XPF_HUMAN
ID XPF_HUMAN Reviewed; 916 AA.
AC Q92889; A5PKV6; A8K111; O00140; Q8TD83;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=DNA repair endonuclease XPF;
DE EC=3.1.-.- {ECO:0000269|PubMed:10413517};
DE AltName: Full=DNA excision repair protein ERCC-4 {ECO:0000303|PubMed:8887684};
DE AltName: Full=DNA repair protein complementing XP-F cells {ECO:0000303|PubMed:8797827};
DE AltName: Full=Xeroderma pigmentosum group F-complementing protein {ECO:0000303|PubMed:8797827};
GN Name=ERCC4 {ECO:0000303|PubMed:8887684, ECO:0000312|HGNC:HGNC:3436};
GN Synonyms=ERCC11, XPF {ECO:0000303|PubMed:8887684};
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 [GENOMIC DNA].
RX PubMed=8887684; DOI=10.1128/mcb.16.11.6553;
RA Brookman K.W., Lamerdin J.E., Thelen M.P., Hwang M., Reardon J.T.,
RA Sancar A., Zhou Z.-Q., Walter C.A., Parris C.N., Thompson L.H.;
RT "ERCC4 (XPF) encodes a human nucleotide excision repair protein with
RT eukaryotic recombination homologs.";
RL Mol. Cell. Biol. 16:6553-6562(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-168; SER-379; GLN-415;
RP PRO-662; THR-706; VAL-873 AND GLY-875.
RG NIEHS SNPs program;
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-415.
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-916 (ISOFORM 1), FUNCTION, VARIANT ASP-703,
RP AND VARIANT XP-F TRP-799.
RC TISSUE=Fibroblast;
RX PubMed=8797827; DOI=10.1016/s0092-8674(00)80155-5;
RA Sijbers A.M., de Laat W.L., Ariza R.R., Biggerstaff M., Wei Y.-F.,
RA Moggs J.G., Carter K.C., Shell B.K., Evans E., de Jong M.C., Rademakers S.,
RA de Rooij J., Jaspers N.G.J., Hoeijmakers J.H.J., Wood R.D.;
RT "Xeroderma pigmentosum group F caused by a defect in a structure-specific
RT DNA repair endonuclease.";
RL Cell 86:811-822(1996).
RN [7]
RP REVIEW ON VARIANTS XP-F.
RX PubMed=10447254;
RX DOI=10.1002/(sici)1098-1004(1999)14:1<9::aid-humu2>3.0.co;2-6;
RA Cleaver J.E., Thompson L.H., Richardson A.S., States J.C.;
RT "A summary of mutations in the UV-sensitive disorders: xeroderma
RT pigmentosum, Cockayne syndrome, and trichothiodystrophy.";
RL Hum. Mutat. 14:9-22(1999).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND INTERACTION WITH ERCC1.
RX PubMed=10413517; DOI=10.1021/bi990591+;
RA McCutchen-Maloney S.L., Giannecchini C.A., Hwang M.H., Thelen M.P.;
RT "Domain mapping of the DNA binding, endonuclease, and ERCC1 binding
RT properties of the human DNA repair protein XPF.";
RL Biochemistry 38:9417-9425(1999).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11790111; DOI=10.1021/bi011614z;
RA Kumaresan K.R., Hwang M., Thelen M.P., Lambert M.W.;
RT "Contribution of XPF functional domains to the 5' and 3' incisions produced
RT at the site of a psoralen interstrand cross-link.";
RL Biochemistry 41:890-896(2002).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SLX4.
RX PubMed=19596235; DOI=10.1016/j.cell.2009.06.030;
RA Svendsen J.M., Smogorzewska A., Sowa M.E., O'Connell B.C., Gygi S.P.,
RA Elledge S.J., Harper J.W.;
RT "Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is
RT required for DNA repair.";
RL Cell 138:63-77(2009).
RN [11]
RP INTERACTION WITH SLX4.
RX PubMed=19596236; DOI=10.1016/j.cell.2009.06.029;
RA Fekairi S., Scaglione S., Chahwan C., Taylor E.R., Tissier A., Coulon S.,
RA Dong M.-Q., Ruse C., Yates J.R. III, Russell P., Fuchs R.P., McGowan C.H.,
RA Gaillard P.-H.L.;
RT "Human SLX4 is a Holliday junction resolvase subunit that binds multiple
RT DNA repair/recombination endonucleases.";
RL Cell 138:78-89(2009).
RN [12]
RP INTERACTION WITH SLX4.
