Q6ZNA4 (RN111_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 93.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: E3 ubiquitin-protein ligase Arkadia EC=6.3.2.- Alternative name(s): RING finger protein 111 | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Reference proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 994 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Acts in the NODAL pathway of mesoderm patterning during embryonic development. Acts downstream AXIN1 as an E3 ubiquitin-protein ligase which promotes the ubiquitination of inhibitory SMADs such as SMAD7, induces their proteasomal degradation and thereby enhances the transcriptional activity of TGF-beta and BMP. Activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. Ref.6 Ref.7 Ref.8 |
| Pathway | |
| Subunit structure | Interacts with SMAD6, SMAD7, AXIN1, AXIN2 and SKIL isoform SNON. Part of a complex containing RNF111, AXIN1 and SMAD7. Interacts (via SIM domains) with SUMO1 and SUMO2. Ref.7 Ref.8 Ref.9 |
| Subcellular location | Nucleus. Cytoplasm. Note: Upon TGF-beta treatment, translocates from nucleus to cytosol. Ref.7 |
| Tissue specificity | Broadly expressed. Ref.6 |
| Sequence similarities | Contains 1 RING-type zinc finger. |
| Sequence caution | The sequence AAH10369.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAC04531.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAD18633.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. |
Ontologies
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q6ZNA4-1) 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. | ||||||
| Isoform 2 (identifier: Q6ZNA4-2) The sequence of this isoform differs from the canonical sequence as follows: 914-921: Missing. | ||||||
| Isoform 3 (identifier: Q6ZNA4-3) The sequence of this isoform differs from the canonical sequence as follows: 766-766: T → TGLFVFCVSR | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 4 (identifier: Q6ZNA4-4) The sequence of this isoform differs from the canonical sequence as follows: 766-766: T → TGLFVFCVSR 914-921: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||
Molecule processing | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 994 | 994 | E3 ubiquitin-protein ligase Arkadia | PRO_0000280690 | ||||||||||||||||||
Regions | ||||||||||||||||||||||
| Zinc finger | 942 – 983 | 42 | RING-type; atypical | |||||||||||||||||||
| Region | 241 – 404 | 164 | Interaction with AXIN1 | |||||||||||||||||||
| Motif | 300 – 304 | 5 | SUMO interaction motif 1 (SIM); mediates the binding to polysumoylated substrates | |||||||||||||||||||
| Motif | 325 – 331 | 7 | SUMO interaction motif 2 (SIM); mediates the binding to polysumoylated substrates | |||||||||||||||||||
| Motif | 382 – 386 | 5 | SUMO interaction motif 3 (SIM); mediates the binding to polysumoylated substrates | |||||||||||||||||||
| Compositional bias | 252 – 464 | 213 | Ser-rich | |||||||||||||||||||
| Compositional bias | 494 – 523 | 30 | His-rich | |||||||||||||||||||
| Compositional bias | 629 – 781 | 153 | Pro-rich | |||||||||||||||||||
Natural variations | ||||||||||||||||||||||
| Alternative sequence | 766 | 1 | T → TGLFVFCVSR in isoform 3 and isoform 4. | VSP_023840 | ||||||||||||||||||
| Alternative sequence | 914 – 921 | 8 | Missing in isoform 2 and isoform 4. | VSP_023841 | ||||||||||||||||||
| Natural variant | 9 | 1 | N → K. Ref.1 Ref.2 Ref.5 Corresponds to variant rs2899642 [ dbSNP | Ensembl ]. | VAR_031185 | ||||||||||||||||||
| Natural variant | 718 | 1 | A → T. Corresponds to variant rs34086812 [ dbSNP | Ensembl ]. | VAR_057216 | ||||||||||||||||||
Experimental info | ||||||||||||||||||||||
| Mutagenesis | 382 | 1 | V → A: Abolishes SUMO binding. Ref.9 | |||||||||||||||||||
| Mutagenesis | 382 | 1 | V → L: Loss of affinity to SUMO1 and SUMO2. Ref.9 | |||||||||||||||||||
| Mutagenesis | 382 | 1 | V → Y: No loss of affinity toward SUMO1 and SUMO2. Ref.9 | |||||||||||||||||||
