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Protein

Exonuclease 1

Gene

EXO1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.12 Publications

Cofactori

Mg2+By similarityNote: 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi30 – 301Magnesium 1By similarity
Metal bindingi78 – 781Magnesium 1By similarity
Metal bindingi150 – 1501Magnesium 1By similarity
Metal bindingi152 – 1521Magnesium 1By similarity
Metal bindingi171 – 1711Magnesium 2By similarity
Metal bindingi173 – 1731Magnesium 2By similarity
Metal bindingi225 – 2251Magnesium 2By similarity

GO - Molecular functioni

  • 5'-3' exodeoxyribonuclease activity Source: UniProtKB
  • 5'-3' exonuclease activity Source: UniProtKB
  • chromatin binding Source: Ensembl
  • DNA binding Source: UniProtKB
  • double-stranded DNA 5'-3' exodeoxyribonuclease activity Source: UniProtKB
  • exonuclease activity Source: ProtInc
  • flap endonuclease activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • RNA-DNA hybrid ribonuclease activity Source: ProtInc
  • single-stranded DNA 5'-3' exodeoxyribonuclease activity Source: UniProtKB

GO - Biological processi

  • DNA recombination Source: UniProtKB
  • DNA repair Source: ProtInc
  • DNA replication Source: Reactome
  • DNA synthesis involved in DNA repair Source: Reactome
  • humoral immune response mediated by circulating immunoglobulin Source: Ensembl
  • isotype switching Source: Ensembl
  • meiotic cell cycle Source: UniProtKB-KW
  • mismatch repair Source: UniProtKB
  • nucleic acid phosphodiester bond hydrolysis Source: GOC
  • regulation of signal transduction by p53 class mediator Source: Reactome
  • RNA phosphodiester bond hydrolysis, endonucleolytic Source: GOC
  • somatic hypermutation of immunoglobulin genes Source: Ensembl
  • strand displacement Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Excision nuclease, Exonuclease, Hydrolase, Nuclease

Keywords - Biological processi

DNA damage, DNA excision, DNA repair, Immunity, Meiosis

Keywords - Ligandi

DNA-binding, Magnesium, Metal-binding

Enzyme and pathway databases

BRENDAi3.1.11.1. 2681.
ReactomeiR-HSA-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-HSA-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
R-HSA-5685938. HDR through Single Strand Annealing (SSA).
R-HSA-5685942. HDR through Homologous Recombination (HRR).
R-HSA-5693554. Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
R-HSA-5693568. Resolution of D-loop Structures through Holliday Junction Intermediates.
R-HSA-5693579. Homologous DNA Pairing and Strand Exchange.
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-HSA-69473. G2/M DNA damage checkpoint.
SIGNORiQ9UQ84.

Names & Taxonomyi

Protein namesi
Recommended name:
Exonuclease 1 (EC:3.1.-.-)
Short name:
hExo1
Alternative name(s):
Exonuclease I
Short name:
hExoI
Gene namesi
Name:EXO1
Synonyms:EXOI, HEX1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:3511. EXO1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi78 – 781D → A: Abrogates double-stranded DNA exonuclease activity and endonuclease activity against 5'-overhanging flap structures. Also reduces DNA-binding to 5'-overhanging flap structures. 1 Publication
Mutagenesisi173 – 1731D → 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. 2 Publications
Mutagenesisi225 – 2251D → A: Abrogates double-stranded DNA exonuclease activity and endonuclease activity against 5'-overhanging flap structures. Also enhances DNA-binding to 5'-overhanging flap structures. 1 Publication
Mutagenesisi418 – 4181K → A or T: Complete loss of nuclear localization. 1 Publication
Mutagenesisi419 – 4191R → A: Complete loss of nuclear localization. 1 Publication
Mutagenesisi454 – 4541S → 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. 1 Publication
Mutagenesisi621 – 6211T → 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. 1 Publication
Mutagenesisi714 – 7141S → 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. 1 Publication

Organism-specific databases

PharmGKBiPA27923.

Polymorphism and mutation databases

BioMutaiEXO1.
DMDMi85700954.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 846846Exonuclease 1PRO_0000154039Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei376 – 3761Phosphoserine1 Publication
Modified residuei422 – 4221PhosphoserineCombined sources1 Publication
Modified residuei454 – 4541Phosphoserine1 Publication
Modified residuei482 – 4821N6-acetyllysine1 Publication
Modified residuei581 – 5811Phosphothreonine1 Publication
Modified residuei598 – 5981Phosphoserine1 Publication
Modified residuei621 – 6211Phosphothreonine1 Publication
Modified residuei623 – 6231Phosphoserine1 Publication
Modified residuei639 – 6391Phosphoserine1 Publication
Modified residuei660 – 6601Phosphoserine1 Publication
Modified residuei674 – 6741Phosphoserine1 Publication
Modified residuei714 – 7141Phosphoserine; by ATR1 Publication
Modified residuei746 – 7461Phosphoserine1 Publication

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9UQ84.
MaxQBiQ9UQ84.
PaxDbiQ9UQ84.
PRIDEiQ9UQ84.