RX PubMed=19595721; DOI=10.1016/j.molcel.2009.06.020;
RA Munoz I.M., Hain K., Declais A.-C., Gardiner M., Toh G.W.,
RA Sanchez-Pulido L., Heuckmann J.M., Toth R., Macartney T., Eppink B.,
RA Kanaar R., Ponting C.P., Lilley D.M.J., Rouse J.;
RT "Coordination of structure-specific nucleases by human SLX4/BTBD12 is
RT required for DNA repair.";
RL Mol. Cell 35:116-127(2009).
RN [13]
RP INTERACTION WITH SLX4.
RX PubMed=19595722; DOI=10.1016/j.molcel.2009.06.019;
RA Andersen S.L., Bergstralh D.T., Kohl K.P., LaRocque J.R., Moore C.B.,
RA Sekelsky J.;
RT "Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA
RT structure-specific endonucleases in DNA repair and recombination.";
RL Mol. Cell 35:128-135(2009).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-289, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [17]
RP INTERACTION WITH ERCC1 AND SLX4.
RX PubMed=25538220; DOI=10.15252/embj.201489184;
RA Perez-Oliva A.B., Lachaud C., Szyniarowski P., Munoz I., Macartney T.,
RA Hickson I., Rouse J., Alessi D.R.;
RT "USP45 deubiquitylase controls ERCC1-XPF endonuclease-mediated DNA damage
RT responses.";
RL EMBO J. 34:326-343(2015).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-500, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [19]
RP FUNCTION, INTERACTION WITH ERCC1, ACETYLATION AT LYS-911, AND MUTAGENESIS
RP OF LYS-911.
RX PubMed=32034146; DOI=10.1038/s41467-020-14564-x;
RA Wang J., He H., Chen B., Jiang G., Cao L., Jiang H., Zhang G., Chen J.,
RA Huang J., Yang B., Zhou C., Liu T.;
RT "Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex assembly and
RT activation.";
RL Nat. Commun. 11:786-786(2020).
RN [20] {ECO:0007744|PDB:2A1J}
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 848-909 IN COMPLEX WITH ERCC1,
RP DNA-BINDING, DOMAINS, AND SUBUNIT.
RX PubMed=16076955; DOI=10.1073/pnas.0504341102;
RA Tsodikov O.V., Enzlin J.H., Scharer O.D., Ellenberger T.;
RT "Crystal structure and DNA binding functions of ERCC1, a subunit of the DNA
RT structure-specific endonuclease XPF-ERCC1.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:11236-11241(2005).
RN [21] {ECO:0007744|PDB:1Z00}
RP STRUCTURE BY NMR OF 834-916 IN COMPLEX WITH ERCC1, AND SUBUNIT.
RX PubMed=16338413; DOI=10.1016/j.str.2005.08.014;
RA Tripsianes K., Folkers G., Ab E., Das D., Odijk H., Jaspers N.G.,
RA Hoeijmakers J.H., Kaptein R., Boelens R.;
RT "The structure of the human ERCC1/XPF interaction domains reveals a
RT complementary role for the two proteins in nucleotide excision repair.";
RL Structure 13:1849-1858(2005).
RN [22]
RP VARIANT SER-379.
RX PubMed=9485007;
RA Shen M.R., Jones I.M., Mohrenweiser H.;
RT "Nonconservative amino acid substitution variants exist at polymorphic
RT frequency in DNA repair genes in healthy humans.";
RL Cancer Res. 58:604-608(1998).
RN [23]
RP VARIANTS XP-F MET-225; TRP-454; GLN-490; LYS-502; ARG-513; THR-529;
RP ALA-567; 605-VAL--GLY-611 DEL AND PRO-608.
RX PubMed=9580660; DOI=10.1093/hmg/7.6.969;
RA Matsumura Y., Nishigori C., Yagi T., Imamura S., Takebe H.;
RT "Characterization of molecular defects in Xeroderma pigmentosum group F in
RT relation to its clinically mild symptoms.";
RL Hum. Mol. Genet. 7:969-974(1998).
RN [24]
RP VARIANT XP-F TRP-799.
RX PubMed=9579555; DOI=10.1046/j.1523-1747.1998.00171.x;
RA Sijbers A.M., van Voorst Vader P.C., Snoek J.W., Raams A., Jaspers N.G.J.,
RA Kleijer W.J.;
RT "Homozygous R788W point mutation in the XPF gene of a patient with
RT xeroderma pigmentosum and late-onset neurologic disease.";
RL J. Invest. Dermatol. 110:832-836(1998).
RN [25]
RP VARIANTS GLN-415; THR-576; THR-717 AND GLY-875.
