DNLI4_HUMAN
ID DNLI4_HUMAN Reviewed; 911 AA.
AC P49917; Q8IY66; Q8TEU5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=DNA ligase 4 {ECO:0000305};
DE EC=6.5.1.1 {ECO:0000255|PROSITE-ProRule:PRU10135, ECO:0000269|PubMed:9809069};
DE AltName: Full=DNA ligase IV {ECO:0000303|PubMed:7760816};
DE AltName: Full=Polydeoxyribonucleotide synthase [ATP] 4;
GN Name=LIG4 {ECO:0000303|PubMed:16357942, ECO:0000312|HGNC:HGNC:6601};
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], PARTIAL PROTEIN SEQUENCE, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Prostate;
RX PubMed=7760816; DOI=10.1128/mcb.15.6.3206;
RA Wei Y.-F., Robins P., Carter K., Caldecott K., Pappin D.J.C., Yu G.-L.,
RA Wang R.-P., Shell B.K., Nash R.A., Schar P., Barnes D.E., Haseltine W.A.,
RA Lindahl T.;
RT "Molecular cloning and expression of human cDNAs encoding a novel DNA
RT ligase IV and DNA ligase III, an enzyme active in DNA repair and
RT recombination.";
RL Mol. Cell. Biol. 15:3206-3216(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-231 AND THR-857.
RG NIEHS SNPs program;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8798671; DOI=10.1074/jbc.271.39.24257;
RA Robins P., Lindahl T.;
RT "DNA ligase IV from HeLa cell nuclei.";
RL J. Biol. Chem. 271:24257-24261(1996).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=9242410; DOI=10.1038/41358;
RA Grawunder U., Wilm M., Wu X., Kulesza P., Wilson T.E., Mann M.,
RA Lieber M.R.;
RT "Activity of DNA ligase IV stimulated by complex formation with XRCC4
RT protein in mammalian cells.";
RL Nature 388:492-495(1997).
RN [7]
RP FUNCTION, AND INTERACTION WITH XRCC4.
RX PubMed=9809069; DOI=10.1016/s1097-2765(00)80147-1;
RA Grawunder U., Zimmer D., Fugmann S., Schwarz K., Lieber M.R.;
RT "DNA ligase IV is essential for V(D)J recombination and DNA double-strand
RT break repair in human precursor lymphocytes.";
RL Mol. Cell 2:477-484(1998).
RN [8]
RP INTERACTION WITH XRCC4.
RX PubMed=9259561; DOI=10.1016/s0960-9822(06)00258-2;
RA Critchlow S.E., Bowater R.P., Jackson S.P.;
RT "Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA
RT ligase IV.";
RL Curr. Biol. 7:588-598(1997).
RN [9]
RP FUNCTION, AND INTERACTION WITH XRCC4; XRCC6; XRCC5 AND PRKDC.
RX PubMed=10854421; DOI=10.1074/jbc.m000491200;
RA Chen L., Trujillo K., Sung P., Tomkinson A.E.;
RT "Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-
RT dependent protein kinase.";
RL J. Biol. Chem. 275:26196-26205(2000).
RN [10]
RP FUNCTION, AND INTERACTION WITH XRCC4.
RX PubMed=12517771;
RA Lee J.W., Yannone S.M., Chen D.J., Povirk L.F.;
RT "Requirement for XRCC4 and DNA ligase IV in alignment-based gap filling for
RT nonhomologous DNA end joining in vitro.";
RL Cancer Res. 63:22-24(2003).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH XRCC5; XRCC6 AND PRKDC.
RX PubMed=12547193; DOI=10.1016/s0022-2836(02)01328-1;
RA Calsou P., Delteil C., Frit P., Drouet J., Salles B.;
RT "Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein
RT kinase on DNA ends is necessary for XRCC4-ligase IV recruitment.";
RL J. Mol. Biol. 326:93-103(2003).
RN [12]
RP FUNCTION, AND INTERACTION WITH XRCC4.
RX PubMed=17290226; DOI=10.1038/sj.emboj.7601559;
RA Gu J., Lu H., Tippin B., Shimazaki N., Goodman M.F., Lieber M.R.;
RT "XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across
RT gaps.";
RL EMBO J. 26:1010-1023(2007).
RN [13]
RP INTERACTION WITH APLF.
RX PubMed=17396150; DOI=10.1038/sj.emboj.7601663;
RA Kanno S., Kuzuoka H., Sasao S., Hong Z., Lan L., Nakajima S., Yasui A.;
RT "A novel human AP endonuclease with conserved zinc-finger-like motifs
RT involved in DNA strand break responses.";
RL EMBO J. 26:2094-2103(2007).
RN [14]
RP INTERACTION WITH XRCC4.
RX PubMed=19837014; DOI=10.1016/j.dnarep.2009.09.007;
RA Recuero-Checa M.A., Dore A.S., Arias-Palomo E., Rivera-Calzada A.,
RA Scheres S.H., Maman J.D., Pearl L.H., Llorca O.;
RT "Electron microscopy of Xrcc4 and the DNA ligase IV-Xrcc4 DNA repair
RT complex.";
RL DNA Repair 8:1380-1389(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 SUBCELLULAR LOCATION, AND INTERACTION WITH XRCC4.