| Mutagenesis | 383 | 1 | V → A: Abolishes SUMO binding. Ref.9 | |||||||||||||||||||
| Mutagenesis | 383 | 1 | V → I: No loss of affinity toward SUMO1 and SUMO2. Ref.9 | |||||||||||||||||||
| Mutagenesis | 384 | 1 | D → A: Abolishes SUMO binding. Ref.9 | |||||||||||||||||||
| Mutagenesis | 384 | 1 | D → E: Loss of affinity to SUMO1 and SUMO2. Ref.9 | |||||||||||||||||||
| Mutagenesis | 384 | 1 | D → N: Loss of affinity to SUMO1 and SUMO2. Ref.9 | |||||||||||||||||||
| Mutagenesis | 385 | 1 | L → A: Abolishes SUMO binding. Ref.9 | |||||||||||||||||||
| Mutagenesis | 385 | 1 | L → I: Loss of affinity to SUMO1 and SUMO2. Ref.9 | |||||||||||||||||||
| Mutagenesis | 386 | 1 | T → A: Abolishes SUMO binding. Ref.9 | |||||||||||||||||||
| Mutagenesis | 386 | 1 | T → S: Loss of affinity to SUMO1 and SUMO2. Ref.9 | |||||||||||||||||||
| Mutagenesis | 386 | 1 | T → V: Loss of affinity to SUMO1 and SUMO2. Ref.9 | |||||||||||||||||||
| Sequence conflict | 165 | 1 | H → R in BX647259. Ref.2 | |||||||||||||||||||
| Sequence conflict | 473 | 1 | A → E in CAD98031. Ref.2 | |||||||||||||||||||
| Sequence conflict | 562 | 1 | Missing in AAH60862. Ref.3 | |||||||||||||||||||
| Sequence conflict | 562 | 1 | Missing in AAH20984. Ref.3 | |||||||||||||||||||
| Sequence conflict | 625 | 1 | M → T in BX647259. Ref.2 | |||||||||||||||||||
| Sequence conflict | 738 | 1 | T → I in BX647259. Ref.2 | |||||||||||||||||||
| Sequence conflict | 809 | 1 | E → G in CAD98031. Ref.2 | |||||||||||||||||||
| Sequence conflict | 931 | 1 | E → G in CAD98031. Ref.2 | |||||||||||||||||||
| Sequence conflict | 938 | 1 | T → A in BX647259. Ref.2 | |||||||||||||||||||
| Sequence conflict | 974 | 1 | I → V in BAD18471. Ref.1 | |||||||||||||||||||
Secondary structure | ||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||
| Turn | 943 – 946 | 4 | ||||||||||||||||||||
| Beta strand | 951 – 953 | 3 | ||||||||||||||||||||
| Beta strand | 955 – 957 | 3 | ||||||||||||||||||||
| Beta strand | 963 – 965 | 3 | ||||||||||||||||||||
| Helix | 966 – 975 | 10 | ||||||||||||||||||||
| Turn | 980 – 982 | 3 | ||||||||||||||||||||
| Beta strand | 984 – 986 | 3 | ||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANT LYS-9. Tissue: Thymus and Tongue. |
| [2] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4), VARIANT LYS-9. Tissue: Amygdala and Endometrium. |
| [3] | "Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. Nusbaum C.Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "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] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 553-994 (ISOFORM 1), VARIANT LYS-9. Tissue: Brain, Colon and Placenta. |
| [6] | "Arkadia amplifies TGF-beta superfamily signaling through degradation of Smad7." Koinuma D., Shinozaki M., Komuro A., Goto K., Saitoh M., Hanyu A., Ebina M., Nukiwa T., Miyazawa K., Imamura T., Miyazono K. EMBO J. 22:6458-6470(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY. |
| [7] | "Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia." Liu W., Rui H., Wang J., Lin S., He Y., Chen M., Li Q., Ye Z., Zhang S., Chan S.C., Chen Y.-G., Han J., Lin S.-C. EMBO J. 25:1646-1658(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AXIN1 AND AXIN2, IDENTIFICATION IN COMPLEX WITH AXIN1 AND SMAD7, SUBCELLULAR LOCATION, FUNCTION. |
| [8] | "Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation." Levy L., Howell M., Das D., Harkin S., Episkopou V., Hill C.S. Mol. Cell. Biol. 27:6068-6083(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SKIL, FUNCTION. |