RX PubMed=10479728; DOI=10.1016/s1383-5726(99)00008-4;
RA Fan F., Liu C., Tavare S., Arnheim N.;
RT "Polymorphisms in the human DNA repair gene XPF.";
RL Mutat. Res. 406:115-120(1999).
RN [26]
RP VARIANT XFEPS PRO-153.
RX PubMed=17183314; DOI=10.1038/nature05456;
RA Niedernhofer L.J., Garinis G.A., Raams A., Lalai A.S., Robinson A.R.,
RA Appeldoorn E., Odijk H., Oostendorp R., Ahmad A., van Leeuwen W.,
RA Theil A.F., Vermeulen W., van der Horst G.T.J., Meinecke P., Kleijer W.J.,
RA Vijg J., Jaspers N.G.J., Hoeijmakers J.H.J.;
RT "A new progeroid syndrome reveals that genotoxic stress suppresses the
RT somatotroph axis.";
RL Nature 444:1038-1043(2006).
RN [27]
RP VARIANTS FANCQ PRO-230 AND SER-689.
RX PubMed=23623386; DOI=10.1016/j.ajhg.2013.04.002;
RA Bogliolo M., Schuster B., Stoepker C., Derkunt B., Su Y., Raams A.,
RA Trujillo J.P., Minguillon J., Ramirez M.J., Pujol R., Casado J.A.,
RA Banos R., Rio P., Knies K., Zuniga S., Benitez J., Bueren J.A.,
RA Jaspers N.G., Schaerer O.D., de Winter J.P., Schindler D., Surralles J.;
RT "Mutations in ERCC4, encoding the DNA-repair endonuclease XPF, cause
RT Fanconi anemia.";
RL Am. J. Hum. Genet. 92:800-806(2013).
RN [28]
RP VARIANTS XPF/CS ARG-236 AND TRP-589.
RX PubMed=23623389; DOI=10.1016/j.ajhg.2013.04.007;
RA Kashiyama K., Nakazawa Y., Pilz D.T., Guo C., Shimada M., Sasaki K.,
RA Fawcett H., Wing J.F., Lewin S.O., Carr L., Li T.S., Yoshiura K., Utani A.,
RA Hirano A., Yamashita S., Greenblatt D., Nardo T., Stefanini M.,
RA McGibbon D., Sarkany R., Fassihi H., Takahashi Y., Nagayama Y.,
RA Mitsutake N., Lehmann A.R., Ogi T.;
RT "Malfunction of nuclease ERCC1-XPF results in diverse clinical
RT manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and
RT Fanconi anemia.";
RL Am. J. Hum. Genet. 92:807-819(2013).
RN [29]
RP VARIANTS CYS-150; HIS-267 AND ALA-621, VARIANTS FANCQ SER-689 AND PHE-786,
RP CHARACTERIZATION OF VARIANT CYS-150, CHARACTERIZATION OF VARIANTS FANCQ
RP SER-689 AND PHE-786, AND FUNCTION.
RX PubMed=24027083; DOI=10.1002/humu.22438;
RA Osorio A., Bogliolo M., Fernandez V., Barroso A., de la Hoya M., Caldes T.,
RA Lasa A., Ramon y Cajal T., Santamarina M., Vega A., Quiles F., Lazaro C.,
RA Diez O., Fernandez D., Gonzalez-Sarmiento R., Duran M., Piqueras J.F.,
RA Marin M., Pujol R., Surralles J., Benitez J.;
RT "Evaluation of rare variants in the new fanconi anemia gene ERCC4 (FANCQ)
RT as familial breast/ovarian cancer susceptibility alleles.";
RL Hum. Mutat. 34:1615-1618(2013).
CC -!- FUNCTION: Catalytic component of a structure-specific DNA repair
CC endonuclease responsible for the 5-prime incision during DNA repair,
CC and which is essential for nucleotide excision repair (NER) and
CC interstrand cross-link (ICL) repair. {ECO:0000269|PubMed:10413517,
CC ECO:0000269|PubMed:11790111, ECO:0000269|PubMed:19596235,
CC ECO:0000269|PubMed:24027083, ECO:0000269|PubMed:32034146,
CC ECO:0000269|PubMed:8797827}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10413517};
CC -!- SUBUNIT: Heterodimer composed of ERCC1 and ERCC4/XPF (PubMed:10413517,
CC PubMed:25538220, PubMed:32034146, PubMed:16076955, PubMed:16338413).
