MSH4

Protein identityUniProt · HPA

UniProt accession

O15457

Gene

MSH4

Ensembl

ENSG00000057468

Chromosome

1

Canonical length

936 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Equatorial segment,Flagellar centriole,Mid piece

OverviewNCBI Gene

This gene encodes a member of the DNA mismatch repair mutS family. This member is a meiosis-specific protein that is not involved in DNA mismatch correction, but is required for reciprocal recombination and proper segregation of homologous chromosomes at meiosis I. This protein and MSH5 form a heterodimer which binds uniquely to a Holliday Junction and its developmental progenitor, thus provoking ADP-ATP exchange, and stabilizing the interaction between parental chromosomes during meiosis double-stranded break repair. [provided by RefSeq, Aug 2011]

Canonical amino-acid sequenceUniProt

936 residues, UniProt reviewed canonical sequence.

>O15457|MSH4
     1  MLRPEISSTS PSAPAVSPSS GETRSPQGPR YNFGLQETPQ SRPSVQVVSA STCPGTSGAA
    61  GDRSSSSSSL PCPAPNSRPA QGSYFGNKRA YAENTVASNF TFGASSSSAR DTNYPQTLKT
   121  PLSTGNPQRS GYKSWTPQVG YSASSSSAIS AHSPSVIVAV VEGRGLARGE IGMASIDLKN
   181  PQIILSQFAD NTTYAKVITK LKILSPLEII MSNTACAVGN STKLFTLITE NFKNVNFTTI
   241  QRKYFNETKG LEYIEQLCIA EFSTVLMEVQ SKYYCLAAVA ALLKYVEFIQ NSVYAPKSLK
   301  ICFQGSEQTA MIDSSSAQNL ELLINNQDYR NNHTLFGVLN YTKTPGGSRR LRSNILEPLV
   361  DIETINMRLD CVQELLQDEE LFFGLQSVIS RFLDTEQLLS VLVQIPKQDT VNAAESKITN
   421  LIYLKHTLEL VDPLKIAMKN CNTPLLRAYY GSLEDKRFGI ILEKIKTVIN DDARYMKGCL
   481  NMRTQKCYAV RSNINEFLDI ARRTYTEIVD DIAGMISQLG EKYSLPLRTS FSSARGFFIQ
   541  MTTDCIALPS DQLPSEFIKI SKVKNSYSFT SADLIKMNER CQESLREIYH MTYMIVCKLL
   601  SEIYEHIHCL YKLSDTVSML DMLLSFAHAC TLSDYVRPEF TDTLAIKQGW HPILEKISAE
   661  KPIANNTYVT EGSNFLIITG PNMSGKSTYL KQIALCQIMA QIGSYVPAEY SSFRIAKQIF
   721  TRISTDDDIE TNSSTFMKEM KEIAYILHNA NDKSLILIDE LGRGTNTEEG IGICYAVCEY
   781  LLSLKAFTLF ATHFLELCHI DALYPNVENM HFEVQHVKNT SRNKEAILYT YKLSKGLTEE
   841  KNYGLKAAEV SSLPPSIVLD AKEITTQITR QILQNQRSTP EMERQRAVYH LATRLVQTAR
   901  NSQLDPDSLR IYLSNLKKKY KEDFPRTEQV PEKTEE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MSH4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

4 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MSH4.

Disease | AllUniProt

Conditions MSH4 is implicated in, by any mechanism.

• Spermatogenic failure 2 (SPGF2) MIM:108420
• Premature ovarian failure 20 (POF20) MIM:619938

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 176 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Spermatogenic failure 2
• Genetic non-acquired premature ovarian failure
• Premature ovarian failure 20
• Non-obstructive azoospermia
• Oligospermia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.99

gnomAD pLI

0

gnomAD missense Z

0.81

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• female gamete generation
• homologous chromosome pairing at meiosis
• mismatch repair
• ovarian follicle development
• reciprocal meiotic recombination
• spermatogenesis

Molecular functions

• ATP binding
• ATP-dependent DNA damage sensor activity
• DNA binding
• double-stranded DNA binding
• mismatched DNA binding

Cellular components

• chromosome
• nucleus
• synaptonemal complex
• recombination nodule

Protein domainsUniProt · Pfam · InterPro

• DNA mismatch repair protein MutS, C-terminal
• DNA mismatch repair protein MutS, core
• DNA mismatch repair protein MutS, connector domain
• DNA mismatch repair protein MutS, clamp
• P-loop containing nucleoside triphosphate hydrolase
• DNA mismatch repair protein MutS, core domain superfamily
• MutS, connector domain superfamily
• DNA mismatch repair MutS
• MutS domain V
• MutS domain II
• MutS family domain IV
• MutS domain III

KeywordsUniProt

• ATP-binding
• Chromosome
• DNA-binding
• Meiosis
• Nucleotide-binding
• Premature ovarian failure

InteractionsUniProt · HPA

Protein binding partners of MSH4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• EIF3F
• MSH5