Q9UQ84 (EXO1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Exonuclease 1
Short name=hExo1
EC=3.1.-.-

Alternative name(s):
Exonuclease I
Short name=hExoI

Gene names

Name:	EXO1
Synonyms:	EXOI, HEX1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	846 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Essential for male and female meiosis. Ref.3 Ref.4 Ref.9 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22
Cofactor	Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding By similarity.
Subunit structure	Interacts with the MLH1-PMS2 heterodimer via MLH1. Interacts with MSH3. Interacts with the MSH2-MSH6 heterodimer via MSH2, and this interaction may increase the processivity of the 5'->3' exonuclease activity. Interacts with PCNA, and this interaction may both stimulate the cryptic 3'->5' exonuclease activity and suppress the 5'->3' exonuclease activity. Interacts with WRN, and this interaction stimulates both the 5'->3' exonuclease activity and cleavage of 5'-overhanging flap structures. Interacts with RECQL/RECQ1, and this interaction stimulates cleavage of 5'-overhanging flap structures. Ref.1 Ref.10 Ref.11 Ref.12 Ref.13 Ref.17 Ref.19 Ref.20 Ref.22
Subcellular location	Nucleus. Note: Colocalizes with PCNA to discrete nuclear foci in S-phase. Ref.12 Ref.20 Ref.23
Tissue specificity	Highly expressed in bone marrow, testis and thymus. Expressed at lower levels in colon, lymph nodes, ovary, placenta, prostate, small intestine, spleen and stomach. Ref.1 Ref.2 Ref.3 Ref.10
Developmental stage	Highly expressed in fetal liver and at lower levels in fetal brain, heart, kidney, spleen and thymus. Ref.10
Post-translational modification	Phosphorylated upon DNA damage and in response to agents stalling DNA replication, probably by ATM or ATR. Phosphorylation at Ser-454, Thr-621 and Ser-714 is induced upon DNA-damage caused by treatment with hydroxyurea (HU) but not upon IR treatment. The HU-induced EXO1 triple phosphorylation facilitates destabilisation/degradation of the protein. Ref.25
Polymorphism	Most naturally occurring variants in this protein are not associated with familial disposition to hereditary non-polyposis colorectal cancer (HNPCC). Furthermore, germline deletions involving this locus are not associated with clinically manifested colorectal tumors.
Sequence similarities	Belongs to the XPG/RAD2 endonuclease family. EXO1 subfamily.
Sequence caution	The sequence AAC33874.1 differs from that shown. Reason: Frameshift at position 793.

Ontologies

Keywords
Biological process	DNA damage DNA excision DNA repair Immunity Meiosis
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding Magnesium Metal-binding
Molecular function	Endonuclease Excision nuclease Exonuclease Hydrolase Nuclease
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA recombination Inferred from genetic interaction Ref.4. Source: UniProtKB humoral immune response mediated by circulating immunoglobulin Inferred from electronic annotation. Source: Compara isotype switching Inferred from electronic annotation. Source: Compara meiosis Inferred from electronic annotation. Source: UniProtKB-KW mismatch repair Inferred from direct assay Ref.18. Source: UniProtKB somatic hypermutation of immunoglobulin genes Inferred from electronic annotation. Source: Compara
Cellular_component	nucleus Inferred from direct assay Ref.12Ref.20. Source: UniProtKB
Molecular_function	DNA binding Inferred from direct assay Ref.15. Source: UniProtKB double-stranded DNA specific 5'-3' exodeoxyribonuclease activity Inferred from direct assay Ref.9Ref.15. Source: UniProtKB flap endonuclease activity Inferred from direct assay Ref.9Ref.15. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW ribonuclease H activity Traceable author statement Ref.4. Source: ProtInc single-stranded DNA specific 5'-3' exodeoxyribonuclease activity Inferred from direct assay Ref.9. Source: UniProtKB structure-specific DNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9UQ84-1)

Also known as: B;

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 2 (identifier: Q9UQ84-4)

Also known as: A;

The sequence of this isoform differs from the canonical sequence as follows:
     803-803: D → F
     804-846: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 846