CC Interacts with SLX4/BTBD12; this interaction is direct and links the
CC ERCC1-ERCC4/XPF complex to SLX4, which may coordinate the action of the
CC structure-specific endonuclease during DNA repair (PubMed:19596235,
CC PubMed:19596236, PubMed:25538220, PubMed:19595721, PubMed:19595722).
CC {ECO:0000269|PubMed:10413517, ECO:0000269|PubMed:16076955,
CC ECO:0000269|PubMed:16338413, ECO:0000269|PubMed:19595721,
CC ECO:0000269|PubMed:19595722, ECO:0000269|PubMed:19596235,
CC ECO:0000269|PubMed:19596236, ECO:0000269|PubMed:25538220,
CC ECO:0000269|PubMed:32034146}.
CC -!- INTERACTION:
CC Q92889; P07992: ERCC1; NbExp=13; IntAct=EBI-2370770, EBI-750962;
CC Q92889; Q92889: ERCC4; NbExp=2; IntAct=EBI-2370770, EBI-2370770;
CC Q92889; Q8IY92: SLX4; NbExp=10; IntAct=EBI-2370770, EBI-2370740;
CC Q92889; O75410-7: TACC1; NbExp=3; IntAct=EBI-2370770, EBI-12007872;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19596235}. Chromosome
CC {ECO:0000269|PubMed:11790111}. Note=Localizes to sites of DNA damage.
CC {ECO:0000269|PubMed:11790111}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92889-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92889-2; Sequence=VSP_056341, VSP_056342;
CC -!- PTM: Acetylation at Lys-911 by KAT5 promotes interaction with ERCC1 by
CC disrupting a salt bridge between Glu-907 and Lys-911, thereby exposing
CC a second binding site for ERCC1 (PubMed:32034146). Deacetylated by
CC SIRT1 (PubMed:32034146). {ECO:0000269|PubMed:32034146}.
CC -!- DISEASE: Xeroderma pigmentosum complementation group F (XP-F)
CC [MIM:278760]: An autosomal recessive pigmentary skin disorder
CC characterized by solar hypersensitivity of the skin, high
CC predisposition for developing cancers on areas exposed to sunlight and,
CC in some cases, neurological abnormalities. The skin develops marked
CC freckling and other pigmentation abnormalities. XP-F patients show a
CC mild phenotype. {ECO:0000269|PubMed:10447254,
CC ECO:0000269|PubMed:8797827, ECO:0000269|PubMed:9579555,
CC ECO:0000269|PubMed:9580660}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: XFE progeroid syndrome (XFEPS) [MIM:610965]: A syndrome
CC characterized by aged bird-like facies, lack of subcutaneous fat,
CC dwarfism, cachexia and microcephaly. Additional features include sun-
CC sensitivity from birth, learning disabilities, hearing loss, and visual
CC impairment. {ECO:0000269|PubMed:17183314}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- DISEASE: Xeroderma pigmentosum type F/Cockayne syndrome (XPF/CS)
CC [MIM:278760]: A variant form of Cockayne syndrome, a disorder
CC characterized by growth retardation, microcephaly, impairment of
CC nervous system development, pigmentary retinopathy, peculiar facies,
CC and progeria together with abnormal skin photosensitivity. Cockayne
CC syndrome dermatological features are milder than those in xeroderma
CC pigmentosum and skin cancers are not found in affected individuals.
CC XPF/CS patients, however, present with severe skin phenotypes,
CC including severe photosensitivity, abnormal skin pigmentation, and skin
CC cancer predisposition. {ECO:0000269|PubMed:23623389}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Fanconi anemia complementation group Q (FANCQ) [MIM:615272]: A
CC disorder affecting all bone marrow elements and resulting in anemia,
CC leukopenia and thrombopenia. It is associated with cardiac, renal and
CC limb malformations, dermal pigmentary changes, and a predisposition to
CC the development of malignancies. At the cellular level it is associated
CC with hypersensitivity to DNA-damaging agents, chromosomal instability
CC (increased chromosome breakage) and defective DNA repair.
CC {ECO:0000269|PubMed:23623386, ECO:0000269|PubMed:24027083}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the XPF family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB07689.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/XPFID299.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ercc4/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L77890; AAB50174.1; -; Genomic_DNA.
DR EMBL; AF491814; AAL91593.1; -; Genomic_DNA.
DR EMBL; AK289726; BAF82415.1; -; mRNA.
DR EMBL; AC010401; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC142631; AAI42632.1; -; mRNA.
DR EMBL; U64315; AAB07689.1; ALT_INIT; mRNA.
DR CCDS; CCDS32390.1; -. [Q92889-1]
DR RefSeq; NP_005227.1; NM_005236.2. [Q92889-1]
DR PDB; 1Z00; NMR; -; B=834-916.
