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Mlh1p
Mlh1p (Saccharomyces cerevisiae) is product of expression of MLH1 gene.

Mlh1p is involved in:

MMR in Saccharomyces cerevisiae
Keywords:


FUNCTION: Required for DNA mismatch repair (MMR), correcting base- base mismatches and insertion-deletion loops (IDLs) resulting from DNA replication, DNA damage or from recombination events between non-identical sequences during meiosis. Component of different MutL heterodimers that form a ternary complex with the MutS heterodimers, which initially recognize the DNA mismatches. This complex is thought to be responsible for directing the downsteam MMR events, including strand discrimination, excision, and resynthesis. Plays a major role in maintaining the genetic stability of simple sequence repeats, the repair of heteroduplex sites present in meiotic recombination intermediates, and the promotion of meiotic crossing-over.

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=69 uM for ATP;

SUBUNIT: Heterodimer of MLH1 and PMS1, called MutLalpha, which is the major MMR MutL activity correcting base-base mismatches as well as IDLs. The heterodimer binds double strand DNA independently of a mismatch with positive cooperativity and has more than one DNA binding site. Forms a ternary complex with either the MSH2-MSH6 (MutSalpha) or the MSH2-MSH3 heterodimer (MutSbeta), which recognize and bind to mismatch DNA. Ternary complex formation is promoted by ATP binding. Heterodimer of MLH1 and MLH3, called MutLbeta, which is involved in correction of a specific subset of IDLs when associated with MutSbeta. Heterodimer of MLH1 and MLH2.

INTERACTION: P38799:-; NbExp=1; IntAct=EBI-11003, EBI-24593; Q02486:ABF2; NbExp=1; IntAct=EBI-11003, EBI-2028; Q07980:MLH2; NbExp=1; IntAct=EBI-11003, EBI-33369; Q12083:MLH3; NbExp=3; IntAct=EBI-11003, EBI-31634; P14242:PMS1; NbExp=1; IntAct=EBI-11003, EBI-13561; P25454:RAD51; NbExp=1; IntAct=EBI-11003, EBI-14709;

SUBCELLULAR LOCATION: Nucleus.

MISCELLANEOUS: Present with 319 molecules/cell in log phase SD medium.

SIMILARITY: Belongs to the DNA mismatch repair mutL/hexB family.

NCBI GenPept GI number(s): 6323819
Species: Saccharomyces cerevisiae

Links to other databases:

Database ID Link
Uniprot P38920 P38920
PFAM: - P38920 (Link - using uniprot id)
InterPro: - P38920 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MSLRIKALDASVVNKIAAGEIIISPVNALKEMMENSIDANATMIDILVKE
GGIKVLQITDNGSGINKADLPILCERFTTSKLQKFEDLSQIQTYGFRGEA
LASISHVARVTVTTKVKEDRCAWRVSYAEGKMLESPKPVAGKDGTTILVE
DLFFNIPSRLRALRSHNDEYSKILDVVGRYAIHSKDIGFSCKKFGDSNYS
LSVKPSYTVQDRIRTVFNKSVASNLITFHISKVEDLNLESVDGKVCNLNF
ISKKSISPIFFINNRLVTCDLLRRALNSVYSNYLPKGNRPFIYLGIVIDP
AAVDVNVHPTKREVRFLSQDEIIEKIANQLHAELSAIDTSRTFKASSIST
NKPESLIPFNDTIESDRNRKSLRQAQVVENSYTTANSQLRKAKRQENKLV
RIDASQAKITSFLSSSQQFNFEGSSTKRQLSEPKVTNVSHSQEAEKLTLN
ESEQPRDANTINDNDLKDQPKKKQKLGDYKVPSIADDEKNALPISKDGYI
RVPKERVNVNLTSIKKLREKVDDSIHRELTDIFANLNYVGVVDEERRLAA
IQHDLKLFLIDYGSVCYELFYQIGLTDFANFGKINLQSTNVSDDIVLYNL
LSEFDELNDDASKEKIISKIWDMSSMLNEYYSIELVNDGLDNDLKSVKLK
SLPLLLKGYIPSLVKLPFFIYRLGKEVDWEDEQECLDGILREIALLYIPD
MVPKVDTSDASLSEDEKAQFINRKEHISSLLEHVLFPCIKRRFLAPRHIL
KDVVEIANLPDLYKVFERC