| [9] | "PolySUMO-binding proteins identified through a string search." Sun H., Hunter T. J. Biol. Chem. 287:42071-42083(2012) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF REPEAT SUMO-INTERACTING MOTIF, INTERACTION WITH SUMO1 AND SUMO2, MUTAGENESIS OF VAL-382; VAL-383; ASP-384; LEU-385 AND THR-386. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | AK095327 mRNA. Translation: BAC04531.1. Different initiation. AK131304 mRNA. Translation: BAD18471.1. AK131488 mRNA. Translation: BAD18633.1. Different initiation. AL157474 mRNA. Translation: CAB75669.2. BX538130 mRNA. Translation: CAD98031.1. BX647259 mRNA. No translation available. AC025918 Genomic DNA. No translation available. AC090515 Genomic DNA. No translation available. AC092757 Genomic DNA. No translation available. CH471082 Genomic DNA. Translation: EAW77561.1. BC010369 mRNA. Translation: AAH10369.1. Different initiation. BC020984 mRNA. Translation: AAH20984.1. BC060862 mRNA. Translation: AAH60862.1. | ||||||||||||
| IPI | IPI00418593. IPI00798384. IPI00829658. | ||||||||||||
| PIR | T46904. | ||||||||||||
| RefSeq | NP_001257457.1. NM_001270528.1. NP_001257458.1. NM_001270529.1. NP_001257459.1. NM_001270530.1. NP_060080.6. NM_017610.7. | ||||||||||||
| UniGene | Hs.404423. Hs.603489. Hs.741727. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
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| ProteinModelPortal | Q6ZNA4. | ||||||||||||
| SMR | Q6ZNA4. Positions 941-994. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | Q6ZNA4. 29 interactions. | ||||||||||||
| MINT | MINT-1187466. | ||||||||||||
| STRING | 9606.ENSP00000288199. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q6ZNA4. | ||||||||||||
Polymorphism databases | |||||||||||||
| DMDM | 308153555. | ||||||||||||
Proteomic databases | |||||||||||||
| PaxDb | Q6ZNA4. | ||||||||||||
| PRIDE | Q6ZNA4. | ||||||||||||
Protocols and materials databases | |||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000348370; ENSP00000288199; ENSG00000157450. ENST00000434298; ENSP00000393641; ENSG00000157450. ENST00000557998; ENSP00000452732; ENSG00000157450. ENST00000559209; ENSP00000453872; ENSG00000157450. ENST00000561186; ENSP00000453015; ENSG00000157450. | ||||||||||||
| GeneID | 54778. | ||||||||||||
| KEGG | hsa:54778. | ||||||||||||
| UCSC | uc002afs.3. human. uc002aft.3. human. uc002afv.3. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 54778. | ||||||||||||
| GeneCards | GC15P059160. | ||||||||||||
| HGNC | HGNC:17384. RNF111. | ||||||||||||
| HPA | HPA038576. HPA038577. | ||||||||||||
| MIM | 605840. gene. | ||||||||||||
| neXtProt | NX_Q6ZNA4. | ||||||||||||
| PharmGKB | PA134868772. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | NOG291583. | ||||||||||||
| HOVERGEN | HBG093884. | ||||||||||||
| InParanoid | Q6ZNA4. | ||||||||||||
| KO | K10635. | ||||||||||||
| OMA | CDDSQKQ. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| Pathway_Interaction_DB | tgfbrpathway. TGF-beta receptor signaling. | ||||||||||||
| Reactome | REACT_111102. Signal Transduction. REACT_6900. Immune System. REACT_71. Gene Expression. | ||||||||||||
| UniPathway | UPA00143. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q6ZNA4. | ||||||||||||
| Bgee | Q6ZNA4. | ||||||||||||
| CleanEx | HS_RNF111. | ||||||||||||
| Genevestigator | Q6ZNA4. | ||||||||||||
Family and domain databases | |||||||||||||
| Gene3D | 3.30.40.10. 1 hit. | ||||||||||||
| InterPro | IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view] | ||||||||||||
| Pfam | PF13639. zf-RING_2. 1 hit. [Graphical view] | ||||||||||||
| SMART | SM00184. RING. 1 hit. [Graphical view] | ||||||||||||
| PROSITE | PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other | |||||||||||||
| GenomeRNAi | 54778. | ||||||||||||
| NextBio | 57437. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | RN111_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q6ZNA4 Secondary accession number(s): C9JUS4 Q9NSR1 | ||||||||
| Entry history |
| ||||||||
| Entry status | 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. | ||||||||
Relevant documents
| Human chromosome 15 Human chromosome 15: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with
