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Basic Information Integrated Annotations
Tag Content
iUUCD ID IUUC-Hsa-046424
UUCD1 version UUC-HoS-00220
Ensembl Protein ID ENSP00000320898.3
UniProt Accession Q8IYW5; Q8NA67; Q96NS4; RN168_HUMAN
Genbank Protein ID BAB70801.1; BAC04060.1; AAH33791.1
Protein Name E3 ubiquitin-protein ligase RNF168; RING finger protein 168; RING-type E3 ubiquitin transferase RNF168
Genbank Nucleotide ID AK054732; AK093113; AC092933
Gene Name RNF168
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000163961.4 ENST00000318037.3 ENSP00000320898.3
ENSG00000163961.4 ENST00000437070.1 ENSP00000396712.1
Annotation
Cancer Mutation
TCGAICGCCOSMICCGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEOArrayExpressTCGAICGC
COSMICHPM
DNA & RNA Element
UTRdbAREsitecircBasecircRNADb
CircNetmiRTarBasemicroRNATRANSFAC
TargetScanRepTarSomamiRmiRcode
RAID2
Protein-protein Interaction
IIDiRefIndexPINAHINT
MenthaInWeb_IM
Protein 3D Structure
PDBMMDB
Disease-associated Information
ClinVarGWASdbOMIM
Post-translational Modifications (PTMs)
CPLMdbPAFPhosphositePlusdbPTM
HPRDPhospho.ELMUniProtBioGRID
mUbiSiDa
DNA Methylation
TCGAICGC
Protein Expression/Proteomics
THPAHPMGPMDB
Status Reviewed
Details
Family Domain References (PMIDs)
UBD/Alpha-Helix/MIU MIU 21041483
UBD/Alpha-Helix/UMI UMI 21041483
E3 activity/RING/RING RING 19500350; 20080757; 22713238; 22980979; 23760478; 24324146
Classification
Family E-value Score Start End
UBD/Alpha-Helix/MIU 2.70e-12 47.7 168 191
E3 activity/RING/RING 1.60e-05 26.9 16 55
Active Site
Position(s) Description Evidence
N/A N/A N/A
Domain Profile

   UBD/Alpha-Helix/MIU
   S: 1    rqkQprtDlELAqqLQqEeyqqfa 24
           +++Q+++D+ELA++L+++++++++
   Q: 168  MEEQLKSDEELARKLSIDINNFCE 191
           89********************97 PP
   

   E3 activity/RING/RING
   S: 1    CaiCledfkdgplvlpCgHvfhadClqkwpglknssskefrCPlCr 46
           C iC+e + + p++lpC+H+ ++ C+q       +++ +  CP Cr
   Q: 16   CGICMEILVE-PVTLPCNHTLCKPCFQST-----VEKASLCCPFCR 55
           9*********.9**************544.....5**********8 PP
   
Organism Homo sapiens
Functional Description
(View)

Functional Description


     E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).
 E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).
Protein Sequence
(Fasta)
MALPKDAIPS LSECQCGICM EILVEPVTLP CNHTLCKPCF QSTVEKASLC CPFCRRRVSS 60
WTRYHTRRNS LVNVELWTII QKHYPRECKL RASGQESEEV ADDYQPVRLL SKPGELRREY 120
It may take some time, please wait.

Protein Fasta Sequence


>IUUC-Hsa-046424|UBD,MIU;UBD,UMI;E3,RING|Homo sapiens
Please wait for a moment...
Nucleotide Sequence
(Fasta)
GCTTGTCCGG TGGCTGCTGC GCTGCCGCAA CGAATAGGGT TTCTGGCTGC GTAGGAGGGA 60
CGGGGGCGCG GAGCTCTGGG AAACTGCGCC AGGCGCCCGA AAGGTGAACA CGGGAGTCGC 120
It may take some time, please wait.