DR PDB; 2A1J; X-ray; 2.70 A; A=848-909.
DR PDB; 2AQ0; NMR; -; A/B=834-916.
DR PDB; 2KN7; NMR; -; A/D=842-908.
DR PDB; 2MUT; NMR; -; B=834-916.
DR PDB; 6SXA; EM; 3.60 A; F=1-916.
DR PDB; 6SXB; EM; 7.90 A; F=1-916.
DR PDBsum; 1Z00; -.
DR PDBsum; 2A1J; -.
DR PDBsum; 2AQ0; -.
DR PDBsum; 2KN7; -.
DR PDBsum; 2MUT; -.
DR PDBsum; 6SXA; -.
DR PDBsum; 6SXB; -.
DR AlphaFoldDB; Q92889; -.
DR BMRB; Q92889; -.
DR SMR; Q92889; -.
DR BioGRID; 108384; 281.
DR ComplexPortal; CPX-478; ERCC1-XPF endonuclease complex.
DR CORUM; Q92889; -.
DR DIP; DIP-42006N; -.
DR IntAct; Q92889; 29.
DR MINT; Q92889; -.
DR STRING; 9606.ENSP00000310520; -.
DR BindingDB; Q92889; -.
DR ChEMBL; CHEMBL3883316; -.
DR iPTMnet; Q92889; -.
DR MetOSite; Q92889; -.
DR PhosphoSitePlus; Q92889; -.
DR BioMuta; ERCC4; -.
DR DMDM; 229463004; -.
DR EPD; Q92889; -.
DR jPOST; Q92889; -.
DR MassIVE; Q92889; -.
DR MaxQB; Q92889; -.
DR PaxDb; Q92889; -.
DR PeptideAtlas; Q92889; -.
DR PRIDE; Q92889; -.
DR ProteomicsDB; 722; -.
DR ProteomicsDB; 75575; -. [Q92889-1]
DR Antibodypedia; 24811; 545 antibodies from 32 providers.
DR DNASU; 2072; -.
DR Ensembl; ENST00000311895.8; ENSP00000310520.7; ENSG00000175595.16. [Q92889-1]
DR Ensembl; ENST00000575156.5; ENSP00000459933.1; ENSG00000175595.16. [Q92889-2]
DR GeneID; 2072; -.
DR KEGG; hsa:2072; -.
DR MANE-Select; ENST00000311895.8; ENSP00000310520.7; NM_005236.3; NP_005227.1.
DR UCSC; uc002dce.3; human. [Q92889-1]
DR CTD; 2072; -.
DR DisGeNET; 2072; -.
DR GeneCards; ERCC4; -.
DR GeneReviews; ERCC4; -.
DR HGNC; HGNC:3436; ERCC4.
DR HPA; ENSG00000175595; Tissue enhanced (skeletal).
DR MalaCards; ERCC4; -.
DR MIM; 133520; gene.
DR MIM; 278760; phenotype.
DR MIM; 610965; phenotype.
DR MIM; 615272; phenotype.
DR neXtProt; NX_Q92889; -.
DR OpenTargets; ENSG00000175595; -.
DR Orphanet; 90321; Cockayne syndrome type 1.
DR Orphanet; 84; Fanconi anemia.
DR Orphanet; 910; Xeroderma pigmentosum.
DR Orphanet; 220295; Xeroderma pigmentosum-Cockayne syndrome complex.
DR PharmGKB; PA27850; -.
DR VEuPathDB; HostDB:ENSG00000175595; -.
DR eggNOG; KOG0442; Eukaryota.
DR GeneTree; ENSGT00390000004394; -.
DR HOGENOM; CLU_002265_0_0_1; -.
DR InParanoid; Q92889; -.
DR OMA; FHKILQA; -.
DR OrthoDB; 324863at2759; -.
DR PhylomeDB; Q92889; -.
DR TreeFam; TF101234; -.
DR PathwayCommons; Q92889; -.
DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-HSA-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-HSA-5696400; Dual Incision in GG-NER.
DR Reactome; R-HSA-6782135; Dual incision in TC-NER.
DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway.
DR SignaLink; Q92889; -.
DR SIGNOR; Q92889; -.
DR BioGRID-ORCS; 2072; 117 hits in 1080 CRISPR screens.
DR EvolutionaryTrace; Q92889; -.
DR GeneWiki; ERCC4; -.
DR GenomeRNAi; 2072; -.
DR Pharos; Q92889; Tbio.
