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Product Info

Source:
Mouse
Application:
ELISA 1:10000, WB 1:500-1:2000, IHC 1:200-1:1000, IF/ICC 1:200-1:1000
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human,Monkey
Clonality:
Monoclonal [AFB1632]
Specificity:
MLH1 antibody detects endogenous levels of total MLH1.
RRID:
AB_2833656
Cite Format: Affinity Biosciences Cat# BF0073, RRID:AB_2833656.
Conjugate:
Unconjugated.
Purification:
Affinity-chromatography.
Storage:
Mouse IgG1 in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
Alias:

Fold/Unfold

COCA 2; COCA2; DNA mismatch repair protein Mlh1; FCC 2; FCC2; hMLH 1; hMLH1; HNPCC 2; HNPCC; HNPCC2; MGC5172; MLH 1; MLH1; MLH1_HUMAN; MutL homolog 1 (E. coli); MutL homolog 1; MutL homolog 1 colon cancer nonpolyposis type 2; MutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli); MutL protein homolog 1; MutL, E. coli, homolog of, 1;

Immunogens

Immunogen:

Purified recombinant fragment of human MLH1 expressed in E. Coli.

Uniprot:
Gene(ID):
Expression:
P40692 MLH1_HUMAN:

Colon, lymphocytes, breast, lung, spleen, testis, prostate, thyroid, gall bladder and heart.

Description:
This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). It is a human homolog of the E. coli DNA mismatch repair gene mutL, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Alternatively spliced transcript variants encoding different isoforms have been described, but their full-length natures have not been determined.
Sequence:
MSFVAGVIRRLDETVVNRIAAGEVIQRPANAIKEMIENCLDAKSTSIQVIVKEGGLKLIQIQDNGTGIRKEDLDIVCERFTTSKLQSFEDLASISTYGFRGEALASISHVAHVTITTKTADGKCAYRASYSDGKLKAPPKPCAGNQGTQITVEDLFYNIATRRKALKNPSEEYGKILEVVGRYSVHNAGISFSVKKQGETVADVRTLPNASTVDNIRSIFGNAVSRELIEIGCEDKTLAFKMNGYISNANYSVKKCIFLLFINHRLVESTSLRKAIETVYAAYLPKNTHPFLYLSLEISPQNVDVNVHPTKHEVHFLHEESILERVQQHIESKLLGSNSSRMYFTQTLLPGLAGPSGEMVKSTTSLTSSSTSGSSDKVYAHQMVRTDSREQKLDAFLQPLSKPLSSQPQAIVTEDKTDISSGRARQQDEEMLELPAPAEVAAKNQSLEGDTTKGTSEMSEKRGPTSSNPRKRHREDSDVEMVEDDSRKEMTAACTPRRRIINLTSVLSLQEEINEQGHEVLREMLHNHSFVGCVNPQWALAQHQTKLYLLNTTKLSEELFYQILIYDFANFGVLRLSEPAPLFDLAMLALDSPESGWTEEDGPKEGLAEYIVEFLKKKAEMLADYFSLEIDEEGNLIGLPLLIDNYVPPLEGLPIFILRLATEVNWDEEKECFESLSKECAMFYSIRKQYISEESTLSGQQSEVPGSIPNSWKWTVEHIVYKALRSHILPPKHFTEDGNILQLANLPDLYKVFERC

PTMs - P40692 As Substrate

Site PTM Type Enzyme
S2 Acetylation
S2 Phosphorylation
K33 Ubiquitination
K57 Ubiquitination
K70 Ubiquitination
K84 Ubiquitination
S87 Phosphorylation
K123 Ubiquitination
K134 Ubiquitination
K140 Ubiquitination
K164 Ubiquitination
K167 Ubiquitination
K175 Ubiquitination
Y183 Phosphorylation
K196 Ubiquitination
T212 Phosphorylation
K236 Ubiquitination
T288 Phosphorylation
Y293 Phosphorylation
S295 Phosphorylation
K333 Ubiquitination
S370 Phosphorylation
K377 Ubiquitination
Y379 Phosphorylation
T386 Phosphorylation
S388 Phosphorylation
K392 Sumoylation
K392 Ubiquitination
K402 Acetylation
K402 Ubiquitination
S406 Phosphorylation Q13315 (ATM) , Q13535 (ATR)
K416 Sumoylation
K416 Ubiquitination
K443 Acetylation
K443 Ubiquitination
S446 Phosphorylation
K453 Ubiquitination
S459 Phosphorylation
K461 Acetylation
S467 Phosphorylation
S477 Phosphorylation
S486 Phosphorylation
K488 Ubiquitination
T495 Phosphorylation
S508 Phosphorylation
K688 Ubiquitination
K732 Ubiquitination
K751 Ubiquitination

Research Backgrounds

Function:

Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis.

Subcellular Location:

Nucleus. Chromosome.
Note: Recruited to chromatin in a MCM9-dependent manner.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

Colon, lymphocytes, breast, lung, spleen, testis, prostate, thyroid, gall bladder and heart.

Subunit Structure:

Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1. Heterodimer of MLH1 and PMS2 (MutL alpha), MLH1 and PMS1 (MutL beta) or MLH1 and MLH3 (MutL gamma). Forms a ternary complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with MCM9; the interaction recruits MLH1 to chromatin. Interacts MCM8. Interacts with PMS2. Interacts with MBD4. Interacts with EXO1. Interacts with MTMR15/FAN1.

Family&Domains:

Belongs to the DNA mismatch repair MutL/HexB family.

Research Fields

· Genetic Information Processing > Replication and repair > Mismatch repair.

· Genetic Information Processing > Replication and repair > Fanconi anemia pathway.

· Human Diseases > Drug resistance: Antineoplastic > Platinum drug resistance.

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Colorectal cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Endometrial cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Gastric cancer.   (View pathway)

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