Nucleotide Fasta Sequence


>IUUC-Hsa-046424|UBD,MIU;UBD,UMI;E3,RING|Homo sapiens
Please wait for a moment...
Sequence Source Ensembl
Keyword

KW-0002--3D-structure
KW-0156--Chromatin regulator
KW-0181--Complete proteome
KW-0227--DNA damage
KW-0234--DNA repair
KW-0479--Metal-binding
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0808--Transferase
KW-0832--Ubl conjugation
KW-0833--Ubl conjugation pathway
KW-0862--Zinc
KW-0863--Zinc-finger
Interpro

IPR034725--RNF168
IPR001841--Znf_RING
IPR013083--Znf_RING/FYVE/PHD
PROSITE

PS50089--ZF_RING_2
SMART

SM00184--RING
Gene Ontology

GO:0005829--C:cytosol
GO:0005654--C:nucleoplasm
GO:0005634--C:nucleus
GO:0043234--C:protein complex
GO:0035861--C:site of double-strand break
GO:0000151--C:ubiquitin ligase complex
GO:0003682--F:chromatin binding
GO:0042393--F:histone binding
GO:0070530--F:K63-linked polyubiquitin binding
GO:0031491--F:nucleosome binding
GO:0043130--F:ubiquitin binding
GO:0004842--F:ubiquitin-protein transferase activity
GO:0008270--F:zinc ion binding
GO:0006974--P:cellular response to DNA damage stimulus
GO:0006302--P:double-strand break repair
GO:0006303--P:double-strand break repair via nonhomologous end joining
GO:0070535--P:histone H2A K63-linked ubiquitination
GO:0035518--P:histone H2A monoubiquitination
GO:0036351--P:histone H2A-K13 ubiquitination
GO:0036352--P:histone H2A-K15 ubiquitination
GO:0036297--P:interstrand cross-link repair
GO:0045190--P:isotype switching
GO:0034244--P:negative regulation of transcription elongation from RNA polymerase II promoter
GO:0045739--P:positive regulation of DNA repair
GO:0070534--P:protein K63-linked ubiquitination
GO:0016567--P:protein ubiquitination
GO:0010212--P:response to ionizing radiation
GO:0006511--P:ubiquitin-dependent protein catabolic process
KEGG hsa:165918
Orthology
iUUCD ID Species Identity E-value Score
IUUC-Aml-001573 Ailuropoda melanoleuca 76.75 0.00e+00 729.00
IUUC-Apl-003963 Anas platyrhynchos 44.81 1.00e-66 247.00
IUUC-Aca-004420 Anolis carolinensis 69.75 1.00e-47 184.00
IUUC-Ath-007019 Arabidopsis thaliana 41.33 1.00e-10 62.40
IUUC-Ame-011521 Astyanax mexicanus 56.03 5.00e-37 149.00
IUUC-Bta-013002 Bos taurus 75.44 0.00e+00 742.00
IUUC-Cja-019945 Callithrix jacchus 85.29 0.00e+00 844.00
IUUC-Cfa-020533 Canis familiaris 76.40 0.00e+00 732.00
IUUC-Cpo-021643 Cavia porcellus 62.05 6.00e-153 534.00
IUUC-Csa-023638 Chlorocebus sabaeus 88.44 0.00e+00 942.00
IUUC-Cho-024319 Choloepus hoffmanni 75.09 0.00e+00 686.00
IUUC-Cin-025679 Ciona intestinalis 37.96 1.00e-20 93.60
IUUC-Csv-026052 Ciona savignyi 35.45 1.00e-18 86.70
IUUC-Dre-028519 Danio rerio 45.98 9.00e-36 144.00
IUUC-Dno-029294 Dasypus novemcinctus 75.87 0.00e+00 728.00
IUUC-Ete-032714 Echinops telfairi 52.32 1.00e-88 320.00
IUUC-Eca-033343 Equus caballus 77.84 0.00e+00 744.00
IUUC-Eeu-034633 Erinaceus europaeus 36.27 7.00e-35 141.00