846

Exonuclease 1

PRO_0000154039

Regions

Region

1 – 99

99

N-domain

Region

129 – 387

259

Interaction with MSH3

Region

138 – 229

92

I-domain

Region

388 – 490

103

Interaction with MLH1

Region

418 – 421

4

Nuclear localization signal

Region

600 – 846

247

Interaction with MSH2

Region

787 – 846

60

Interaction with MLH1

Sites

Metal binding

30

1

Magnesium 1 By similarity

Metal binding

78

1

Magnesium 1 By similarity

Metal binding

150

1

Magnesium 1 By similarity

Metal binding

152

1

Magnesium 1 By similarity

Metal binding

171

1

Magnesium 2 By similarity

Metal binding

173

1

Magnesium 2 By similarity

Metal binding

225

1

Magnesium 2 By similarity

Amino acid modifications

Modified residue

376

1

Phosphoserine Ref.25

Modified residue

422

1

Phosphoserine Ref.25 Ref.26

Modified residue

454

1

Phosphoserine Ref.25

Modified residue

482

1

N6-acetyllysine Ref.25

Modified residue

581

1

Phosphothreonine Ref.25

Modified residue

598

1

Phosphoserine Ref.25

Modified residue

621

1

Phosphothreonine Ref.25

Modified residue

623

1

Phosphoserine Ref.25

Modified residue

639

1

Phosphoserine Ref.25

Modified residue

660

1

Phosphoserine Ref.25

Modified residue

674

1

Phosphoserine Ref.25

Modified residue

714

1

Phosphoserine; by ATR Ref.25

Modified residue

746

1

Phosphoserine Ref.25

Natural variations

Alternative sequence

803

1

D → F in isoform 2.

VSP_017029

Alternative sequence

804 – 846

43

Missing in isoform 2.

VSP_017030

Natural variant

27

1

V → A. Ref.27

VAR_024966

Natural variant

76

1

V → I. Ref.5
Corresponds to variant rs4149864 [ dbSNP | Ensembl ].

VAR_024967

Natural variant

93

1

R → G. Ref.5
Corresponds to variant rs4149865 [ dbSNP | Ensembl ].

VAR_024968

Natural variant

109

1

E → K Abrogates exonuclease activity. Ref.13 Ref.27

VAR_024969

Natural variant

137

1

A → S. Ref.28

VAR_024970

Natural variant

279

1

N → S. Ref.5
Corresponds to variant rs4149909 [ dbSNP | Ensembl ].

VAR_024971

Natural variant

299

1

N → S. Ref.5
Corresponds to variant rs4149910 [ dbSNP | Ensembl ].

VAR_024972

Natural variant

354

1

H → R. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5
Corresponds to variant rs735943 [ dbSNP | Ensembl ].

VAR_024973

Natural variant

410

1

L → R Abrogates exonuclease activity. Ref.13 Ref.27 Ref.28

VAR_024974

Natural variant

428

1

D → N. Ref.5
Corresponds to variant rs4149962 [ dbSNP | Ensembl ].

VAR_024975

Natural variant

438

1

F → C. Ref.28

VAR_024976

Natural variant

439

1

T → M May be associated with an increased risk of colorectal cancer. Ref.5 Ref.29 Ref.30
Corresponds to variant rs4149963 [ dbSNP | Ensembl ].

VAR_024977

Natural variant

456

1

S → Y. Ref.5
Corresponds to variant rs4149964 [ dbSNP | Ensembl ].

VAR_024978

Natural variant

458

1

V → M. Ref.5
Corresponds to variant rs4149965 [ dbSNP | Ensembl ].

VAR_024979

Natural variant

460

1

V → L. Ref.5
Corresponds to variant rs4149966 [ dbSNP | Ensembl ].

VAR_024980

Natural variant

503

1

R → T. Ref.5
Corresponds to variant rs4149967 [ dbSNP | Ensembl ].

VAR_024981

Natural variant

589

1

E → K. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.8
Corresponds to variant rs1047840 [ dbSNP | Ensembl ].

VAR_024982

Natural variant

610

1

S → G. Ref.27 Ref.28
Corresponds to variant rs12122770 [ dbSNP | Ensembl ].

VAR_024983

Natural variant

634

1

R → Q. Ref.5
Corresponds to variant rs4149978 [ dbSNP | Ensembl ].

VAR_024984

Natural variant

640

1

P → A. Ref.27 Ref.28

VAR_024985

Natural variant

640

1

P → S Reduces interaction with MSH2; abrogates interaction with MSH2; when associated with L-770. Ref.13 Ref.27 Ref.28

VAR_024986

Natural variant

670

1

E → G. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8 Ref.29
Corresponds to variant rs1776148 [ dbSNP | Ensembl ].

