GEN1

Protein identityUniProt · HPA

UniProt accession

Q17RS7

Gene

GEN1

Ensembl

ENSG00000178295

Chromosome

2

Canonical length

908 aa

Protein class

Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

This gene encodes a member of the Rad2/xeroderma pigmentosum group G nuclease family, whose members are characterized by N-terminal and internal xeroderma pigmentosum group G nuclease domains followed by helix-hairpin-helix domains and disordered C-terminal domains. The protein encoded by this gene is involved in resolution of Holliday junctions, which are intermediate four-way structures that covalently link DNA during homologous recombination and double-strand break repair. The protein resolves Holliday junctions by creating dual incisions across the junction to produce nicked duplex products that can be ligated. In addition, this protein has been found to localize to centrosomes where it has been implicated in regulation of centrosome integrity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

908 residues, UniProt reviewed canonical sequence.

>Q17RS7|GEN1
     1  MGVNDLWQIL EPVKQHIPLR NLGGKTIAVD LSLWVCEAQT VKKMMGSVMK PHLRNLFFRI
    61  SYLTQMDVKL VFVMEGEPPK LKADVISKRN QSRYGSSGKS WSQKTGRSHF KSVLRECLHM
   121  LECLGIPWVQ AAGEAEAMCA YLNAGGHVDG CLTNDGDTFL YGAQTVYRNF TMNTKDPHVD
   181  CYTMSSIKSK LGLDRDALVG LAILLGCDYL PKGVPGVGKE QALKLIQILK GQSLLQRFNR
   241  WNETSCNSSP QLLVTKKLAH CSVCSHPGSP KDHERNGCRL CKSDKYCEPH DYEYCCPCEW
   301  HRTEHDRQLS EVENNIKKKA CCCEGFPFHE VIQEFLLNKD KLVKVIRYQR PDLLLFQRFT
   361  LEKMEWPNHY ACEKLLVLLT HYDMIERKLG SRNSNQLQPI RIVKTRIRNG VHCFEIEWEK
   421  PEHYAMEDKQ HGEFALLTIE EESLFEAAYP EIVAVYQKQK LEIKGKKQKR IKPKENNLPE
   481  PDEVMSFQSH MTLKPTCEIF HKQNSKLNSG ISPDPTLPQE SISASLNSLL LPKNTPCLNA
   541  QEQFMSSLRP LAIQQIKAVS KSLISESSQP NTSSHNISVI ADLHLSTIDW EGTSFSNSPA
   601  IQRNTFSHDL KSEVESELSA IPDGFENIPE QLSCESERYT ANIKKVLDED SDGISPEEHL
   661  LSGITDLCLQ DLPLKERIFT KLSYPQDNLQ PDVNLKTLSI LSVKESCIAN SGSDCTSHLS
   721  KDLPGIPLQN ESRDSKILKG DQLLQEDYKV NTSVPYSVSN TVVKTCNVRP PNTALDHSRK
   781  VDMQTTRKIL MKKSVCLDRH SSDEQSAPVF GKAKYTTQRM KHSSQKHNSS HFKESGHNKL
   841  SSPKIHIKET EQCVRSYETA ENEESCFPDS TKSSLSSLQC HKKENNSGTC LDSPLPLRQR
   901  LKLRFQST

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GEN1 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)

0.49

Highest tissue expression

14 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GEN1.

Disease | AutoantibodyPubMed

Conditions in which antibodies against GEN1 are reported. Each links to that disease's full target list.

• Arthritis, Rheumatoid 3

ReferencesPubMed · IEDB

Publications for GEN1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.95

gnomAD pLI

0

gnomAD missense Z

0.1

DepMap mean gene effect

-0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• double-strand break repair via homologous recombination
• positive regulation of mitotic cell cycle spindle assembly checkpoint
• regulation of centrosome duplication
• replication fork processing
• resolution of DNA recombination intermediates
• resolution of mitotic recombination intermediates

Molecular functions

• 5'-flap endonuclease activity
• crossover junction DNA endonuclease activity
• four-way junction DNA binding
• magnesium ion binding
• protein homodimerization activity

Cellular components

• centrosome
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• XPG/Rad2 endonuclease
• XPG, N-terminal
• XPG-I domain
• Helix-hairpin-helix motif, class 2
• PIN-like domain superfamily
• 5'-3' exonuclease, C-terminal domain superfamily
• XPG N-terminal domain
• XPG I-region
• Flap endonuclease GEN, chromatin organization modifier domain
• Chromatin organization modifier domain 2

KeywordsUniProt

• DNA damage
• DNA repair
• Endonuclease
• Hydrolase
• Magnesium
• Metal-binding
• Nuclease
• Nucleus
• Phosphoprotein