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FLASH GENE

Symbol

MSH5

contributors: mct - updated : 30-03-2021

HGNC name	mutS homolog 5 (E. coli)
HGNC id	7328

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	POF13 premature ovarian failure 13
Location	6p21.33      Physical location : 2.993.298 - 31.730.450
Synonym symbol(s)	NG23, MutSH5, MGC2939, G7, MUTSH5, POF13, MGC2939, DKFZp434C1615

DNA

TYPE	functioning gene
STRUCTURE	22.67 kb     25 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter (CAAT box) (TATA box)
	cytosine-phosphate-guanine/HTF
text structure	a TATAAA box and several CCAAT boxes in the 5-prime untranslated region
	a 117-bp CpG island in the exon 1A

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_025259 25 splicing 2685 NP_079535 - 822 - 2008 17977839 NM_172165 25 splicing 2742 NP_751897 - 835 - 2008 17977839 using two alternate splice sites in the coding region maintaining the reading frame NM_002441 25 splicing 2879 NP_002432 92.9 834 - 2008 17977839 differring in the 5' UTR and using an alternate in-frame splice site in the coding region encoding the same isoform than variant 4 NM_172166 25 splicing 2721 NP_751898 92.9 834 - 2008 17977839 using an alternate in-frame splice site in the coding region encoding the same isoform than variant 3 MSH5 sv - splicing 2847 - 868 - 2008 17977839 retention of the last 51 bp of hMSH5 intron 6, in which the encoded 17-amino acid insertion between codons 179 and 180 does not compromise its capability to interact with hMSH4

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive female system ovary         male system testis     highly   male system prostate     highly Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone

cells

System Cell Pubmed Species Stage Rna symbol Reproductive germ cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a CRM1-dependent nuclear export signal (NES)
	a nuclear localization signal that participates to its nuclear targeting

mono polymer

heteromer , oligo

HOMOLOGY

interspecies	ortholog to yeast S.cerevisiae meiosis-specific protein
	ortholog to murine Msh5
	homolog to C.elegans H26D21.2
	homolog to rattus Rn.44043

Homologene

FAMILY

DNA mismatch repair MUTS family

CATEGORY

DNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,chromatin/chromosome
text	MSH5 shuttles between the nucleus and the cytoplasm, being much less stable in the nucleus than in the cytoplasm

basic FUNCTION	putatively required for chromosome pairing in meiosis and DNA replicative mismatch repair
	gonadal maintenance in females
	involved in Mt DNA metabolism
	facilitating crossovers between homologs during meiosis
	playing functional roles in an array of cellular processes such as DNA damage response and meiotic homologous recombination
	involved in DNA mismatch repair (MMR) and meiotic recombination, and deficiency of MMR has been documented to have a role in lung cancer (Wang 2008)
	MutS-homologous protein required for meiotic DNA recombination
	MSH5 implicated in homologous recombination (HR)-mediated DSB repair and the DNA damage response
	MSH5 promotes HR-based DSB repair, and this property resides in the carboxyl-terminal portion of the protein

CELLULAR PROCESS	cell cycle,division,meiosis
	nucleotide, recombination
	nucleotide, repair, mismatch repair

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

heterooligomer of MSH4 and MSH5

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	binding to MSH4
	role for MSH5 in DNA damage response involving ABL1 and TP73, suggesting that mutations impairing this process could significantly affect normal cellular responses to anti-cancer treatments
	MSH5 stimulates mtDNA repair in response to DNA damage induced by oxidative stress
	functional interplay between MSH5 and BRIP1 in double-strand break repair induced by replication stress
	MSH5 is the target of HCP5 during DNA double-strand breaks (DSBs) repair
	HCP5 regulated MSH5 expression and Granulosa cells function through direct binding with YBX1 and modulating its subcellular localization

cell & other

REGULATION

activated by

HCP5, that is a novel transcriptional activator of MSH5

ASSOCIATED DISORDERS

corresponding disease(s)

POF13

Susceptibility

to lung cancer to azoospermia or oligozoospermia

Variant & Polymorphism other	variant rs3131379 in intron 10 associated to lung cancer (Wang 2008)
	(rs2075789, Pro29Ser) seem to be risk factors for the development of azoospermia or oligozoospermia

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Msh5 null mutation mouse