GEN_MOUSE
ID GEN_MOUSE Reviewed; 908 AA.
AC Q8BMI4; B2RR04; Q3TYY2; Q5CZW6; Q8C0J0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Flap endonuclease GEN homolog 1;
DE EC=3.1.-.-;
GN Name=Gen1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-804 (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Forelimb, Inner ear, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Head;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-794 AND SER-795, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=27010503; DOI=10.1371/journal.pone.0152278;
RA Braun J., Meixner A., Brachner A., Foisner R.;
RT "The GIY-YIG type endonuclease ankyrin repeat and LEM domain-containing
RT protein 1 (ANKLE1) is dispensable for mouse hematopoiesis.";
RL PLoS ONE 11:E0152278-E0152278(2016).
CC -!- FUNCTION: Endonuclease which resolves Holliday junctions (HJs) by the
CC introduction of symmetrically related cuts across the junction point,
CC to produce nicked duplex products in which the nicks can be readily
CC ligated. Four-way DNA intermediates, also known as Holliday junctions,
CC are formed during homologous recombination and DNA repair, and their
CC resolution is necessary for proper chromosome segregation. Cleaves HJs
CC by a nick and counter-nick mechanism involving dual coordinated
CC incisions that lead to the formation of ligatable nicked duplex
CC products. Cleavage of the first strand is rate limiting, while second
CC strand cleavage is rapid. Largely monomeric, dimerizes on the HJ and
CC the first nick occurs upon dimerization at the junction. Efficiently
CC cleaves both single and double HJs contained within large recombination
CC intermediates. Exhibits a weak sequence preference for incision between
CC two G residues that reside in a T-rich region of DNA. Has also
CC endonuclease activity on 5'-flap and replication fork (RF) DNA
CC substrates. {ECO:0000250|UniProtKB:Q17RS7}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q17RS7};
CC Note=Binds 2 magnesium ions per subunit. They probably participate in
CC the reaction catalyzed by the enzyme. May bind an additional third
CC magnesium ion after substrate binding. {ECO:0000250|UniProtKB:Q17RS7};
CC -!- SUBUNIT: Largely monomeric, dimerizes on the Holliday junction and the
CC first nick occurs upon dimerization at the junction.
CC {ECO:0000250|UniProtKB:Q17RS7}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q17RS7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BMI4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BMI4-2; Sequence=VSP_030216;
CC -!- TISSUE SPECIFICITY: Expressed in bone marrow and testis and to a lesser
CC extent in thymus, spleen, brain and colon.
CC {ECO:0000269|PubMed:27010503}.
CC -!- DOMAIN: XPG-N, XPG-I,5'-3' exonuclease domains interact with DNA.
CC Contains a chromodomain that acts as additional DNA interaction site
CC and is required for efficient DNA recognition and cleavage.
CC {ECO:0000250|UniProtKB:Q17RS7}.
CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. GEN subfamily.
CC {ECO:0000305}.
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DR EMBL; AK030995; BAC27207.1; -; mRNA.
DR EMBL; AK031077; BAC27242.1; -; mRNA.
DR EMBL; AK158255; BAE34428.1; -; mRNA.
DR EMBL; BC090653; AAH90653.1; -; mRNA.
DR EMBL; BC138157; AAI38158.1; -; mRNA.
DR EMBL; BC138158; AAI38159.1; -; mRNA.
DR CCDS; CCDS36403.1; -. [Q8BMI4-1]
DR RefSeq; NP_796305.3; NM_177331.4. [Q8BMI4-1]
DR RefSeq; XP_006515102.1; XM_006515039.3. [Q8BMI4-1]
DR RefSeq; XP_006515103.1; XM_006515040.3. [Q8BMI4-1]
DR RefSeq; XP_006515104.1; XM_006515041.2. [Q8BMI4-1]
DR RefSeq; XP_006515105.1; XM_006515042.3. [Q8BMI4-2]
DR AlphaFoldDB; Q8BMI4; -.
DR SMR; Q8BMI4; -.
DR STRING; 10090.ENSMUSP00000132098; -.
DR iPTMnet; Q8BMI4; -.
DR PhosphoSitePlus; Q8BMI4; -.
DR EPD; Q8BMI4; -.
DR MaxQB; Q8BMI4; -.
DR PaxDb; Q8BMI4; -.
DR PeptideAtlas; Q8BMI4; -.
DR PRIDE; Q8BMI4; -.
DR ProteomicsDB; 268864; -. [Q8BMI4-1]
DR ProteomicsDB; 268865; -. [Q8BMI4-2]
DR Antibodypedia; 56005; 102 antibodies from 21 providers.
DR Ensembl; ENSMUST00000166117; ENSMUSP00000132098; ENSMUSG00000051235. [Q8BMI4-1]
DR GeneID; 209334; -.
DR KEGG; mmu:209334; -.
DR UCSC; uc007nav.1; mouse. [Q8BMI4-1]
DR CTD; 348654; -.
DR MGI; MGI:2443149; Gen1.
DR VEuPathDB; HostDB:ENSMUSG00000051235; -.
DR eggNOG; KOG2519; Eukaryota.
DR GeneTree; ENSGT00940000159266; -.
DR HOGENOM; CLU_013777_0_0_1; -.
DR InParanoid; Q8BMI4; -.
DR OMA; CKSDRYC; -.
DR OrthoDB; 1094524at2759; -.
DR PhylomeDB; Q8BMI4; -.
DR TreeFam; TF323403; -.
DR Reactome; R-MMU-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR BioGRID-ORCS; 209334; 1 hit in 109 CRISPR screens.