PTM databases

iPTMnetiQ9UQ84.
PhosphoSiteiQ9UQ84.

Expressioni

Tissue specificityi

Highly expressed in bone marrow, testis and thymus. Expressed at lower levels in colon, lymph nodes, ovary, placenta, prostate, small intestine, spleen and stomach.4 Publications

Developmental stagei

Highly expressed in fetal liver and at lower levels in fetal brain, heart, kidney, spleen and thymus.1 Publication

Gene expression databases

BgeeiQ9UQ84.
CleanExiHS_EXO1.
ExpressionAtlasiQ9UQ84. baseline and differential.
GenevisibleiQ9UQ84. HS.

Interactioni

Subunit structurei

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.9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MSH2P432463EBI-944694,EBI-355888
RBBP8Q997083EBI-944667,EBI-745715

Protein-protein interaction databases

BioGridi114602. 25 interactions.
DIPiDIP-36701N.
IntActiQ9UQ84. 14 interactions.
MINTiMINT-84735.
STRINGi9606.ENSP00000311873.

Structurei

Secondary structure

1
846
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi6 – 94Combined sources
Turni10 – 123Combined sources
Beta strandi13 – 186Combined sources
Helixi19 – 224Combined sources
Beta strandi25 – 306Combined sources
Helixi32 – 4110Combined sources
Helixi43 – 475Combined sources
Helixi54 – 6815Combined sources
Beta strandi72 – 776Combined sources
Turni83 – 853Combined sources
Helixi86 – 10621Combined sources
Turni107 – 1093Combined sources
Helixi113 – 1197Combined sources
Helixi120 – 1223Combined sources
Helixi127 – 13913Combined sources
Beta strandi143 – 1464Combined sources
Helixi151 – 16010Combined sources
Beta strandi165 – 1684Combined sources
Helixi172 – 1776Combined sources
Beta strandi180 – 1856Combined sources
Beta strandi190 – 1967Combined sources
Helixi197 – 2004Combined sources
Turni204 – 2085Combined sources
Helixi212 – 22211Combined sources
Beta strandi225 – 2273Combined sources
Helixi235 – 24410Combined sources
Helixi250 – 2545Combined sources
Helixi257 – 2615Combined sources
Helixi269 – 28416Combined sources
Beta strandi286 – 2894Combined sources
Turni290 – 2934Combined sources
Beta strandi294 – 2996Combined sources
Helixi307 – 3093Combined sources
Helixi311 – 3133Combined sources
Helixi319 – 3268Combined sources
Turni332 – 3343Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QE9X-ray2.51Y/Z1-352[»]
3QEAX-ray3.10Z1-352[»]
3QEBX-ray3.00Z1-352[»]
ProteinModelPortaliQ9UQ84.
SMRiQ9UQ84. Positions 2-346.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UQ84.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 9999N-domainAdd
BLAST
Regioni129 – 387259Interaction with MSH3Add
BLAST
Regioni138 – 22992I-domainAdd
BLAST
Regioni388 – 490103Interaction with MLH1Add
BLAST
Regioni600 – 846247Interaction with MSH2Add
BLAST
Regioni787 – 84660Interaction with MLH1Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi418 – 4214Nuclear localization signal

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2518. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00510000047676.
HOVERGENiHBG081488.
InParanoidiQ9UQ84.
KOiK10746.
OMAiEPIHVRK.
OrthoDBiEOG7RNJZZ.
PhylomeDBiQ9UQ84.
TreeFamiTF314997.