VAR_024987

Natural variant

723

1

R → C. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8
Corresponds to variant rs1635498 [ dbSNP | Ensembl ].

VAR_024988

Natural variant

726

1

H → P. Ref.29

VAR_024989

Natural variant

757

1

P → L May be associated with a reduced risk of colorectal cancer. Ref.1 Ref.5 Ref.29 Ref.30
Corresponds to variant rs9350 [ dbSNP | Ensembl ].

VAR_024990

Natural variant

759

1

G → E Reduces interaction with MSH2; abrogates interaction with MSH2; when associated with L-770. Ref.5 Ref.13 Ref.27 Ref.28
Corresponds to variant rs4150001 [ dbSNP | Ensembl ].

VAR_024991

Natural variant

770

1

P → L Reduces interaction with MSH2; abrogates interaction with MSH2; when associated with S-640 or E-759. Ref.13 Ref.27

VAR_024992

Natural variant

827

1

A → V. Ref.28

VAR_024993

Experimental info

Mutagenesis

78

1

D → A: Abrogates double-stranded DNA exonuclease activity and endonuclease activity against 5'-overhanging flap structures. Also reduces DNA-binding to 5'-overhanging flap structures. Ref.15

Mutagenesis

173

1

D → A: Abrogates double-stranded DNA exonuclease activity and endonuclease activity against 5'-overhanging flap structures. No effect on DNA-binding to 5'-overhanging flap structures. Ref.15 Ref.19

Mutagenesis

225

1

D → A: Abrogates double-stranded DNA exonuclease activity and endonuclease activity against 5'-overhanging flap structures. Also enhances DNA-binding to 5'-overhanging flap structures. Ref.15

Mutagenesis

418

1

K → A or T: Complete loss of nuclear localization. Ref.23

Mutagenesis

419

1

R → A: Complete loss of nuclear localization. Ref.23

Mutagenesis

454

1

S → A: No rescue of HU-induced degradation. No rescue of HU-induced degradation; when associated with A-714. Loss of HU-sensitivity and resistance to HU-induced degradation; when associated with A-621 and A-714. Ref.25

Mutagenesis

621

1

T → A: No rescue of HU-induced degradation. No rescue of HU-induced degradation; when associated with A-714. Loss of HU-sensitivity and resistance to HU-induced degradation; when associated with A-454 and A-714. Ref.25

Mutagenesis

714

1

S → A: No rescue of HU-induced degradation and loss of HU-induced increase of phosphorylation. No rescue of HU-induced degradation; when associated with A-621. No rescue of HU-induced degradation; when associated with A-454. Loss of HU-sensitivity and resistance to HU-induced degradation; when associated with A-454 and A-621. Ref.25

Secondary structure

1

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846

Helix Strand Turn

Details...

