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LIG4

Protein FULL name:

DNA ligase 4, DNA ligase IV, Polydeoxyribonucleotide synthase [ATP] 4.,


LIG4 (Homo sapiens) is product of expression of LIG4 gene.

Human diseases related to this protein:

LIG4 is involved in:

NHEJ in Homo sapiens

Keywords:



FUNCTION: Efficiently joins single-strand breaks in a double- stranded polydeoxynucleotide in an ATP-dependent reaction. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA- dependent protein kinase complex DNA-PK to these DNA ends.

CATALYTIC ACTIVITY: ATP + (deoxyribonucleotide)(n) + (deoxyribonucleotide)(m) = AMP + diphosphate + (deoxyribonucleotide)(n+m).

COFACTOR: Magnesium (By similarity).

SUBUNIT: Binds to XRCC4. The LIG4-XRCC4 complex has probably a 1:2 stoichiometry. The LIG4-XRCC4 heteromer associates in a DNA- dependent manner with the DNA-dependent protein kinase complex DNA-PK, formed by the Ku p70/p86 dimer (G22P1/G22P2) and PRKDC. Interacts with APLF.

INTERACTION: Q9H9Q4:NHEJ1; NbExp=4; IntAct=EBI-847896, EBI-847807; Q96T60:PNKP; NbExp=1; IntAct=EBI-847896, EBI-1045072;

SUBCELLULAR LOCATION: Nucleus.

TISSUE SPECIFICITY: Testis, thymus, prostate and heart.

DISEASE: Defects in LIG4 are the cause of LIG4 syndrome [MIM:606593]. This disease is characterized by immunodeficiency and developmental and growth delay. Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and various skin abnormalities.

DISEASE: Defects in LIG4 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell- negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:602450]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T- cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity.

SIMILARITY: Belongs to the ATP-dependent DNA ligase family.

SIMILARITY: Contains 2 BRCT domains.

SEQUENCE CAUTION: Sequence=AAL77435.1; Type=Erroneous initiation; Sequence=CAA58467.1; Type=Erroneous initiation;

WEB RESOURCE: Name=LIG4base; Note=LIG4 mutation db; [LINK]

WEB RESOURCE: Name=NIEHS-SNPs; [LINK]

WEB RESOURCE: Name=Wikipedia; Note=DNA ligase entry; [LINK]


NCBI GenPept GI number(s): 88911290
23199993
148539894
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot P49917 P49917
PFAM: PF00533
PF04679
PF01068
PF04675
PF11411
PF00533
PF04679
PF01068
PF04675
PF11411
InterPro: IPR001357
IPR000977
IPR012309
IPR012310
IPR012308
IPR016059
IPR021536
IPR012340
IPR001357
IPR000977
IPR012309
IPR012310
IPR012308
IPR016059
IPR021536
IPR012340
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MAASQTSQTVASHVPFADLCSTLERIQKSKGRAEKIRHFREFLDSWRKFH
DALHKNHKDVTDSFYPAMRLILPQLERERMAYGIKETMLAKLYIELLNLP
RDGKDALKLLNYRTPTGTHGDAGDFAMIAYFVLKPRCLQKGSLTIQQVND
LLDSIASNNSAKRKDLIKKSLLQLITQSSALEQKWLIRMIIKDLKLGVSQ
QTIFSVFHNDAAELHNVTTDLEKVCRQLHDPSVGLSDISITLFSAFKPML
AAIADIEHIEKDMKHQSFYIETKLDGERMQMHKDGDVYKYFSRNGYNYTD
QFGASPTEGSLTPFIHNAFKADIQICILDGEMMAYNPNTQTFMQKGTKFD
IKRMVEDSDLQTCYCVFDVLMVNNKKLGHETLRKRYEILSSIFTPIPGRI
EIVQKTQAHTKNEVIDALNEAIDKREEGIMVKQPLSIYKPDKRGEGWLKI
KPEYVSGLMDELDILIVGGYWGKGSRGGMMSHFLCAVAEKPPPGEKPSVF
HTLSRVGSGCTMKELYDLGLKLAKYWKPFHRKAPPSSILCGTEKPEVYIE
PCNSVIVQIKAAEIVPSDMYKTGCTLRFPRIEKIRDDKEWHECMTLDDLE
QLRGKASGKLASKHLYIGGDDEPQEKKRKAAPKMKKVIGIIEHLKAPNLT
NVNKISNIFEDVEFCVMSGTDSQPKPDLENRIAEFGGYIVQNPGPDTYCV
IAGSENIRVKNIILSNKHDVVKPAWLLECFKTKSFVPWQPRFMIHMCPST
KEHFAREYDCYGDSYFIDTDLNQLKEVFSGIKNSNEQTPEEMASLIADLE
YRYSWDCSPLSMFRRHTVYLDSYAVINDLSTKNEGTRLAIKALELRFHGA
KVVSCLAEGVSHVIIGEDHSRVADFKAFRRTFKRKFKILKESWVTDSIDK
CELQEENQYLI

