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Entry version 194 (13 Nov 2019)
Sequence version 1 (01 Nov 1998)
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Protein

E3 ubiquitin-protein ligase RNF8

Gene

RNF8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes '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. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites (PubMed:11322894, PubMed:14981089, PubMed:17724460, PubMed:18001824, PubMed:18001825, PubMed:18006705, PubMed:18077395, PubMed:18337245, PubMed:18948756, PubMed:19015238, PubMed:19124460, PubMed:19202061, PubMed:19203578, PubMed:19203579, PubMed:20550933, PubMed:21558560, PubMed:21857671, PubMed:21911360, PubMed:22266820, PubMed:22373579, PubMed:22531782, PubMed:22705371, PubMed:22865450, PubMed:22980979). Following DNA damage, mediates the ubiquitination and degradation of POLD4/p12, a subunit of DNA polymerase delta. In the absence of POLD4, DNA polymerase delta complex exhibits higher proofreading activity (PubMed:23233665). In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggravating telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2 (PubMed:11322894, PubMed:14981089, PubMed:17724460, PubMed:18001824, PubMed:18001825, PubMed:18006705, PubMed:18077395, PubMed:18337245, PubMed:18948756, PubMed:19015238, PubMed:19124460, PubMed:19202061, PubMed:19203578, PubMed:19203579, PubMed:20550933, PubMed:21558560, PubMed:21857671, PubMed:21911360, PubMed:22266820, PubMed:22373579, PubMed:22531782, PubMed:22705371, PubMed:22865450, PubMed:22980979).25 Publications

Caution

According to a well-established model, RNF8 initiate H2A 'Lys-63'-linked ubiquitination leading to recruitment of RNF168 to amplify H2A 'Lys-63'-linked ubiquitination (PubMed:19203578 and PubMed:19203579). However, other data suggest that RNF168 is the priming ubiquitin ligase by mediating monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub respectively) (PubMed:22980979). These data suggest that RNF168 might be recruited to DSBs sites in a RNF8-dependent manner by binding to non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is then amplified by RNF8 (PubMed:22980979). Additional evidence is however required to confirm these data.UniRule annotation1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

  • S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.UniRule annotation EC:2.3.2.27

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.UniRule annotation
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section specifies the position(s) and type(s) of zinc fingers within the protein.<p><a href='/help/zn_fing' target='_top'>More...</a></p>Zinc fingeri403 – 441RING-typeUniRule annotationAdd BLAST39

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionChromatin regulator, Transferase
Biological processCell cycle, Cell division, DNA damage, DNA repair, Mitosis, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-69473 G2/M DNA damage checkpoint

SIGNOR Signaling Network Open Resource

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SIGNORi
O76064

UniPathway: a resource for the exploration and annotation of metabolic pathways

More...
UniPathwayi
UPA00143

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF8UniRule annotation (EC:2.3.2.27UniRule annotation)
Short name:
hRNF8
Alternative name(s):
RING finger protein 8UniRule annotation
RING-type E3 ubiquitin transferase RNF8UniRule annotation
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:RNF8UniRule annotation
Synonyms:KIAA0646
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:10071 RNF8

Online Mendelian Inheritance in Man (OMIM)

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MIMi
611685 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_O76064

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus, Telomere

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi42R → A: Abolishes interaction with ATM-phosphorylated MDC1. Abolishes interaction with human herpesvirus 1 ICP0. Abolishes recruitment to DNA damage sites after UV irradiation, ionizing radiation, or treatment with an alkylating agent. 4 Publications1
Mutagenesisi403C → S: Marked reduction of E2-dependent ubiquitination of histone H2A. Loss of UBE2E2- and UBE2N-binding. Loss of nuclear localization. 4 Publications1
Mutagenesisi405I → A: Impairs interaction with UBE2L6/UBCH8 and ability to mediate 'Lys-48'-linked ubiquitination E3 ligase activity, while it still catalyzes 'Lys-63'-linked ubiquitination and still interacts with UBE2N/UBC13. 3 Publications1
Mutagenesisi406C → S: Abolishes ubiquitin-ligase activity. 1 Publication1
Mutagenesisi443D → R: Does not affect the monomeric structure but abolishes ability to monoubiquitinate H2A in nucleosomes. 1 Publication1

Organism-specific databases

DisGeNET

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DisGeNETi
9025

Open Targets

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OpenTargetsi
ENSG00000112130