IUUC-Fca-036251 Felis catus 76.84 0.00e+00 752.00
IUUC-Fal-037048 Ficedula albicollis 45.88 7.00e-80 291.00
IUUC-Gmo-039400 Gadus morhua 46.96 6.00e-31 126.00
IUUC-Gga-040444 Gallus gallus 42.28 7.00e-73 268.00
IUUC-Gac-041735 Gasterosteus aculeatus 45.45 2.00e-34 139.00
IUUC-Gma-044332 Glycine max 37.50 2.00e-13 70.50
IUUC-Ggo-044940 Gorilla gorilla 98.25 0.00e+00 774.00
IUUC-Itr-048965 Ictidomys tridecemlineatus 74.25 0.00e+00 687.00
IUUC-Lch-050649 Latimeria chalumnae 38.49 3.00e-55 209.00
IUUC-Loc-051847 Lepisosteus oculatus 36.31 5.00e-48 185.00
IUUC-Laf-053938 Loxodonta africana 70.88 0.00e+00 743.00
IUUC-Mcc-055360 Macaca mulatta 87.92 0.00e+00 914.00
IUUC-Meu-056684 Macropus eugenii 49.74 6.00e-117 414.00
IUUC-Mga-059699 Meleagris gallopavo 42.66 4.00e-72 265.00
IUUC-Mmr-060779 Microcebus murinus 77.97 0.00e+00 795.00
IUUC-Mdo-062225 Monodelphis domestica 51.11 6.00e-114 404.00
IUUC-Mmu-064239 Mus musculus 64.39 3.00e-158 551.00
IUUC-Mpu-066141 Mustela putorius furo 75.78 0.00e+00 743.00
IUUC-Mlu-067945 Myotis lucifugus 77.27 0.00e+00 761.00
IUUC-Nle-069769 Nomascus leucogenys 94.92 0.00e+00 977.00
IUUC-Opr-070905 Ochotona princeps 62.94 7.00e-175 607.00
IUUC-Ont-071477 Oreochromis niloticus 53.91 7.00e-34 138.00
IUUC-Oan-073531 Ornithorhynchus anatinus 42.78 2.00e-62 233.00
IUUC-Ocu-073832 Oryctolagus cuniculus 69.58 0.00e+00 647.00
IUUC-Oru-084946 Oryza rufipogon 32.71 4.00e-08 52.80
IUUC-Ola-086478 Oryzias latipes 50.41 2.00e-33 134.00
IUUC-Oga-088318 Otolemur garnettii 77.70 0.00e+00 778.00
IUUC-Oar-089647 Ovis aries 74.04 0.00e+00 716.00
IUUC-Ptr-090516 Pan troglodytes 99.12 0.00e+00 1028.00
IUUC-Pan-092302 Papio anubis 87.24 0.00e+00 913.00
IUUC-Psi-093604 Pelodiscus sinensis 42.23 1.00e-81 297.00
IUUC-Pfo-096441 Poecilia formosa 47.93 1.00e-32 134.00
IUUC-Pab-097729 Pongo abelii 96.15 0.00e+00 993.00
IUUC-Pca-100552 Procavia capensis 61.62 2.00e-117 416.00
IUUC-Ppe-102024 Prunus persica 39.58 9.00e-12 66.20
IUUC-Pva-102780 Pteropus vampyrus 76.35 0.00e+00 753.00
IUUC-Rno-105461 Rattus norvegicus 64.29 1.00e-162 566.00
IUUC-Sha-106809 Sarcophilus harrisii 53.38 2.00e-129 456.00
IUUC-Sly-111317 Solanum lycopersicum 37.00 5.00e-15 75.90
IUUC-Stu-112446 Solanum tuberosum 37.27 2.00e-14 73.60
IUUC-Sar-113579 Sorex araneus 61.43 4.00e-159 554.00
IUUC-Tgu-117187 Taeniopygia guttata 65.61 2.00e-46 178.00
IUUC-Tru-118182 Takifugu rubripes 49.59 2.00e-33 136.00
IUUC-Tsy-119217 Tarsius syrichta 58.16 1.00e-68 253.00
IUUC-Tni-120205 Tetraodon nigroviridis 51.64 2.00e-33 136.00
IUUC-Tvi-122557 Trichoderma virens 30.49 6.00e-05 42.40
IUUC-Tbe-127622 Tupaia belangeri 75.35 0.00e+00 753.00
IUUC-Ttr-128988 Tursiops truncatus 80.59 0.00e+00 791.00
IUUC-Vpa-130302 Vicugna pacos 71.30 1.00e-135 477.00
Created Date 25-Jun-2017

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