Gene

KWMTBOMO15656

Annotation

PREDICTED:_DNA_mismatch_repair_protein_Mlh1_isoform_X1_[Amyelois_transitella]

Location

Bomo_Chr26(+):5342227-5349336      View in EpiBrowser

Full name

DNA mismatch repair protein Mlh1      

Alternative Name

MutL protein homolog 1

Location in the cell

Cytoplasmic   Reliability : 1.796 Nuclear   Reliability : 1.77

CDS

ATGAATGAGCCAGGAATAATTCGAAAACTGAGTGAAGAAGTTGTGAACCGTATTGCTGCTGGTGAAATAGTGCAAAGACCAGCTAATGCATTAAAAGAACTTATAGAAAACAGCTTGGATGCCAAATCAACTAACATCATTATTACAGTGAAGTCTGGTGGTTTGAAGTTCTTACAGATACAGGACAATGGGACAGGTATAAGAAATGAAGACTTAGATATCGTATGTGAGAGATTCACAACATCTAAACTCAGAAAATATGAGGACTTACAAGAAATCAGTACCTACGGATTTCGTGGAGAGGCTCTCGCGAGTATCAGTCATATTGCACACCTTACAATATTGACAAAAACTGCACAAGACAAATGTGCTTACAAAGCCTCATATGAAAATGGAAAACTGAAAGGCCCCATAAAAGCTTGTGCTGGCAACAACGGCACTCAGATAACCGTTGAAGATTTATTTTATAACGTTGTGGCACGTAAAGGGGCATTGCGTAGTCCTACAGAAGAATACACGCGTTTAATGGAAGTGGTCGGAGGATATGCTATACATAATAGTCAAGTTGGATTTACTTTGAAAAAATTCAGTGAGAATACTGACTTGAAAACAGCGATGAAATCATCTGTCATAGAAAATGTTAGAATTATTTATGGTAACACAATAGCAAGAGAGCTGATAGAGGTTGAAATTTTGGATGCAAACTTGAAGCTGTCGATACATGGATACATTACAAACGTTAATTATTCCAATAAGAAAGGGATACTGCTCCTGTTCATCAATCATAGGCTTGTGGATTCACAGGCAATAAGAAAAGCCGTGGATTCTGTTTACTCAACATATTTACCAAAAAACTCACACGCATTTGTATACTTGAGCATTGAATTAGATCCGAAAAACGTGGACGTCAACGTTCATCCAACGAAACACGAAGTTCAGTTTCTTTACGAGGAGCAAATCGTCGAGAAGATCAAGACGTGCATCGAAACGAAACTCTTGGGCTGTAGCTCCACGCGCGTGCTGTACACGCAGGCCCGCCTCCCCGGCGCCGCCCAGCCCAGGGACGTCGCGGACAAGCCCACGGACGCGGCAAAAACTTCCGCCGCACACATGGTACGCGTCAACCCTAACGTCCAGAAGATCGACAAGTTCTTTGAACTTGAACCAAATAAAACGAATCAACCGACTGGAGATAATGCGAGTGACGTAGTAAATGATGTAGATCAACAACAGAAAATACCTAGTGAACAAGACTTGAACAATTCTATAGTAAAAGAGCCAGCAGAAGATAATAAAGTACAAGAGAAATGGAAACAGTATACTGAGGCGGGCCAAGCCAACATTACGTACGTAGACCCTAAAGATTCCTTCAAGACTAGAACGTTTCAATACCAGAGGATAGAAACGAAACTGACCAGCGTAAAACAGCTCAGATTAGAAGTGGAGAACAATTGTAACTCAAATCTAAGGGAAATCTTGGCTAATTTAATATTCATAGCCTGTATAGATTGTCACAAGTCATTAATACAGCACTCTACGAAACTGTATCTTTGTGATACGACAAGATTGACGGAGGAATTGTTTTACGAGACATTACTATACGATTTTCAAAACTTCGGTTTCATCAAACTGTCGAATCCATTGCCATTGGAAGAATTATTTGTTCTTGGTCTGAACGGGAGCACTCAAAACTCCGAACAGGATTCTGAGCTCGGAGATACAGGAGAAATGGCTCAACATATGACCCAACTATTGTTGAGCAAACGCGCAATGCTCTACGAATACTTTTCTCTGGAAGTAAATGGAGAAGGAGAATTATTGGCCCTACCATTACTTTTGGATGGTCACGCTCCGTTCGTGGGTGCTTTACCGACGTATTTAGTCCGTCTCGTTACCGAAGTCAATTGGGATTCTGAAAAGGAGTGCTTTGAGACTTTCTGCAGACAGACGGCCAAGTTTTATGCTCAACCTAATCCGGACCCTAATGTCGAGAGCGTGTCGTCGGAGCACAGGAGACAAGAGCACGTGATATTCCCTGCTATAAGAAAATATTTCCTACCGCCAAGTAGCTTTATAAGTAATGGAGCTATACTGCAAATAGCTAGTTTAAATGATTTGTATAAGGTTTTTGAACGTTGTTGA

