Reviewed, UniProtKB/Swiss-Prot P18858 (DNLI1_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA ligase 1
    EC=6.5.1.1
Alternative name(s):
    DNA ligase I
    Polydeoxyribonucleotide synthase [ATP] 1

Gene names

Name:

LIG1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	919 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	DNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair.
Catalytic activity	ATP + (deoxyribonucleotide)(n) + (deoxyribonucleotide)(m) = AMP + diphosphate + (deoxyribonucleotide)(n+m).
Cofactor	Magnesium. Ref.14
Subcellular location	Nucleus.
Involvement in disease	Defects in LIG1 seem to cause immunodeficiencies and cellular hypersensitivity to DNA-damaging agents.
Sequence similarities	Belongs to the ATP-dependent DNA ligase family.

Ontologies

Keywords
Biological process	Cell cycle Cell division DNA damage DNA recombination DNA repair DNA replication
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	DNA recombination Inferred from electronic annotation. Source: UniProtKB-KW DNA replication Inferred from electronic annotation. Source: UniProtKB-KW anatomical structure morphogenesis Traceable author statement. Source: ProtInc cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell division Inferred from electronic annotation. Source: UniProtKB-KW nucleotide-excision repair, DNA gap filling Inferred from Experiment. Source: Reactome
Cellular component	nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Traceable author statement. Source: ProtInc DNA ligase (ATP) activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 919

919

DNA ligase 1

PRO_0000059570

Regions

Region

449 – 458

10

Interaction with target DNA

Region

642 – 644

3

Interaction with target DNA

Sites

Active site

568

1

N6-AMP-lysine intermediate By similarity

Metal binding

621

1

Magnesium 1 Probable

Metal binding

720

1

Magnesium 2 Probable

Binding site

566

1

ATP

Binding site

573

1

ATP

Binding site

589

1

ATP

Binding site

725

1

ATP

Binding site

738

1

ATP By similarity

Binding site

744

1

ATP

Site

305

1

Interaction with target DNA

Site

590

1

Interaction with target DNA

Site

770

1

Interaction with target DNA

Site

795

1

Interaction with target DNA

Amino acid modifications

Modified residue

49

1

Phosphoserine Ref.6 Ref.10

Modified residue

51

1

Phosphoserine Ref.10 Ref.7 Ref.12

Modified residue

66

1

Phosphoserine Ref.6 Ref.7 Ref.12 Ref.5 Ref.9

Modified residue

76

1

Phosphoserine Ref.6 Ref.7 Ref.12 Ref.5 Ref.9

Modified residue

141

1

Phosphoserine Ref.6 Ref.10 Ref.12 Ref.5

Modified residue

195

1

Phosphothreonine Ref.6 Ref.7 Ref.12 Ref.5

Modified residue

201

1

Phosphoserine Ref.6 Ref.12

Modified residue

230

1

Phosphoserine Ref.8

Modified residue

233

1

Phosphothreonine Ref.6 Ref.7 Ref.12 Ref.11

Modified residue

911

1

Phosphoserine Ref.12 Ref.5

Modified residue

913

1

Phosphoserine Ref.12

Natural variations

Natural variant

24

1

A → V: dbSNP rs3730855. Ref.2

VAR_018802

Natural variant

52

1

P → L: dbSNP rs4987181.

VAR_020194

Natural variant

62

1

R → W: dbSNP rs3730863. Ref.2

VAR_018803

Natural variant

72

1

D → G: dbSNP rs4987070.

VAR_020195

Natural variant

152

1

K → E in a colorectal cancer sample; somatic mutation. Ref.16

VAR_036511

Natural variant

249

1

G → E: dbSNP rs3730911. Ref.2

VAR_016766

Natural variant

267

1

N → S: dbSNP rs3730933. Ref.2

VAR_016767

Natural variant

349

1

V → M: dbSNP rs3730947. Ref.2

VAR_018804

Natural variant

369

1

V → I: dbSNP rs3730966. Ref.2

VAR_018805

Natural variant

409

1

R → H: dbSNP rs4987068.

VAR_016768

Natural variant

480

1

M → V: dbSNP rs3730980. Ref.2

VAR_016769

Natural variant

566

1

E → K in LIG1 deficiency.

VAR_002262

Natural variant

612

1

S → L in a colorectal cancer sample; somatic mutation. Ref.16

VAR_036512

Natural variant

614

1

T → I: dbSNP rs3731003. Ref.2

VAR_016770

Natural variant

677

1

R → L: dbSNP rs3731008. Ref.2

VAR_018806

Natural variant

771

1

R → W in LIG1 deficiency.

VAR_002263

Secondary structure

1

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919

Helix Strand Turn

Details...

