UniProtKB - Q6ZSG1 (RN165_HUMAN)
Protein
E3 ubiquitin-protein ligase RNF165
Gene
RNF165
Organism
Homo sapiens (Human)
Status
Functioni
E3 ubiquitin-protein ligase that acts as a regulator of motor axon elongation. Required for efficient motor axon extension in the dorsal forelimb by enhancing the transcriptional responses of the SMAD1/SMAD5/SMAD8 effectors, which are activated downstream of BMP. Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD6, SMAD7, SKI and SNON isoform of SKIL.By similarity
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.1 Publication EC:2.3.2.27
Activity regulationi
Binds free ubiquitin non-covalently via its RING-type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-protein ligase activity by stabilizing the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and activating ubiquitin transfer (PubMed:26656854).
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 294 | ZincCombined sources1 Publication | 1 | |
Metal bindingi | 297 | ZincCombined sources1 Publication | 1 | |
Metal bindingi | 317 | ZincCombined sources1 Publication | 1 | |
Metal bindingi | 320 | ZincCombined sources1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 294 – 335 | RING-type; atypicalPROSITE-ProRule annotationAdd BLAST | 42 |
GO - Molecular functioni
- ubiquitin protein ligase activity Source: GO_Central
- zinc ion binding Source: InterPro
GO - Biological processi
- forelimb morphogenesis Source: Ensembl
- innervation Source: Ensembl
- motor neuron axon guidance Source: GO_Central
- multicellular organism aging Source: Ensembl
- muscle structure development Source: Ensembl
- positive regulation of BMP signaling pathway Source: GO_Central
- protein catabolic process Source: Ensembl
- protein polyubiquitination Source: Ensembl
Keywordsi
Molecular function | Transferase |
Biological process | Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q6ZSG1 |
Names & Taxonomyi
Protein namesi | Recommended name: E3 ubiquitin-protein ligase RNF165Curated (EC:2.3.2.271 Publication)Alternative name(s): RING finger protein 165Imported |
Gene namesi | Name:RNF165Imported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:31696, RNF165 |
neXtProti | NX_Q6ZSG1 |
VEuPathDBi | HostDB:ENSG00000141622.13 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Nucleus
- nucleus Source: GO_Central
Other locations
- protein-containing complex Source: Ensembl
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 309 | R → A: Reduced binding to free ubiquitin. 1 Publication | 1 | |
Mutagenesisi | 313 | M → A: Reduced binding to free ubiquitin and reduced E3 ubiquitin-protein ligase activity. 1 Publication | 1 | |
Mutagenesisi | 335 | R → A: Reduced ubiquitin discharge. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 494470 |
OpenTargetsi | ENSG00000141622 |
PharmGKBi | PA134972127 |
Miscellaneous databases
Pharosi | Q6ZSG1, Tdark |
Genetic variation databases
BioMutai | RNF165 |
DMDMi | 74762404 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000245587 | 1 – 346 | E3 ubiquitin-protein ligase RNF165Add BLAST | 346 |
Proteomic databases
PaxDbi | Q6ZSG1 |
PeptideAtlasi | Q6ZSG1 |
PRIDEi | Q6ZSG1 |
ProteomicsDBi | 3753 68216 [Q6ZSG1-1] |
Expressioni
Gene expression databases
Bgeei | ENSG00000141622, Expressed in forebrain and 165 other tissues |
ExpressionAtlasi | Q6ZSG1, baseline and differential |
Genevisiblei | Q6ZSG1, HS |
Organism-specific databases
HPAi | ENSG00000141622, Tissue enhanced (brain) |
Interactioni
Subunit structurei
Monomer; binding to the ubiquitin-conjugating enzyme E2 does not trigger homodimerization (PubMed:26656854).
