Reviewed, UniProtKB/Swiss-Prot P49916 (DNLI3_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA ligase 3
    EC=6.5.1.1
Alternative name(s):
    DNA ligase III
    Polydeoxyribonucleotide synthase [ATP] 3

Gene names

Name:

LIG3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	922 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Interacts with DNA-repair protein XRCC1 and can correct defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents.
Catalytic activity	ATP + (deoxyribonucleotide)(n) + (deoxyribonucleotide)(m) = AMP + diphosphate + (deoxyribonucleotide)(n+m).
Subcellular location	Nucleus.
Tissue specificity	Testis, thymus, prostate and heart.
Sequence similarities	Belongs to the ATP-dependent DNA ligase family. Contains 1 BRCT domain. Contains 1 PARP-type zinc finger.

Ontologies

Keywords
Biological process	Cell cycle Cell division DNA damage DNA recombination DNA repair DNA replication
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA repair Ref.2 Traceable author statement. Source: ProtInc DNA replication Inferred from electronic annotation. Source: InterPro cell division Inferred from electronic annotation. Source: UniProtKB-KW reciprocal meiotic recombination Ref.2 Traceable author statement. Source: ProtInc spermatogenesis Ref.2 Traceable author statement. Source: ProtInc
Cellular component	nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro DNA binding Ref.2 Traceable author statement. Source: ProtInc DNA ligase (ATP) activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-1753381,EBI-375543
CRK	P46108	1	EBI-1753381,EBI-886
PIK3R1	P27986	1	EBI-1753381,EBI-79464
PLCG1	P19174	1	EBI-1753381,EBI-79387
SRC	P12931	1	EBI-1753381,EBI-621482

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha (identifier: P49916-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Beta (identifier: P49916-2)

The sequence of this isoform differs from the canonical sequence as follows:
     846-922: VLLDIFTGVR...IRKRRLVAPC → RRPASEQRGRTVPAGRR

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 922

922

DNA ligase 3

PRO_0000059574

Regions

Domain

846 – 922

77

BRCT

Zinc finger

6 – 98

93

PARP-type

Sites

Active site

421

1

N6-AMP-lysine intermediate By similarity

Amino acid modifications

Modified residue

122

1

Phosphothreonine By similarity

Modified residue

123

1

Phosphoserine

Modified residue

140

1

Phosphoserine

Modified residue

155

1

Phosphoserine

Natural variations

Alternative sequence

846 – 922

77

VLLDI…LVAPC → RRPASEQRGRTVPAGRR in isoform Beta.

VSP_001302

Natural variant

137

1

R → W: dbSNP rs3744356.

VAR_020196

Natural variant

630

1

D → N in a colorectal cancer sample; somatic mutation.

VAR_036513

Natural variant

780

1

R → H: dbSNP rs3136025.

VAR_018807

Natural variant

811

1

K → T: dbSNP rs4986974.

VAR_021938

Natural variant

899

1

P → S: dbSNP rs4986973.

VAR_020197

Secondary structure

1

.

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922

Helix Strand Turn

Details...