LIG4 (Homo sapiens) is able to recognize following damages:
LIG4 (Homo sapiens) belongs to following protein families:
References:

Title Authors Journal
Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination. Wei YF, Robins P, Carter K, Caldecott K, Pappin DJ, Yu GL, Wang RP, Shell BK, Nash RA, Schar P, et al. Mol Cell Biol June 1, 1995
DNA ligase IV from HeLa cell nuclei. Robins P, Lindahl T J Biol Chem Sept. 27, 1996
Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV. Critchlow SE, Bowater RP, Jackson SP Curr Biol Aug. 1, 1997
DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes. Grawunder U, Zimmer D, Fugmann S, Schwarz K, Lieber MR Mol Cell Oct. 1, 1998
Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient. Riballo E, Critchlow SE, Teo SH, Doherty AJ, Priestley A, Broughton B, Kysela B, Beamish H, Plowman N, Arlett CF, Lehmann AR, Jackson SP, Jeggo PA Curr Biol July 1, 1999
Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase. Chen L, Trujillo K, Sung P, Tomkinson AE J Biol Chem Aug. 25, 2000
Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity. Riballo E, Doherty AJ, Dai Y, Stiff T, Oettinger MA, Jeggo PA, Kysela B J Biol Chem Aug. 17, 2001
Crystal structure of an Xrcc4-DNA ligase IV complex. Sibanda BL, Critchlow SE, Begun J, Pei XY, Jackson SP, Blundell TL, Pellegrini L Nat Struct Biol Dec. 1, 2001
DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. O'Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B, Hirsch B, Gennery A, Palmer SE, Seidel J, Gatti RA, Varon R, Oettinger MA, Neitzel H, Jeggo PA, Concannon P Mol Cell Dec. 1, 2001
Genetic variants of NHEJ DNA ligase IV can affect the risk of developing multiple myeloma, a tumour characterised by aberrant class switch recombination. Roddam PL, Rollinson S, O'Driscoll M, Jeggo PA, Jack A, Morgan GJ J Med Genet Dec. 1, 2002
Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment. Calsou P, Delteil C, Frit P, Drouet J, Salles B J Mol Biol Jan. 7, 2003
The DNA sequence and analysis of human chromosome 13. Dunham A, Matthews LH, Burton J, Ashurst JL, Howe KL, Ashcroft KJ, Beare DM, Burford DC, Hunt SE, Griffiths-Jones S, Jones MC, Keenan SJ, Oliver K, Scott CE, Ainscough R, Almeida JP, Ambrose KD, Andrews DT, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Bannerjee R, Barlow KF, Bates K, Beasley H, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burrill W, Carder C, Carter NP, Chapman JC, Clamp ME, Clark SY, Clarke G, Clee CM, Clegg SC, Cobley V, Collins JE, Corby N, Coville GJ, Deloukas P, Dhami P, Dunham I, Dunn M, Earthrowl ME, Ellington AG, Faulkner L, Frankish AG, Frankland J, French L, Garner P, Garnett J, Gilbert JG, Gilson CJ, Ghori J, Grafham DV, Gribble SM, Griffiths C, Hall RE, Hammond S, Harley JL, Hart EA, Heath PD, Howden PJ, Huckle EJ, Hunt PJ, Hunt AR, Johnson C, Johnson D, Kay M, Kimberley AM, King A, Laird GK, Langford CJ, Lawlor S, Leongamornlert DA, Lloyd DM, Lloyd C, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, McLaren SJ, McMurray A, Milne S, Moore MJ, Nickerson T, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter KM, Rice CM, Searle S, Sehra HK, Shownkeen R, Skuce CD, Smith M, Steward CA, Sycamore N, Tester J, Thomas DW, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Wilming L, Wray PW, Wright MW, Young L, Coulson A, Durbin R, Hubbard T, Sulston JE, Beck S, Bentley DR, Rogers J, Ross MT Nature April 1, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
A new type of radiosensitive T-B-NK+ severe combined immunodeficiency caused by a LIG4 mutation. van der Burg M, van Veelen LR, Verkaik NS, Wiegant WW, Hartwig NG, Barendregt BH, Brugmans L, Raams A, Jaspers NG, Zdzienicka MZ, van Dongen JJ, van Gent DC J Clin Invest Feb. 1, 2006
A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses. Kanno S, Kuzuoka H, Sasao S, Hong Z, Lan L, Nakajima S, Yasui A EMBO J April 18, 2007
Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column. Imami K, Sugiyama N, Kyono Y, Tomita M, Ishihama Y Anal Sci Feb. 1, 2008


Last modification of this entry: Oct. 16, 2010.

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