RX PubMed=21982441; DOI=10.1016/j.dnarep.2011.09.012;
RA Berg E., Christensen M.O., Dalla Rosa I., Wannagat E., Jaenicke R.U.,
RA Roesner L.M., Dirks W.G., Boege F., Mielke C.;
RT "XRCC4 controls nuclear import and distribution of Ligase IV and exchanges
RT faster at damaged DNA in complex with Ligase IV.";
RL DNA Repair 10:1232-1242(2011).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH XRCC4.
RX PubMed=24984242; DOI=10.1016/j.dnarep.2014.05.010;
RA Francis D.B., Kozlov M., Chavez J., Chu J., Malu S., Hanna M., Cortes P.;
RT "DNA Ligase IV regulates XRCC4 nuclear localization.";
RL DNA Repair 21:36-42(2014).
RN [18]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH XRCC4.
RX PubMed=25934149; DOI=10.1016/j.bbrc.2015.04.093;
RA Fukuchi M., Wanotayan R., Liu S., Imamichi S., Sharma M.K., Matsumoto Y.;
RT "Lysine 271 but not lysine 210 of XRCC4 is required for the nuclear
RT localization of XRCC4 and DNA ligase IV.";
RL Biochem. Biophys. Res. Commun. 461:687-694(2015).
RN [19]
RP SUBUNIT.
RX PubMed=25941166; DOI=10.1038/cdd.2015.22;
RA Craxton A., Somers J., Munnur D., Jukes-Jones R., Cain K., Malewicz M.;
RT "XLS (c9orf142) is a new component of mammalian DNA double-stranded break
RT repair.";
RL Cell Death Differ. 22:890-897(2015).
RN [20]
RP SUBUNIT.
RX PubMed=25670504; DOI=10.1038/ncomms7233;
RA Xing M., Yang M., Huo W., Feng F., Wei L., Jiang W., Ning S., Yan Z.,
RA Li W., Wang Q., Hou M., Dong C., Guo R., Gao G., Ji J., Zha S., Lan L.,
RA Liang H., Xu D.;
RT "Interactome analysis identifies a new paralogue of XRCC4 in non-homologous
RT end joining DNA repair pathway.";
RL Nat. Commun. 6:6233-6233(2015).
RN [21]
RP SUBUNIT.
RX PubMed=25574025; DOI=10.1126/science.1261971;
RA Ochi T., Blackford A.N., Coates J., Jhujh S., Mehmood S., Tamura N.,
RA Travers J., Wu Q., Draviam V.M., Robinson C.V., Blundell T.L.,
RA Jackson S.P.;
RT "DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote
RT DNA double-strand break repair.";
RL Science 347:185-188(2015).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 748-784 IN COMPLEX WITH XRCC4, AND
RP INTERACTION WITH XRCC4.
RX PubMed=11702069; DOI=10.1038/nsb725;
RA Sibanda B.L., Critchlow S.E., Begun J., Pei X.Y., Jackson S.P.,
RA Blundell T.L., Pellegrini L.;
RT "Crystal structure of an Xrcc4-DNA ligase IV complex.";
RL Nat. Struct. Biol. 8:1015-1019(2001).
RN [23] {ECO:0007744|PDB:3II6}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 654-911 IN COMPLEX WITH XRCC4,
RP AND INTERACTION WITH XRCC4.
RX PubMed=19332554; DOI=10.1128/mcb.01895-08;
RA Wu P.Y., Frit P., Meesala S., Dauvillier S., Modesti M., Andres S.N.,
RA Huang Y., Sekiguchi J., Calsou P., Salles B., Junop M.S.;
RT "Structural and functional interaction between the human DNA repair
RT proteins DNA ligase IV and XRCC4.";
RL Mol. Cell. Biol. 29:3163-3172(2009).
RN [24]
RP STRUCTURE BY NMR OF 654-759.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first BRCT domain of human DNA ligase IV.";
RL Submitted (DEC-2006) to the PDB data bank.
RN [25] {ECO:0007744|PDB:7LSY, ECO:0007744|PDB:7LT3}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.6 ANGSTROMS) IN COMPLEX WITH THE NHEJ
RP COMPLEX, AND IDENTIFICATION IN THE NHEJ COMPLEX.
RX PubMed=33854234; DOI=10.1038/s41586-021-03458-7;
RA Chen S., Lee L., Naila T., Fishbain S., Wang A., Tomkinson A.E.,
RA Lees-Miller S.P., He Y.;
RT "Structural basis of long-range to short-range synaptic transition in
RT NHEJ.";
RL Nature 593:294-298(2021).
RN [26]
RP VARIANT LEUKEMIA HIS-278.
RX PubMed=10395545; DOI=10.1016/s0960-9822(99)80311-x;
RA Riballo E., Critchlow S.E., Teo S.-H., Doherty A.J., Priestley A.,
RA Broughton B.C., Kysela B., Beamish H., Plowman N., Arlett C.F.,
RA Lehmann A.R., Jackson S.P., Jeggo P.A.;
RT "Identification of a defect in DNA ligase IV in a radiosensitive leukaemia
RT patient.";
RL Curr. Biol. 9:699-702(1999).
RN [27]
RP CHARACTERIZATION OF VARIANT HIS-278.
