Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

DNA repair protein RAD50

Gene

Rad50

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11A to prevent nucleolytic degradation past a given point. The complex may also be required for DNA damage signaling via activation of the ATM kinase. In telomeres the MRN complex may modulate t-loop formation (By similarity).By similarity2 Publications

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per homodimer.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi681 – 6811ZincPROSITE-ProRule annotation
Metal bindingi684 – 6841ZincPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi36 – 438ATPSequence analysis

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair, Meiosis

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
DNA repair protein RAD50 (EC:3.6.-.-)
Short name:
mRad50
Gene namesi
Name:Rad50
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:109292. Rad50.

Subcellular locationi

  • Nucleus By similarity
  • Chromosometelomere By similarity

  • Note: Localizes to discrete nuclear foci after treatment with genotoxic agents.By similarity

GO - Cellular componenti

  • membrane Source: MGI
  • Mre11 complex Source: MGI
  • nuclear chromosome, telomeric region Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
  • pronucleus Source: MGI
  • site of double-strand break Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus, Telomere

Pathology & Biotechi

Disruption phenotypei

Defects cause embryonic stem cell lethality, abnormal embryonic development and sensitivity to ionizing radiation.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi22 – 221K → M in Rad50S; hypomorphic allele that induces growth defects and cancer predisposition. Homozygous individuals die with complete bone marrow depletion as a result of progressive hematopoietic stem cell failure. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13121312DNA repair protein RAD50PRO_0000138642Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei635 – 6351PhosphoserineCombined sources
Modified residuei690 – 6901PhosphothreonineCombined sources
Modified residuei959 – 9591N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP70388.
MaxQBiP70388.
PaxDbiP70388.
PRIDEiP70388.

PTM databases

iPTMnetiP70388.
PhosphoSiteiP70388.

Expressioni

Tissue specificityi

In adult, it is expressed at very low level in most tissues, except in heart, lung and aorta. Expressed at high level in testis.1 Publication

Developmental stagei

Widely expressed. Expressed at higher level in heart, liver and thymus from E18. By neonatal day 1.5, it decreases in brain, liver, gut and skin, while it is expressed in spleen.1 Publication

Gene expression databases

CleanExiMM_RAD50.

Interactioni

Subunit structurei

Component of the MRN complex composed of two heterodimers RAD50/MRE11A associated with a single NBN. Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11A and NBN. Found in a complex with TERF2. Interacts with RINT1. Interacts with BRCA1 via its N-terminal domain. Interacts with DCLRE1C/Artemis (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-46805N.
IntActiP70388. 3 interactions.
MINTiMINT-4131642.
STRINGi10090.ENSMUSP00000020649.

Structurei

3D structure databases

ProteinModelPortaliP70388.
SMRiP70388. Positions 7-60, 1201-1291.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini635 – 734100Zinc-hookPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili200 – 532333Sequence analysisAdd
BLAST
Coiled coili635 – 67339Sequence analysisAdd
BLAST
Coiled coili706 – 73429Sequence analysisAdd
BLAST
Coiled coili776 – 942167Sequence analysisAdd
BLAST
Coiled coili1043 – 107533Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1201 – 123838Ala/Asp-rich (DA-box)Add
BLAST

Domaini

The zinc-hook, which separates the large intramolecular coiled coil regions, contains 2 Cys residues that coordinate one molecule of zinc with the help of the 2 Cys residues of the zinc-hook of another RAD50 molecule, thereby forming a V-shaped homodimer. The two heads of the homodimer, which constitute the ATP-binding domain, interact with the MRE11A homodimer (By similarity).By similarity