Mlh1p (Saccharomyces cerevisiae) belongs to following protein families:
References:

Title Authors Journal
Dual requirement in yeast DNA mismatch repair for MLH1 and PMS1, two homologs of the bacterial mutL gene. Prolla TA, Christie DM, Liskay RM Mol Cell Biol Feb. 1, 1994
The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII. Bowman S, Churcher C, Badcock K, Brown D, Chillingworth T, Connor R, Dedman K, Devlin K, Gentles S, Hamlin N, Hunt S, Jagels K, Lye G, Moule S, Odell C, Pearson D, Rajandream M, Rice P, Skelton J, Walsh S, Whitehead S, Barrell B Nature May 1, 1997
Functional domains of the Saccharomyces cerevisiae Mlh1p and Pms1p DNA mismatch repair proteins and their relevance to human hereditary nonpolyposis colorectal cancer-associated mutations. Pang Q, Prolla TA, Liskay RM Mol Cell Biol Aug. 1, 1997
ATP-dependent assembly of a ternary complex consisting of a DNA mismatch and the yeast MSH2-MSH6 and MLH1-PMS1 protein complexes. Habraken Y, Sung P, Prakash L, Prakash S J Biol Chem April 17, 1998
Functional specificity of MutL homologs in yeast: evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction. Wang TF, Kleckner N, Hunter N Proc Natl Acad Sci U S A Nov. 23, 1999
Functional studies on the candidate ATPase domains of Saccharomyces cerevisiae MutLalpha. Tran PT, Liskay RM Mol Cell Biol Sept. 1, 2000
Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae. Ellison AR, Lofing J, Bitter GA Hum Mol Genet Sept. 1, 2001
Differential ATP binding and intrinsic ATP hydrolysis by amino-terminal domains of the yeast Mlh1 and Pms1 proteins. Hall MC, Shcherbakova PV, Kunkel TA J Biol Chem Jan. 1, 2002
DNA binding properties of the yeast Msh2-Msh6 and Mlh1-Pms1 heterodimers. Drotschmann K, Hall MC, Shcherbakova PV, Wang H, Erie DA, Brownewell FR, Kool ET, Kunkel TA Biol Chem June 1, 2002
Systematic mutagenesis of the Saccharomyces cerevisiae MLH1 gene reveals distinct roles for Mlh1p in meiotic crossing over and in vegetative and meiotic mismatch repair. Argueso JL, Kijas AW, Sarin S, Heck J, Waase M, Alani E Mol Cell Biol Jan. 1, 2003
DNA binding by yeast Mlh1 and Pms1: implications for DNA mismatch repair. Hall MC, Shcherbakova PV, Fortune JM, Borchers CH, Dial JM, Tomer KB, Kunkel TA Nucleic Acids Res April 15, 2003
Global analysis of protein expression in yeast. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O'Shea EK, Weissman JS Nature Oct. 16, 2003
Global analysis of protein localization in budding yeast. Huh WK, Falvo JV, Gerke LC, Carroll AS, Howson RW, Weissman JS, O'Shea EK Nature Oct. 16, 2003
Negative epistasis between natural variants of the Saccharomyces cerevisiae MLH1 and PMS1 genes results in a defect in mismatch repair. Heck JA, Argueso JL, Gemici Z, Reeves RG, Bernard A, Aquadro CF, Alani E Proc Natl Acad Sci U S A Jan. 28, 2006
Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. Smolka MB, Albuquerque CP, Chen SH, Zhou H Proc Natl Acad Sci U S A June 19, 2007
A multidimensional chromatography technology for in-depth phosphoproteome analysis. Albuquerque CP, Smolka MB, Payne SH, Bafna V, Eng J, Zhou H Mol Cell Proteomics July 1, 2008

Last modification of this entry: Oct. 6, 2010.

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