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Protein

DNA repair protein RAD50

Gene

RAD50

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 MRE11. 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 MRE11 to prevent nucleolytic degradation past a given point (PubMed:11741547, PubMed:9590181, PubMed:9705271, PubMed:9651580). The complex may also be required for DNA damage signaling via activation of the ATM kinase (PubMed:15064416). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888).6 Publications

Miscellaneous

In case of infection by adenovirus E4, the MRN complex is inactivated and degraded by viral oncoproteins, thereby preventing concatenation of viral genomes in infected cells.

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi681ZincPROSITE-ProRule annotation1
Metal bindingi684ZincPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi36 – 43ATPSequence analysis8

GO - Molecular functioni

GO - Biological processi

  • cellular response to DNA damage stimulus Source: MGI
  • chromosome organization involved in meiotic cell cycle Source: GO_Central
  • DNA double-strand break processing Source: Reactome
  • DNA duplex unwinding Source: BHF-UCL
  • DNA recombination Source: UniProtKB
  • DNA repair Source: UniProtKB
  • DNA replication Source: Reactome
  • double-strand break repair Source: UniProtKB
  • double-strand break repair via homologous recombination Source: GO_Central
  • double-strand break repair via nonhomologous end joining Source: Reactome
  • negative regulation of telomere capping Source: BHF-UCL
  • nucleic acid phosphodiester bond hydrolysis Source: GOC
  • positive regulation of kinase activity Source: BHF-UCL
  • positive regulation of protein autophosphorylation Source: BHF-UCL
  • positive regulation of telomere maintenance Source: BHF-UCL
  • reciprocal meiotic recombination Source: ProtInc
  • regulation of mitotic recombination Source: UniProtKB
  • telomere maintenance Source: BHF-UCL
  • telomere maintenance via recombination Source: GO_Central
  • telomere maintenance via telomerase Source: UniProtKB
  • telomeric 3' overhang formation Source: BHF-UCL
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionHydrolase
Biological processCell cycle, DNA damage, DNA repair, Host-virus interaction, Meiosis
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence
R-HSA-5685938 HDR through Single Strand Annealing (SSA)
R-HSA-5685939 HDR through MMEJ (alt-NHEJ)
R-HSA-5685942 HDR through Homologous Recombination (HRR)
R-HSA-5693548 Sensing of DNA Double Strand Breaks
R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-69473 G2/M DNA damage checkpoint
R-HSA-912446 Meiotic recombination
SIGNORiQ92878

Names & Taxonomyi

Protein namesi
Recommended name:
DNA repair protein RAD50 (EC:3.6.-.-)
Short name:
hRAD50
Gene namesi
Name:RAD50
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113522.13
HGNCiHGNC:9816 RAD50
MIMi604040 gene
neXtProtiNX_Q92878

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus, Telomere

Pathology & Biotechi

Involvement in diseasei

Nijmegen breakage syndrome-like disorder (NBSLD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder similar to Nijmegen breakage syndrome and characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, short stature and bird-like face. Immunodeficiency is absent.
See also OMIM:613078

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42K → N: Abolishes ability to degrade ATP. 1 Publication1
Mutagenesisi1231D → A: Abolishes ability to degrade ATP. 1 Publication1

Organism-specific databases

DisGeNETi10111
MalaCardsiRAD50
MIMi613078 phenotype
OpenTargetsiENSG00000113522
Orphaneti145 Hereditary breast and ovarian cancer syndrome
240760 Nijmegen breakage syndrome-like disorder
PharmGKBiPA34175

Polymorphism and mutation databases

BioMutaiRAD50
DMDMi60392986

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001386411 – 1312DNA repair protein RAD50Add BLAST1312

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei635PhosphoserineCombined sources1
Modified residuei690PhosphothreonineCombined sources1
Modified residuei959N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ92878
MaxQBiQ92878
PaxDbiQ92878
PeptideAtlasiQ92878
PRIDEiQ92878
ProteomicsDBi75562
75563 [Q92878-2]
75564 [Q92878-3]

PTM databases

iPTMnetiQ92878
PhosphoSitePlusiQ92878

Expressioni

Tissue specificityi

Expressed at very low level in most tissues, except in testis where it is expressed at higher level. Expressed in fibroblasts.1 Publication

Gene expression databases

BgeeiENSG00000113522
CleanExiHS_RAD50
ExpressionAtlasiQ92878 baseline and differential
GenevisibleiQ92878 HS

Organism-specific databases

HPAiCAB022103
CAB024979
HPA052291

Interactioni

Subunit structurei

Component of the MRN complex composed of two heterodimers RAD50/MRE11 associated with a single NBN (PubMed:8756642, PubMed:9590181, PubMed:9705271, PubMed:10839544). Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN (PubMed:10783165). Found in a complex with TERF2 (PubMed:10888888). Interacts with RINT1 (PubMed:11096100). Interacts with BRCA1 via its N-terminal domain (PubMed:10426999). Interacts with DCLRE1C/Artemis (PubMed:15456891, PubMed:15723659). Interacts with MRNIP (PubMed:27568553).11 Publications
(Microbial infection) Interacts with herpes simplex virus 1 protein UL12 (PubMed:20943970).1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein binding, bridging Source: UniProtKB