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA34445

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
O76064

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
RNF8

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000560481 – 485E3 ubiquitin-protein ligase RNF8Add BLAST485

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei157PhosphoserineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Autoubiquitinated through 'Lys-48' and 'Lys-63' of ubiquitin. 'Lys-63' polyubiquitination is mediated by UBE2N. 'Lys-29'-type polyubiquitination is also observed, but it doesn't require its own functional RING-type zinc finger.UniRule annotation1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
O76064

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
O76064

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
O76064

MaxQB - The MaxQuant DataBase

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MaxQBi
O76064

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
O76064

PeptideAtlas

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PeptideAtlasi
O76064

PRoteomics IDEntifications database

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PRIDEi
O76064

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
50370 [O76064-1]
50371 [O76064-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
O76064

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
O76064

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Ubiquitous. In fetal tissues, highest expression in brain, thymus and liver. In adult tissues, highest levels in brain and testis, lowest levels in peripheral blood cells.2 Publications

<p>This subsection of the ‘Expression’ section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified ‘at the protein level’.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

Low levels at the G1-S boundary increase in intensity during S phase and until the end of the G2 phase. Abruptly decreases in late mitosis (at protein level). Barely detectable in anaphase.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000112130 Expressed in 217 organ(s), highest expression level in frontal cortex

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
O76064 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O76064 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA050731
HPA064925

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer.

Forms a E2-E3 ubiquitin ligase complex composed of the RNF8 homodimer and a E2 heterodimer of UBE2N and UBE2V2.

Interacts with class III E2s, including UBE2E1, UBE2E2, and UBE2E3 and with UBE2N.

Interacts with RXRA.

Interacts (via FHA domain) with ATM-phosphorylated MDC1.

Interacts (via FHA domain) with 'Thr-4827' phosphorylated HERC2 (via C-terminus).

Interacts with PIWIL1; leading to sequester RNF8 in the cytoplasm (By similarity).

Interacts with WRAP53/TCAB1 (PubMed:25512560).

By similarity12 Publications

(Microbial infection) Interacts (via FHA domain) with phosphorylated human herpesvirus 1 ICP0 protein; leading to RNF8 degradation by the proteasome.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
114492, 68 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
O76064

Database of interacting proteins

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DIPi
DIP-31265N

Protein interaction database and analysis system

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IntActi
O76064, 69 interactors

Molecular INTeraction database

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MINTi
O76064

STRING: functional protein association networks

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STRINGi
9606.ENSP00000362578

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1485
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
O76064

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
O76064

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini38 – 92FHAUniRule annotationAdd BLAST55

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni68 – 72Required for interaction with PIWIL1UniRule annotation5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi276 – 345Gln-richAdd BLAST70

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1 and 'Thr-4827' phosphorylated HERC2 (PubMed:18001824). This domain is required for proper recruitment to DNA damage sites after UV irradiation, ionizing radiation, or treatment with an alkylating agent (PubMed:23233665).2 Publications

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the RNF8 family.UniRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri403 – 441RING-typeUniRule annotationAdd BLAST39

Keywords - Domaini

Zinc-finger

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
ENOG410INBI Eukaryota
ENOG410Z9IW LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00400000022349

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000154169

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
O76064

KEGG Orthology (KO)

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KOi
K10667

Identification of Orthologs from Complete Genome Data

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OMAi
SYCISEW

Database of Orthologous Groups

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OrthoDBi
1585372at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O76064

TreeFam database of animal gene trees

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TreeFami
TF330957

Family and domain databases

Conserved Domains Database

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CDDi
cd00060 FHA, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
3.30.40.10, 1 hit

HAMAP database of protein families

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HAMAPi
MF_03067 RNF8, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR000253 FHA_dom
IPR017335 RNF8
IPR008984 SMAD_FHA_dom_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS

Pfam protein domain database

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Pfami
View protein in Pfam
PF00498 FHA, 1 hit