Helix

6 – 9

4

Turn

10 – 12

3

Beta strand

13 – 18

6

Helix

19 – 22

4

Beta strand

25 – 30

6

Helix

32 – 41

10

Helix

43 – 47

5

Helix

54 – 68

15

Beta strand

72 – 77

6

Turn

83 – 85

3

Helix

86 – 106

21

Turn

107 – 109

3

Helix

113 – 119

7

Helix

120 – 122

3

Helix

127 – 139

13

Beta strand

143 – 146

4

Helix

151 – 160

10

Beta strand

165 – 168

4

Helix

172 – 177

6

Beta strand

180 – 185

6

Beta strand

190 – 196

7

Helix

197 – 200

4

Turn

204 – 208

5

Helix

212 – 222

11

Beta strand

225 – 227

3

Helix

235 – 244

10

Helix

250 – 254

5

Helix

257 – 261

5

Helix

269 – 284

16

Beta strand

286 – 289

4

Turn

290 – 293

4

Beta strand

294 – 299

6

Helix

307 – 309

3

Helix

311 – 313

3

Helix

319 – 326

8

Turn

332 – 334

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (B) [UniParc]. Last modified January 24, 2006. Version 2. Checksum: 850BC21CA9790D08	FASTA	846	94,103
	10 20 30 40 50 60 MGIQGLLQFI KEASEPIHVR KYKGQVVAVD TYCWLHKGAI ACAEKLAKGE PTDRYVGFCM 70 80 90 100 110 120 KFVNMLLSHG IKPILVFDGC TLPSKKEVER SRRERRQANL LKGKQLLREG KVSEARECFT 130 140 150 160 170 180 RSINITHAMA HKVIKAARSQ GVDCLVAPYE ADAQLAYLNK AGIVQAIITE DSDLLAFGCK 190 200 210 220 230 240 KVILKMDQFG NGLEIDQARL GMCRQLGDVF TEEKFRYMCI LSGCDYLSSL RGIGLAKACK 250 260 270 280 290 300 VLRLANNPDI VKVIKKIGHY LKMNITVPED YINGFIRANN TFLYQLVFDP IKRKLIPLNA 310 320 330 340 350 360 YEDDVDPETL SYAGQYVDDS IALQIALGNK DINTFEQIDD YNPDTAMPAH SRSHSWDDKT 370 380 390 400 410 420 CQKSANVSSI WHRNYSPRPE SGTVSDAPQL KENPSTVGVE RVISTKGLNL PRKSSIVKRP 430 440 450 460 470 480 RSAELSEDDL LSQYSLSFTK KTKKNSSEGN KSLSFSEVFV PDLVNGPTNK KSVSTPPRTR 490 500 510 520 530 540 NKFATFLQRK NEESGAVVVP GTRSRFFCSS DSTDCVSNKV SIQPLDETAV TDKENNLHES 550 560 570 580 590 600 EYGDQEGKRL VDTDVARNSS DDIPNNHIPG DHIPDKATVF TDEESYSFES SKFTRTISPP 610 620 630 640 650 660 TLGTLRSCFS WSGGLGDFSR TPSPSPSTAL QQFRRKSDSP TSLPENNMSD VSQLKSEESS 670 680 690 700 710 720 DDESHPLREE ACSSQSQESG EFSLQSSNAS KLSQCSSKDS DSEESDCNIK LLDSQSDQTS 730 740 750 760 770 780 KLRLSHFSKK DTPLRNKVPG LYKSSSADSL STTKIKPLGP ARASGLSKKP ASIQKRKHHN 790 800 810 820 830 840 AENKPGLQIK LNELWKNFGF KKDSEKLPPC KKPLSPVRDN IQLTPEAEED IFNKPECGRV QRAIFQ
	Isoform 2 (A) [UniParc]. Checksum: 1EDC61DB5D70A0B6	FASTA	803	89,231
	10 20 30 40 50 60 MGIQGLLQFI KEASEPIHVR KYKGQVVAVD TYCWLHKGAI ACAEKLAKGE PTDRYVGFCM 70 80 90 100 110 120 KFVNMLLSHG IKPILVFDGC TLPSKKEVER SRRERRQANL LKGKQLLREG KVSEARECFT 130 140 150 160 170 180 RSINITHAMA HKVIKAARSQ GVDCLVAPYE ADAQLAYLNK AGIVQAIITE DSDLLAFGCK 190 200 210 220 230 240 KVILKMDQFG NGLEIDQARL GMCRQLGDVF TEEKFRYMCI LSGCDYLSSL RGIGLAKACK 250 260 270 280 290 300 VLRLANNPDI VKVIKKIGHY LKMNITVPED YINGFIRANN TFLYQLVFDP IKRKLIPLNA 310 320 330 340 350 360 YEDDVDPETL SYAGQYVDDS IALQIALGNK DINTFEQIDD YNPDTAMPAH SRSHSWDDKT 370 380 390 400 410 420 CQKSANVSSI WHRNYSPRPE SGTVSDAPQL KENPSTVGVE RVISTKGLNL PRKSSIVKRP 430 440 450 460 470 480 RSAELSEDDL LSQYSLSFTK KTKKNSSEGN KSLSFSEVFV PDLVNGPTNK KSVSTPPRTR 490 500 510 520 530 540 NKFATFLQRK NEESGAVVVP GTRSRFFCSS DSTDCVSNKV SIQPLDETAV TDKENNLHES 550 560 570 580 590 600 EYGDQEGKRL VDTDVARNSS DDIPNNHIPG DHIPDKATVF TDEESYSFES SKFTRTISPP 610 620 630 640 650 660 TLGTLRSCFS WSGGLGDFSR TPSPSPSTAL QQFRRKSDSP TSLPENNMSD VSQLKSEESS 670 680 690 700 710 720 DDESHPLREE ACSSQSQESG EFSLQSSNAS KLSQCSSKDS DSEESDCNIK LLDSQSDQTS 730 740 750 760 770 780 KLRLSHFSKK DTPLRNKVPG LYKSSSADSL STTKIKPLGP ARASGLSKKP ASIQKRKHHN 790 800 AENKPGLQIK LNELWKNFGF KKF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human exonuclease I interacts with the mismatch repair protein hMSH2." Schmutte C., Marinescu R.C., Sadoff M.M., Guerrette S., Overhauser J., Fishel R. Cancer Res. 58:4537-4542(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH MSH2, TISSUE SPECIFICITY, VARIANTS ARG-354; LYS-589; GLY-670; CYS-723 AND LEU-757.
[2]	"Identification of a human gene encoding a homologue of Saccharomyces cerevisiae EXO1, an exonuclease implicated in mismatch repair and recombination." Tishkoff D.X., Amin N.S., Viars C.S., Arden K.C., Kolodner R.D. Cancer Res. 58:5027-5031(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING, TISSUE SPECIFICITY, VARIANTS ARG-354; LYS-589; GLY-670 AND CYS-723.