Family and domain databases

Gene3Di3.40.50.1010. 1 hit.
InterProiIPR020045. 5-3_exonuclease_C.
IPR032641. Exo1.
IPR008918. HhH2.
IPR029060. PIN_domain-like.
IPR006086. XPG-I_dom.
IPR006084. XPG/Rad2.
IPR019974. XPG_CS.
IPR006085. XPG_DNA_repair_N.
[Graphical view]
PANTHERiPTHR11081. PTHR11081. 1 hit.
PTHR11081:SF8. PTHR11081:SF8. 1 hit.
PfamiPF00867. XPG_I. 1 hit.
PF00752. XPG_N. 1 hit.
[Graphical view]
PRINTSiPR00853. XPGRADSUPER.
SMARTiSM00279. HhH2. 1 hit.
SM00484. XPGI. 1 hit.
SM00485. XPGN. 1 hit.
[Graphical view]
SUPFAMiSSF47807. SSF47807. 1 hit.
SSF88723. SSF88723. 1 hit.
PROSITEiPS00841. XPG_1. 1 hit.
PS00842. XPG_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UQ84-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGIQGLLQFI KEASEPIHVR KYKGQVVAVD TYCWLHKGAI ACAEKLAKGE
60 70 80 90 100
PTDRYVGFCM KFVNMLLSHG IKPILVFDGC TLPSKKEVER SRRERRQANL
110 120 130 140 150
LKGKQLLREG KVSEARECFT RSINITHAMA HKVIKAARSQ GVDCLVAPYE
160 170 180 190 200
ADAQLAYLNK AGIVQAIITE DSDLLAFGCK KVILKMDQFG NGLEIDQARL
210 220 230 240 250
GMCRQLGDVF TEEKFRYMCI LSGCDYLSSL RGIGLAKACK VLRLANNPDI
260 270 280 290 300
VKVIKKIGHY LKMNITVPED YINGFIRANN TFLYQLVFDP IKRKLIPLNA
310 320 330 340 350
YEDDVDPETL SYAGQYVDDS IALQIALGNK DINTFEQIDD YNPDTAMPAH
360 370 380 390 400
SRSHSWDDKT CQKSANVSSI WHRNYSPRPE SGTVSDAPQL KENPSTVGVE
410 420 430 440 450
RVISTKGLNL PRKSSIVKRP RSAELSEDDL LSQYSLSFTK KTKKNSSEGN
460 470 480 490 500
KSLSFSEVFV PDLVNGPTNK KSVSTPPRTR NKFATFLQRK NEESGAVVVP
510 520 530 540 550
GTRSRFFCSS DSTDCVSNKV SIQPLDETAV TDKENNLHES EYGDQEGKRL
560 570 580 590 600
VDTDVARNSS DDIPNNHIPG DHIPDKATVF TDEESYSFES SKFTRTISPP
610 620 630 640 650
TLGTLRSCFS WSGGLGDFSR TPSPSPSTAL QQFRRKSDSP TSLPENNMSD
660 670 680 690 700
VSQLKSEESS DDESHPLREE ACSSQSQESG EFSLQSSNAS KLSQCSSKDS
710 720 730 740 750
DSEESDCNIK LLDSQSDQTS KLRLSHFSKK DTPLRNKVPG LYKSSSADSL
760 770 780 790 800
STTKIKPLGP ARASGLSKKP ASIQKRKHHN AENKPGLQIK LNELWKNFGF
810 820 830 840
KKDSEKLPPC KKPLSPVRDN IQLTPEAEED IFNKPECGRV QRAIFQ
Length:846
Mass (Da):94,103
Last modified:January 24, 2006 - v2
Checksum:i850BC21CA9790D08
GO
Isoform 2 (identifier: Q9UQ84-4) [UniParc]FASTAAdd to basket

Also known as: A

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

Show »
Length:803
Mass (Da):89,231
Checksum:i1EDC61DB5D70A0B6
GO

Sequence cautioni

The sequence AAC33874.1 differs from that shown. Reason: Frameshift at position 793. Curated

Polymorphismi

Most naturally occurring variants in this protein are not associated with familial disposition to hereditary non-polyposis colorectal cancer (HNPCC) (PubMed:12517792). Furthermore, germline deletions involving this locus are not associated with clinically manifested colorectal tumors (PubMed:14623461).2 Publications

