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Protein

Exonuclease 1

Gene

Exo1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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.2 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

GO - Biological processi

  • DNA recombination Source: UniProtKB
  • humoral immune response mediated by circulating immunoglobulin Source: MGI
  • isotype switching Source: MGI
  • meiotic cell cycle Source: UniProtKB-KW
  • mismatch repair Source: UniProtKB
  • nucleic acid phosphodiester bond hydrolysis Source: MGI
  • nucleobase-containing compound metabolic process Source: MGI
  • somatic hypermutation of immunoglobulin genes Source: MGI
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

ReactomeiR-MMU-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-MMU-5685938. HDR through Single Strand Annealing (SSA).
R-MMU-5685942. HDR through Homologous Recombination (HRR).
R-MMU-5693554. Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
R-MMU-5693568. Resolution of D-loop Structures through Holliday Junction Intermediates.
R-MMU-5693579. Homologous DNA Pairing and Strand Exchange.
R-MMU-5693607. Processing of DNA double-strand break ends.
R-MMU-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.

Names & Taxonomyi

Protein namesi
Recommended name:
Exonuclease 1 (EC:3.1.-.-)
Short name:
mExo1
Alternative name(s):
Exonuclease I
Gene namesi
Name:Exo1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1349427. Exo1.

Subcellular locationi

  • Nucleus By similarity

  • Note: Colocalizes with PCNA to discrete nuclear foci in S-phase.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 837837Exonuclease 1PRO_0000154040Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei480 – 4801N6-acetyllysineBy similarity
Modified residuei589 – 5891PhosphoserineBy similarity
Modified residuei612 – 6121PhosphothreonineBy similarity
Modified residuei614 – 6141PhosphoserineBy similarity
Modified residuei666 – 6661PhosphoserineBy similarity
Modified residuei737 – 7371PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated upon DNA damage and in response to agents stalling DNA replication, probably by ATM or ATR.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9QZ11.
MaxQBiQ9QZ11.
PaxDbiQ9QZ11.
PRIDEiQ9QZ11.

PTM databases

PhosphoSiteiQ9QZ11.

Expressioni

Tissue specificityi

Highly expressed in the spleen and testis. Also expressed in the bone marrow, brain, lung, lymph node and thymus.1 Publication

Developmental stagei

Postnatal expression in the testis is elevated at the onset of pachytene (day 14).1 Publication

Gene expression databases

BgeeiQ9QZ11.
CleanExiMM_EXO1.
ExpressionAtlasiQ9QZ11. baseline and differential.
GenevisibleiQ9QZ11. MM.

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 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000039376.

Structurei

3D structure databases

ProteinModelPortaliQ9QZ11.
SMRiQ9QZ11. Positions 2-345.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 9999N-domainAdd
BLAST
Regioni129 – 386258Interaction with MSH3By similarityAdd
BLAST
Regioni138 – 22992I-domainAdd
BLAST
Regioni387 – 488102Interaction with MLH1By similarityAdd
BLAST
Regioni591 – 837247Interaction with MSH2By similarityAdd
BLAST
Regioni778 – 83760Interaction with MLH1By similarityAdd
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2518. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00510000047676.
HOGENOMiHOG000112413.
HOVERGENiHBG081488.
InParanoidiQ9QZ11.
KOiK10746.
OMAiEPIHVRK.
OrthoDBiEOG7RNJZZ.
PhylomeDBiQ9QZ11.
TreeFamiTF314997.

Family and domain databases

Gene3Di3.40.50.1010. 1 hit.
InterProiIPR020045. 5-3_exonuclease_C.
IPR008918. HhH2.
IPR029060. PIN_domain-like.
IPR006086. XPG-I_dom.
IPR006084. XPG/Rad2.
IPR019974. XPG_CS.
IPR006085. XPG_DNA_repair_N.
[Graphical view]
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]

Sequencei

Sequence statusi: Complete.