Protein

MNEPGIIRKLSEEVVNRIAAGEIVQRPANALKELIENSLDAKSTNIIITVKSGGLKFLQIQDNGTGIRNEDLDIVCERFTTSKLRKYEDLQEISTYGFRGEALASISHIAHLTILTKTAQDKCAYKASYENGKLKGPIKACAGNNGTQITVEDLFYNVVARKGALRSPTEEYTRLMEVVGGYAIHNSQVGFTLKKFSENTDLKTAMKSSVIENVRIIYGNTIARELIEVEILDANLKLSIHGYITNVNYSNKKGILLLFINHRLVDSQAIRKAVDSVYSTYLPKNSHAFVYLSIELDPKNVDVNVHPTKHEVQFLYEEQIVEKIKTCIETKLLGCSSTRVLYTQARLPGAAQPRDVADKPTDAAKTSAAHMVRVNPNVQKIDKFFELEPNKTNQPTGDNASDVVNDVDQQQKIPSEQDLNNSIVKEPAEDNKVQEKWKQYTEAGQANITYVDPKDSFKTRTFQYQRIETKLTSVKQLRLEVENNCNSNLREILANLIFIACIDCHKSLIQHSTKLYLCDTTRLTEELFYETLLYDFQNFGFIKLSNPLPLEELFVLGLNGSTQNSEQDSELGDTGEMAQHMTQLLLSKRAMLYEYFSLEVNGEGELLALPLLLDGHAPFVGALPTYLVRLVTEVNWDSEKECFETFCRQTAKFYAQPNPDPNVESVSSEHRRQEHVIFPAIRKYFLPPSSFISNGAILQIASLNDLYKVFERC

Description

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 (By similarity).
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.

Subunit

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.
Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). 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 (PubMed:10783165). This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains (PubMed:10097147). Interacts with MCM9; the interaction recruits MLH1 to chromatin (PubMed:26300262). Interacts MCM8 (PubMed:26300262). Interacts with PMS2 (PubMed:11427529, PubMed:22753075). Interacts with MBD4 (PubMed:10097147). Interacts with EXO1 (PubMed:11427529, PubMed:11429708, PubMed:12414623, PubMed:14676842, PubMed:22753075). Interacts with MTMR15/FAN1 (PubMed:20603073).

Similarity

Belongs to the DNA mismatch repair MutL/HexB family.

Keywords

ATP-binding   Cell cycle   Chromosome   Complete proteome   DNA damage   DNA repair   Nucleotide-binding   Nucleus   Phosphoprotein   Reference proteome   3D-structure   Acetylation   Alternative splicing   Disease mutation   Hereditary nonpolyposis colorectal cancer   Polymorphism   Tumor suppressor  

Feature

chain  DNA mismatch repair protein Mlh1
splice variant  In isoform 2.
sequence variant  In HNPCC2; dbSNP:rs367654552.