RX PubMed=11349135; DOI=10.1074/jbc.m103866200;
RA Riballo E., Doherty A.J., Dai Y., Stiff T., Oettinger M.A., Jeggo P.A.,
RA Kysela B.;
RT "Cellular and biochemical impact of a mutation in DNA ligase IV conferring
RT clinical radiosensitivity.";
RL J. Biol. Chem. 276:31124-31132(2001).
RN [28]
RP VARIANTS LIG4S HIS-278; GLU-469; 580-ARG--ILE-911 DEL AND 814-ARG--ILE-911
RP DEL.
RX PubMed=11779494; DOI=10.1016/s1097-2765(01)00408-7;
RA O'Driscoll M., Cerosaletti K.M., Girard P.-M., Dai Y., Stumm M., Kysela B.,
RA Hirsch B., Gennery A., Palmer S.E., Seidel J., Gatti R.A., Varon R.,
RA Oettinger M.A., Neitzel H., Jeggo P.A., Concannon P.;
RT "DNA ligase IV mutations identified in patients exhibiting developmental
RT delay and immunodeficiency.";
RL Mol. Cell 8:1175-1185(2001).
RN [29]
RP VARIANTS VAL-3 AND ILE-9, AND ASSOCIATION WITH RESISTANCE TO MULTIPLE
RP MYELOMA.
RX PubMed=12471202; DOI=10.1136/jmg.39.12.900;
RA Roddam P.L., Rollinson S., O'Driscoll M., Jeggo P.A., Jack A., Morgan G.J.;
RT "Genetic variants of NHEJ DNA ligase IV can affect the risk of developing
RT multiple myeloma, a tumour characterised by aberrant class switch
RT recombination.";
RL J. Med. Genet. 39:900-905(2002).
RN [30]
RP VARIANT RSSCID GLN-433 DEL.
RX PubMed=16357942; DOI=10.1172/jci26121;
RA van der Burg M., van Veelen L.R., Verkaik N.S., Wiegant W.W., Hartwig N.G.,
RA Barendregt B.H., Brugmans L., Raams A., Jaspers N.G.J., Zdzienicka M.Z.,
RA van Dongen J.J.M., van Gent D.C.;
RT "A new type of radiosensitive T-B-NK(+) severe combined immunodeficiency
RT caused by a LIG4 mutation.";
RL J. Clin. Invest. 116:137-145(2006).
RN [31]
RP VARIANT PRO-774.
RX PubMed=25728776; DOI=10.1016/j.ajhg.2015.01.013;
RA Murray J.E., van der Burg M., Ijspeert H., Carroll P., Wu Q., Ochi T.,
RA Leitch A., Miller E.S., Kysela B., Jawad A., Bottani A., Brancati F.,
RA Cappa M., Cormier-Daire V., Deshpande C., Faqeih E.A., Graham G.E.,
RA Ranza E., Blundell T.L., Jackson A.P., Stewart G.S., Bicknell L.S.;
RT "Mutations in the NHEJ component XRCC4 cause primordial dwarfism.";
RL Am. J. Hum. Genet. 96:412-424(2015).
CC -!- FUNCTION: DNA ligase involved in DNA non-homologous end joining (NHEJ);
CC required for double-strand break (DSB) repair and V(D)J recombination
CC (PubMed:8798671, PubMed:9242410, PubMed:9809069, PubMed:12517771,
CC PubMed:17290226). Catalyzes the NHEJ ligation step of the broken DNA
CC during DSB repair by resealing the DNA breaks after the gap filling is
CC completed (PubMed:9242410, PubMed:9809069, PubMed:12517771,
CC PubMed:17290226). Joins single-strand breaks in a double-stranded
CC polydeoxynucleotide in an ATP-dependent reaction (PubMed:9242410,
CC PubMed:9809069, PubMed:12517771, PubMed:17290226). LIG4 is
CC mechanistically flexible: it can ligate nicks as well as compatible DNA
CC overhangs alone, while in the presence of XRCC4, it can ligate ends
CC with 2-nucleotides (nt) microhomology and 1-nt gaps (PubMed:17290226).
CC Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible
CC for the NHEJ ligation step and XRCC4 enhances the joining activity of
CC LIG4 (PubMed:9242410, PubMed:9809069). Binding of the LIG4-XRCC4
CC complex to DNA ends is dependent on the assembly of the DNA-dependent
CC protein kinase complex DNA-PK to these DNA ends (PubMed:10854421). LIG4
CC regulates nuclear localization of XRCC4 (PubMed:24984242).
CC {ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:12517771,
CC ECO:0000269|PubMed:17290226, ECO:0000269|PubMed:24984242,
CC ECO:0000269|PubMed:8798671, ECO:0000269|PubMed:9242410,
CC ECO:0000269|PubMed:9809069}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-
CC (deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP +
CC diphosphate.; EC=6.5.1.1; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10135, ECO:0000269|PubMed:9809069};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P18858};
CC -!- SUBUNIT: Interacts with XRCC4; the LIG4-XRCC4 subcomplex has a 1:2
CC stoichiometry and XRCC4 is required for LIG4 stability (PubMed:9259561,
CC PubMed:9809069, PubMed:10854421, PubMed:12517771, PubMed:17290226,
CC PubMed:19837014, PubMed:21982441, PubMed:24984242, PubMed:25934149,
CC PubMed:11702069, PubMed:19332554). Component of the core long-range
CC non-homologous end joining (NHEJ) complex (also named DNA-PK complex)
CC composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF
CC (PubMed:25670504, PubMed:12547193, PubMed:33854234). Additional
CC component of the NHEJ complex includes PAXX (PubMed:25574025,
CC PubMed:25941166). Following autophosphorylation, PRKDC dissociates from
CC DNA, leading to formation of the short-range NHEJ complex, composed of
CC LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (PubMed:33854234).