Q9QZ11-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGIQGLLQFI QEASEPVNVK KYKGQAVAVD TYCWLHKGAI ACAEKLAKGE
60 70 80 90 100
PTDRYVGFCM KFVNMLLSYG VKPILIFDGC TLPSKKEVER SRRERRQSNL
110 120 130 140 150
LKGKQLLREG KVSEARDCFA RSINITHAMA HKVIKAARAL GVDCLVAPYE
160 170 180 190 200
ADAQLAYLNK AGIVQAVITE DSDLLAFGCK KVILKMDQFG NGLEVDQARL
210 220 230 240 250
GMCKQLGDVF TEEKFRYMCI LSGCDYLASL RGIGLAKACK VLRLANNPDI
260 270 280 290 300
VKVIKKIGHY LRMNITVPED YITGFIRANN TFLYQLVFDP IQRKLVPLNA
310 320 330 340 350
YGDDVNPETL TYAGQYVGDS VALQIALGNR DVNTFEQIDD YSPDTMPAHS
360 370 380 390 400
RSHSWNEKAG QKPPGTNSIW HKNYCPRLEV NSVSHAPQLK EKPSTLGLKQ
410 420 430 440 450
VISTKGLNLP RKSCVLKRPR NEALAEDDLL SQYSSVSKKI KENGCGDGTS
460 470 480 490 500
PNSSKMSKSC PDSGTAHKTD AHTPSKMRNK FATFLQRRNE ESGAVVVPGT
510 520 530 540 550
RSRFFCSSQD FDNFIPKKES GQPLNETVAT GKATTSLLGA LDCPDTEGHK
560 570 580 590 600
PVDANGTHNL SSQIPGNAAV SPEDEAQSSE TSKLLGAMSP PSLGTLRSCF
610 620 630 640 650
SWSGTLREFS RTPSPSASTT LQQFRRKSDP PACLPEASAV VTDRCDSKSE
660 670 680 690 700
MLGETSQPLH ELGCSSRSQE SMDSSCGLNT SSLSQPSSRD SGSEESDCNN
710 720 730 740 750
KSLDNQGEQN SKQHLPHFSK KDGLRRNKVP GLCRSSSMDS FSTTKIKPLV
760 770 780 790 800
PARVSGLSKK SGSMQTRKHH DVENKPGLQT KISELWKNFG FKKDSEKLPS
810 820 830
CKKPLSPVKD NIQLTPETED EIFNKPECVR AQRAIFH
Length:837
Mass (Da):92,022
Last modified:January 24, 2006 - v2
Checksum:i5AE4AC617535DEBC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti366 – 3661T → A in CAB51863 (PubMed:10497278).Curated
Sequence conflicti366 – 3661T → A in BAE38768 (PubMed:16141072).Curated
Sequence conflicti523 – 5231P → T in BAE38768 (PubMed:16141072).Curated
Sequence conflicti557 – 5571T → M in CAB51863 (PubMed:10497278).Curated
Sequence conflicti560 – 5601L → P in BAE38768 (PubMed:16141072).Curated
Sequence conflicti648 – 6481K → Q in CAB51863 (PubMed:10497278).Curated
Sequence conflicti652 – 6521L → P in CAB51863 (PubMed:10497278).Curated
Sequence conflicti652 – 6521L → P in BAE38768 (PubMed:16141072).Curated
Sequence conflicti666 – 6661S → L in CAB51863 (PubMed:10497278).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ238213 mRNA. Translation: CAB51863.1.
AK028728 mRNA. Translation: BAC26086.1.
AK166425 mRNA. Translation: BAE38768.1.
BC006671 mRNA. Translation: AAH06671.1.
CCDSiCCDS15551.1.
RefSeqiNP_036142.2. NM_012012.4.
XP_006496925.1. XM_006496862.2.
XP_006496926.1. XM_006496863.2.
UniGeneiMm.283046.