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti27 – 271V → A.1 Publication
VAR_024966
Natural varianti76 – 761V → I.1 Publication
Corresponds to variant rs4149864 [ dbSNP | Ensembl ].
VAR_024967
Natural varianti93 – 931R → G.1 Publication
Corresponds to variant rs4149865 [ dbSNP | Ensembl ].
VAR_024968
Natural varianti109 – 1091E → K Abrogates exonuclease activity. 2 Publications
VAR_024969
Natural varianti137 – 1371A → S.1 Publication
VAR_024970
Natural varianti279 – 2791N → S.1 Publication
Corresponds to variant rs4149909 [ dbSNP | Ensembl ].
VAR_024971
Natural varianti299 – 2991N → S.1 Publication
Corresponds to variant rs4149910 [ dbSNP | Ensembl ].
VAR_024972
Natural varianti354 – 3541H → R.5 Publications
Corresponds to variant rs735943 [ dbSNP | Ensembl ].
VAR_024973
Natural varianti410 – 4101L → R Abrogates exonuclease activity. 3 Publications
VAR_024974
Natural varianti428 – 4281D → N.1 Publication
Corresponds to variant rs4149962 [ dbSNP | Ensembl ].
VAR_024975
Natural varianti438 – 4381F → C.1 Publication
VAR_024976
Natural varianti439 – 4391T → M May be associated with an increased risk of colorectal cancer. 3 Publications
Corresponds to variant rs4149963 [ dbSNP | Ensembl ].
VAR_024977
Natural varianti456 – 4561S → Y.1 Publication
Corresponds to variant rs4149964 [ dbSNP | Ensembl ].
VAR_024978
Natural varianti458 – 4581V → M.1 Publication
Corresponds to variant rs4149965 [ dbSNP | Ensembl ].
VAR_024979
Natural varianti460 – 4601V → L.1 Publication
Corresponds to variant rs4149966 [ dbSNP | Ensembl ].
VAR_024980
Natural varianti503 – 5031R → T.1 Publication
Corresponds to variant rs4149967 [ dbSNP | Ensembl ].
VAR_024981
Natural varianti589 – 5891E → K.6 Publications
Corresponds to variant rs1047840 [ dbSNP | Ensembl ].
VAR_024982
Natural varianti610 – 6101S → G.2 Publications
Corresponds to variant rs12122770 [ dbSNP | Ensembl ].
VAR_024983
Natural varianti634 – 6341R → Q.1 Publication
Corresponds to variant rs4149978 [ dbSNP | Ensembl ].
VAR_024984
Natural varianti640 – 6401P → A.2 Publications
Corresponds to variant rs61736331 [ dbSNP | Ensembl ].
VAR_024985
Natural varianti640 – 6401P → S Reduces interaction with MSH2; abrogates interaction with MSH2; when associated with L-770. 3 Publications
Corresponds to variant rs61736331 [ dbSNP | Ensembl ].
VAR_024986
Natural varianti670 – 6701E → G.8 Publications
Corresponds to variant rs1776148 [ dbSNP | Ensembl ].
VAR_024987
Natural varianti723 – 7231R → C.7 Publications
Corresponds to variant rs1635498 [ dbSNP | Ensembl ].
VAR_024988
Natural varianti726 – 7261H → P.1 Publication
VAR_024989
Natural varianti757 – 7571P → L May be associated with a reduced risk of colorectal cancer. 4 Publications
Corresponds to variant rs9350 [ dbSNP | Ensembl ].
VAR_024990
Natural varianti759 – 7591G → E Reduces interaction with MSH2; abrogates interaction with MSH2; when associated with L-770. 4 Publications
Corresponds to variant rs4150001 [ dbSNP | Ensembl ].
VAR_024991
Natural varianti770 – 7701P → L Reduces interaction with MSH2; abrogates interaction with MSH2; when associated with S-640 or E-759. 2 Publications
VAR_024992
Natural varianti827 – 8271A → V.1 Publication
VAR_024993

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei803 – 8031D → F in isoform 2. 1 PublicationVSP_017029
Alternative sequencei804 – 84643Missing in isoform 2. 1 PublicationVSP_017030Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1620.1. [Q9UQ84-1]
CCDS44336.1. [Q9UQ84-4]
PIRiT12524.
RefSeqiNP_003677.4. NM_003686.4. [Q9UQ84-4]
NP_006018.4. NM_006027.4. [Q9UQ84-1]
NP_569082.2. NM_130398.3. [Q9UQ84-1]
XP_006711903.1. XM_006711840.1. [Q9UQ84-1]
XP_011542623.1. XM_011544321.1. [Q9UQ84-1]
XP_011542624.1. XM_011544322.1. [Q9UQ84-1]
UniGeneiHs.498248.

Genome annotation databases

EnsembliENST00000348581; ENSP00000311873; ENSG00000174371. [Q9UQ84-1]
ENST00000366548; ENSP00000355506; ENSG00000174371. [Q9UQ84-1]
ENST00000518483; ENSP00000430251; ENSG00000174371. [Q9UQ84-4]
GeneIDi9156.
KEGGihsa:9156.
UCSCiuc001hzh.4. human. [Q9UQ84-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1620.1. [Q9UQ84-1]
CCDS44336.1. [Q9UQ84-4]
PIRiT12524.
RefSeqiNP_003677.4. NM_003686.4. [Q9UQ84-4]
NP_006018.4. NM_006027.4. [Q9UQ84-1]
NP_569082.2. NM_130398.3. [Q9UQ84-1]
XP_006711903.1. XM_006711840.1. [Q9UQ84-1]
XP_011542623.1. XM_011544321.1. [Q9UQ84-1]
XP_011542624.1. XM_011544322.1. [Q9UQ84-1]
UniGeneiHs.498248.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QE9X-ray2.51Y/Z1-352[»]
3QEAX-ray3.10Z1-352[»]
3QEBX-ray3.00Z1-352[»]
ProteinModelPortaliQ9UQ84.
SMRiQ9UQ84. Positions 2-346.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114602. 25 interactions.
DIPiDIP-36701N.
IntActiQ9UQ84. 14 interactions.
MINTiMINT-84735.
STRINGi9606.ENSP00000311873.