Sequence similaritiesi

Belongs to the SMC family. RAD50 subfamily.Curated
Contains 1 zinc-hook domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0962. Eukaryota.
COG0419. LUCA.
HOGENOMiHOG000090195.
HOVERGENiHBG058033.
InParanoidiP70388.
PhylomeDBiP70388.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR027417. P-loop_NTPase.
IPR004584. Rad50_eukaryotes.
IPR013134. Zn_hook_RAD50.
[Graphical view]
PANTHERiPTHR18867. PTHR18867. 1 hit.
PfamiPF04423. Rad50_zn_hook. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 3 hits.
TIGRFAMsiTIGR00606. rad50. 1 hit.
PROSITEiPS51131. ZN_HOOK. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P70388-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSRIEKMSIL GVRSFGIEDK DKQIISFFSP LTILVGPNGA GKTTIIECLK
60 70 80 90 100
YICTGDFPPG TKGNTFVHDP KVAQETDVRA QIRLQFRDVN GEMVAVHRSM
110 120 130 140 150
LCSQKNKKTE FKTLEGVITR MKHGEKVSLS SKCAEIDREM ISCLGVSKSV
160 170 180 190 200
LNNVIFCHQE DSNWPLSEGK ALKQKFDEIF SATRYIKALD TLRQVRQTQG
210 220 230 240 250
QKVKECQTEL KYLKQNKEKA CEIRDQITSK EAQLASSQEI VRSYEDELEP
260 270 280 290 300
LKNRLKEIEH NLSKIMKLDN EIKALESRKK QMEKDNSELE QKMEKVFQGT
310 320 330 340 350
DEQLNDLYHN HQRTVREKER RLVDCQRELE KLNKEARLLN QEKAELLVEQ
360 370 380 390 400
GRLQLQADRH QEHIRARDSL IQSLATHLEL DGFERGPFSE RQIKNFHELV
410 420 430 440 450
KERQEREAKT ASQLLSDLTD KEALKQRQLD ELRDRKSGLG RTIELKTEIL
460 470 480 490 500
TKKQSELRHV RSELQQLEGS SDRILELDQE LTKAERELSK AEKNSSIETL
510 520 530 540 550
KAEVMSLQNE KADLDRSLRK LDQEMEQLNH HTTTRTQMEM LTKDKTDKDE
560 570 580 590 600
QIRKIKSRHS DELTSLLGYF PNKKQLEDWL HSKSKEINQT RDRLAKLNKE
610 620 630 640 650
LASAEQNKNH INNELKKKEE QLSSYEDKLF DVCGSQDLES DLGRLKEEIE
660 670 680 690 700
KSSKQRAMLA GATAVYSQFI TQLTDENQSC CPVCQRVFQT EAELQEVISD
710 720 730 740 750
LQSKLRLAPD KLKSTESELK KKERRRDEML GLVPVRQSII DLKEKEIPEL
760 770 780 790 800
RNRLQSVNRD IQRLKNDIEE QETLLGTIMP EEESAKVCLT DVTIMERFQM
810 820 830 840 850
ELKDVERKIA QQAAKLQGVD LDRTVQQVNQ EKQEKQHRLD TVTSKIELNR
860 870 880 890 900
KLIQDQQEQI QHLKSKTNEL KSEKLQIATN LQRRQQMEEQ SVELSTEVQS
910 920 930 940 950
LNREIKDAKE QISPLETALE KLQQEKEELI HRKHTSNKMA QDKINDIKEK
960 970 980 990 1000
VKNIHGYMKD IENYIQDGKD DYKKQKETEL NGVAVQLNEC EKHREKINKD
1010 1020 1030 1040 1050
MGTMRQDIDT QKIQERWLQD NLTLRKRRDE LKEVEEEPKQ HLKEMGQMQV
1060 1070 1080 1090 1100
LQMKNEHQKL EENIDTIKRN HSLALGRQKG YEDEILHFKK ELREPQFRDA
1110 1120 1130 1140 1150
EEKYREMMIV MRTTELVNKD LDIYYKTLDQ AIMKFHSMKM EEINKIIRDL
1160 1170 1180 1190 1200
WRSTYRGQDI EYIEIRSDAD ENVSASDKRR NYNYRVVMLK GDTALDMRGR
1210 1220 1230 1240 1250
CSAGQKVLAS LIIRLALAET FCLNCGILAL DEPTTNLDRE NIESLAHALV
1260 1270 1280 1290 1300
EIIKSRSQQR NFQLLVITHD EDFVELLGRS EYVEKFYRVK KNMDQCSEIV
1310
KCSISSLGSY VH
Length:1,312
Mass (Da):153,488
Last modified:February 1, 1997 - v1
Checksum:i4AF9AF9AD9E1D7A2
GO
Isoform 2 (identifier: P70388-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     485-545: Missing.

Note: No experimental confirmation available.
Show »
Length:1,251
Mass (Da):146,317
Checksum:iC8583CBF04603CD5
GO
Isoform 3 (identifier: P70388-3) [UniParc]FASTAAdd to basket

Also known as: 3.1 kb splice variant

The sequence of this isoform differs from the canonical sequence as follows:
     1-886: Missing.

Show »
Length:426
Mass (Da):50,408
Checksum:iD52552F467A47A85
GO
Isoform 4 (identifier: P70388-4) [UniParc]FASTAAdd to basket

Also known as: 1.6 kb splice variant

The sequence of this isoform differs from the canonical sequence as follows:
     485-496: ERELSKAEKNSS → IYFLELVRWLSG
     497-1312: Missing.