Protein-protein interaction databases

BioGridi115417, 120 interactors
CORUMiQ92878
DIPiDIP-33606N
IntActiQ92878, 57 interactors
MINTiQ92878
STRINGi9606.ENSP00000265335

Structurei

Secondary structure

11312
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi586 – 632Combined sources47
Helixi638 – 673Combined sources36
Turni674 – 676Combined sources3
Beta strandi682 – 684Combined sources3
Helixi691 – 704Combined sources14
Turni705 – 707Combined sources3
Helixi708 – 731Combined sources24
Helixi733 – 744Combined sources12
Helixi746 – 764Combined sources19

3D structure databases

ProteinModelPortaliQ92878
SMRiQ92878
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini635 – 734Zinc-hookPROSITE-ProRule annotationAdd BLAST100

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili228 – 359Sequence analysisAdd BLAST132
Coiled coili401 – 598Sequence analysisAdd BLAST198
Coiled coili635 – 673Sequence analysisAdd BLAST39
Coiled coili706 – 734Sequence analysisAdd BLAST29
Coiled coili789 – 1079Sequence analysisAdd BLAST291

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1201 – 1238Ala/Asp-rich (DA-box)Add BLAST38

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 MRE11 homodimer (By similarity).By similarity

Sequence similaritiesi

Belongs to the SMC family. RAD50 subfamily.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0962 Eukaryota
COG0419 LUCA
GeneTreeiENSGT00390000018781
HOGENOMiHOG000090195
HOVERGENiHBG058033
InParanoidiQ92878
KOiK10866
OMAiRSMVCTQ
OrthoDBiEOG091G01KA
PhylomeDBiQ92878
TreeFamiTF101217

Family and domain databases

InterProiView protein in InterPro
IPR027417 P-loop_NTPase
IPR038729 Rad50/SbcC_AAA
IPR004584 Rad50_eukaryotes
IPR013134 Zn_hook_RAD50
PfamiView protein in Pfam
PF13476 AAA_23, 1 hit
PF04423 Rad50_zn_hook, 1 hit
SUPFAMiSSF52540 SSF52540, 3 hits
TIGRFAMsiTIGR00606 rad50, 1 hit
PROSITEiView protein in PROSITE
PS51131 ZN_HOOK, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92878-1) [UniParc]FASTAAdd to basket
Also known as: RAD50-1, RAD50-2

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 DKQIITFFSP LTILVGPNGA GKTTIIECLK
60 70 80 90 100
YICTGDFPPG TKGNTFVHDP KVAQETDVRA QIRLQFRDVN GELIAVQRSM
110 120 130 140 150
VCTQKSKKTE FKTLEGVITR TKHGEKVSLS SKCAEIDREM ISSLGVSKAV
160 170 180 190 200
LNNVIFCHQE DSNWPLSEGK ALKQKFDEIF SATRYIKALE TLRQVRQTQG
210 220 230 240 250
QKVKEYQMEL KYLKQYKEKA CEIRDQITSK EAQLTSSKEI VKSYENELDP
260 270 280 290 300
LKNRLKEIEH NLSKIMKLDN EIKALDSRKK QMEKDNSELE EKMEKVFQGT
310 320 330 340 350
DEQLNDLYHN HQRTVREKER KLVDCHRELE KLNKESRLLN QEKSELLVEQ
360 370 380 390 400
GRLQLQADRH QEHIRARDSL IQSLATQLEL DGFERGPFSE RQIKNFHKLV
410 420 430 440 450
RERQEGEAKT ANQLMNDFAE KETLKQKQID EIRDKKTGLG RIIELKSEIL
460 470 480 490 500
SKKQNELKNV KYELQQLEGS SDRILELDQE LIKAERELSK AEKNSNVETL
510 520 530 540 550
KMEVISLQNE KADLDRTLRK LDQEMEQLNH HTTTRTQMEM LTKDKADKDE
560 570 580 590 600
QIRKIKSRHS DELTSLLGYF PNKKQLEDWL HSKSKEINQT RDRLAKLNKE
610 620 630 640 650
LASSEQNKNH INNELKRKEE QLSSYEDKLF DVCGSQDFES DLDRLKEEIE
660 670 680 690 700
KSSKQRAMLA GATAVYSQFI TQLTDENQSC CPVCQRVFQT EAELQEVISD
710 720 730 740 750
LQSKLRLAPD KLKSTESELK KKEKRRDEML GLVPMRQSII DLKEKEIPEL
760 770 780 790 800
RNKLQNVNRD IQRLKNDIEE QETLLGTIMP EEESAKVCLT DVTIMERFQM
810 820 830 840 850
ELKDVERKIA QQAAKLQGID LDRTVQQVNQ EKQEKQHKLD TVSSKIELNR
860 870 880 890 900
KLIQDQQEQI QHLKSTTNEL KSEKLQISTN LQRRQQLEEQ TVELSTEVQS
910 920 930 940 950
LYREIKDAKE QVSPLETTLE KFQQEKEELI NKKNTSNKIA QDKLNDIKEK
960 970 980 990 1000
VKNIHGYMKD IENYIQDGKD DYKKQKETEL NKVIAQLSEC EKHKEKINED
1010 1020 1030 1040 1050
MRLMRQDIDT QKIQERWLQD NLTLRKRNEE LKEVEEERKQ HLKEMGQMQV
1060 1070 1080 1090 1100
LQMKSEHQKL EENIDNIKRN HNLALGRQKG YEEEIIHFKK 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 FCLNCGIIAL DEPTTNLDRE NIESLAHALV
1260 1270 1280 1290 1300
EIIKSRSQQR NFQLLVITHD EDFVELLGRS EYVEKFYRIK KNIDQCSEIV
1310
KCSVSSLGFN VH
Length:1,312
Mass (Da):153,892
Last modified:February 1, 1997 - v1
Checksum:i1F208C3817FC41FC
GO
Isoform 2 (identifier: Q92878-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-5: MSRIE → MLIFSVRDMFA