DR ChiTaRS; Gen1; mouse.
DR PRO; PR:Q8BMI4; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8BMI4; protein.
DR Bgee; ENSMUSG00000051235; Expressed in embryonic post-anal tail and 127 other tissues.
DR ExpressionAtlas; Q8BMI4; baseline and differential.
DR Genevisible; Q8BMI4; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0017108; F:5'-flap endonuclease activity; ISS:UniProtKB.
DR GO; GO:0008821; F:crossover junction endodeoxyribonuclease activity; ISS:UniProtKB.
DR GO; GO:0000400; F:four-way junction DNA binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; ISS:UniProtKB.
DR GO; GO:0010824; P:regulation of centrosome duplication; ISS:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; ISS:UniProtKB.
DR GO; GO:0071140; P:resolution of mitotic recombination intermediates; ISS:UniProtKB.
DR GO; GO:0071139; P:resolution of recombination intermediates; ISS:UniProtKB.
DR InterPro; IPR036279; 5-3_exonuclease_C_sf.
DR InterPro; IPR041012; GEN_chromo.
DR InterPro; IPR008918; HhH2.
DR InterPro; IPR029060; PIN-like_dom_sf.
DR InterPro; IPR006086; XPG-I_dom.
DR InterPro; IPR006084; XPG/Rad2.
DR InterPro; IPR006085; XPG_DNA_repair_N.
DR PANTHER; PTHR11081; PTHR11081; 1.
DR Pfam; PF18704; Chromo_2; 1.
DR Pfam; PF00867; XPG_I; 1.
DR Pfam; PF00752; XPG_N; 1.
DR PRINTS; PR00853; XPGRADSUPER.
DR SMART; SM00279; HhH2; 1.
DR SMART; SM00484; XPGI; 1.
DR SMART; SM00485; XPGN; 1.
DR SUPFAM; SSF47807; SSF47807; 1.
DR SUPFAM; SSF88723; SSF88723; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA damage; DNA repair; Endonuclease; Hydrolase;
KW Magnesium; Metal-binding; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..908
FT /note="Flap endonuclease GEN homolog 1"
FT /id="PRO_0000314147"
FT REGION 2..96
FT /note="XPG-N domain"
FT /evidence="ECO:0000250|UniProtKB:Q17RS7"
FT REGION 122..208
FT /note="XPG-I domain"
FT /evidence="ECO:0000250|UniProtKB:Q17RS7"
FT REGION 208..383
FT /note="5'-3' exonuclease domain"
FT /evidence="ECO:0000250|UniProtKB:Q17RS7"
FT REGION 389..463
FT /note="Chromodomain"
FT /evidence="ECO:0000250|UniProtKB:Q17RS7"
FT REGION 460..482
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 629..650
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 792..834
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 853..886
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 812..834
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 30
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 75
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q17RS7"
FT BINDING 134
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q17RS7"
FT BINDING 136
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 157
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 208
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 794
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 795
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..65
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030216"
FT CONFLICT 48
FT /note="V -> I (in Ref. 1; BAC27242)"
FT /evidence="ECO:0000305"
FT CONFLICT 716
FT /note="L -> H (in Ref. 1; BAC27207)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 908 AA; 101779 MW; 1D3D1A1A10601AD3 CRC64;
MGVNDLWQIL EPVKQHIHLQ DLSGKTIAVD LSLWVCEAQT VKKMIGTVKK PHLRNLFFRI
SYLTQMNVKL VFVMEGEPPM LKADVISKRT QTRYGPSGKS RSQKTGRSHF KSVLRECLEM
LECLGMPWVQ AAGEAEAMCA YLNASGHVDG CLTNDGDAFL YGAQTVYRNF TMNTKDPHVD
CYTISSIKSK LGLDRDALVG LAVLLGCDYL PKGVPGVGKE QALKLLQIFK GQSLLQRFNQ
WIEDPCYSVP QSAPKKVVHC SVCSHPGSPK DHERNGCILC KSDKYCEPHD YDYLCPCEWH
QTDHNRHLSE IENNIKKKAC SCEGFPFHEV IQEFLLNKNK MLKPITYQRP DLLLFQRFTV
QKMEWPSHYA CEKLLVLLTR YDMIERKHGR KTSNQLQPIR IVKPRVRNGV HCLEIEWEKP
EHYVVEDGDP GKLSLLTMEE ASLFEAAYPD AVAVYQKQLS ETKGRKQKSM KNKPKGSHLP
EADDVINSQS LMTLKPTSKA FPKQNPKINL ENSPDPILAQ ESTSPSLNSF VSPENAPCLN
LQEQLVPSPR TLAIKQSKDV SHFLVSECSQ PSSSSHDISV ITDLQLSTID WAGTSFSNSP
AVQRNTFSQD LASESESSAI LPDFEQLSYE SEQGTSDSEG SGRDLQQSNP EEQLLSGISA
LHLHDLPLKE RIRIKSSCPQ YNVGADAGLE SLPLKLKGSC IAYSSSDGSS NFSKDLTGVY
LHKESRNSKV LDSRLQENCG ANTSLPYSFS DKAVKTSSLQ VGLPTAAIPH NPRVAVKTTK
NLVMKNSVCL ERDSSDEDNA PGSWKSKYTA PEMKHSSQKH SLVHVRDSTH NKLRNPKVES
KETKLCNESF KTAEDEENGF SDLGRSPQSF RPCHDKDENS TASWENPLPL RQRLKLRFQN
TQSGFYNT