Show »
Length:496
Mass (Da):57,589
Checksum:i8D296981D5BD922F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti97 – 971H → Q in BAB31030 (PubMed:16141072).Curated
Sequence conflicti200 – 2001G → V in AAH58180 (PubMed:15489334).Curated
Sequence conflicti474 – 4741I → V in BAC40074 (PubMed:16141072).Curated
Sequence conflicti718 – 7181E → A in BAC40074 (PubMed:16141072).Curated
Sequence conflicti719 – 7191L → K in AAH58180 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 886886Missing in isoform 3. 1 PublicationVSP_012592Add
BLAST
Alternative sequencei485 – 54561Missing in isoform 2. 1 PublicationVSP_012593Add
BLAST
Alternative sequencei485 – 49612ERELS…EKNSS → IYFLELVRWLSG in isoform 4. 1 PublicationVSP_012594Add
BLAST
Alternative sequencei497 – 1312816Missing in isoform 4. 1 PublicationVSP_012595Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U66887 mRNA. Translation: AAC52894.1.
AK018001 mRNA. Translation: BAB31030.1.
AK087982 mRNA. Translation: BAC40074.1.
BC058180 mRNA. Translation: AAH58180.1.
CCDSiCCDS24684.1. [P70388-1]
PIRiT30845.
UniGeneiMm.4888.

Genome annotation databases

UCSCiuc011xus.1. mouse. [P70388-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U66887 mRNA. Translation: AAC52894.1.
AK018001 mRNA. Translation: BAB31030.1.
AK087982 mRNA. Translation: BAC40074.1.
BC058180 mRNA. Translation: AAH58180.1.
CCDSiCCDS24684.1. [P70388-1]
PIRiT30845.
UniGeneiMm.4888.

3D structure databases

ProteinModelPortaliP70388.
SMRiP70388. Positions 7-60, 1201-1291.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-46805N.
IntActiP70388. 3 interactions.
MINTiMINT-4131642.
STRINGi10090.ENSMUSP00000020649.

PTM databases

iPTMnetiP70388.
PhosphoSiteiP70388.

Proteomic databases

EPDiP70388.
MaxQBiP70388.
PaxDbiP70388.
PRIDEiP70388.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiuc011xus.1. mouse. [P70388-2]

Organism-specific databases

MGIiMGI:109292. Rad50.

Phylogenomic databases

eggNOGiKOG0962. Eukaryota.
COG0419. LUCA.
HOGENOMiHOG000090195.
HOVERGENiHBG058033.
InParanoidiP70388.
PhylomeDBiP70388.

Miscellaneous databases

ChiTaRSiRad50. mouse.
PROiP70388.
SOURCEiSearch...

Gene expression databases

CleanExiMM_RAD50.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR027417. P-loop_NTPase.
IPR004584. Rad50_eukaryotes.
IPR013134. Zn_hook_RAD50.
[Graphical view]
PANTHERiPTHR18867. PTHR18867. 1 hit.
PfamiPF04423. Rad50_zn_hook. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 3 hits.
TIGRFAMsiTIGR00606. rad50. 1 hit.
PROSITEiPS51131. ZN_HOOK. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mouse RAD50 has limited epitopic homology to p53 and is expressed in the adult myocardium."
    Kim K.K., Daud A.I., Wong S.C., Pajak L., Tsai S.-C., Wang H., Henzel W.J., Field L.J.
    J. Biol. Chem. 271:29255-29264(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), PROTEIN SEQUENCE OF 113-120; 132-140; 175-202; 230-248; 295-310; 815-832; 840-845; 1012-1026 AND 1079-1089, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-214 AND 443-743 (ISOFORM 1).
    Strain: C57BL/6J and NOD.
    Tissue: Thymus.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-722 (ISOFORM 2).
    Strain: NMRI.
    Tissue: Mammary tumor.
  4. "Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation."
    Luo G., Yao M.S., Bender C.F., Mills M., Bladl A.R., Bradley A., Petrini J.H.J.
    Proc. Natl. Acad. Sci. U.S.A. 96:7376-7381(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  5. Cited for: FUNCTION, MUTAGENESIS OF LYS-22.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-635 AND THR-690, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.

Entry informationi

Entry nameiRAD50_MOUSE
AccessioniPrimary (citable) accession number: P70388
Secondary accession number(s): Q6PEB0, Q8C2T7, Q9CU59
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: February 1, 1997
Last modified: March 16, 2016
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.