Protein: Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) (mRif1) (Q6PR54)
Organism: Mus musculus (Mouse)
Function: Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs. In response to DNA damage, interacts with ATM-phosphorylated TP53BP1. Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (By similarity). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs. In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase. Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs. Promotes NHEJ of dysfunctional telomeres.
Subcellular location: Nucleus {ECO:0000269|PubMed:15042697}. Chromosome {ECO:0000269|PubMed:23306437, ECO:0000269|PubMed:23306439, ECO:0000269|PubMed:23333305}. Chromosome, telomere {ECO:0000269|PubMed:15042697}. Cytoplasm, cytoskeleton, spindle {ECO:0000250|UniProtKB:Q5UIP0}. Note=Exhibits ATM- and TP53BP1-dependent localization to uncapped or aberrant telomeres and to DNA double strand breaks (DSBs). Following interaction with TP53BP1, recruited to sites of DNA damage, such as DSBs (PubMed:23306437, PubMed:23306439, PubMed:23333305). Localizes to microtubules of the midzone of the mitotic spindle during anaphase, and to condensed chromosomes in telophase (By similarity). While the majority of the protein appears nuclear and distinct from normal telomere structures, a small fraction may bind to telomeres in embryonic stem cells (PubMed:15042697). {ECO:0000250|UniProtKB:Q5UIP0, ECO:0000269|PubMed:15042697, ECO:0000269|PubMed:23306437, ECO:0000269|PubMed:23306439, ECO:0000269|PubMed:23333305}.
Interaction partners:
- PAX-interacting protein 1
- TP53-binding protein 1
- Serine-protein kinase ATM
- E3 ubiquitin-protein ligase RNF168
Sequence:
MTAPGRSPLEPLLETWEDPSVPPGEQTDAYLTLTSRMTGEEGKEVIAEIEKNLSRLYTVLKAHISSQNSELSSAALQALGFCLYNPRITSGLSEANIQELLLTLNGIIKSSDKNVCTRALWVISKQTFPAELVSKMVSSIIDSLEVILSKGEIHSAVVDFEALNVIIRLIEQAPVQMGEESVRWAKLVIPLVVHSAQKVHLRGATALEMGMPLLLQKQQEIALITEHLMTTKLISELQKLFKNKNETYVLKLWPLFVKLLGKTLHRSGSFINSLLQLEELGFRSGTPMIKKIAFIAWKSLIDNFALNPDILCSAKRLKLLMQPLSSIHVRTETLALTKLEVWWYLLMRLGPQLPANFEQVCVPLIQSTISVDSIPSPQGNSSRGSASPGLSPLTPGHKGASPYGSPRGNLSSNTGGMAAIPSIQLLGLEMMLHFLLGPEVLSFAKQHKIVLSLEPLEHPLISSPSFFSKYAHTLITAVHDSFVSVGKDASDAVVSAIWKELISLVKSVTEAGNRKEKSGSEVLTLLLKSLENIVKSEVFPVSKTLVLMEITVKGLPPKVLGSPAYQVANMDILNGTPALFLIQLIFNNNLLECGVEDEKFFLNLETLVGCVLSGPTSPLAFSDSVLTVINQNAKQLVNKEHLWRMWSMIVSPLTDVIHQTNEVNQGDALEHNFSAIYGALTLPINHIFSAQTFPTGTMKALLKTWSELYRAFTRCASLVATAEENLCCEELSSKIMCSLEDEVLSDLLFLDRISHIIIVMVDCIDFSPYNKKYQPKIKSPQRSSDWSRKKKEPLGKLASLFKLIVKVIDTFHTLSLKETFSDTLLAIGNSIISMLSNVFGHISLPSMIREIFATFTRPLALLYENSKLDEAPKVYTSLNNKLEKLLGEIVACLQFSYLGAYDSELLEHLSPLLCVIFLHKNKQIRKQSALLWNATFAKATALVYPEELKPILRQAKQKILLLLPGLENVEMMDESSEPYSESTENSQLNVKISGMERKSSGKRDSILAHTKDKKKKVKLSAKLKLESSSPKIKSGKLLEEEKSTDFVFIPPEGKETKARVLTEHQKEVLKTKRCDIPALYNNLDASQDTLFSAQFSQEESMESLTLTEKPKEDAKIIKEEQMESTIFIHQDAPENCGIDEHSENASLPNCGGSVAETNPETLITGFDARKEVLISSKILSAESSSSTETSVVSSSSVSNATFSGTPPQPTSRRQTFITLEKFDGSETRPFSPSPLNNISSTVTVRNNQDNTTNTDMPPKARKREVTNSKSDSENLANAGKKSSRRWSKAEQSVTKKSKPSLTSEQEEHSSENNSPDLLSPTEHVSENDDHPSEATLEHKDGDPKPAVENASLEDLTTEEKNVGINMESKESTASVVARTEQIVNEDSQAAALAPNPKTLRRSSRRRSEAVDSCSDSQERESGQQKKERRKEEEKIISKSPLRIKDDKLPTQKLTDESPIQENLTEKGNTLPERTSGEPSVNAEIDQNRRKPDLENVSSEGGGGTLDNLDKSSEKPLRGRTRYQTRRASQGLISAVENSESDSSEAKEEVSRKKRSGKWKNRSSDSVDIEEQEEKKAEEEVMKTANQTLDGQAVPDVDVNAAAQVCEKSTNNNRVILQDSAGPADSLQAPPKGEEKSKINKCVDSSFVSLPVPESNLRTRNASKRLLYKQDNDSNVRVSDSSLSPEKFTQVECQHKRSRRVRRSKSCDCCGEKSQSQEKSFIGLKNTESYAIKSVEKKKTDLQVPETAPETREARDHAETKLAGEEPLVNFHVGLKEENCTTGDSVKSEAELQEASLPPEIVTVKEKTYDTDASEAVSEIQGPCSENHSPAEDPGLSECKDISQKQLSENGELDISDVGKACKVIAGSSPEGVETMELNVRNDAFVAADSEKSTQMDVSVDVATEEDNKKDECEAVTTEVNVEGVATEDFNSGMDLSDTPIPVSKDVETEHAASGEIEGESNESDSGSCEEMNKEMGSHKAQMSTEIDSARVKETDILASASKSEEALIGRLDVNTQSFVSDIEMSSGERTVNCKTETSIELNKLDEAKLSGNEATVGNDTLQEVCFTSEKVEKLPQCLLVQVASELGAESNTTSPEKLELDSFGSVNESPSGMQQARCVWSPLASPSTSILKRGLKRSQEDEISPVNKIRRVSFADPIYQAGLADDIDRRCSVVRSHSSNSSPIIKSVKTSPTSHSKHNTTSAKGFLSPGSQSSKFKSPKKCLITEMAQESMLSPTESVYPALVNCAASVDIILPQITSNMWARGLGQLIRAKNIKTIGDLSTLTASEIKTLPIRSPKVFNVKKALRVYHEQQMKSRGLEEIPIFDISEKAVNGVESRTVSTDEERFASDLIEPVTLDTPLSKNLVAQISALALQLDSEDLYSYTGSQLFEMHEKLGTMANSIIRNLQSRWRSPAHENS