RAD50_RAT
ID RAD50_RAT Reviewed; 1312 AA.
AC Q9JIL8;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=DNA repair protein RAD50;
DE EC=3.6.-.-;
GN Name=Rad50;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=10908350; DOI=10.1093/nar/28.15.2882;
RA Lanson N.A. Jr., Egeland D.B., Royals B.A., Claycomb W.C.;
RT "The MRE11-NBS1-RAD50 pathway is perturbed in SV40 large T antigen-
RT immortalized AT-1, AT-2 and HL-1 cardiomyocytes.";
RL Nucleic Acids Res. 28:2882-2892(2000).
RN [2]
RP PROTEIN SEQUENCE OF 454-458; 726-736; 824-832 AND 1127-1134, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U., Lubec S.;
RL Submitted (SEP-2007) to UniProtKB.
CC -!- FUNCTION: Component of the MRN complex, which plays a central role in
CC double-strand break (DSB) repair, DNA recombination, maintenance of
CC telomere integrity and meiosis. The complex possesses single-strand
CC endonuclease activity and double-strand-specific 3'-5' exonuclease
CC activity, which are provided by MRE11. RAD50 may be required to bind
CC DNA ends and hold them in close proximity. This could facilitate
CC searches for short or long regions of sequence homology in the
CC recombining DNA templates, and may also stimulate the activity of DNA
CC ligases and/or restrict the nuclease activity of MRE11 to prevent
CC nucleolytic degradation past a given point. The complex may also be
CC required for DNA damage signaling via activation of the ATM kinase. In
CC telomeres the MRN complex may modulate t-loop formation (By
CC similarity). {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per homodimer. {ECO:0000250};
CC -!- SUBUNIT: Component of the MRN complex composed of two heterodimers
CC RAD50/MRE11 associated with a single NBN. As part of the MRN complex,
CC interacts with MCM8 and MCM9; the interaction recruits the complex to
CC DNA repair sites. Component of the BASC complex, at least composed of
CC BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN. Found in a
CC complex with TERF2. Interacts with RINT1. Interacts with BRCA1 via its
CC N-terminal domain. Interacts with DCLRE1C/Artemis. Interacts with MRNIP
CC (By similarity). Interacts with CYREN (via XLF motif) (By similarity).
CC {ECO:0000250|UniProtKB:P70388, ECO:0000250|UniProtKB:Q92878}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q92878}.
CC Chromosome, telomere {ECO:0000250|UniProtKB:Q92878}. Chromosome
CC {ECO:0000250|UniProtKB:Q92878}. Note=Localizes to discrete nuclear foci
CC after treatment with genotoxic agents. {ECO:0000250|UniProtKB:Q92878}.
CC -!- TISSUE SPECIFICITY: Present at low levels in the heart at fetal-day 17,
CC at relatively constant levels at postnatal days 10, 17 and 21 and at
CC slightly lower levels in the adult heart. Detected in liver, kidney and
CC lung. Barely detectable in skeletal muscle with slightly higher levels
CC observed in brain and the ventricles of the heart (at protein level).
CC {ECO:0000269|PubMed:10908350}.
CC -!- DOMAIN: The zinc-hook, which separates the large intramolecular coiled
CC coil regions, contains 2 Cys residues that coordinate one molecule of
CC zinc with the help of the 2 Cys residues of the zinc-hook of another
CC RAD50 molecule, thereby forming a V-shaped homodimer. The two heads of
CC the homodimer, which constitute the ATP-binding domain, interact with
CC the MRE11 homodimer (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the SMC family. RAD50 subfamily. {ECO:0000305}.
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DR EMBL; AF218576; AAF91229.1; -; mRNA.
DR RefSeq; NP_071582.1; NM_022246.1.
DR AlphaFoldDB; Q9JIL8; -.
DR SMR; Q9JIL8; -.
DR BioGRID; 248931; 1.
DR STRING; 10116.ENSRNOP00000062378; -.