1 PublicationBinary interactionsi
Q6ZSG1
With | #Exp. | IntAct |
---|---|---|
SKI [P12755] | 2 | EBI-2129206,EBI-347281 |
Protein-protein interaction databases
BioGRIDi | 138966, 10 interactors |
DIPi | DIP-52693N |
IntActi | Q6ZSG1, 12 interactors |
STRINGi | 9606.ENSP00000269439 |
Miscellaneous databases
RNActi | Q6ZSG1, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q6ZSG1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 266 – 268 | Ubiquitin bindingCombined sources1 Publication | 3 | |
Regioni | 309 – 313 | Ubiquitin bindingCombined sources1 Publication | 5 |
Domaini
The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin (PubMed:26656854). Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates ubiquitin transfer (PubMed:26656854).1 Publication
Sequence similaritiesi
Belongs to the Arkadia family.Curated
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 294 – 335 | RING-type; atypicalPROSITE-ProRule annotationAdd BLAST | 42 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG0800, Eukaryota |
GeneTreei | ENSGT00940000156997 |
HOGENOMi | CLU_056012_0_0_1 |
InParanoidi | Q6ZSG1 |
OMAi | FSRHQHS |
PhylomeDBi | Q6ZSG1 |
TreeFami | TF317681 |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR001841, Znf_RING IPR011016, Znf_RING-CH IPR013083, Znf_RING/FYVE/PHD |
Pfami | View protein in Pfam PF13639, zf-RING_2, 1 hit |
SMARTi | View protein in SMART SM00184, RING, 1 hit SM00744, RINGv, 1 hit |
PROSITEi | View protein in PROSITE PS50089, ZF_RING_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q6ZSG1-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MVLVHVGYLV LPVFGSVRNR GAPFQRSQHP HATSCRHFHL GPPQPQQLAP
60 70 80 90 100
DFPLAHPVQS QPGLSAHMAP AHQHSGALHQ SLTPLPTLQF QDVTGPSFLP
110 120 130 140 150
QALHQQYLLQ QQLLEAQHRR LVSHPRRSQE RVSVHPHRLH PSFDFGQLQT
160 170 180 190 200
PQPRYLAEGT DWDLSVDAGL SPAQFQVRPI PQHYQHYLAT PRMHHFPRNS
210 220 230 240 250
SSTQMVVHEI RNYPYPQLHF LALQGLNPSR HTSAVRESYE ELLQLEDRLG
260 270 280 290 300
NVTRGAVQNT IERFTFPHKY KKRRPQDGKG KKDEGEESDT DEKCTICLSM
310 320 330 340
LEDGEDVRRL PCMHLFHQLC VDQWLAMSKK CPICRVDIET QLGADS
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketK7EPZ9 | K7EPZ9_HUMAN | E3 ubiquitin-protein ligase RNF165 | RNF165 | 68 | Annotation score: | ||
K7EQ96 | K7EQ96_HUMAN | E3 ubiquitin-protein ligase RNF165 | RNF165 | 156 | Annotation score: | ||
K7EIS4 | K7EIS4_HUMAN | E3 ubiquitin-protein ligase RNF165 | RNF165 | 28 | Annotation score: | ||
K7ELT0 | K7ELT0_HUMAN | E3 ubiquitin-protein ligase RNF165 | RNF165 | 22 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_045128 | 1 – 192 | Missing in isoform 2. 1 PublicationAdd BLAST | 192 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK127467 mRNA Translation: BAC86992.1 AK122819 mRNA Translation: BAG53743.1 AC015959 Genomic DNA No translation available. AC018931 Genomic DNA No translation available. AC021763 Genomic DNA No translation available. |
CCDSi | CCDS32823.1 [Q6ZSG1-1] CCDS58621.1 [Q6ZSG1-2] |
RefSeqi | NP_001243687.1, NM_001256758.1 [Q6ZSG1-2] NP_689683.2, NM_152470.2 [Q6ZSG1-1] |
Genome annotation databases
Ensembli | ENST00000269439; ENSP00000269439; ENSG00000141622 [Q6ZSG1-1] ENST00000543885; ENSP00000444285; ENSG00000141622 [Q6ZSG1-2] |