DR PRO; PR:Q92889; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q92889; protein.
DR Bgee; ENSG00000175595; Expressed in adrenal tissue and 156 other tissues.
DR ExpressionAtlas; Q92889; baseline and differential.
DR Genevisible; Q92889; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:UniProtKB.
DR GO; GO:0070522; C:ERCC4-ERCC1 complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000109; C:nucleotide-excision repair complex; IDA:MGI.
DR GO; GO:0000110; C:nucleotide-excision repair factor 1 complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IMP:UniProtKB.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IEA:Ensembl.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; IBA:GO_Central.
DR GO; GO:0001094; F:TFIID-class transcription factor complex binding; IEA:Ensembl.
DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:BHF-UCL.
DR GO; GO:1905768; P:negative regulation of double-stranded telomeric DNA binding; IDA:BHF-UCL.
DR GO; GO:1905765; P:negative regulation of protection from non-homologous end joining at telomere; IMP:BHF-UCL.
DR GO; GO:0032205; P:negative regulation of telomere maintenance; IMP:UniProtKB.
DR GO; GO:1904357; P:negative regulation of telomere maintenance via telomere lengthening; IDA:BHF-UCL.
DR GO; GO:0006289; P:nucleotide-excision repair; IDA:UniProtKB.
DR GO; GO:1901255; P:nucleotide-excision repair involved in interstrand cross-link repair; IDA:UniProtKB.
DR GO; GO:0033683; P:nucleotide-excision repair, DNA incision; IDA:ComplexPortal.
DR GO; GO:0006295; P:nucleotide-excision repair, DNA incision, 3'-to lesion; IMP:UniProtKB.
DR GO; GO:0006296; P:nucleotide-excision repair, DNA incision, 5'-to lesion; IMP:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IEA:Ensembl.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:GO_Central.
DR GO; GO:0009411; P:response to UV; IMP:UniProtKB.
DR GO; GO:0000723; P:telomere maintenance; IMP:BHF-UCL.
DR GO; GO:0061819; P:telomeric DNA-containing double minutes formation; IMP:BHF-UCL.
DR GO; GO:0009650; P:UV protection; IEA:Ensembl.
DR InterPro; IPR006166; ERCC4_domain.
DR InterPro; IPR011335; Restrct_endonuc-II-like.
DR InterPro; IPR010994; RuvA_2-like.
DR InterPro; IPR006167; XPF.
DR Pfam; PF02732; ERCC4; 1.
DR SMART; SM00891; ERCC4; 1.
DR SUPFAM; SSF47781; SSF47781; 1.
DR SUPFAM; SSF52980; SSF52980; 1.
DR TIGRFAMs; TIGR00596; rad1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromosome;
KW Cockayne syndrome; Disease variant; DNA damage; DNA repair; DNA-binding;
KW Dwarfism; Endonuclease; Fanconi anemia; Hydrolase; Isopeptide bond;
KW Magnesium; Nuclease; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ubl conjugation; Xeroderma pigmentosum.
FT CHAIN 1..916
FT /note="DNA repair endonuclease XPF"
FT /id="PRO_0000198853"
FT DOMAIN 683..763
FT /note="ERCC4"
FT REGION 1..457
FT /note="Helicase-like"
FT /evidence="ECO:0000269|PubMed:16076955"
FT REGION 233..254
FT /note="Leucine-zipper 1"
FT /evidence="ECO:0000305|PubMed:8887684"
FT REGION 270..298
FT /note="Leucine-zipper 2"
FT /evidence="ECO:0000305|PubMed:8887684"
FT REGION 460..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 502..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 658..813
FT /note="Nuclease"
FT /evidence="ECO:0000269|PubMed:16076955"
FT REGION 660..679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 837..905
FT /note="HhH2, dimerization with ERCC1"
FT /evidence="ECO:0000269|PubMed:16076955"
FT MOTIF 486..491
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 511..526
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 289
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZD4"
FT MOD_RES 764
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZD4"
FT MOD_RES 911
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:32034146"
FT CROSSLNK 500
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 368..372
FT /note="ETKKE -> GILWG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056341"
FT VAR_SEQ 373..916
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056342"
FT VARIANT 33
FT /note="V -> L (in dbSNP:rs34205098)"
FT /id="VAR_057477"
FT VARIANT 150