Helix

263 – 265

3

Helix

275 – 278

4

Helix

289 – 300

12

Helix

305 – 322

18

Helix

324 – 326

3

Helix

327 – 335

9

Helix

341 – 343

3

Helix

351 – 362

12

Helix

366 – 376

11

Helix

379 – 382

4

Helix

401 – 413

13

Helix

419 – 433

15

Helix

438 – 446

9

Helix

456 – 469

14

Turn

483 – 486

4

Helix

489 – 509

21

Helix

513 – 527

15

Helix

529 – 531

3

Beta strand

544 – 550

7

Helix

551 – 557

7

Turn

558 – 560

3

Beta strand

563 – 578

16

Beta strand

584 – 587

4

Turn

595 – 597

3

Helix

599 – 603

5

Helix

606 – 608

3

Beta strand

616 – 625

10

Turn

627 – 629

3

Helix

635 – 638

4

Helix

648 – 650

3

Beta strand

653 – 665

13

Helix

675 – 685

11

Turn

690 – 692

3

Beta strand

693 – 695

3

Helix

704 – 716

13

Beta strand

718 – 730

13

Turn

735 – 737

3

Beta strand

739 – 746

8

Helix

747 – 751

5

Beta strand

755 – 767

13

Beta strand

774 – 784

11

Turn

785 – 788

4

Beta strand

789 – 796

8

Helix

802 – 814

13

Beta strand

816 – 819

4

Beta strand

827 – 829

3

Beta strand

833 – 836

4

Beta strand

841 – 854

14

Turn

857 – 861

5

Beta strand

867 – 872

6

Beta strand

874 – 878

5

Helix

884 – 886

3

Helix

890 – 900

11

Sequences

	Sequence		Length	Mass (Da)
	P18858-1 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: B2854DAE38A8D4AD	FASTA	919	101,736
	10 20 30 40 50 60 MQRSIMSFFH PKKEGKAKKP EKEASNSSRE TEPPPKAALK EWNGVVSESD SPVKRPGRKA 70 80 90 100 110 120 ARVLGSEGEE EDEALSPAKG QKPALDCSQV SPPRPATSPE NNASLSDTSP MDSSPSGIPK 130 140 150 160 170 180 RRTARKQLPK RTIQEVLEEQ SEDEDREAKR KKEEEEEETP KESLTEAEVA TEKEGEDGDQ 190 200 210 220 230 240 PTTPPKPLKT SKAETPTESV SEPEVATKQE LQEEEEQTKP PRRAPKTLSS FFTPRKPAVK 250 260 270 280 290 300 KEVKEEEPGA PGKEGAAEGP LDPSGYNPAK NNYHPVEDAC WKPGQKVPYL AVARTFEKIE 310 320 330 340 350 360 EVSARLRMVE TLSNLLRSVV ALSPPDLLPV LYLSLNHLGP PQQGLELGVG DGVLLKAVAQ 370 380 390 400 410 420 ATGRQLESVR AEAAEKGDVG LVAENSRSTQ RLMLPPPPLT ASGVFSKFRD IARLTGSAST 430 440 450 460 470 480 AKKIDIIKGL FVACRHSEAR FIARSLSGRL RLGLAEQSVL AALSQAVSLT PPGQEFPPAM 490 500 510 520 530 540 VDAGKGKTAE ARKTWLEEQG MILKQTFCEV PDLDRIIPVL LEHGLERLPE HCKLSPGIPL 550 560 570 580 590 600 KPMLAHPTRG ISEVLKRFEE AAFTCEYKYD GQRAQIHALE GGEVKIFSRN QEDNTGKYPD 610 620 630 640 650 660 IISRIPKIKL PSVTSFILDT EAVAWDREKK QIQPFQVLTT RKRKEVDASE IQVQVCLYAF 670 680 690 700 710 720 DLIYLNGESL VREPLSRRRQ LLRENFVETE GEFVFATSLD TKDIEQIAEF LEQSVKDSCE 730 740 750 760 770 780 GLMVKTLDVD ATYEIAKRSH NWLKLKKDYL DGVGDTLDLV VIGAYLGRGK RAGRYGGFLL 790 800 810 820 830 840 ASYDEDSEEL QAICKLGTGF SDEELEEHHQ SLKALVLPSP RPYVRIDGAV IPDHWLDPSA 850 860 870 880 890 900 VWEVKCADLS LSPIYPAARG LVDSDKGISL RFPRFIRVRE DKQPEQATTS AQVACLYRKQ 910 SQIQNQQGED SGSDPEDTY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human DNA ligase I cDNA: cloning and functional expression in Saccharomyces cerevisiae." Barnes D.E., Johnston L.H., Kodama K., Tomkinson A.E., Lasko D.D., Lindahl T. Proc. Natl. Acad. Sci. U.S.A. 87:6679-6683(1990) [PubMed: 2204063] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: T lymphoblast.
[2]	NIEHS SNPs program Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-24; TRP-62; GLU-249; SER-267; MET-349; ILE-369; VAL-480; ILE-614 AND LEU-677.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[4]	"A wild-type DNA ligase I gene is expressed in Bloom's syndrome cells." Petrini J.H.J., Huwiler K.G., Weaver D.T. Proc. Natl. Acad. Sci. U.S.A. 88:7615-7619(1991) [PubMed: 1881902] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 716-753.
[5]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-66; SER-76; SER-141; THR-195 AND SER-911, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49; SER-66; SER-76; SER-141; THR-195; SER-201 AND THR-233, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-66; SER-76; THR-195 AND THR-233, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-230, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction." Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R. Mol. Cell. Proteomics 6:1952-1967(2007) [PubMed: 17693683] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-66 AND SER-76, MASS SPECTROMETRY.
[10]	"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. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49; SER-51 AND SER-141, MASS SPECTROMETRY.
[11]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-233, MASS SPECTROMETRY.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-66; SER-76; SER-141; THR-195; SER-201; THR-233; SER-911 AND SER-913, MASS SPECTROMETRY.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"Human DNA ligase I completely encircles and partially unwinds nicked DNA." Pascal J.M., O'Brien P.J., Tomkinson A.E., Ellenberger T. Nature 432:473-478(2004) [PubMed: 15565146] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 233-919 IN COMPLEX WITH NICKED DNA AND AMP, COFACTOR, ACTIVE SITE.
[15]	"Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents." Barnes D.E., Tomkinson A.E., Lehmann A.R., Webster A.D.B., Lindahl T. Cell 69:495-503(1992) [PubMed: 1581963] [Abstract] Cited for: VARIANTS LYS-566 AND TRP-771.
[16]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLU-152 AND LEU-612.
+	Additional computationally mapped references.