CC Interacts with APLF (PubMed:17396150). {ECO:0000269|PubMed:10854421,
CC ECO:0000269|PubMed:11702069, ECO:0000269|PubMed:12517771,
CC ECO:0000269|PubMed:12547193, ECO:0000269|PubMed:17290226,
CC ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:19332554,
CC ECO:0000269|PubMed:19837014, ECO:0000269|PubMed:21982441,
CC ECO:0000269|PubMed:24984242, ECO:0000269|PubMed:25574025,
CC ECO:0000269|PubMed:25670504, ECO:0000269|PubMed:25934149,
CC ECO:0000269|PubMed:25941166, ECO:0000269|PubMed:33854234,
CC ECO:0000269|PubMed:9259561, ECO:0000269|PubMed:9809069}.
CC -!- INTERACTION:
CC P49917; Q8IW19: APLF; NbExp=3; IntAct=EBI-847896, EBI-1256044;
CC P49917; Q96SD1: DCLRE1C; NbExp=16; IntAct=EBI-847896, EBI-11694104;
CC P49917; Q9H9Q4: NHEJ1; NbExp=5; IntAct=EBI-847896, EBI-847807;
CC P49917; Q13426: XRCC4; NbExp=19; IntAct=EBI-847896, EBI-717592;
CC P49917; Q13426-2: XRCC4; NbExp=11; IntAct=EBI-847896, EBI-15891375;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21982441,
CC ECO:0000269|PubMed:24984242, ECO:0000269|PubMed:25934149,
CC ECO:0000269|PubMed:8798671}.
CC -!- TISSUE SPECIFICITY: Testis, thymus, prostate and heart.
CC {ECO:0000269|PubMed:7760816}.
CC -!- DISEASE: LIG4 syndrome (LIG4S) [MIM:606593]: Characterized by
CC immunodeficiency and developmental and growth delay. Patients display
CC unusual facial features, microcephaly, growth and/or developmental
CC delay, pancytopenia, and various skin abnormalities.
CC {ECO:0000269|PubMed:11779494}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Severe combined immunodeficiency autosomal recessive T-cell-
CC negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing
CC radiation (RSSCID) [MIM:602450]: A form of severe combined
CC immunodeficiency, a genetically and clinically heterogeneous group of
CC rare congenital disorders characterized by impairment of both humoral
CC and cell-mediated immunity, leukopenia, and low or absent antibody
CC levels. Patients present in infancy with recurrent, persistent
CC infections by opportunistic organisms. The common characteristic of all
CC types of SCID is absence of T-cell-mediated cellular immunity due to a
CC defect in T-cell development. Individuals affected by RS-SCID show
CC defects in the DNA repair machinery necessary for coding joint
CC formation and the completion of V(D)J recombination. A subset of cells
CC from such patients show increased radiosensitivity.
CC {ECO:0000269|PubMed:16357942}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ATP-dependent DNA ligase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL77435.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA58467.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=LIG4base; Note=LIG4 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/LIG4base/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/lig4/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=DNA ligase entry;
CC URL="https://en.wikipedia.org/wiki/DNA_ligase";
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DR EMBL; X83441; CAA58467.1; ALT_INIT; mRNA.
DR EMBL; AF479264; AAL77435.1; ALT_INIT; Genomic_DNA.
DR EMBL; AL157762; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC037491; AAH37491.1; -; mRNA.
DR CCDS; CCDS9508.1; -.
DR PIR; I37079; I37079.
DR RefSeq; NP_001091738.1; NM_001098268.1.
DR RefSeq; NP_001317524.1; NM_001330595.1.
DR RefSeq; NP_002303.2; NM_002312.3.
DR RefSeq; NP_996820.1; NM_206937.1.
DR RefSeq; XP_005254113.1; XM_005254056.1.
DR RefSeq; XP_005254114.1; XM_005254057.4.
DR RefSeq; XP_005254115.1; XM_005254058.3.
DR RefSeq; XP_006720014.1; XM_006719951.3.
DR RefSeq; XP_006720015.1; XM_006719952.1.
DR RefSeq; XP_011519393.1; XM_011521091.2.
DR RefSeq; XP_011519394.1; XM_011521092.2.
DR RefSeq; XP_016876058.1; XM_017020569.1.
DR RefSeq; XP_016876059.1; XM_017020570.1.
DR RefSeq; XP_016876060.1; XM_017020571.1.
DR RefSeq; XP_016876062.1; XM_017020573.1.
DR PDB; 1IK9; X-ray; 2.30 A; C=748-784.
DR PDB; 2E2W; NMR; -; A=654-759.
DR PDB; 3II6; X-ray; 2.40 A; X/Y=654-911.
DR PDB; 3VNN; X-ray; 2.90 A; A=268-406.
DR PDB; 3W1B; X-ray; 2.40 A; A=1-609.
DR PDB; 3W1G; X-ray; 2.55 A; A=1-609.