PTM databases

iPTMnetiQ9UQ84.
PhosphoSiteiQ9UQ84.

Polymorphism and mutation databases

BioMutaiEXO1.
DMDMi85700954.

Proteomic databases

EPDiQ9UQ84.
MaxQBiQ9UQ84.
PaxDbiQ9UQ84.
PRIDEiQ9UQ84.

Protocols and materials databases

DNASUi9156.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000348581; ENSP00000311873; ENSG00000174371. [Q9UQ84-1]
ENST00000366548; ENSP00000355506; ENSG00000174371. [Q9UQ84-1]
ENST00000518483; ENSP00000430251; ENSG00000174371. [Q9UQ84-4]
GeneIDi9156.
KEGGihsa:9156.
UCSCiuc001hzh.4. human. [Q9UQ84-1]

Organism-specific databases

CTDi9156.
GeneCardsiEXO1.
H-InvDBHIX0022634.
HGNCiHGNC:3511. EXO1.
MIMi606063. gene.
neXtProtiNX_Q9UQ84.
PharmGKBiPA27923.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2518. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00510000047676.
HOVERGENiHBG081488.
InParanoidiQ9UQ84.
KOiK10746.
OMAiEPIHVRK.
OrthoDBiEOG7RNJZZ.
PhylomeDBiQ9UQ84.
TreeFamiTF314997.

Enzyme and pathway databases

BRENDAi3.1.11.1. 2681.
ReactomeiR-HSA-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-HSA-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
R-HSA-5685938. HDR through Single Strand Annealing (SSA).
R-HSA-5685942. HDR through Homologous Recombination (HRR).
R-HSA-5693554. Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
R-HSA-5693568. Resolution of D-loop Structures through Holliday Junction Intermediates.
R-HSA-5693579. Homologous DNA Pairing and Strand Exchange.
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-HSA-69473. G2/M DNA damage checkpoint.
SIGNORiQ9UQ84.

Miscellaneous databases

EvolutionaryTraceiQ9UQ84.
GeneWikiiExonuclease_1.
GenomeRNAii9156.
PROiQ9UQ84.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UQ84.
CleanExiHS_EXO1.
ExpressionAtlasiQ9UQ84. baseline and differential.
GenevisibleiQ9UQ84. HS.

Family and domain databases

Gene3Di3.40.50.1010. 1 hit.
InterProiIPR020045. 5-3_exonuclease_C.
IPR032641. Exo1.
IPR008918. HhH2.
IPR029060. PIN_domain-like.
IPR006086. XPG-I_dom.
IPR006084. XPG/Rad2.
IPR019974. XPG_CS.
IPR006085. XPG_DNA_repair_N.
[Graphical view]
PANTHERiPTHR11081. PTHR11081. 1 hit.
PTHR11081:SF8. PTHR11081:SF8. 1 hit.
PfamiPF00867. XPG_I. 1 hit.
PF00752. XPG_N. 1 hit.
[Graphical view]
PRINTSiPR00853. XPGRADSUPER.
SMARTiSM00279. HhH2. 1 hit.
SM00484. XPGI. 1 hit.
SM00485. XPGN. 1 hit.
[Graphical view]
SUPFAMiSSF47807. SSF47807. 1 hit.
SSF88723. SSF88723. 1 hit.
PROSITEiPS00841. XPG_1. 1 hit.
PS00842. XPG_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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. Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-418 AND ARG-419.
  24. 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, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF SER-454; THR-621 AND SER-714.
  26. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-422, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  27. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  28. "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.
  29. "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.
  30. "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.
  31. "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.

Entry informationi

Entry nameiEXO1_HUMAN
AccessioniPrimary (citable) accession number: Q9UQ84
Secondary accession number(s): O60545
, O75214, O75466, Q5T396, Q96IJ1, Q9UG38, Q9UNW0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2006
Last sequence update: January 24, 2006
Last modified: June 8, 2016
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.