[3]	"Hex1: a new human Rad2 nuclease family member with homology to yeast exonuclease 1." Wilson D.M. III, Carney J.P., Coleman M.A., Adamson A.W., Christensen M., Lamerdin J.E. Nucleic Acids Res. 26:3762-3768(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING, FUNCTION, TISSUE SPECIFICITY, VARIANTS ARG-354; LYS-589; GLY-670 AND CYS-723. Tissue: Sperm.
[4]	"Human exonuclease 1 functionally complements its yeast homologues in DNA recombination, RNA primer removal, and mutation avoidance." Qiu J., Qian Y., Chen V., Guan M.-X., Shen B. J. Biol. Chem. 274:17893-17900(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 1-7 (ISOFORMS 1/2), FUNCTION, VARIANTS ARG-354; LYS-589; GLY-670 AND CYS-723.
[5]	NIEHS SNPs program Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-76; GLY-93; SER-279; SER-299; ARG-354; ASN-428; MET-439; TYR-456; MET-458; LEU-460; THR-503; LYS-589; GLN-634; GLY-670; CYS-723; LEU-757 AND GLU-759.
[6]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS GLY-670 AND CYS-723. Tissue: Skin.
[8]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 175-846 (ISOFORM 1), VARIANTS LYS-589; GLY-670 AND CYS-723. Tissue: Testis.
[9]	"The RAD2 domain of human exonuclease 1 exhibits 5' to 3' exonuclease and flap structure-specific endonuclease activities." Lee B.-I., Wilson D.M. III J. Biol. Chem. 274:37763-37769(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Identification of factors interacting with hMSH2 in the fetal liver utilizing the yeast two-hybrid system. In vivo interaction through the C-terminal domains of hEXO1 and hMSH2 and comparative expression analysis." Rasmussen L.J., Rasmussen M., Lee B.-I., Rasmussen A.K., Wilson D.M. III, Nielsen F.C., Bisgaard H.C. Mutat. Res. 460:41-52(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MSH2, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[11]	"The interaction of DNA mismatch repair proteins with human exonuclease I." Schmutte C., Sadoff M.M., Shim K.-S., Acharya S., Fishel R. J. Biol. Chem. 276:33011-33018(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MLH1; MSH2 AND MSH3.
[12]	"HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence assembly of hMutLalpha and hMLH1-hEXO1 complexes." Jaeger A.C., Rasmussen M., Bisgaard H.C., Singh K.K., Nielsen F.C., Rasmussen L.J. Oncogene 20:3590-3595(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MLH1 AND MSH2, SUBCELLULAR LOCATION.
[13]	"Functional alterations of human exonuclease 1 mutants identified in atypical hereditary nonpolyposis colorectal cancer syndrome." Sun X., Zheng L., Shen B. Cancer Res. 62:6026-6030(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MLH1 AND MSH2, CHARACTERIZATION OF VARIANTS LYS-109; ARG-410; SER-640; GLU-759 AND LEU-770.
[14]	"Human exonuclease I is required for 5' and 3' mismatch repair." Genschel J., Bazemore L.R., Modrich P. J. Biol. Chem. 277:13302-13311(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"Molecular interactions of human Exo1 with DNA." Lee B.-I., Nguyen L.H., Barsky D., Fernandes M., Wilson D.M. III Nucleic Acids Res. 30:942-949(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DNA-BINDING, MUTAGENESIS OF ASP-78; ASP-173 AND ASP-225.
[16]	"Germline deletions of EXO1 do not cause colorectal tumors and lesions which are null for EXO1 do not have microsatellite instability." Alam N.A., Gorman P., Jaeger E.E.M., Kelsell D., Leigh I.M., Ratnavel R., Murdoch M.E., Houlston R.S., Aaltonen L.A., Roylance R.R., Tomlinson I.P.M. Cancer Genet. Cytogenet. 147:121-127(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN COLORECTAL CANCER.
[17]	"The exonucleolytic and endonucleolytic cleavage activities of human exonuclease 1 are stimulated by an interaction with the carboxyl-terminal region of the Werner syndrome protein." Sharma S., Sommers J.A., Driscoll H.C., Uzdilla L.A., Wilson T.M., Brosh R.M. Jr. J. Biol. Chem. 278:23487-23496(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH WRN.
[18]	"Mechanism of 5'-directed excision in human mismatch repair." Genschel J., Modrich P. Mol. Cell 12:1077-1086(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[19]	"A defined human system that supports bidirectional mismatch-provoked excision." Dzantiev L., Constantin N., Genschel J., Iyer R.R., Burgers P.M., Modrich P. Mol. Cell 15:31-41(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PCNA, MUTAGENESIS OF ASP-173.