Beta strand

5 – 10

6

Beta strand

30 – 37

8

Helix

53 – 62

10

Beta strand

65 – 67

3

Beta strand

74 – 78

5

Turn

79 – 81

3

Helix

84 – 98

15

Beta strand

101 – 103

3

Helix

837 – 840

4

Beta strand

849 – 851

3

Helix

865 – 875

11

Beta strand

891 – 893

3

Helix

906 – 915

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified October 1, 1996. Version 1. Checksum: FC3C60F988868808	FASTA	922	102,691
	10 20 30 40 50 60 MAEQRFCVDY AKRGTAGCKK CKEKIVKGVC RIGKVVPNPF SESGGDMKEW YHIKCMFEKL 70 80 90 100 110 120 ERARATTKKI EDLTELEGWE ELEDNEKEQI TQHIADLSSK AAGTPKKKAV VQAKLTTTGQ 130 140 150 160 170 180 VTSPVKGASF VTSTNPRKFS GFSAKPNNSG EAPSSPTPKR SLSSSKCDPR HKDCLLREFR 190 200 210 220 230 240 KLCAMVADNP SYNTKTQIIQ DFLRKGSAGD GFHGDVYLTV KLLLPGVIKT VYNLNDKQIV 250 260 270 280 290 300 KLFSRIFNCN PDDMARDLEQ GDVSETIRVF FEQSKSFPPA AKSLLTIQEV DEFLLRLSKL 310 320 330 340 350 360 TKEDEQQQAL QDIASRCTAN DLKCIIRLIK HDLKMNSGAK HVLDALDPNA YEAFKASRNL 370 380 390 400 410 420 QDVVERVLHN AQEVEKEPGQ RRALSVQASL MTPVQPMLAE ACKSVEYAMK KCPNGMFSEI 430 440 450 460 470 480 KYDGERVQVH KNGDHFSYFS RSLKPVLPHK VAHFKDYIPQ AFPGGHSMIL DSEVLLIDNK 490 500 510 520 530 540 TGKPLPFGTL GVHKKAAFQD ANVCLFVFDC IYFNDVSLMD RPLCERRKFL HDNMVEIPNR 550 560 570 580 590 600 IMFSEMKRVT KALDLADMIT RVIQEGLEGL VLKDVKGTYE PGKRHWLKVK KDYLNEGAMA 610 620 630 640 650 660 DTADLVVLGA FYGQGSKGGM MSIFLMGCYD PGSQKWCTVT KCAGGHDDAT LARLQNELDM 670 680 690 700 710 720 VKISKDPSKI PSWLKVNKIY YPDFIVPDPK KAAVWEITGA EFSKSEAHTA DGISIRFPRC 730 740 750 760 770 780 TRIRDDKDWK SATNLPQLKE LYQLSKEKAD FTVVAGDEGS STTGGSSEEN KGPSGSAVSR 790 800 810 820 830 840 KAPSKPSAST KKAEGKLSNS NSKDGNMQTA KPSAMKVGEK LATKSSPVKV GEKRKAADET 850 860 870 880 890 900 LCQTKVLLDI FTGVRLYLPP STPDFSRLRR YFVAFDGDLV QEFDMTSATH VLGSRDKNPA 910 920 AQQVSPEWIW ACIRKRRLVA PC
	Isoform Beta [UniParc]. Checksum: F6A3C6B1422FD895		862	95,802
	10 20 30 40 50 60 MAEQRFCVDY AKRGTAGCKK CKEKIVKGVC RIGKVVPNPF SESGGDMKEW YHIKCMFEKL 70 80 90 100 110 120 ERARATTKKI EDLTELEGWE ELEDNEKEQI TQHIADLSSK AAGTPKKKAV VQAKLTTTGQ 130 140 150 160 170 180 VTSPVKGASF VTSTNPRKFS GFSAKPNNSG EAPSSPTPKR SLSSSKCDPR HKDCLLREFR 190 200 210 220 230 240 KLCAMVADNP SYNTKTQIIQ DFLRKGSAGD GFHGDVYLTV KLLLPGVIKT VYNLNDKQIV 250 260 270 280 290 300 KLFSRIFNCN PDDMARDLEQ GDVSETIRVF FEQSKSFPPA AKSLLTIQEV DEFLLRLSKL 310 320 330 340 350 360 TKEDEQQQAL QDIASRCTAN DLKCIIRLIK HDLKMNSGAK HVLDALDPNA YEAFKASRNL 370 380 390 400 410 420 QDVVERVLHN AQEVEKEPGQ RRALSVQASL MTPVQPMLAE ACKSVEYAMK KCPNGMFSEI 430 440 450 460 470 480 KYDGERVQVH KNGDHFSYFS RSLKPVLPHK VAHFKDYIPQ AFPGGHSMIL DSEVLLIDNK 490 500 510 520 530 540 TGKPLPFGTL GVHKKAAFQD ANVCLFVFDC IYFNDVSLMD RPLCERRKFL HDNMVEIPNR 550 560 570 580 590 600 IMFSEMKRVT KALDLADMIT RVIQEGLEGL VLKDVKGTYE PGKRHWLKVK KDYLNEGAMA 610 620 630 640 650 660 DTADLVVLGA FYGQGSKGGM MSIFLMGCYD PGSQKWCTVT KCAGGHDDAT LARLQNELDM 670 680 690 700 710 720 VKISKDPSKI PSWLKVNKIY YPDFIVPDPK KAAVWEITGA EFSKSEAHTA DGISIRFPRC 730 740 750 760 770 780 TRIRDDKDWK SATNLPQLKE LYQLSKEKAD FTVVAGDEGS STTGGSSEEN KGPSGSAVSR 790 800 810 820 830 840 KAPSKPSAST KKAEGKLSNS NSKDGNMQTA KPSAMKVGEK LATKSSPVKV GEKRKAADET 850 860 LCQTKRRPAS EQRGRTVPAG RR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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 Y.-F., Robins P., Carter K., Caldecott K., Pappin D.J.C., Yu G.-L., Wang R.-P., Shell B.K., Nash R.A., Schar P., Barnes D.E., Haseltine W.A., Lindahl T. Mol. Cell. Biol. 15:3206-3216(1995) [PubMed: 7760816] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA). Tissue: Prostate.
[2]	"Mammalian DNA ligase III: molecular cloning, chromosomal localization, and expression in spermatocytes undergoing meiotic recombination." Chen J., Tomkinson A.E., Ramos W., Mackey Z.B., Danehower S., Walter C.A., Schultz R.A., Besterman J.M., Husain I. Mol. Cell. Biol. 15:5412-5422(1995) [PubMed: 7565692] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA). Tissue: Testis.
[3]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Rieder M.J., Braun A.C., Montoya M.A., Chung M.-W., Nguyen C.P., Nguyen D.A., Livingston R.J., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A. Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-780.
[4]	"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-123, MASS SPECTROMETRY. Tissue: Epithelium.
[5]	"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-123, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"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-123, MASS SPECTROMETRY.
[7]	"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-140 AND SER-155, MASS SPECTROMETRY.
[8]	"Expression, purification, and biophysical characterization of the BRCT domain of human DNA ligase IIIalpha." Thornton K.H., Krishnan V.V., West M.G., Popham J., Ramirez M., Thelen M.P., Cosman M. Protein Expr. Purif. 21:401-411(2001) [PubMed: 11281714] [Abstract] Cited for: STRUCTURE BY NMR OF 837-922.
[9]	"Solution structure and DNA binding of the zinc-finger domain from DNA ligase IIIalpha." Kulczyk A.W., Yang J.C., Neuhaus D. J. Mol. Biol. 341:723-738(2004) [PubMed: 15288782] [Abstract] Cited for: STRUCTURE BY NMR OF 1-117.
[10]	"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: VARIANT [LARGE SCALE ANALYSIS] ASN-630.
+	Additional computationally mapped references.

