ID   EME2_HUMAN              Reviewed;         379 AA.
AC   A4GXA9; Q8TEP2; Q96RY3;
DT   05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   14-MAY-2014, sequence version 3.
DT   03-AUG-2022, entry version 109.
DE   RecName: Full=Probable crossover junction endonuclease EME2;
DE            EC=3.1.22.-;
GN   Name=EME2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INTERACTION WITH
RP   MUS81.
RX   PubMed=17289582; DOI=10.1016/j.molcel.2007.01.003;
RA   Ciccia A., Ling C., Coulthard R., Yan Z., Xue Y., Meetei A.R.,
RA   Laghmani el H., Joenje H., McDonald N., de Winter J.P., Wang W., West S.C.;
RT   "Identification of FAAP24, a Fanconi anemia core complex protein that
RT   interacts with FANCM.";
RL   Mol. Cell 25:331-343(2007).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Spleen;
RX   PubMed=12693554; DOI=10.1093/dnares/10.1.49;
RA   Jikuya H., Takano J., Kikuno R., Hirosawa M., Nagase T., Nomura N.,
RA   Ohara O.;
RT   "Characterization of long cDNA clones from human adult spleen. II. The
RT   complete sequences of 81 cDNA clones.";
RL   DNA Res. 10:49-57(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA   Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C.,
RA   Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.;
RT   "Sequence, structure and pathology of the fully annotated terminal 2 Mb of
RT   the short arm of human chromosome 16.";
RL   Hum. Mol. Genet. 10:339-352(2001).
CC   -!- FUNCTION: Interacts with MUS81 to form a DNA structure-specific
CC       endonuclease which cleaves substrates such as 3'-flap structures.
CC       {ECO:0000269|PubMed:17289582}.
CC   -!- SUBUNIT: Interacts with MUS81. {ECO:0000269|PubMed:17289582}.
CC   -!- INTERACTION:
CC       A4GXA9; Q96NY9: MUS81; NbExp=3; IntAct=EBI-7838486, EBI-2370806;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=A4GXA9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=A4GXA9-2; Sequence=VSP_030938, VSP_030939;
CC   -!- SIMILARITY: Belongs to the EME1/MMS4 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAK61292.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=BAB84906.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; EF452422; ABO21766.1; -; mRNA.
DR   EMBL; AK074080; BAB84906.2; ALT_INIT; mRNA.
DR   EMBL; AE006639; AAK61292.1; ALT_SEQ; Genomic_DNA.
DR   CCDS; CCDS58404.1; -. [A4GXA9-1]
DR   RefSeq; NP_001244299.1; NM_001257370.1. [A4GXA9-1]
DR   PDB; 7F6L; X-ray; 3.20 A; B=1-379.
DR   PDBsum; 7F6L; -.
DR   AlphaFoldDB; A4GXA9; -.
DR   SMR; A4GXA9; -.
DR   BioGRID; 128252; 5.
DR   ComplexPortal; CPX-586; Deoxyribonuclease complex MUS81-EME2.
DR   IntAct; A4GXA9; 2.
DR   MINT; A4GXA9; -.
DR   STRING; 9606.ENSP00000457353; -.
DR   iPTMnet; A4GXA9; -.
DR   PhosphoSitePlus; A4GXA9; -.
DR   BioMuta; EME2; -.
DR   jPOST; A4GXA9; -.
DR   MassIVE; A4GXA9; -.
DR   PeptideAtlas; A4GXA9; -.
DR   PRIDE; A4GXA9; -.
DR   ProteomicsDB; 678; -. [A4GXA9-2]
DR   Antibodypedia; 65797; 91 antibodies from 16 providers.
DR   DNASU; 197342; -.
DR   Ensembl; ENST00000568449.7; ENSP00000457353.1; ENSG00000197774.14. [A4GXA9-1]
DR   GeneID; 197342; -.
DR   KEGG; hsa:197342; -.
DR   MANE-Select; ENST00000568449.7; ENSP00000457353.1; NM_001257370.2; NP_001244299.1.
DR   UCSC; uc010brw.2; human. [A4GXA9-1]
DR   CTD; 197342; -.
DR   DisGeNET; 197342; -.
DR   GeneCards; EME2; -.
DR   HGNC; HGNC:27289; EME2.