DR CarbonylDB; Q9JIL8; -.
DR iPTMnet; Q9JIL8; -.
DR PhosphoSitePlus; Q9JIL8; -.
DR jPOST; Q9JIL8; -.
DR PaxDb; Q9JIL8; -.
DR PRIDE; Q9JIL8; -.
DR GeneID; 64012; -.
DR KEGG; rno:64012; -.
DR UCSC; RGD:621542; rat.
DR CTD; 10111; -.
DR RGD; 621542; Rad50.
DR eggNOG; KOG0962; Eukaryota.
DR InParanoid; Q9JIL8; -.
DR OrthoDB; 179362at2759; -.
DR PhylomeDB; Q9JIL8; -.
DR Reactome; R-RNO-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-RNO-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-RNO-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-RNO-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-RNO-5693548; Sensing of DNA Double Strand Breaks.
DR Reactome; R-RNO-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-RNO-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-RNO-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-RNO-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-RNO-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-RNO-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-RNO-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-RNO-69473; G2/M DNA damage checkpoint.
DR PRO; PR:Q9JIL8; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070533; C:BRCA1-C complex; ISO:RGD.
DR GO; GO:0000785; C:chromatin; IDA:RGD.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:RGD.
DR GO; GO:0000794; C:condensed nuclear chromosome; IDA:RGD.
DR GO; GO:0016234; C:inclusion body; IDA:RGD.
DR GO; GO:0030870; C:Mre11 complex; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0045120; C:pronucleus; ISO:RGD.
DR GO; GO:0035861; C:site of double-strand break; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0003691; F:double-stranded telomeric DNA binding; IBA:GO_Central.
DR GO; GO:0051880; F:G-quadruplex DNA binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:UniProtKB.
DR GO; GO:0043047; F:single-stranded telomeric DNA binding; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEP:RGD.
DR GO; GO:0051276; P:chromosome organization; ISO:RGD.
DR GO; GO:0070192; P:chromosome organization involved in meiotic cell cycle; ISO:RGD.
DR GO; GO:0032508; P:DNA duplex unwinding; ISO:RGD.
DR GO; GO:0006310; P:DNA recombination; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; IEP:RGD.
DR GO; GO:1904354; P:negative regulation of telomere capping; ISO:RGD.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IMP:RGD.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IBA:GO_Central.
DR GO; GO:0033674; P:positive regulation of kinase activity; ISO:RGD.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; ISO:RGD.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; ISO:RGD.
DR GO; GO:0007131; P:reciprocal meiotic recombination; TAS:RGD.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; ISO:RGD.
DR GO; GO:0000019; P:regulation of mitotic recombination; ISS:UniProtKB.
DR GO; GO:0044752; P:response to human chorionic gonadotropin; IEP:RGD.
DR GO; GO:0000723; P:telomere maintenance; TAS:RGD.
DR GO; GO:0000722; P:telomere maintenance via recombination; IBA:GO_Central.
DR GO; GO:0007004; P:telomere maintenance via telomerase; ISS:UniProtKB.
DR GO; GO:0031860; P:telomeric 3' overhang formation; ISO:RGD.
DR CDD; cd03240; ABC_Rad50; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR045171; ABC_Rad50.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR038729; Rad50/SbcC_AAA.
DR InterPro; IPR004584; Rad50_eukaryotes.
DR InterPro; IPR013134; Zn_hook_RAD50.
DR Pfam; PF13476; AAA_23; 1.
DR Pfam; PF04423; Rad50_zn_hook; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR TIGRFAMs; TIGR00606; rad50; 1.
DR PROSITE; PS51131; ZN_HOOK; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cell cycle; Chromosome; Coiled coil;
KW Direct protein sequencing; DNA damage; DNA repair; Hydrolase; Meiosis;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Telomere; Zinc.
