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EXO1

Protein FULL name:

exonuclease 1 isoform a [Homo sapiens].


EXO1 (Homo sapiens) is product of expression of EXO1 gene.


EXO1 is involved in:

MMR in Homo sapiens
     


Keywords:



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.

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: 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.

INTERACTION: P43246:MSH2; NbExp=2; IntAct=EBI-944694, EBI-355888;

SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with PCNA to discrete nuclear foci in S-phase.

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.

DEVELOPMENTAL STAGE: Highly expressed in fetal liver and at lower levels in fetal brain, heart, kidney, spleen and thymus.

PTM: 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.

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.

SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. EXO1 subfamily.

SEQUENCE CAUTION: Sequence=AAC33874.1; Type=Frameshift; Positions=793;

WEB RESOURCE: Name=NIEHS-SNPs; [LINK]


NCBI GenPept GI number(s): 39995069
39995071
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q9UQ84 Q9UQ84
PFAM: - Q9UQ84 (Link - using uniprot id)
InterPro: - Q9UQ84 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MGIQGLLQFIKEASEPIHVRKYKGQVVAVDTYCWLHKGAIACAEKLAKGE
PTDRYVGFCMKFVNMLLSHGIKPILVFDGCTLPSKKEVERSRRERRQANL
LKGKQLLREGKVSEARECFTRSINITHAMAHKVIKAARSQGVDCLVAPYE
ADAQLAYLNKAGIVQAIITEDSDLLAFGCKKVILKMDQFGNGLEIDQARL
GMCRQLGDVFTEEKFRYMCILSGCDYLSSLRGIGLAKACKVLRLANNPDI
VKVIKKIGHYLKMNITVPEDYINGFIRANNTFLYQLVFDPIKRKLIPLNA
YEDDVDPETLSYAGQYVDDSIALQIALGNKDINTFEQIDDYNPDTAMPAH
SRSHSWDDKTCQKSANVSSIWHRNYSPRPESGTVSDAPQLKENPSTVGVE
RVISTKGLNLPRKSSIVKRPRSAELSEDDLLSQYSLSFTKKTKKNSSEGN
KSLSFSEVFVPDLVNGPTNKKSVSTPPRTRNKFATFLQRKNEESGAVVVP
GTRSRFFCSSDSTDCVSNKVSIQPLDETAVTDKENNLHESEYGDQEGKRL
VDTDVARNSSDDIPNNHIPGDHIPDKATVFTDEESYSFESSKFTRTISPP
TLGTLRSCFSWSGGLGDFSRTPSPSPSTALQQFRRKSDSPTSLPENNMSD
VSQLKSEESSDDESHPLREGACSSQSQESGEFSLQSSNASKLSQCSSKDS
DSEESDCNIKLLDSQSDQTSKLCLSHFSKKDTPLRNKVPGLYKSSSADSL
STTKIKPLGPARASGLSKKPASIQKRKHHNAENKPGLQIKLNELWKNFGF
KKF

EXO1 (Homo sapiens) is able to recognize following damages:
References:

Title Authors Journal
Hex1: a new human Rad2 nuclease family member with homology to yeast exonuclease 1. Wilson DM 3rd, Carney JP, Coleman MA, Adamson AW, Christensen M, Lamerdin JE Nucleic Acids Res Aug. 15, 1998
Human exonuclease I interacts with the mismatch repair protein hMSH2. Schmutte C, Marinescu RC, Sadoff MM, Guerrette S, Overhauser J, Fishel R Cancer Res Oct. 15, 1998
Identification of a human gene encoding a homologue of Saccharomyces cerevisiae EXO1, an exonuclease implicated in mismatch repair and recombination. Tishkoff DX, Amin NS, Viars CS, Arden KC, Kolodner RD Cancer Res Nov. 15, 1998
Human exonuclease 1 functionally complements its yeast homologues in DNA recombination, RNA primer removal, and mutation avoidance. Qiu J, Qian Y, Chen V, Guan MX, Shen B J Biol Chem June 18, 1999
The RAD2 domain of human exonuclease 1 exhibits 5' to 3' exonuclease and flap structure-specific endonuclease activities. Lee BI, Wilson DM 3rd J Biol Chem Dec. 31, 1999
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 LJ, Rasmussen M, Lee B, Rasmussen AK, Wilson DM 3rd, Nielsen FC, Bisgaard HC Mutat Res June 1, 2000
Germline mutations of EXO1 gene in patients with hereditary nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms. Wu Y, Berends MJ, Post JG, Mensink RG, Verlind E, Van Der Sluis T, Kempinga C, Sijmons RH, van der Zee AG, Hollema H, Kleibeuker JH, Buys CH, Hofstra RM Gastroenterology June 1, 2001
HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence assembly of hMutLalpha and hMLH1-hEXO1 complexes. Jager AC, Rasmussen M, Bisgaard HC, Singh KK, Nielsen FC, Rasmussen LJ Oncogene June 14, 2001
The interaction of DNA mismatch repair proteins with human exonuclease I. Schmutte C, Sadoff MM, Shim KS, Acharya S, Fishel R J Biol Chem Aug. 31, 2001
Molecular interactions of human Exo1 with DNA. Lee Bi BI, Nguyen LH, Barsky D, Fernandes M, Wilson DM 3rd Nucleic Acids Res Jan. 15, 2002
Human exonuclease I is required for 5' and 3' mismatch repair. Genschel J, Bazemore LR, Modrich P J Biol Chem April 12, 2002
Functional alterations of human exonuclease 1 mutants identified in atypical hereditary nonpolyposis colorectal cancer syndrome. Sun X, Zheng L, Shen B Cancer Res Nov. 1, 2002
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 TF, Moller P, Vasen H, Tops C, Kolodner RD, Mecklin JP, Jarvinen H, Bevan S, Houlston RS, Aaltonen LA, Fodde R, Wijnen J, Karhu A Cancer Res Feb. 1, 2003
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 JA, Driscoll HC, Uzdilla L, Wilson TM, Brosh RM Jr J Biol Chem June 27, 2003
Mechanism of 5'-directed excision in human mismatch repair. Genschel J, Modrich P Mol Cell Nov. 1, 2003
Germline deletions of EXO1 do not cause colorectal tumors and lesions which are null for EXO1 do not have microsatellite instability. Alam NA, Gorman P, Jaeger EE, Kelsell D, Leigh IM, Ratnavel R, Murdoch ME, Houlston RS, Aaltonen LA, Roylance RR, Tomlinson IP Cancer Genet Cytogenet Dec. 1, 2003
Characterization of human exonuclease 1 in complex with mismatch repair proteins, subcellular localization and association with PCNA. Nielsen FC, Jager AC, Lutzen A, Bundgaard JR, Rasmussen LJ Oncogene Jan. 19, 2004
Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations. Thompson E, Meldrum CJ, Crooks R, McPhillips M, Thomas L, Spigelman AD, Scott RJ Clin Genet March 1, 2004
A defined human system that supports bidirectional mismatch-provoked excision. Dzantiev L, Constantin N, Genschel J, Iyer RR, Burgers PM, Modrich P Mol Cell July 2, 2004
Large-scale characterization of HeLa cell nuclear phosphoproteins. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP Proc Natl Acad Sci U S A Aug. 17, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
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 Jan. 1, 2005
RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination. Doherty KM, Sharma S, Uzdilla LA, Wilson TM, Cui S, Vindigni A, Brosh RM Jr J Biol Chem July 1, 2005
Reconstitution of 5'-directed human mismatch repair in a purified system. Zhang Y, Yuan F, Presnell SR, Tian K, Gao Y, Tomkinson AE, Gu L, Li GM Cell Sept. 9, 2005
The DNA sequence and biological annotation of human chromosome 1. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E Nature May 18, 2006
The full-ORF clone resource of the German cDNA Consortium. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I BMC Genomics Jan. 1, 2007
Nuclear localization of human DNA mismatch repair protein exonuclease 1 (hEXO1). Knudsen NO, Nielsen FC, Vinther L, Bertelsen R, Holten-Andersen S, Liberti SE, Hofstra R, Kooi K, Rasmussen LJ Nucleic Acids Res Jan. 1, 2007
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ Science May 25, 2007
ATR-dependent pathways control hEXO1 stability in response to stalled forks. El-Shemerly M, Hess D, Pyakurel AK, Moselhy S, Ferrari S Nucleic Acids Res Jan. 1, 2008
Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd J Proteome Res March 1, 2008
A quantitative atlas of mitotic phosphorylation. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP Proc Natl Acad Sci U S A Aug. 5, 2008
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S Anal Chem June 1, 2009
Lysine acetylation targets protein complexes and co-regulates major cellular functions. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M Science Aug. 14, 2009


Last modification of this entry: Oct. 12, 2010.

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