FT /note="R -> C (rare functional variant; causes mild
FT disruption of interstrand cross-link repair activity;
FT partial loss of protein stability; dbSNP:rs145402255)"
FT /evidence="ECO:0000269|PubMed:24027083"
FT /id="VAR_072084"
FT VARIANT 153
FT /note="R -> P (in XFEPS; dbSNP:rs121913050)"
FT /evidence="ECO:0000269|PubMed:17183314"
FT /id="VAR_034802"
FT VARIANT 168
FT /note="A -> V (in dbSNP:rs2020961)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_014769"
FT VARIANT 225
FT /note="I -> M (in XP-F; dbSNP:rs764731249)"
FT /evidence="ECO:0000269|PubMed:9580660"
FT /id="VAR_008200"
FT VARIANT 230
FT /note="L -> P (in FANCQ; dbSNP:rs397509402)"
FT /evidence="ECO:0000269|PubMed:23623386"
FT /id="VAR_070086"
FT VARIANT 236
FT /note="C -> R (in XPF/CS; dbSNP:rs397509403)"
FT /evidence="ECO:0000269|PubMed:23623389"
FT /id="VAR_070087"
FT VARIANT 267
FT /note="R -> H (in dbSNP:rs143479220)"
FT /evidence="ECO:0000269|PubMed:24027083"
FT /id="VAR_072085"
FT VARIANT 379
FT /note="P -> S (in dbSNP:rs1799802)"
FT /evidence="ECO:0000269|PubMed:9485007, ECO:0000269|Ref.2"
FT /id="VAR_013395"
FT VARIANT 415
FT /note="R -> Q (in dbSNP:rs1800067)"
FT /evidence="ECO:0000269|PubMed:10479728,
FT ECO:0000269|PubMed:14702039, ECO:0000269|Ref.2"
FT /id="VAR_013396"
FT VARIANT 454
FT /note="R -> W (in XP-F)"
FT /evidence="ECO:0000269|PubMed:9580660"
FT /id="VAR_008201"
FT VARIANT 490
FT /note="R -> Q (in XP-F; dbSNP:rs912480692)"
FT /evidence="ECO:0000269|PubMed:9580660"
FT /id="VAR_008202"
FT VARIANT 502
FT /note="E -> K (in XP-F)"
FT /evidence="ECO:0000269|PubMed:9580660"
FT /id="VAR_008203"
FT VARIANT 513
FT /note="G -> R (in XP-F; dbSNP:rs769679311)"
FT /evidence="ECO:0000269|PubMed:9580660"
FT /id="VAR_008204"
FT VARIANT 529
FT /note="I -> T (in XP-F)"
FT /evidence="ECO:0000269|PubMed:9580660"
FT /id="VAR_008205"
FT VARIANT 567
FT /note="T -> A (in XP-F)"
FT /evidence="ECO:0000269|PubMed:9580660"
FT /id="VAR_008206"
FT VARIANT 576
FT /note="R -> T (in dbSNP:rs1800068)"
FT /evidence="ECO:0000269|PubMed:10479728"
FT /id="VAR_013397"
FT VARIANT 589
FT /note="R -> W (in XPF/CS; dbSNP:rs147105770)"
FT /evidence="ECO:0000269|PubMed:23623389"
FT /id="VAR_070088"
FT VARIANT 605..611
FT /note="Missing (in XP-F)"
FT /evidence="ECO:0000269|PubMed:9580660"
FT /id="VAR_008207"
FT VARIANT 608
FT /note="L -> P (in XP-F)"
FT /evidence="ECO:0000269|PubMed:9580660"
FT /id="VAR_013398"
FT VARIANT 621
FT /note="T -> A"
FT /evidence="ECO:0000269|PubMed:24027083"
FT /id="VAR_072086"
FT VARIANT 662
FT /note="S -> P (in dbSNP:rs2020955)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_014770"
FT VARIANT 689
FT /note="R -> S (in FANCQ; disruption of interstrand cross-
FT link repair activity; no effect on protein stability;
FT dbSNP:rs149364215)"
FT /evidence="ECO:0000269|PubMed:23623386,
FT ECO:0000269|PubMed:24027083"
FT /id="VAR_070089"
FT VARIANT 703
FT /note="G -> D"
FT /evidence="ECO:0000269|PubMed:8797827"
FT /id="VAR_005849"
FT VARIANT 706
FT /note="I -> T (in dbSNP:rs1800069)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_014771"
FT VARIANT 717
FT /note="I -> T"
FT /evidence="ECO:0000269|PubMed:10479728"
FT /id="VAR_013399"
FT VARIANT 768
FT /note="S -> F (in dbSNP:rs12928650)"
FT /id="VAR_057478"
FT VARIANT 786
FT /note="S -> F (in FANCQ; disruption of interstrand cross-
FT link repair activity; no effect on protein stability;
FT dbSNP:rs1451008479)"
FT /evidence="ECO:0000269|PubMed:24027083"
FT /id="VAR_072087"
FT VARIANT 799
FT /note="R -> W (in XP-F; mild; significant residual repair
FT activity; dbSNP:rs121913049)"
FT /evidence="ECO:0000269|PubMed:8797827,
FT ECO:0000269|PubMed:9579555"
FT /id="VAR_005850"
FT VARIANT 860
FT /note="A -> D (in dbSNP:rs4986933)"
FT /id="VAR_057479"
FT VARIANT 873
FT /note="I -> V (in dbSNP:rs2020957)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_019201"
FT VARIANT 875
FT /note="E -> G (in dbSNP:rs1800124)"
FT /evidence="ECO:0000269|PubMed:10479728, ECO:0000269|Ref.2"
FT /id="VAR_013408"
FT VARIANT 912
FT /note="G -> E (in dbSNP:rs2020956)"
FT /id="VAR_014772"
FT MUTAGEN 911
FT /note="K->Q: Mimics acetylation; promoting interaction with
FT ERCC1."