DR PDB; 3W5O; X-ray; 2.84 A; A/B=1-609.
DR PDB; 4HTO; X-ray; 2.81 A; A=1-240.
DR PDB; 4HTP; X-ray; 2.25 A; A/B=1-240.
DR PDB; 6BKF; X-ray; 3.25 A; A=1-620.
DR PDB; 6BKG; X-ray; 2.40 A; A=1-620.
DR PDB; 7D9K; X-ray; 2.90 A; A=1-240.
DR PDB; 7D9Y; X-ray; 2.76 A; A=1-240.
DR PDB; 7LSY; EM; 8.40 A; X/Y=1-911.
DR PDB; 7LT3; EM; 4.60 A; X/Y=1-911.
DR PDB; 7NFC; EM; 4.14 A; M/P=1-911.
DR PDB; 7NFE; EM; 4.29 A; J=1-911.
DR PDBsum; 1IK9; -.
DR PDBsum; 2E2W; -.
DR PDBsum; 3II6; -.
DR PDBsum; 3VNN; -.
DR PDBsum; 3W1B; -.
DR PDBsum; 3W1G; -.
DR PDBsum; 3W5O; -.
DR PDBsum; 4HTO; -.
DR PDBsum; 4HTP; -.
DR PDBsum; 6BKF; -.
DR PDBsum; 6BKG; -.
DR PDBsum; 7D9K; -.
DR PDBsum; 7D9Y; -.
DR PDBsum; 7LSY; -.
DR PDBsum; 7LT3; -.
DR PDBsum; 7NFC; -.
DR PDBsum; 7NFE; -.
DR AlphaFoldDB; P49917; -.
DR SMR; P49917; -.
DR BioGRID; 110169; 139.
DR CORUM; P49917; -.
DR DIP; DIP-37958N; -.
DR IntAct; P49917; 17.
DR MINT; P49917; -.
DR STRING; 9606.ENSP00000484288; -.
DR BindingDB; P49917; -.
DR ChEMBL; CHEMBL4523595; -.
DR iPTMnet; P49917; -.
DR PhosphoSitePlus; P49917; -.
DR BioMuta; LIG4; -.
DR DMDM; 88911290; -.
DR EPD; P49917; -.
DR jPOST; P49917; -.
DR MassIVE; P49917; -.
DR MaxQB; P49917; -.
DR PaxDb; P49917; -.
DR PeptideAtlas; P49917; -.
DR PRIDE; P49917; -.
DR ProteomicsDB; 56183; -.
DR Antibodypedia; 705; 316 antibodies from 32 providers.
DR CPTC; P49917; 1 antibody.
DR DNASU; 3981; -.
DR Ensembl; ENST00000405925.2; ENSP00000385955.1; ENSG00000174405.15.
DR Ensembl; ENST00000442234.6; ENSP00000402030.1; ENSG00000174405.15.
DR Ensembl; ENST00000611712.4; ENSP00000484288.1; ENSG00000174405.15.
DR Ensembl; ENST00000685338.1; ENSP00000510567.1; ENSG00000174405.15.
DR Ensembl; ENST00000686095.1; ENSP00000509942.1; ENSG00000174405.15.
DR Ensembl; ENST00000686204.1; ENSP00000509685.1; ENSG00000174405.15.
DR Ensembl; ENST00000686913.1; ENSP00000509299.1; ENSG00000174405.15.
DR Ensembl; ENST00000686926.1; ENSP00000509122.1; ENSG00000174405.15.
DR Ensembl; ENST00000687164.1; ENSP00000508512.1; ENSG00000174405.15.
DR Ensembl; ENST00000687822.1; ENSP00000509344.1; ENSG00000174405.15.
DR Ensembl; ENST00000688396.1; ENSP00000509564.1; ENSG00000174405.15.
DR Ensembl; ENST00000688455.1; ENSP00000509304.1; ENSG00000174405.15.
DR Ensembl; ENST00000688529.1; ENSP00000509906.1; ENSG00000174405.15.
DR Ensembl; ENST00000688595.1; ENSP00000509502.1; ENSG00000174405.15.
DR Ensembl; ENST00000692222.1; ENSP00000509226.1; ENSG00000174405.15.
DR Ensembl; ENST00000693040.1; ENSP00000510014.1; ENSG00000174405.15.
DR GeneID; 3981; -.
DR KEGG; hsa:3981; -.
DR MANE-Select; ENST00000442234.6; ENSP00000402030.1; NM_206937.2; NP_996820.1.
DR UCSC; uc001vqn.4; human.
DR CTD; 3981; -.
DR DisGeNET; 3981; -.
DR GeneCards; LIG4; -.
DR HGNC; HGNC:6601; LIG4.
DR HPA; ENSG00000174405; Low tissue specificity.
DR MalaCards; LIG4; -.
DR MIM; 601837; gene.
DR MIM; 602450; phenotype.
DR MIM; 606593; phenotype.
DR neXtProt; NX_P49917; -.
DR OpenTargets; ENSG00000174405; -.
DR Orphanet; 235; Dubowitz syndrome.
DR Orphanet; 99812; LIG4 syndrome.
DR Orphanet; 39041; Omenn syndrome.
DR PharmGKB; PA30375; -.
DR VEuPathDB; HostDB:ENSG00000174405; -.