Show »
Length:1,318
Mass (Da):154,587
Checksum:i54B578956FC29852
GO
Isoform 3 (identifier: Q92878-3) [UniParc]FASTAAdd to basket
Also known as: RAD50-3

The sequence of this isoform differs from the canonical sequence as follows:
     1-139: Missing.

Show »
Length:1,173
Mass (Da):138,432
Checksum:iD6734A4E4D898AAE
GO

Sequence cautioni

The sequence AAH62603 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti204K → E in CAA99729 (Ref. 3) Curated1
Sequence conflicti723E → K in AAH62603 (PubMed:15489334).Curated1
Sequence conflicti723E → K in AAH73850 (PubMed:15489334).Curated1
Sequence conflicti733V → A in CAA99729 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02552694I → L1 PublicationCorresponds to variant dbSNP:rs28903085EnsemblClinVar.1
Natural variantiVAR_029168127V → I. Corresponds to variant dbSNP:rs28903086EnsemblClinVar.1
Natural variantiVAR_022085191T → I. Corresponds to variant dbSNP:rs2230017EnsemblClinVar.1
Natural variantiVAR_029169193R → W. Corresponds to variant dbSNP:rs28903087EnsemblClinVar.1
Natural variantiVAR_025527224R → H1 PublicationCorresponds to variant dbSNP:rs28903088EnsemblClinVar.1
Natural variantiVAR_034436315V → L. Corresponds to variant dbSNP:rs28903090EnsemblClinVar.1
Natural variantiVAR_061779469G → A. Corresponds to variant dbSNP:rs55653181EnsemblClinVar.1
Natural variantiVAR_020958616K → E1 PublicationCorresponds to variant dbSNP:rs1047380Ensembl.1
Natural variantiVAR_020959697V → A1 PublicationCorresponds to variant dbSNP:rs1047382Ensembl.1
Natural variantiVAR_029170842V → A. Corresponds to variant dbSNP:rs28903093EnsemblClinVar.1
Natural variantiVAR_020960964Y → H1 PublicationCorresponds to variant dbSNP:rs1047386Ensembl.1
Natural variantiVAR_020961973K → M1 PublicationCorresponds to variant dbSNP:rs1129482Ensembl.1
Natural variantiVAR_0209621038R → G. Corresponds to variant dbSNP:rs1047387Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0125901 – 139Missing in isoform 3. 1 PublicationAdd BLAST139
Alternative sequenceiVSP_0125911 – 5MSRIE → MLIFSVRDMFA in isoform 2. 1 Publication5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U63139 mRNA Translation: AAB07119.1
AF057299 mRNA Translation: AAD50325.1
AF057300 mRNA Translation: AAD50326.1
Z75311 mRNA Translation: CAA99729.1
AC116366 Genomic DNA No translation available.
AC004042 Genomic DNA No translation available.
CH471062 Genomic DNA Translation: EAW62329.1
BC062603 mRNA Translation: AAH62603.1 Sequence problems.
BC073850 mRNA Translation: AAH73850.1
BC136436 mRNA Translation: AAI36437.1
CCDSiCCDS34233.1 [Q92878-1]
RefSeqiNP_005723.2, NM_005732.3 [Q92878-1]
UniGeneiHs.633509

Genome annotation databases

EnsembliENST00000378823; ENSP00000368100; ENSG00000113522 [Q92878-1]
GeneIDi10111
KEGGihsa:10111
UCSCiuc003kxi.4 human [Q92878-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiRAD50_HUMAN
AccessioniPrimary (citable) accession number: Q92878
Secondary accession number(s): B9EGF5
, O43254, Q6GMT7, Q6P5X3, Q9UP86
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: February 1, 1997
Last modified: July 18, 2018
This is version 171 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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