P97679 (MLH1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA mismatch repair protein Mlh1

Alternative name(s):
MutL protein homolog 1

Gene names

Name:

Mlh1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	757 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

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-Msh6) 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.
Subunit structure	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 MBD4. Interacts with EXO1 and MTMR15/FAN1 By similarity.
Subcellular location	Nucleus By similarity.
Sequence similarities	Belongs to the DNA mismatch repair MutL/HexB family.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair
Cellular component	Nucleus
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to organic cyclic compound Inferred from expression pattern PubMed 16471326. Source: RGD mismatch repair Inferred from Biological aspect of Ancestor. Source: RefGenome reciprocal meiotic recombination Inferred from Biological aspect of Ancestor. Source: RefGenome response to drug Inferred from expression pattern PubMed 18253720. Source: RGD response to hypoxia Inferred from expression pattern PubMed 15942958. Source: RGD response to toxin Inferred from expression pattern PubMed 20127075. Source: RGD somatic hypermutation of immunoglobulin genes Inferred from Biological aspect of Ancestor. Source: RefGenome spermatogenesis Inferred from expression pattern PubMed 10644444. Source: RGD
Cellular_component	MutLalpha complex Inferred from Biological aspect of Ancestor. Source: RefGenome MutLbeta complex Inferred from Biological aspect of Ancestor. Source: RefGenome chiasma Inferred from Biological aspect of Ancestor. Source: RefGenome synaptonemal complex Inferred from direct assay PubMed 16968740. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: InterPro ATPase activity Inferred from Biological aspect of Ancestor. Source: RefGenome MutSalpha complex binding Inferred from Biological aspect of Ancestor. Source: RefGenome mismatched DNA binding Inferred from electronic annotation. Source: InterPro single-stranded DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 757	757	DNA mismatch repair protein Mlh1		PRO_0000178002
Regions
	Region	412 – 652	241	Interaction with EXO1 By similarity
Amino acid modifications
	Modified residue	479	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P97679 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 27E3A007D8BAB287	FASTA	757	84,540
	10 20 30 40 50 60 MSFVAGVIRR LDETVVNRIA AGEVIQRPAN AIKEMTENCL DAKSTNIQVI VREGGLKLIQ 70 80 90 100 110 120 IQDNGTGIRK EDLDIVCERF TTSKLQTFED LAMISTYGFR GEALASISHV AHVTITTKTA 130 140 150 160 170 180 DGKCAYRASY SDGKLQAPPK PCAGNQGTLI TVEDLFYNII TRKKALKNPS EEYGKILEVV 190 200 210 220 230 240 GRYSIHNSGI SFSVKKQGET VSDVRTLPNA TTVDNIRSIF GNAVSRELIE VGCEDKTLAF 250 260 270 280 290 300 KMNGYISNAN YSVKKCIFLL FINHRLVESA ALKKAIEAVY AAYLPKNTHP FLYLILEISP 310 320 330 340 350 360 QNVDVNVHPT KHEVHFLHEE SILERVQQHI ESKLLGSNSS RMYFTQTLLP GLAGPSGEAV 370 380 390 400 410 420 KSTTGIASSS TSGSGDKVHA YQMVRTDSRD QKLDAFMQPV SRRLPSQPQD PVPGNRTEGS 430 440 450 460 470 480 PEKAMQKDQE ISELPAPMEA AADSASLERE SVIGASEVVA PQRHPSSPGS SRKRHPEDSD 490 500 510 520 530 540 VEMMENDSRK EMTAACYPRR RIINLTSVLS LQEEINDRGH ETLREMLRNH TFVGCVNPQW 550 560 570 580 590 600 ALAQHQTKLY LLNTTKLSEE LFYQILIYDF ANFGVLRLPE PAPLFDFAML ALDSPESGWT 610 620 630 640 650 660 EEDGPKEGLA EYIVEFLKKK AKMLADYFSV EIDEEGNLIG LPLLIDSYVP PLEGLPIFIL 670 680 690 700 710 720 RLATEVNWDE EECFESLSKE CAVFYSIRKQ YILEESALSG QQSDMPGSPS KPWKWTVEHI 730 740 750 IYKAFRSHLL PPKHFTEDGN VLQLANLPDL CKVFERC

References

[1]	"Cloning and sequencing of rat mismatch repair gene MLH1." Vani G.R., Rao M.R.S. Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U80054 mRNA. Translation: AAB38506.1.
IPI	IPI00947906.
RefSeq	NP_112315.1. NM_031053.1.
UniGene	Rn.20391.
3D structure databases
ProteinModelPortal	P97679.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000043097.
Proteomic databases
PaxDb	P97679.
PRIDE	P97679.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	81685.
KEGG	rno:81685.
UCSC	RGD:620937. rat.
Organism-specific databases
CTD	4292.
RGD	620937. Mlh1.
Phylogenomic databases
eggNOG	COG0323.
HOGENOM	HOG000176000.
HOVERGEN	HBG006374.
InParanoid	P97679.
KO	K08734.
Gene expression databases
ArrayExpress	P97679.
Genevestigator	P97679.
GermOnline	ENSRNOG00000033809. Rattus norvegicus.
Family and domain databases
Gene3D	3.30.230.10. 1 hit. 3.30.565.10. 1 hit.
InterPro	IPR002099. DNA_mismatch_repair. IPR013507. DNA_mismatch_repair_C. IPR014762. DNA_mismatch_repair_CS. IPR011186. DNA_mismatch_repair_MLH1. IPR014763. DNA_mismatch_repair_N. IPR003594. HATPase_ATP-bd. IPR020568. Ribosomal_S5_D2-typ_fold. IPR014721. Ribosomal_S5_D2-typ_fold_subgr. [Graphical view]
PANTHER	PTHR10073. PTHR10073. 1 hit. PTHR10073:SF11. PTHR10073:SF11. 1 hit.
Pfam	PF01119. DNA_mis_repair. 1 hit. [Graphical view]
SMART	SM00387. HATPase_c. 1 hit. [Graphical view]
SUPFAM	SSF55874. ATP_bd_ATPase. 1 hit. SSF54211. Ribosomal_S5_D2-typ_fold. 1 hit.
TIGRFAMs	TIGR00585. mutl. 1 hit.
PROSITE	PS00058. DNA_MISMATCH_REPAIR_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	615316.

Entry information

Entry name

MLH1_RAT

Accession

Primary (citable) accession number: P97679

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program