKHSSEEE DEKEWQERMN QKQALQEEFF
   181  HNPQAIDIES EDFSSLPPEV KHEILTDMKE FTKRRRTLFE AMPEESDDFS QYQLKGLLKK
   241  NYLNQHIEHV QKEMNQQHSG HIRRQYEDEG GFLKEVESRR VVSEDTSHYI LIKGIQAKTV
   301  AEVDSESLPS SSKMHGMSFD VKSSPCEKLK TEKEPDATPP SPRTLLAMQA ALLGSSSEEE
   361  LESENRRQAR GRNAPAAVDE GSISPRTLSA IKRALDDDED VKVCAGDDVQ TGGPGAEEMR
   421  INSSTENSDE GLKVRDGKGI PFTATLASSS VNSAEEHVAS TNEGREPTDS VPKEQMSLVH
   481  VGTEAFPISD ESMIKDRKDR LPLESAVVRH SDAPGLPNGR ELTPASPTCT NSVSKNETHA
   541  EVLEQQNELC PYESKFDSSL LSSDDETKCK PNSASEVIGP VSLQETSSIV SVPSEAVDNV
   601  ENVVSFNAKE HENFLETIQE QQTTESAGQD LISIPKAVEP MEIDSEESES DGSFIEVQSV
   661  ISDEELQAEF PETSKPPSEQ GEEELVGTRE GEAPAESESL LRDNSERDDV DGEPQEAEKD
   721  AEDSLHEWQD INLEELETLE SNLLAQQNSL KAQKQQQERI AATVTGQMFL ESQELLRLFG
   781  IPYIQAPMEA EAQCAILDLT DQTSGTITDD SDIWLFGARH VYRNFFNKNK FVEYYQYVDF
   841  HNQLGLDRNK LINLAYLLGS DYTEGIPTVG CVTAMEILNE FPGHGLEPLL KFSEWWHEAQ
   901  KNPKIRPNPH DTKVKKKLRT LQLTPGFPNP AVAEAYLKPV VDDSKGSFLW GKPDLDKIRE
   961  FCQRYFGWNR TKTDESLFPV LKQLDAQQTQ LRIDSFFRLA QQEKEDAKRI KSQRLNRAVT
  1021  CMLRKEKEAA ASEIEAVSVA MEKEFELLDK AKGKTQKRGI TNTLEESSSL KRKRLSDSKG
  1081  KNTCGGFLGE TCLSESSDGS SSEDAESSSL MNVQRRTAAK EPKTSASDSQ NSVKEAPVKN
  1141  GGATTSSSSD SDDDGGKEKM VLVTARSVFG KKRRKLRRAR GRKRKT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ERCC5 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)

0.53

Highest tissue expression

19 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ERCC5.

Disease | AllUniProt

Conditions ERCC5 is implicated in, by any mechanism.

• Xeroderma pigmentosum complementation group G (XP-G) MIM:278780
• Cerebro-oculo-facio-skeletal syndrome 3 (COFS3) MIM:616570

Disease | GeneticClinVar

75 pathogenic / likely-pathogenic of 463 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Xeroderma pigmentosum, group G
• Cerebrooculofacioskeletal syndrome 3
• Xeroderma pigmentosum
• Xeroderma pigmentosum group G/Cockayne syndrome
• ERCC5-related disorder

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)

0.81

gnomAD pLI

0

gnomAD missense Z

0.12

DepMap mean gene effect

0.04

DepMap dependency class

none

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

• base-excision repair, AP site formation
• double-strand break repair via homologous recombination
• negative regulation of apoptotic process
• nucleotide-excision repair
• response to UV
• response to UV-C
• transcription-coupled nucleotide-excision repair

Molecular functions

• bubble DNA binding
• damaged DNA binding
• DNA endonuclease activity
• double-stranded DNA binding
• endonuclease activity
• enzyme activator activity
• hydrolase activity, acting on ester bonds
• metal ion binding
• protein homodimerization activity
• protein-containing complex binding
• RNA polymerase II complex binding
• single-stranded DNA binding

Cellular components

• chromosome
• nucleoplasm
• nucleotide-excision repair complex
• nucleus
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• XPG/Rad2 endonuclease
• XPG, N-terminal
• XPG-I domain
• Helix-hairpin-helix motif, class 2
• XPG conserved site
• PIN-like domain superfamily
• 5'-3' exonuclease, C-terminal domain superfamily
• XPG N-terminal domain
• XPG I-region
• XPG/Rad2 endonuclease, eukaryotes

KeywordsUniProt

• Acetylation
• Chromosome
• Cockayne syndrome
• Deafness
• DNA damage
• DNA repair
• DNA-binding
• Dwarfism
• Endonuclease
• Hydrolase
• Magnesium
• Metal-binding
• Nuclease
• Nucleus
• Phosphoprotein
• Xeroderma pigmentosum

InteractionsUniProt · HPA

Protein binding partners of ERCC5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BRCA1
• BRCA2
• NTHL1
• PALB2
• PCNA
• CDK7