[20]	"Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNA." Nielsen F.C., Jaeger A.C., Luetzen A., Bundgaard J.R., Rasmussen L.J. Oncogene 23:1457-1468(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MLH1 AND MSH2, SUBCELLULAR LOCATION.
[21]	"Reconstitution of 5'-directed human mismatch repair in a purified system." Zhang Y., Yuan F., Presnell S.R., Tian K., Gao Y., Tomkinson A.E., Gu L., Li G.-M. Cell 122:693-705(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[22]	"RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination." Doherty K.M., Sharma S., Uzdilla L.A., Wilson T.M., Cui S., Vindigni A., Brosh R.M. Jr. J. Biol. Chem. 280:28085-28094(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RECQL.
[23]	"Nuclear localization of human DNA mismatch repair protein exonuclease 1 (hEXO1)." Knudsen N.O., Nielsen F.C., Vinther L., Bertelsen R., Holten-Andersen S., Liberti S.E., Hofstra R., Kooi K., Rasmussen L.J. Nucleic Acids Res. 35:2609-2619(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-418 AND ARG-419.
[24]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[25]	"ATR-dependent pathways control hEXO1 stability in response to stalled forks." El-Shemerly M., Hess D., Pyakurel A.K., Moselhy S., Ferrari S. Nucleic Acids Res. 36:511-519(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-376; SER-422; SER-454; THR-581; SER-598; THR-621; SER-623; SER-639; SER-660; SER-674; SER-714 AND SER-746, ACETYLATION AT LYS-482, MASS SPECTROMETRY, MUTAGENESIS OF SER-454; THR-621 AND SER-714.
[26]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-422, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[27]	"Germline mutations of EXO1 gene in patients with hereditary nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms." Wu Y., Berends M.J.W., Post J.G., Mensink R.G.J., Verlind E., van der Sluis T., Kempinga C., Sijmons R.H., van der Zee A.G.J., Hollema H., Kleibeuker J.H., Buys C.H.C.M., Hofstra R.M.W. Gastroenterology 120:1580-1587(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ALA-27; LYS-109; ARG-410; GLY-610; ALA-640; SER-640; GLU-759 AND LEU-770.
[28]	"EXO1 variants occur commonly in normal population: evidence against a role in hereditary nonpolyposis colorectal cancer." Jagmohan-Changur S., Poikonen T., Vilkki S., Launonen V., Wikman F., Orntoft T.F., Moeller P., Vasen H., Tops C., Kolodner R.D., Mecklin J.-P., Jaervinen H., Bevan S., Houlston R.S., Aaltonen L.A., Fodde R., Wijnen J., Karhu A. Cancer Res. 63:154-158(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS SER-137; ARG-410; CYS-438; GLY-610; ALA-640; SER-640; GLU-759 AND VAL-827.
[29]	"Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations." Thompson E., Meldrum C.J., Crooks R., McPhillips M., Thomas L., Spigelman A.D., Scott R.J. Clin. Genet. 65:215-225(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MET-439; GLY-670; PRO-726 AND LEU-757.
[30]	"Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal cancer in a Japanese population." Yamamoto H., Hanafusa H., Ouchida M., Yano M., Suzuki H., Murakami M., Aoe M., Shimizu N., Nakachi K., Shimizu K. Carcinogenesis 26:411-416(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MET-439 AND LEU-757.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF084974 mRNA. Translation: AAD13754.1.
AF091740 mRNA. Translation: AAC63043.1.
AF091754 , AF091742, AF091743, AF091744, AF091745, AF091746, AF091747, AF091748, AF091749, AF091750, AF091751, AF091752, AF091753 Genomic DNA. Translation: AAC69879.1.
AF091754 , AF091742, AF091743, AF091744, AF091745, AF091746, AF091747, AF091748, AF091749, AF091750, AF091751, AF091752, AF091753 Genomic DNA. Translation: AAC69880.1.
AF042282 mRNA. Translation: AAC32259.1.
AC004783 Genomic DNA. Translation: AAC32424.1.
AF060479 mRNA. Translation: AAC33874.1. Frameshift.
AF549168 Genomic DNA. Translation: AAN39382.1.
AL365366 Genomic DNA. Translation: CAI15658.1.
BC007491 mRNA. Translation: AAH07491.1.
AL080139 mRNA. Translation: CAB45733.1.