Uniprot

A0A194QIA4   A0A2A4J730   A0A2W1BJ81   A0A3S2M0G3   A0A2H1WVL2   A0A1A8MXV9   + More
A0A1A8NKX3   A0A3Q1IF16   A0A1A8EP69   A0A1A8JBC5   A0A1A8CT25   A0A1A7ZFT8   A0A1A8D7L7   H2V8A2   A0A3B5BFC6   A0A3Q0R8T3   A0A3Q1ATQ8   A0A3Q3A5A3   A0A3P8UHI1   A0A147B2U5   I3JVJ6   A0A3Q3MJH2   A0A3P8WP48   A0A3Q2WPX6   A0A3P8QP15   A0A3P9BXD5   N6UIA2   A0A060VUS2   A0A1W4YPA0   A0A3B4CLB8   A0A2M4BGC7   A0A3Q1IEZ7   A0A1S3N2R6   A0A3Q2DRB8   A0A3P9MXL2   A0A195FX28   A0A3Q2VMU2   A0A3Q1FLH9   A0A3B4TLS6   A0A0F8C3Z0   A0A061I7W4   A0A3Q3IY45   A0A2I4AZJ2   A0A2U9CCK6   K7IN39   C3Y458   A0A3B4YQ70   A0A3B3XS72   A0A1W4YNV8   Q9JK91   A0A3Q3WPT4   V9KFJ8   A0A250Y541   A0A195CXK8   A0A087Y5T2   A0A1A7XZX0   A0A3B3CF03   I3M618   A0A061I5I4   A0A1S2ZC56   A0A3B3HRQ1   A0A2K6Q8L6   A0A2K5PMB6   A0A218UZY5   A0A3B3UVR8   A0A093GK37   A0A2K6EAM3   G7NYL5   A0A0D9RNU4   G7MJ24   A0A232F9W4   A0A151WW18   Q8VDI4   A0A2K5Y4B2   A0A2K5NFX5   A0A1U7THD7   A0A091FJK2   A0A2K5DJK9   A0A0M9ACB3   A0A2M4BGM0   I3LT92   A0A096MTT9   A0A2J8WYG5   A0A2K6TQ60   A0A154PF65   G1QYL9   U6CWA1   A0A2R9AM85   H9FUL2   H2QMA1   A0A3B4BG63   G3RJQ3   H0WYF6   A0A158P0T6   Q5GJ64   B2R6K0   P40692   W5MBU0   A0A2K5UB34   D3K5L8  

Pubmed

26354079    28756777    21551351    25186727    24487278    23537049    + More
24755649    25835551    23929341    20075255    18563158    16141072    8674118    21183079    24402279    28087693    29451363    17554307    25362486    22002653    28648823    15489334    30723633    22722832    25319552    16136131    25463417    22398555    21347285    8145827    8128251    7812952    7757073    14702039    16641997    10783165    10097147    11427529    11429708    12414623    14676842    8751876    16873062    18206974    16188885    16873053    18157157    18669648    19690332    20603073    21269460    21406692    22223895    23186163    24275569    26300262    26249686    20020535    21120944    7661930    8571956    8566964    8872463    8797773    8609062    9311737    8993976    9087566    9218993    9048925    9272156    9067757    9259192    9298827    9399661    9032648    9326924    9718327    9611074    9559627    9526167    10627141    10660333    10671064    9833759    10375096    9927034    10573010    10323887    10480359    10598809    10386556    10413423    10777691    10713887    10882759    12132870    11369138    11389087    11726306    11555625    11139242    11748856    12095971    12373605    12115348    11781295    11839723    11793442    11754112    12200596    11870161    12362047    12658575    14504054    12655562    12655564    14635101    15139004    15365995    15365996    14961575    15064764    15184898    16083711    16451135    17440981    17510385    17301300    18033691    18561205    22753075    28494185   