DR eggNOG; KOG0966; Eukaryota.
DR GeneTree; ENSGT00860000133881; -.
DR InParanoid; P49917; -.
DR OMA; EGIMIKH; -.
DR OrthoDB; 274264at2759; -.
DR PhylomeDB; P49917; -.
DR TreeFam; TF312980; -.
DR BRENDA; 6.5.1.1; 2681.
DR PathwayCommons; P49917; -.
DR Reactome; R-HSA-164843; 2-LTR circle formation.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR SignaLink; P49917; -.
DR SIGNOR; P49917; -.
DR BioGRID-ORCS; 3981; 69 hits in 1080 CRISPR screens.
DR ChiTaRS; LIG4; human.
DR EvolutionaryTrace; P49917; -.
DR GeneWiki; LIG4; -.
DR GenomeRNAi; 3981; -.
DR Pharos; P49917; Tbio.
DR PRO; PR:P49917; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P49917; protein.
DR Bgee; ENSG00000174405; Expressed in endothelial cell and 192 other tissues.
DR ExpressionAtlas; P49917; baseline and differential.
DR Genevisible; P49917; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; IC:BHF-UCL.
DR GO; GO:0000793; C:condensed chromosome; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0032807; C:DNA ligase IV complex; IMP:UniProtKB.
DR GO; GO:0005958; C:DNA-dependent protein kinase-DNA ligase 4 complex; IDA:MGI.
DR GO; GO:0070419; C:nonhomologous end joining complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0003910; F:DNA ligase (ATP) activity; IDA:UniProtKB.
DR GO; GO:0003909; F:DNA ligase activity; IDA:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IGI:UniProtKB.
DR GO; GO:0071285; P:cellular response to lithium ion; IEA:Ensembl.
DR GO; GO:0007417; P:central nervous system development; ISS:UniProtKB.
DR GO; GO:0051276; P:chromosome organization; ISS:UniProtKB.
DR GO; GO:1904155; P:DN2 thymocyte differentiation; IEA:Ensembl.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:InterPro.
DR GO; GO:0006266; P:DNA ligation; IDA:UniProtKB.
DR GO; GO:0051102; P:DNA ligation involved in DNA recombination; ISS:UniProtKB.
DR GO; GO:0051103; P:DNA ligation involved in DNA repair; IDA:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB.
DR GO; GO:0097680; P:double-strand break repair via classical nonhomologous end joining; IMP:BHF-UCL.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IDA:UniProtKB.
DR GO; GO:0075713; P:establishment of integrated proviral latency; TAS:Reactome.
DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0033152; P:immunoglobulin V(D)J recombination; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; ISS:UniProtKB.
DR GO; GO:0045190; P:isotype switching; ISS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0022008; P:neurogenesis; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0006297; P:nucleotide-excision repair, DNA gap filling; IDA:UniProtKB.
DR GO; GO:2001252; P:positive regulation of chromosome organization; IMP:BHF-UCL.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISS:UniProtKB.
DR GO; GO:0050769; P:positive regulation of neurogenesis; ISS:UniProtKB.
DR GO; GO:0002328; P:pro-B cell differentiation; ISS:UniProtKB.
DR GO; GO:0010332; P:response to gamma radiation; ISS:UniProtKB.
DR GO; GO:0010165; P:response to X-ray; IMP:UniProtKB.
DR GO; GO:0000012; P:single strand break repair; IDA:UniProtKB.
DR GO; GO:0035019; P:somatic stem cell population maintenance; ISS:UniProtKB.
DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB.
DR GO; GO:0033153; P:T cell receptor V(D)J recombination; ISS:UniProtKB.
DR GO; GO:0033151; P:V(D)J recombination; IDA:UniProtKB.
DR CDD; cd07903; Adenylation_DNA_ligase_IV; 1.
DR Gene3D; 1.10.3260.10; -; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.40.50.10190; -; 2.
DR InterPro; IPR044125; Adenylation_DNA_ligase_IV.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR000977; DNA_ligase_ATP-dep.
DR InterPro; IPR012309; DNA_ligase_ATP-dep_C.
DR InterPro; IPR012310; DNA_ligase_ATP-dep_cent.
DR InterPro; IPR016059; DNA_ligase_ATP-dep_CS.
DR InterPro; IPR012308; DNA_ligase_ATP-dep_N.
DR InterPro; IPR021536; DNA_ligase_IV_dom.
DR InterPro; IPR036599; DNA_ligase_N_sf.
DR InterPro; IPR029710; LIG4.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR PANTHER; PTHR45997; PTHR45997; 1.
DR Pfam; PF00533; BRCT; 2.
DR Pfam; PF04679; DNA_ligase_A_C; 1.
DR Pfam; PF01068; DNA_ligase_A_M; 1.
DR Pfam; PF04675; DNA_ligase_A_N; 1.
DR Pfam; PF11411; DNA_ligase_IV; 1.
DR SMART; SM00292; BRCT; 2.
DR SUPFAM; SSF117018; SSF117018; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF52113; SSF52113; 2.
DR TIGRFAMs; TIGR00574; dnl1; 1.
DR PROSITE; PS50172; BRCT; 2.
DR PROSITE; PS00697; DNA_LIGASE_A1; 1.
DR PROSITE; PS00333; DNA_LIGASE_A2; 1.