FT /evidence="ECO:0000269|PubMed:32034146"
FT MUTAGEN 911
FT /note="K->R: Abolished acetylation by KAT5, leading to
FT decreased interaction with ERCC1."
FT /evidence="ECO:0000269|PubMed:32034146"
FT TURN 835..837
FT /evidence="ECO:0007829|PDB:2AQ0"
FT HELIX 839..842
FT /evidence="ECO:0007829|PDB:1Z00"
FT HELIX 850..853
FT /evidence="ECO:0007829|PDB:2A1J"
FT HELIX 860..869
FT /evidence="ECO:0007829|PDB:2A1J"
FT STRAND 870..872
FT /evidence="ECO:0007829|PDB:2KN7"
FT HELIX 873..877
FT /evidence="ECO:0007829|PDB:2A1J"
FT HELIX 881..888
FT /evidence="ECO:0007829|PDB:2A1J"
FT HELIX 891..902
FT /evidence="ECO:0007829|PDB:2A1J"
FT HELIX 905..908
FT /evidence="ECO:0007829|PDB:1Z00"
FT STRAND 911..913
FT /evidence="ECO:0007829|PDB:1Z00"
SQ SEQUENCE 916 AA; 104486 MW; C58CDE900378CCA8 CRC64;
MESGQPARRI AMAPLLEYER QLVLELLDTD GLVVCARGLG ADRLLYHFLQ LHCHPACLVL
VLNTQPAEEE YFINQLKIEG VEHLPRRVTN EITSNSRYEV YTQGGVIFAT SRILVVDFLT
DRIPSDLITG ILVYRAHRII ESCQEAFILR LFRQKNKRGF IKAFTDNAVA FDTGFCHVER
VMRNLFVRKL YLWPRFHVAV NSFLEQHKPE VVEIHVSMTP TMLAIQTAIL DILNACLKEL
KCHNPSLEVE DLSLENAIGK PFDKTIRHYL DPLWHQLGAK TKSLVQDLKI LRTLLQYLSQ
YDCVTFLNLL ESLRATEKAF GQNSGWLFLD SSTSMFINAR ARVYHLPDAK MSKKEKISEK
MEIKEGEETK KELVLESNPK WEALTEVLKE IEAENKESEA LGGPGQVLIC ASDDRTCSQL
RDYITLGAEA FLLRLYRKTF EKDSKAEEVW MKFRKEDSSK RIRKSHKRPK DPQNKERAST
KERTLKKKKR KLTLTQMVGK PEELEEEGDV EEGYRREISS SPESCPEEIK HEEFDVNLSS
DAAFGILKEP LTIIHPLLGC SDPYALTRVL HEVEPRYVVL YDAELTFVRQ LEIYRASRPG
KPLRVYFLIY GGSTEEQRYL TALRKEKEAF EKLIREKASM VVPEEREGRD ETNLDLVRGT
ASADVSTDTR KAGGQEQNGT QQSIVVDMRE FRSELPSLIH RRGIDIEPVT LEVGDYILTP
EMCVERKSIS DLIGSLNNGR LYSQCISMSR YYKRPVLLIE FDPSKPFSLT SRGALFQEIS
SNDISSKLTL LTLHFPRLRI LWCPSPHATA ELFEELKQSK PQPDAATALA ITADSETLPE
SEKYNPGPQD FLLKMPGVNA KNCRSLMHHV KNIAELAALS QDELTSILGN AANAKQLYDF
IHTSFAEVVS KGKGKK