DR   HPA; ENSG00000197774; Tissue enhanced (pituitary).
DR   MalaCards; EME2; -.
DR   MIM; 610886; gene.
DR   neXtProt; NX_A4GXA9; -.
DR   OpenTargets; ENSG00000197774; -.
DR   PharmGKB; PA134863517; -.
DR   VEuPathDB; HostDB:ENSG00000197774; -.
DR   eggNOG; ENOG502RQYN; Eukaryota.
DR   GeneTree; ENSGT00530000063937; -.
DR   HOGENOM; CLU_034099_1_0_1; -.
DR   InParanoid; A4GXA9; -.
DR   OMA; CRIEPQR; -.
DR   OrthoDB; 1595761at2759; -.
DR   TreeFam; TF325310; -.
DR   PathwayCommons; A4GXA9; -.
DR   Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR   Reactome; R-HSA-6783310; Fanconi Anemia Pathway.
DR   SignaLink; A4GXA9; -.
DR   BioGRID-ORCS; 197342; 11 hits in 1080 CRISPR screens.
DR   ChiTaRS; EME2; human.
DR   GenomeRNAi; 197342; -.
DR   Pharos; A4GXA9; Tbio.
DR   PRO; PR:A4GXA9; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; A4GXA9; protein.
DR   Bgee; ENSG00000197774; Expressed in oviduct epithelium and 158 other tissues.
DR   ExpressionAtlas; A4GXA9; baseline and differential.
DR   GO; GO:1905347; C:endodeoxyribonuclease complex; IPI:ComplexPortal.
DR   GO; GO:0048476; C:Holliday junction resolvase complex; IBA:GO_Central.
DR   GO; GO:0043596; C:nuclear replication fork; IC:ComplexPortal.
DR   GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR   GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0006302; P:double-strand break repair; IDA:ComplexPortal.
DR   GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IBA:GO_Central.
DR   GO; GO:0031297; P:replication fork processing; IDA:ComplexPortal.
DR   GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:GO_Central.
DR   Gene3D; 1.10.150.670; -; 1.
DR   InterPro; IPR042530; EME1/EME2_C.
DR   InterPro; IPR006166; ERCC4_domain.
DR   InterPro; IPR033310; Mms4/EME1/EME2.
DR   PANTHER; PTHR21077; PTHR21077; 1.
DR   Pfam; PF02732; ERCC4; 1.
DR   SMART; SM00891; ERCC4; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; DNA damage; DNA recombination;
KW   DNA repair; Endonuclease; Hydrolase; Nuclease; Nucleus; Reference proteome.
FT   CHAIN           1..379
FT                   /note="Probable crossover junction endonuclease EME2"
FT                   /id="PRO_0000317373"
FT   REGION          1..55
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..134
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12693554"
FT                   /id="VSP_030938"
FT   VAR_SEQ         135..190
FT                   /note="AAGEQELLLLLEPEEFLQGVATLTQISGPTHWVPWISPETTARPHLAVIGLD
FT                   AYLW -> MPTAGLAGTGVQGRWAHFWGCCGTADPTSPGGLWQRPSSGRAGPMGSGEEW
FT                   SPLLR (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12693554"
FT                   /id="VSP_030939"
SQ   SEQUENCE   379 AA;  41178 MW;  95483C4A4A1C1946 CRC64;
     MARVGPGRAG VSCQGRGRGR GGSGQRRPPT WEISDSDAED SAGSEAAARA RDPAGERRAA
     AEALRLLRPE QVLKRLAVCV DTAILEDAGA DVLMEALEAL GCECRIEPQR PARSLRWTRA
     SPDPCPRSLP PEVWAAGEQE LLLLLEPEEF LQGVATLTQI SGPTHWVPWI SPETTARPHL
     AVIGLDAYLW SRQHVSRGTQ QPESPKVAGA EVAVSWPEVE EALVLLQLWA NLDVLLVASW
     QELSRHVCAV TKALAQYPLK QYRESQAFSF CTAGRWAAGE PVARDGAGLQ AAWRRQIRQF
     SRVSPAVADA VVTAFPSPRL LQQALEACST ERERMGLLAD LPVPPSEGGR PRRVGPDLSR
     RICLFLTTAN PDLLLDLGS