DR PROSITE; PS50160; DNA_LIGASE_A3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell cycle; Cell division;
KW Direct protein sequencing; Disease variant; DNA damage; DNA recombination;
KW DNA repair; DNA replication; Ligase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Reference proteome; Repeat; SCID.
FT CHAIN 1..911
FT /note="DNA ligase 4"
FT /id="PRO_0000059576"
FT DOMAIN 654..743
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 808..911
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT ACT_SITE 273
FT /note="N6-AMP-lysine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10135"
FT BINDING 271
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P18858"
FT BINDING 278
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P18858"
FT BINDING 331
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P18858"
FT BINDING 331
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255"
FT BINDING 427
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255"
FT BINDING 432
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P18858"
FT BINDING 449
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P18858"
FT VARIANT 3
FT /note="A -> V (associated with resistance to multiple
FT myeloma; dbSNP:rs1805389)"
FT /evidence="ECO:0000269|PubMed:12471202"
FT /id="VAR_029352"
FT VARIANT 9
FT /note="T -> I (associated with resistance to multiple
FT myeloma; dbSNP:rs1805388)"
FT /evidence="ECO:0000269|PubMed:12471202"
FT /id="VAR_033884"
FT VARIANT 62
FT /note="D -> H (in dbSNP:rs3093763)"
FT /id="VAR_029353"
FT VARIANT 231
FT /note="P -> S (in dbSNP:rs3093765)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_018808"
FT VARIANT 278
FT /note="R -> H (in LIG4S and leukemia; impairs activity;
FT dbSNP:rs104894421)"
FT /evidence="ECO:0000269|PubMed:10395545,
FT ECO:0000269|PubMed:11349135, ECO:0000269|PubMed:11779494"
FT /id="VAR_012774"
FT VARIANT 433
FT /note="Missing (in RSSCID)"
FT /evidence="ECO:0000269|PubMed:16357942"
FT /id="VAR_044123"
FT VARIANT 461
FT /note="E -> G (in dbSNP:rs2232640)"
FT /id="VAR_044124"
FT VARIANT 469
FT /note="G -> E (in LIG4S; dbSNP:rs104894420)"
FT /evidence="ECO:0000269|PubMed:11779494"
FT /id="VAR_012775"
FT VARIANT 539
FT /note="L -> F (in dbSNP:rs3742212)"
FT /id="VAR_016771"
FT VARIANT 580..911
FT /note="Missing (in LIG4S)"
FT /evidence="ECO:0000269|PubMed:11779494"
FT /id="VAR_084970"
FT VARIANT 658
FT /note="I -> V (in dbSNP:rs2232641)"
FT /id="VAR_016772"
FT VARIANT 774
FT /note="L -> P (found in a patient with microcephalic
FT primordial dwarfism; unknown pathological significance;
FT dbSNP:rs1060499662)"
FT /evidence="ECO:0000269|PubMed:25728776"
FT /id="VAR_075826"
FT VARIANT 814..911
FT /note="Missing (in LIG4S)"
FT /evidence="ECO:0000269|PubMed:11779494"
FT /id="VAR_084971"
FT VARIANT 857
FT /note="A -> T (in dbSNP:rs2232642)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_016773"
FT CONFLICT 246
FT /note="F -> S (in Ref. 1; CAA58467)"
FT /evidence="ECO:0000305"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:4HTP"
FT HELIX 16..28
FT /evidence="ECO:0007829|PDB:4HTP"
FT HELIX 32..53
FT /evidence="ECO:0007829|PDB:4HTP"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:4HTP"
FT HELIX 65..71
FT /evidence="ECO:0007829|PDB:4HTP"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:4HTP"
FT HELIX 86..96
FT /evidence="ECO:0007829|PDB:4HTP"
FT HELIX 104..110
FT /evidence="ECO:0007829|PDB:4HTP"
FT TURN 111..113
FT /evidence="ECO:0007829|PDB:6BKG"
FT HELIX 125..133
FT /evidence="ECO:0007829|PDB:4HTP"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 145..160
FT /evidence="ECO:0007829|PDB:4HTP"
FT HELIX 164..176
FT /evidence="ECO:0007829|PDB:4HTP"
FT HELIX 180..191
FT /evidence="ECO:0007829|PDB:4HTP"
FT HELIX 200..207
FT /evidence="ECO:0007829|PDB:4HTP"
FT HELIX 211..218
FT /evidence="ECO:0007829|PDB:4HTP"
FT HELIX 221..227
FT /evidence="ECO:0007829|PDB:4HTP"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:6BKF"
FT STRAND 250..253
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:3W1B"
FT TURN 263..265
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 268..272
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 276..284
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 287..292
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 299..302
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 308..311
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 312..315