Web resources

LIG1base

LIG1 mutation db

NIEHS-SNPs

Wikipedia

DNA ligase entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

M36067 mRNA. Translation: AAA59518.1.
AF527418 Genomic DNA. Translation: AAM77697.1.
BC108318 mRNA. Translation: AAI08319.1.

IPI

IPI00219841.

PIR

A41275. A36048.

RefSeq

NP_000225.1.

UniGene

Hs.1770

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X9N	X-ray	3.00	A	233-919	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:24215N.

IntAct

P18858. 2 interactions.

PTM databases

PhosphoSite

P18858.

Proteomic databases

PeptideAtlas

P18858.

PRIDE

P18858.

Genome annotation databases

Ensembl

ENSG00000105486. Homo sapiens. [Contig view]

GeneID

3978.

KEGG

hsa:3978.

UCSC

uc002pia.1. human.

Organism-specific databases

GeneCards

GC19M053310.

H-InvDB

HIX0040136.

HGNC

HGNC:6598. LIG1.

MIM

126391. gene.

PharmGKB

PA30372.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P18858.

HOVERGEN

P18858.

OMA

P18858. RNWLKLK.

Enzyme and pathway databases

BRENDA

6.5.1.1. 247.

Reactome

REACT_216. DNA Repair.

Gene expression databases

ArrayExpress

P18858.

Bgee

P18858.

CleanEx

HS_LIG1.

GermOnline

ENSG00000105486. Homo sapiens.

Family and domain databases

InterPro

IPR000977. DNA_ligase.
IPR012309. DNA_ligase_A_C.
IPR012310. DNA_ligase_A_M.
IPR012308. DNA_ligase_A_N.
IPR016059. DNA_ligase_CS.
IPR012340. NA-bd_OB-fold.
[Graphical view]

Gene3D

G3DSA:2.40.50.140. OB_NA_bd_sub. 1 hit.

Pfam

PF04679. DNA_ligase_A_C. 1 hit.
PF01068. DNA_ligase_A_M. 1 hit.
PF04675. DNA_ligase_A_N. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00574. dnl1. 1 hit.

PROSITE

PS00697. DNA_LIGASE_A1. 1 hit.
PS00333. DNA_LIGASE_A2. 1 hit.
PS50160. DNA_LIGASE_A3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00290. Bleomycin.

NextBio

15592.

SOURCE

Search...

Entry information

Entry name

DNLI1_HUMAN

Accession

Primary (citable) accession number: P18858
Secondary accession number(s): Q32P23

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	July 7, 2009
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)