PIRSF; a whole-protein classification database

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PIRSFi
PIRSF037950 E3_ubiquit_lig_RNF8, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00240 FHA, 1 hit
SM00184 RING, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF49879 SSF49879, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50006 FHA_DOMAIN, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O76064-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
MGEPGFFVTG DRAGGRSWCL RRVGMSAGWL LLEDGCEVTV GRGFGVTYQL
60 70 80 90 100
VSKICPLMIS RNHCVLKQNP EGQWTIMDNK SLNGVWLNRA RLEPLRVYSI
110 120 130 140 150
HQGDYIQLGV PLENKENAEY EYEVTEEDWE TIYPCLSPKN DQMIEKNKEL
160 170 180 190 200
RTKRKFSLDE LAGPGAEGPS NLKSKINKVS CESGQPVKSQ GKGEVASTPS
210 220 230 240 250
DNLDPKLTAL EPSKTTGAPI YPGFPKVTEV HHEQKASNSS ASQRSLQMFK
260 270 280 290 300
VTMSRILRLK IQMQEKHEAV MNVKKQTQKG NSKKVVQMEQ ELQDLQSQLC
310 320 330 340 350
AEQAQQQARV EQLEKTFQEE EQHLQGLEIA QGEKDLKQQL AQALQEHWAL
360 370 380 390 400
MEELNRSKKD FEAIIQAKNK ELEQTKEEKE KMQAQKEEVL SHMNDVLENE
410 420 430 440 450
LQCIICSEYF IEAVTLNCAH SFCSYCINEW MKRKIECPIC RKDIKSKTYS
460 470 480
LVLDNCINKM VNNLSSEVKE RRIVLIRERK AKRLF
Length:485
Mass (Da):55,518
Last modified:November 1, 1998 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i54650B2FFC9948B1
GO
Isoform 2 (identifier: O76064-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     81-98: SLNGVWLNRARLEPLRVY → SFPSEKAEDFTAAGERFL
     99-485: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.
Show »
Length:98
Mass (Da):10,846
Checksum:i0E5E5F3D13560D56
GO
Isoform 3 (identifier: O76064-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     413-448: AVTLNCAHSFCSYCINEWMKRKIECPICRKDIKSKT → QRDCSEDRALRAFERLPGSASLRWSGGFSLAVTPLL
     449-485: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:448
Mass (Da):50,829
Checksum:iC20C2E1E5A761106
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J858C9J858_HUMAN
E3 ubiquitin-protein ligase RNF8
RNF8
205Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H7C4L7H7C4L7_HUMAN
E3 ubiquitin-protein ligase RNF8
RNF8
208Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8WEW6F8WEW6_HUMAN
E3 ubiquitin-protein ligase RNF8
RNF8
89Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8WDH8F8WDH8_HUMAN
E3 ubiquitin-protein ligase RNF8
RNF8
49Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence BAA31621 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence BAG60572 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated
The sequence EAX03945 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti230V → A in BAD96485 (Ref. 6) Curated1
Sequence conflicti334K → R in BAD96485 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_052096162A → T. Corresponds to variant dbSNP:rs34338974Ensembl.1
Natural variantiVAR_052097473I → V. Corresponds to variant dbSNP:rs1139944Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_03667181 – 98SLNGV…PLRVY → SFPSEKAEDFTAAGERFL in isoform 2. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_03783199 – 485Missing in isoform 2. 1 PublicationAdd BLAST387
Alternative sequenceiVSP_054037413 – 448AVTLN…IKSKT → QRDCSEDRALRAFERLPGSA SLRWSGGFSLAVTPLL in isoform 3. CuratedAdd BLAST36
Alternative sequenceiVSP_054038449 – 485Missing in isoform 3. CuratedAdd BLAST37

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AB012770 Genomic DNA Translation: BAA33557.1
AF334675 mRNA Translation: AAQ14887.1
AB014546 mRNA Translation: BAA31621.2 Different initiation.
AK298319 mRNA Translation: BAG60572.1 Sequence problems.
BT007446 mRNA Translation: AAP36114.1
AK222765 mRNA Translation: BAD96485.1
AL096712 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX03944.1
CH471081 Genomic DNA Translation: EAX03945.1 Sequence problems.
BC007517 mRNA Translation: AAH07517.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS4833.1 [O76064-3]
CCDS4834.1 [O76064-1]

NCBI Reference Sequences

More...
RefSeqi
NP_003949.1, NM_003958.3 [O76064-1]
NP_898901.1, NM_183078.2 [O76064-3]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000229866; ENSP00000229866; ENSG00000112130 [O76064-2]
ENST00000373479; ENSP00000362578; ENSG00000112130 [O76064-1]
ENST00000469731; ENSP00000418879; ENSG00000112130 [O76064-3]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
9025