IPI

IPI00219173.
IPI00556476.

PIR

T12524.

RefSeq

NP_003677.4. NM_003686.4.
NP_006018.4. NM_006027.4.
NP_569082.2. NM_130398.3.

UniGene

Hs.498248.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3QE9	X-ray	2.51	Y/Z	1-352	[»]
3QEA	X-ray	3.10	Z	1-352	[»]
3QEB	X-ray	3.00	Z	1-352	[»]

ProteinModelPortal

Q9UQ84.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UQ84. 2 interactions.

STRING

9606.ENSP00000311873.

PTM databases

PhosphoSite

Q9UQ84.

Polymorphism databases

DMDM

85700954.

Proteomic databases

PaxDb

Q9UQ84.

PRIDE

Q9UQ84.

Protocols and materials databases

DNASU

9156.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000348581; ENSP00000311873; ENSG00000174371.
ENST00000366548; ENSP00000355506; ENSG00000174371.
ENST00000518483; ENSP00000430251; ENSG00000174371.

GeneID

9156.

KEGG

hsa:9156.

UCSC

uc001hzh.3. human.
uc021plk.1. human.

Organism-specific databases

CTD

9156.

GeneCards

GC01P242011.

H-InvDB

HIX0022634.

HGNC

HGNC:3511. EXO1.

MIM

606063. gene.

neXtProt

NX_Q9UQ84.

PharmGKB

PA27923.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0258.

HOVERGEN

HBG081488.

InParanoid

Q9UQ84.

KO

K10746.

OMA

EPIHVRK.

OrthoDB

EOG4M91QT.

PhylomeDB

Q9UQ84.

Enzyme and pathway databases

BRENDA

3.1.11.1. 2681.

Gene expression databases

ArrayExpress

Q9UQ84.

Bgee

Q9UQ84.

CleanEx

HS_EXO1.

Genevestigator

Q9UQ84.

GermOnline

ENSG00000174371. Homo sapiens.

Family and domain databases

InterPro

IPR020045. 5-3_exonuclease_C.
IPR008918. HhH2.
IPR006086. XPG-I_dom.
IPR006084. XPG/Rad2.
IPR019974. XPG_CS.
IPR006085. XPG_DNA_repair_N.
[Graphical view]

PANTHER

PTHR11081. PTHR11081. 1 hit.

Pfam

PF00867. XPG_I. 1 hit.
PF00752. XPG_N. 1 hit.
[Graphical view]

PRINTS

PR00853. XPGRADSUPER.

SMART

SM00279. HhH2. 1 hit.
SM00484. XPGI. 1 hit.
SM00485. XPGN. 1 hit.
[Graphical view]

SUPFAM

SSF47807. 5_3_exo_C. 1 hit.

PROSITE

PS00841. XPG_1. 1 hit.
PS00842. XPG_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UQ84.

GenomeRNAi

9156.

NextBio

34349.

SOURCE

Search...

Entry information

Entry name

EXO1_HUMAN

Accession

Primary (citable) accession number: Q9UQ84
Secondary accession number(s): O60545 , O75214, O75466, Q5T396, Q96IJ1, Q9UG38, Q9UNW0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2006
Last sequence update:	January 24, 2006
Last modified:	May 1, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.