Genome annotation databases

EnsembliENSMUST00000039725; ENSMUSP00000039376; ENSMUSG00000039748.
GeneIDi26909.
KEGGimmu:26909.
UCSCiuc007dtu.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ238213 mRNA. Translation: CAB51863.1.
AK028728 mRNA. Translation: BAC26086.1.
AK166425 mRNA. Translation: BAE38768.1.
BC006671 mRNA. Translation: AAH06671.1.
CCDSiCCDS15551.1.
RefSeqiNP_036142.2. NM_012012.4.
XP_006496925.1. XM_006496862.2.
XP_006496926.1. XM_006496863.2.
UniGeneiMm.283046.

3D structure databases

ProteinModelPortaliQ9QZ11.
SMRiQ9QZ11. Positions 2-345.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000039376.

PTM databases

PhosphoSiteiQ9QZ11.

Proteomic databases

EPDiQ9QZ11.
MaxQBiQ9QZ11.
PaxDbiQ9QZ11.
PRIDEiQ9QZ11.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000039725; ENSMUSP00000039376; ENSMUSG00000039748.
GeneIDi26909.
KEGGimmu:26909.
UCSCiuc007dtu.2. mouse.

Organism-specific databases

CTDi9156.
MGIiMGI:1349427. Exo1.

Phylogenomic databases

eggNOGiKOG2518. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00510000047676.
HOGENOMiHOG000112413.
HOVERGENiHBG081488.
InParanoidiQ9QZ11.
KOiK10746.
OMAiEPIHVRK.
OrthoDBiEOG7RNJZZ.
PhylomeDBiQ9QZ11.
TreeFamiTF314997.

Enzyme and pathway databases

ReactomeiR-MMU-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-MMU-5685938. HDR through Single Strand Annealing (SSA).
R-MMU-5685942. HDR through Homologous Recombination (HRR).
R-MMU-5693554. Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
R-MMU-5693568. Resolution of D-loop Structures through Holliday Junction Intermediates.
R-MMU-5693579. Homologous DNA Pairing and Strand Exchange.
R-MMU-5693607. Processing of DNA double-strand break ends.
R-MMU-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.

Miscellaneous databases

NextBioi304777.
PROiQ9QZ11.
SOURCEiSearch...

Gene expression databases

BgeeiQ9QZ11.
CleanExiMM_EXO1.
ExpressionAtlasiQ9QZ11. baseline and differential.
GenevisibleiQ9QZ11. MM.

Family and domain databases

Gene3Di3.40.50.1010. 1 hit.
InterProiIPR020045. 5-3_exonuclease_C.
IPR008918. HhH2.
IPR029060. PIN_domain-like.
IPR006086. XPG-I_dom.
IPR006084. XPG/Rad2.
IPR019974. XPG_CS.
IPR006085. XPG_DNA_repair_N.
[Graphical view]
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. "Expression specificity of the mouse exonuclease 1 (mExo1) gene."
    Lee B.-I., Shannon M., Stubbs L., Wilson D.M. III
    Nucleic Acids Res. 27:4114-4120(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Mammary gland and Skin.
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary gland.
  4. "Inactivation of exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility."
    Wei K., Clark A.B., Wong E., Kane M.F., Mazur D.J., Parris T., Kolas N.K., Russell R., Hou H. Jr., Kneitz B., Yang G., Kunkel T.A., Kolodner R.D., Cohen P.E., Edelmann W.
    Genes Dev. 17:603-614(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice."
    Bardwell P.D., Woo C.J., Wei K., Li Z., Martin A., Sack S.Z., Parris T., Edelmann W., Scharff M.D.
    Nat. Immunol. 5:224-229(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiEXO1_MOUSE
AccessioniPrimary (citable) accession number: Q9QZ11
Secondary accession number(s): Q3TLM4, Q923A5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2006
Last sequence update: January 24, 2006
Last modified: March 16, 2016
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.