FT CHAIN 1..1312
FT /note="DNA repair protein RAD50"
FT /id="PRO_0000138643"
FT DOMAIN 635..734
FT /note="Zinc-hook"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00471"
FT COILED 200..534
FT /evidence="ECO:0000255"
FT COILED 635..673
FT /evidence="ECO:0000255"
FT COILED 706..734
FT /evidence="ECO:0000255"
FT COILED 754..954
FT /evidence="ECO:0000255"
FT COILED 1019..1075
FT /evidence="ECO:0000255"
FT BINDING 36..43
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 681
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00471"
FT BINDING 684
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00471"
FT MOD_RES 635
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92878"
FT MOD_RES 690
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q92878"
FT MOD_RES 959
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q92878"
SQ SEQUENCE 1312 AA; 153784 MW; F13C041BD2C05932 CRC64;
MSRIEKMSTL GVRSFGIEDK DKQIISFFSP LTILVGPNGA GKTTIIECLK YICTGDFPPG
TKGNTFVHDP KVAQETDVRA QIRLQFRDVN GEMVLVQRSM LCSQKSKKTE FKTLEGVITR
IKHGEKVSLS SKCAEIDREM ISCLGVSKSV LNNVIFCHQE DSNWPLSEGK ALKQKFDEIF
SATRYIKALD TLRQVRQTQG QKVKECQTEL KYLRQNKEKA CEIRDQITSK EAQLASSREI
VKAYENELEP LKNRLKEIEH NLSKIMRLDN EIKALDSRKK QMEKDNSELE QKMEKVFQGT
DEQLNDLYHN HQRTVREKER RLVDCQRELE KLSKEARLLN QERAELLVEQ GRLQLQADRH
QEHIRARDSL IQSLAAHLEL DGFERGPFSE RQIKNFHELV RERQEREAKT ASQLLSDLTD
KEALKQRQMD EMRDKKSGLG RMIELKTEIL TKKQTELRNV RNELQQLEGS SDRILELDQE
LTKAERELSK AEKNSSIETL KAEILNLQSE KADLDRNLRK LDQEMEQLNH HTTTRTQMEM
LTKDKTDKDE QIRKIKSRHS DELTSLLGYF PNKKQLEDWL HSKSKEINQT RDRLAKLNKE
LASAEQNKNH INNELKKKEE QLSSYEDKLF DVCGSQDFES DLDRLKEDIE KSSKQRAMLA
GATAVYSQFI TQLTDENQSC CPGCQRVFQT EAELQEVISD LQSKLRLAPD KLKSTESELK
KKERRRDEML GLVPMRQSII DLKEKEIPEL RNRLQSVNRD IQRLKNDIEE QETLLGTVMP
EEESAKVCLT DVTIMERFQM ELKDVERKIA QQAAKLQGVD LDRTVQQVNQ EKQEKQHKLD
TVSSKIELNR KLIQDQQEQI QHLKSKTNEL KSEKLQIATN LQRRQQMEEQ TVELSTEVQS
LNREIKDAKE QINPLEIALE KLQQEKEELI HRKNTSNKMA QDKINDIKEK VKNIHGYMKD
IENYIQDGKD DYKKQKETEL NEVVIQLNEC DKHKEKINKE MGTMRQDIDT KKIQERWLQD
NLTLRKRREE LKEVEEERKQ HLKEMGQMQV LQMKNEHQKL EENIDTIKRN HSLALGRQKG
YEEEILHFKK ELREPQFRDA EEKYREMMIV MRTTELVNKD LDIYYKTLDH AIMKFHSMKM
EEINKIIRDL WRSTYRGQDI EYIEIRSDAD ENVSASDKRR NYNYRVVMLK GDTALDMRGR
CSAGQKVLAS LIIRLALAET FCLNCGILAL DEPTTNLDRE NIESLAHALV EIIKSRSQQR
NFQLLVITHD EDFVELLGRS EYVEKFYRVK KNIDQCSEIV KSSINSLGSY VH