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:9025

UCSC genome browser

More...
UCSCi
uc003onq.4 human [O76064-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB012770 Genomic DNA Translation: BAA33557.1
AF334675 mRNA Translation: AAQ14887.1
AB014546 mRNA Translation: BAA31621.2 Different initiation.
AK298319 mRNA Translation: BAG60572.1 Sequence problems.
BT007446 mRNA Translation: AAP36114.1
AK222765 mRNA Translation: BAD96485.1
AL096712 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX03944.1
CH471081 Genomic DNA Translation: EAX03945.1 Sequence problems.
BC007517 mRNA Translation: AAH07517.1
CCDSiCCDS4833.1 [O76064-3]
CCDS4834.1 [O76064-1]
RefSeqiNP_003949.1, NM_003958.3 [O76064-1]
NP_898901.1, NM_183078.2 [O76064-3]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CSWNMR-A8-139[»]
2PIEX-ray1.35A13-146[»]
4AYCX-ray1.90A/B351-485[»]
4ORHX-ray4.80C/G/H/K/L345-485[»]
4WHVX-ray8.30C/D/I/J345-485[»]
SMRiO76064
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi114492, 68 interactors
CORUMiO76064
DIPiDIP-31265N
IntActiO76064, 69 interactors
MINTiO76064
STRINGi9606.ENSP00000362578

PTM databases

iPTMnetiO76064
PhosphoSitePlusiO76064

Polymorphism and mutation databases

BioMutaiRNF8

Proteomic databases

EPDiO76064
jPOSTiO76064
MassIVEiO76064
MaxQBiO76064
PaxDbiO76064
PeptideAtlasiO76064
PRIDEiO76064
ProteomicsDBi50370 [O76064-1]
50371 [O76064-2]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
9025

Genome annotation databases

EnsembliENST00000229866; ENSP00000229866; ENSG00000112130 [O76064-2]
ENST00000373479; ENSP00000362578; ENSG00000112130 [O76064-1]
ENST00000469731; ENSP00000418879; ENSG00000112130 [O76064-3]
GeneIDi9025
KEGGihsa:9025
UCSCiuc003onq.4 human [O76064-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
9025
DisGeNETi9025

GeneCards: human genes, protein and diseases

More...
GeneCardsi
RNF8
HGNCiHGNC:10071 RNF8
HPAiHPA050731
HPA064925
MIMi611685 gene
neXtProtiNX_O76064
OpenTargetsiENSG00000112130
PharmGKBiPA34445

Human Unidentified Gene-Encoded large proteins database

More...
HUGEi
Search...

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiENOG410INBI Eukaryota
ENOG410Z9IW LUCA
GeneTreeiENSGT00400000022349
HOGENOMiHOG000154169
InParanoidiO76064
KOiK10667
OMAiSYCISEW
OrthoDBi1585372at2759
PhylomeDBiO76064
TreeFamiTF330957

Enzyme and pathway databases

UniPathwayiUPA00143
ReactomeiR-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-69473 G2/M DNA damage checkpoint
SIGNORiO76064

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
RNF8 human
EvolutionaryTraceiO76064

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
RNF8

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
9025
PharosiO76064

Protein Ontology

More...
PROi
PR:O76064

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000112130 Expressed in 217 organ(s), highest expression level in frontal cortex
ExpressionAtlasiO76064 baseline and differential
GenevisibleiO76064 HS

Family and domain databases

CDDicd00060 FHA, 1 hit
Gene3Di3.30.40.10, 1 hit
HAMAPiMF_03067 RNF8, 1 hit
InterProiView protein in InterPro
IPR000253 FHA_dom
IPR017335 RNF8
IPR008984 SMAD_FHA_dom_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PfamiView protein in Pfam
PF00498 FHA, 1 hit
PIRSFiPIRSF037950 E3_ubiquit_lig_RNF8, 1 hit
SMARTiView protein in SMART
SM00240 FHA, 1 hit
SM00184 RING, 1 hit
SUPFAMiSSF49879 SSF49879, 1 hit
PROSITEiView protein in PROSITE
PS50006 FHA_DOMAIN, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiRNF8_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O76064
Secondary accession number(s): A6NN24
, A8MYC0, B4DPG0, Q53H16, Q5NKW5
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: November 1, 1998
Last modified: November 13, 2019
This is version 194 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: 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. SIMILARITY comments
    Index of protein domains and families
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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