EMBL

KQ459193    KPJ03181.1    NWSH01002958    PCG67223.1    KZ150086    PZC73765.1    + More
RSAL01000087    RVE48250.1    ODYU01011328    SOQ57006.1    HAEF01020185    SBR61344.1    HAEH01002739    SBR69534.1    HAEB01002140    SBQ48667.1    HAED01020495    SBR07066.1    HADZ01018004    SBP81945.1    HADY01003019    SBP41504.1    HAEA01001627    SBQ30107.1    GCES01001225    JAR85098.1    AERX01006539    AERX01006540    APGK01024678    KB740558    ENN80366.1    FR904307    CDQ58586.1    GGFJ01002951    MBW52092.1    KQ981200    KYN44993.1    KQ042804    KKF10442.1    KE674453    ERE76413.1    CP026257    AWP14307.1    GG666484    EEN65084.1    AF250844    AK168849    U60872    U59881    U59882    U59883    U59884    JW864554    AFO97071.1    GFFV01001291    JAV38654.1    KQ977141    KYN05381.1    AYCK01020172    HADX01001068    SBP23300.1    AGTP01006768    ERE76412.1    MUZQ01000082    OWK59218.1    KL215897    KFV67159.1    CM001277    EHH51433.1    AQIB01119299    CM001254    EHH16516.1    NNAY01000599    OXU27465.1    KQ982691    KYQ52073.1    BC021815    AAH21815.1    KL447035    KFO69289.1    KQ435706    KOX80229.1    GGFJ01003002    MBW52143.1    AEMK02000085    DQIR01169089    DQIR01215976    DQIR01230351    DQIR01246560    DQIR01268204    DQIR01268205    DQIR01268206    DQIR01289569    DQIR01292542    DQIR01293419    DQIR01298061    HDB24566.1    HDB85828.1    AHZZ02020311    NDHI03003375    PNJ74806.1    KQ434892    KZC10526.1    ADFV01172234    ADFV01172235    ADFV01172236    ADFV01172237    ADFV01172238    ADFV01172239    HAAF01002301    CCP74127.1    AJFE02091605    AJFE02091606    AJFE02091607    JU334568    JU475654    JV047104    AFE78321.1    AFH32458.1    AFI37175.1    AACZ04000223    AACZ04000224    GABC01008247    GABF01003843    GABD01008642    NBAG03000225    JAA03091.1    JAA18302.1    JAA24458.1    PNI73893.1    CABD030020751    CABD030020752    CABD030020753    CABD030020754    AAQR03005980    AAQR03005981    AAQR03005982    AAQR03005983    AAQR03005984    ADTU01005783    AY517558    AAT44531.1    AK312609    BAG35497.1    U07343    U07418    U40978    U40960    U40961    U40962    U40963    U40964    U40965    U40966    U40967    U40968    U40969    U40970    U40971    U40972    U40973    U40974    U40975    U40976    U40977    U17857    U17839    U17840    U17841    U17842    U17843    U17844    U17845    U17846    U17847    U17848    U17849    U17851    U17852    U17853    U17854    U17855    U17856    AY217549    AK295359    AK298324    AK298583    AK316074    AK316264    AC006583    AC011816    CH471055    BC006850    AHAT01021992    AQIA01039189    AQIA01039190    AQIA01039191    AQIA01039192    GU373696    ADC38896.1   

Proteomes

UP000053268    UP000218220    UP000283053    UP000265040    UP000005226    UP000261400    + More
UP000261340    UP000257160    UP000264800    UP000265080    UP000005207    UP000261640    UP000265120    UP000264840    UP000265100    UP000265160    UP000019118    UP000193380    UP000192224    UP000261440    UP000087266    UP000265020    UP000242638    UP000078541    UP000257200    UP000261420    UP000030759    UP000261600    UP000192220    UP000246464    UP000002358    UP000001554    UP000261360    UP000261480    UP000000589    UP000261620    UP000078542    UP000028760    UP000261560    UP000005215    UP000079721    UP000001038    UP000233200    UP000233040    UP000197619    UP000261500    UP000053875    UP000233120    UP000009130    UP000029965    UP000215335    UP000075809    UP000233140    UP000233060    UP000189704    UP000053760    UP000233020    UP000053105    UP000008227    UP000028761    UP000233220    UP000076502    UP000001073    UP000240080    UP000002277    UP000261520    UP000001519    UP000005225    UP000005205    UP000005640    UP000018468    UP000233100   

PRIDE

Q9JK91    I3LT92    Q5GJ64    B2R6K0    P40692   

Pfam

PF16413   Mlh1_C        + More
PF01119   DNA_mis_repair
PF17065   UPF0669

Interpro

IPR013507   DNA_mismatch_S5_2-like        + More
IPR038973   MutL/Mlh/Pms       
IPR032189   Mlh1_C       
IPR014762   DNA_mismatch_repair_CS       
IPR003594   HATPase_C       
IPR020568   Ribosomal_S5_D2-typ_fold       
IPR036890   HATPase_C_sf       
IPR014721   Ribosomal_S5_D2-typ_fold_subgr       
IPR002099   DNA_mismatch_repair_N       
IPR031420   UPF0669       