Web resources

Wikipedia

DNA ligase entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

X84740 mRNA. Translation: CAA59230.1.
U40671 mRNA. Translation: AAA85022.1.
AF491645 Genomic DNA. Translation: AAL91592.1.

PIR

I37292.

RefSeq

NP_002302.2.
NP_039269.2.

UniGene

Hs.100299

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IMO	NMR	-	A	837-922	[»]
1IN1	NMR	-	A	837-922	[»]
1UW0	NMR	-	A	1-117	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P49916.

PTM databases

PhosphoSite

P49916.

Polymorphism databases

NIEHS-SNPs

Search...

Genome annotation databases

Ensembl

ENSG00000005156. Homo sapiens. [Contig view]

GeneID

3980.

KEGG

hsa:3980.

Organism-specific databases

H-InvDB

HIX0027160.

HGNC

HGNC:6600. LIG3.

HPA

HPA006723.

MIM

600940. gene.

PharmGKB

PA30374.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P49916.

Enzyme and pathway databases

Reactome

REACT_216. DNA Repair.

Gene expression databases

ArrayExpress

P49916.

CleanEx

HS_LIG3.

GermOnline

ENSG00000005156. Homo sapiens.

Family and domain databases

InterPro

IPR001357. BRCT.
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.
IPR001510. Znf_PARP.
[Graphical view]

Gene3D

G3DSA:2.40.50.140. OB_NA_bd_sub. 1 hit.
G3DSA:3.30.1740.10. Znf_PARP. 1 hit.

Pfam

PF04679. DNA_ligase_A_C. 1 hit.
PF01068. DNA_ligase_A_M. 1 hit.
PF04675. DNA_ligase_A_N. 1 hit.
PF00645. zf-PARP. 1 hit.
[Graphical view]

ProDom

PD004675. Znf_PolyADPpol. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00292. BRCT. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00574. dnl1. 1 hit.

PROSITE

PS50172. BRCT. 1 hit.
PS00697. DNA_LIGASE_A1. 1 hit.
PS00333. DNA_LIGASE_A2. 1 hit.
PS50160. DNA_LIGASE_A3. 1 hit.
PS00347. PARP_ZN_FINGER_1. 1 hit.
PS50064. PARP_ZN_FINGER_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00290. Bleomycin.

NextBio

15598.

SOURCE

Search...

Entry information

Entry name

DNLI3_HUMAN

Accession

Primary (citable) accession number: P49916
Secondary accession number(s): Q16714

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 25, 2008
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)