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 324..336
FT /evidence="ECO:0007829|PDB:3W1B"
FT TURN 337..340
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 351..356
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 359..372
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:3VNN"
FT HELIX 382..392
FT /evidence="ECO:0007829|PDB:3W1B"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 405..408
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 411..423
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 429..432
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 443..450
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 452..454
FT /evidence="ECO:0007829|PDB:6BKG"
FT HELIX 458..460
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 462..471
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 474..478
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 479..488
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 500..507
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 513..522
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 523..525
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 536..539
FT /evidence="ECO:0007829|PDB:6BKG"
FT STRAND 546..548
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 551..553
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 556..560
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 562..566
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 568..570
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 573..578
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 580..584
FT /evidence="ECO:0007829|PDB:3W1B"
FT STRAND 586..588
FT /evidence="ECO:0007829|PDB:6BKF"
FT HELIX 590..592
FT /evidence="ECO:0007829|PDB:3W1B"
FT HELIX 596..603
FT /evidence="ECO:0007829|PDB:3W1B"
FT TURN 606..608
FT /evidence="ECO:0007829|PDB:6BKG"
FT STRAND 609..611
FT /evidence="ECO:0007829|PDB:6BKG"
FT TURN 658..661
FT /evidence="ECO:0007829|PDB:3II6"
FT STRAND 663..666
FT /evidence="ECO:0007829|PDB:3II6"
FT STRAND 671..673
FT /evidence="ECO:0007829|PDB:2E2W"
FT HELIX 675..684
FT /evidence="ECO:0007829|PDB:3II6"
FT STRAND 687..692
FT /evidence="ECO:0007829|PDB:2E2W"
FT STRAND 697..701
FT /evidence="ECO:0007829|PDB:3II6"
FT HELIX 707..714
FT /evidence="ECO:0007829|PDB:3II6"
FT HELIX 723..732
FT /evidence="ECO:0007829|PDB:3II6"
FT HELIX 740..742
FT /evidence="ECO:0007829|PDB:3II6"
FT STRAND 743..745
FT /evidence="ECO:0007829|PDB:3II6"
FT HELIX 748..753
FT /evidence="ECO:0007829|PDB:3II6"
FT TURN 754..757
FT /evidence="ECO:0007829|PDB:3II6"
FT STRAND 764..767
FT /evidence="ECO:0007829|PDB:1IK9"
FT HELIX 771..779
FT /evidence="ECO:0007829|PDB:1IK9"
FT HELIX 789..802
FT /evidence="ECO:0007829|PDB:3II6"
FT HELIX 809..811
FT /evidence="ECO:0007829|PDB:3II6"
FT TURN 812..815
FT /evidence="ECO:0007829|PDB:3II6"
FT STRAND 817..820
FT /evidence="ECO:0007829|PDB:3II6"
FT STRAND 823..825
FT /evidence="ECO:0007829|PDB:3II6"
FT HELIX 829..831
FT /evidence="ECO:0007829|PDB:3II6"
FT HELIX 837..847
FT /evidence="ECO:0007829|PDB:3II6"
FT STRAND 851..855
FT /evidence="ECO:0007829|PDB:3II6"
FT STRAND 862..865
FT /evidence="ECO:0007829|PDB:3II6"
FT HELIX 872..880
FT /evidence="ECO:0007829|PDB:3II6"
FT STRAND 887..890
FT /evidence="ECO:0007829|PDB:3II6"
FT HELIX 892..899
FT /evidence="ECO:0007829|PDB:3II6"
FT HELIX 906..908
FT /evidence="ECO:0007829|PDB:3II6"
SQ SEQUENCE 911 AA; 103971 MW; 2122813E1EFA63B9 CRC64;
MAASQTSQTV ASHVPFADLC STLERIQKSK GRAEKIRHFR EFLDSWRKFH DALHKNHKDV
TDSFYPAMRL ILPQLERERM AYGIKETMLA KLYIELLNLP RDGKDALKLL NYRTPTGTHG
DAGDFAMIAY FVLKPRCLQK GSLTIQQVND LLDSIASNNS AKRKDLIKKS LLQLITQSSA
LEQKWLIRMI IKDLKLGVSQ QTIFSVFHND AAELHNVTTD LEKVCRQLHD PSVGLSDISI
TLFSAFKPML AAIADIEHIE KDMKHQSFYI ETKLDGERMQ MHKDGDVYKY FSRNGYNYTD
QFGASPTEGS LTPFIHNAFK ADIQICILDG EMMAYNPNTQ TFMQKGTKFD IKRMVEDSDL
QTCYCVFDVL MVNNKKLGHE TLRKRYEILS SIFTPIPGRI EIVQKTQAHT KNEVIDALNE
AIDKREEGIM VKQPLSIYKP DKRGEGWLKI KPEYVSGLMD ELDILIVGGY WGKGSRGGMM
SHFLCAVAEK PPPGEKPSVF HTLSRVGSGC TMKELYDLGL KLAKYWKPFH RKAPPSSILC
GTEKPEVYIE PCNSVIVQIK AAEIVPSDMY KTGCTLRFPR IEKIRDDKEW HECMTLDDLE
QLRGKASGKL ASKHLYIGGD DEPQEKKRKA APKMKKVIGI IEHLKAPNLT NVNKISNIFE
DVEFCVMSGT DSQPKPDLEN RIAEFGGYIV QNPGPDTYCV IAGSENIRVK NIILSNKHDV
VKPAWLLECF KTKSFVPWQP RFMIHMCPST KEHFAREYDC YGDSYFIDTD LNQLKEVFSG
IKNSNEQTPE EMASLIADLE YRYSWDCSPL SMFRRHTVYL DSYAVINDLS TKNEGTRLAI
KALELRFHGA KVVSCLAEGV SHVIIGEDHS RVADFKAFRR TFKRKFKILK ESWVTDSIDK
CELQEENQYL I