SUPFAM

SSF54211   SSF54211        + More
SSF55874   SSF55874       

Gene 3D

3.30.230.10     3.30.565.10    

CDD

cd00075  HATPase_c

ProteinModelPortal

A0A194QIA4   A0A2A4J730   A0A2W1BJ81   A0A3S2M0G3   A0A2H1WVL2   A0A1A8MXV9   + More
A0A1A8NKX3   A0A3Q1IF16   A0A1A8EP69   A0A1A8JBC5   A0A1A8CT25   A0A1A7ZFT8   A0A1A8D7L7   H2V8A2   A0A3B5BFC6   A0A3Q0R8T3   A0A3Q1ATQ8   A0A3Q3A5A3   A0A3P8UHI1   A0A147B2U5   I3JVJ6   A0A3Q3MJH2   A0A3P8WP48   A0A3Q2WPX6   A0A3P8QP15   A0A3P9BXD5   N6UIA2   A0A060VUS2   A0A1W4YPA0   A0A3B4CLB8   A0A2M4BGC7   A0A3Q1IEZ7   A0A1S3N2R6   A0A3Q2DRB8   A0A3P9MXL2   A0A195FX28   A0A3Q2VMU2   A0A3Q1FLH9   A0A3B4TLS6   A0A0F8C3Z0   A0A061I7W4   A0A3Q3IY45   A0A2I4AZJ2   A0A2U9CCK6   K7IN39   C3Y458   A0A3B4YQ70   A0A3B3XS72   A0A1W4YNV8   Q9JK91   A0A3Q3WPT4   V9KFJ8   A0A250Y541   A0A195CXK8   A0A087Y5T2   A0A1A7XZX0   A0A3B3CF03   I3M618   A0A061I5I4   A0A1S2ZC56   A0A3B3HRQ1   A0A2K6Q8L6   A0A2K5PMB6   A0A218UZY5   A0A3B3UVR8   A0A093GK37   A0A2K6EAM3   G7NYL5   A0A0D9RNU4   G7MJ24   A0A232F9W4   A0A151WW18   Q8VDI4   A0A2K5Y4B2   A0A2K5NFX5   A0A1U7THD7   A0A091FJK2   A0A2K5DJK9   A0A0M9ACB3   A0A2M4BGM0   I3LT92   A0A096MTT9   A0A2J8WYG5   A0A2K6TQ60   A0A154PF65   G1QYL9   U6CWA1   A0A2R9AM85   H9FUL2   H2QMA1   A0A3B4BG63   G3RJQ3   H0WYF6   A0A158P0T6   Q5GJ64   B2R6K0   P40692   W5MBU0   A0A2K5UB34   D3K5L8  

PDB

4P7A     E-value=2.91519e-129,     Score=1185

KEGG

101740968    K08734 DNA mismatch repair protein MLH1 | (RefSeq) DNA mismatch repair protein Mlh1

PATHWAY

03430    Mismatch repair - Bombyx mori (domestic silkworm)
03460    Fanconi anemia pathway - Bombyx mori (domestic silkworm)

GO

GO:0005524   GO:0032300   GO:0030983   GO:0016887   GO:0006298   GO:0016021   GO:0043060   GO:0007141   GO:0051026   GO:0007283   GO:0016321   GO:0032407   GO:0008630   GO:0045141   GO:0032137   GO:0000289   GO:0007129   GO:0032389   GO:0000795   GO:0016446   GO:0003697   GO:0001673   GO:0005654   GO:0048477   GO:0003682   GO:0006303   GO:0009617   GO:0048298   GO:0019899   GO:0045950   GO:0005712   GO:0051257   GO:0000712   GO:0045190   GO:0007060   GO:0005715   GO:0048304   GO:0007140   GO:0051321   GO:0005634   GO:0002204   GO:0007131   GO:0005694   GO:0016447   GO:0045143   GO:0006281   GO:0000794   GO:0000793   GO:0006974   GO:0045132   GO:0016020   GO:0003676   GO:0051287   GO:0030117   GO:0006418   GO:0003707   GO:0006259  

PANTHER

PTHR10073  

Subcellular location

Nucleus   Recruited to chromatin in a MCM9-dependent manner.   With evidence from 2 publications.
Chromosome   Recruited to chromatin in a MCM9-dependent manner.   With evidence from 2 publications.

Length:

713

Number of predicted TMHs:

0

Exp number of AAs in TMHs:

0.15105

Exp number, first 60 AAs:

0

Total prob of N-in:

0.00024

outside

1  -  713

 

 

Pi

219.827901

Theta

179.197157

Tajima's D

0.75113

CLR

0.105628

CSRT

0.589720513974301

Interpretation

Uncertain