GeneIDi | 494470 |
KEGGi | hsa:494470 |
UCSCi | uc002lcb.2, human [Q6ZSG1-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK127467 mRNA Translation: BAC86992.1 AK122819 mRNA Translation: BAG53743.1 AC015959 Genomic DNA No translation available. AC018931 Genomic DNA No translation available. AC021763 Genomic DNA No translation available. |
CCDSi | CCDS32823.1 [Q6ZSG1-1] CCDS58621.1 [Q6ZSG1-2] |
RefSeqi | NP_001243687.1, NM_001256758.1 [Q6ZSG1-2] NP_689683.2, NM_152470.2 [Q6ZSG1-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5D0I | X-ray | 1.90 | A/B | 255-346 | [»] | |
5D0K | X-ray | 2.65 | C/F/I/L | 255-346 | [»] | |
5D0M | X-ray | 1.91 | C | 255-346 | [»] | |
5ULH | X-ray | 1.95 | C | 255-346 | [»] | |
5ULK | X-ray | 2.38 | C | 255-346 | [»] | |
SMRi | Q6ZSG1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 138966, 10 interactors |
DIPi | DIP-52693N |
IntActi | Q6ZSG1, 12 interactors |
STRINGi | 9606.ENSP00000269439 |
Genetic variation databases
BioMutai | RNF165 |
DMDMi | 74762404 |
Proteomic databases
PaxDbi | Q6ZSG1 |
PeptideAtlasi | Q6ZSG1 |
PRIDEi | Q6ZSG1 |
ProteomicsDBi | 3753 68216 [Q6ZSG1-1] |
Protocols and materials databases
Antibodypediai | 9062, 133 antibodies |
Genome annotation databases
Ensembli | ENST00000269439; ENSP00000269439; ENSG00000141622 [Q6ZSG1-1] ENST00000543885; ENSP00000444285; ENSG00000141622 [Q6ZSG1-2] |
GeneIDi | 494470 |
KEGGi | hsa:494470 |
UCSCi | uc002lcb.2, human [Q6ZSG1-1] |
Organism-specific databases
CTDi | 494470 |
DisGeNETi | 494470 |
GeneCardsi | RNF165 |
HGNCi | HGNC:31696, RNF165 |
HPAi | ENSG00000141622, Tissue enhanced (brain) |
neXtProti | NX_Q6ZSG1 |
OpenTargetsi | ENSG00000141622 |
PharmGKBi | PA134972127 |
VEuPathDBi | HostDB:ENSG00000141622.13 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0800, Eukaryota |
GeneTreei | ENSGT00940000156997 |
HOGENOMi | CLU_056012_0_0_1 |
InParanoidi | Q6ZSG1 |
OMAi | FSRHQHS |
PhylomeDBi | Q6ZSG1 |
TreeFami | TF317681 |
Enzyme and pathway databases
PathwayCommonsi | Q6ZSG1 |
Miscellaneous databases
BioGRID-ORCSi | 494470, 6 hits in 874 CRISPR screens |
ChiTaRSi | RNF165, human |
GenomeRNAii | 494470 |
Pharosi | Q6ZSG1, Tdark |
PROi | PR:Q6ZSG1 |
RNActi | Q6ZSG1, protein |
Gene expression databases
Bgeei | ENSG00000141622, Expressed in forebrain and 165 other tissues |
ExpressionAtlasi | Q6ZSG1, baseline and differential |
Genevisiblei | Q6ZSG1, HS |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR001841, Znf_RING IPR011016, Znf_RING-CH IPR013083, Znf_RING/FYVE/PHD |
Pfami | View protein in Pfam PF13639, zf-RING_2, 1 hit |
SMARTi | View protein in SMART SM00184, RING, 1 hit SM00744, RINGv, 1 hit |
PROSITEi | View protein in PROSITE PS50089, ZF_RING_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | RN165_HUMAN | |
Accessioni | Q6ZSG1Primary (citable) accession number: Q6ZSG1 Secondary accession number(s): B3KVD1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 11, 2006 |
Last sequence update: | July 5, 2004 | |
Last modified: | February 10, 2021 | |
This is version 137 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 18
Human chromosome 18: entries, gene names and cross-references to MIM