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Q99ML9 (RN111_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase Arkadia

EC=6.3.2.-
Alternative name(s):
RING finger protein 111
Gene names
Name:Rnf111
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length989 AA.
Sequence statusComplete.
Protein existenceEvidence 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 By similarity. Ref.1 Ref.4

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with AXIN1 and AXIN2. Part of a complex containing RNF111, AXIN1 and SMAD7 By similarity. Interacts with SMAD6 and SMAD7. Interacts with SKIL isoform 1 By similarity. Interacts (via SIM domains) with SUMO1 and SUMO2 By similarity. Ref.4

Subcellular location

Nucleus. Cytoplasm By similarity. Note: Upon TGF-beta treatment, translocates from nucleus to cytosol By similarity. Ref.4

Tissue specificity

Ubiquitously expressed. Ref.1

Developmental stage

Ubiquitously expressed from ES cells to midgestation. Ref.1

Disruption phenotype

Mice rarely develop beyond 15 somites, have a reduced head, fail to undergo turning and die at midgestation. Ref.1

Sequence similarities

Contains 1 RING-type zinc finger.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainZinc-finger
   LigandMetal-binding
Zinc
   Molecular functionDevelopmental protein
Ligase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processpattern specification process

Inferred from mutant phenotype Ref.1. Source: MGI

positive regulation of protein ubiquitination

Inferred from direct assay PubMed 16601693. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 16601693. Source: BHF-UCL

positive regulation of transforming growth factor beta receptor signaling pathway

Inferred from direct assay PubMed 16601693. Source: MGI

protein polyubiquitination

Inferred from mutant phenotype PubMed 16601693. Source: BHF-UCL

ubiquitin-dependent SMAD protein catabolic process

Inferred from mutant phenotype PubMed 16601693. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 16601693. Source: BHF-UCL

nucleolus

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 16601693. Source: BHF-UCL

protein complex

Inferred from direct assay PubMed 16601693. Source: MGI

   Molecular_functionSUMO polymer binding

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin-protein ligase activity

Inferred from mutant phenotype PubMed 16601693. Source: BHF-UCL

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

AXIN1O151695EBI-646015,EBI-710484From a different organism.
Axin1O356254EBI-646015,EBI-2365912
SMAD7O151052EBI-646015,EBI-3861591From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99ML9-1)

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: Q99ML9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     909-916: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 989989E3 ubiquitin-protein ligase Arkadia
PRO_0000280691

Regions

Zinc finger937 – 97842RING-type; atypical
Region240 – 402163Interaction with AXIN1 By similarity
Motif298 – 3025SUMO interaction motif 1 (SIM); mediates the binding to polysumoylated substrates By similarity
Motif323 – 3297SUMO interaction motif 2 (SIM); mediates the binding to polysumoylated substrates By similarity
Motif380 – 3845SUMO interaction motif 3 (SIM); mediates the binding to polysumoylated substrates By similarity
Compositional bias218 – 2214Poly-Ser
Compositional bias250 – 451202Ser-rich
Compositional bias492 – 52130His-rich
Compositional bias624 – 776153Pro-rich

Natural variations

Alternative sequence909 – 9168Missing in isoform 2.
VSP_023842

Experimental info

Mutagenesis9371C → A: No effect on TGF-beta and BMP signaling. Ref.4
Sequence conflict1211L → V in BAC29394. Ref.2
Sequence conflict2191S → G in BAC33245. Ref.2
Sequence conflict2561S → N in BAC33245. Ref.2
Sequence conflict8051L → V in AAH54842. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 212E3C37BC70DCB5

FASTA989107,896
        10         20         30         40         50         60 
MSQWTPEFNE LYTLKVAMKS GTPDAPTTQE SLKAVLLHPQ PLGATKSFPA EVEMINSKVG 

        70         80         90        100        110        120 
NEFSHLCDDS QKQEKDMTGN QQEQEKSGVV RKKRKSQQAG PSYVQNCVKE NQEILGRRQQ 

       130        140        150        160        170        180 
LETPSDEDND SSLSECLSSP SSSLHFGGSD TVTSDEDKEV SVRHTQPVLS AKSRSHSARS 

       190        200        210        220        230        240 
HKWPRTEADP VPSLLMKRPC FHGSALRRVT CRKRLVKSSS SQRTQKQKER MLVQRKKREA 

       250        260        270        280        290        300 
LAQRKYALLS SSSSSSENDL SSDSSSSSST DGEEDLCASA SENPSNPAAP SGSIDEDVVV 

       310        320        330        340        350        360 
IEASFTPQVT ANEEINVTST DSEVEIVTVG ESYRSRSTLG HSRSHWSQGS SSHTGRPQES 

       370        380        390        400        410        420 
RNRSRISTVI QPLRQNAAEV VDLTVDEDEP TIVPTTSARM DSQTTSASIN NSNPSTSEQA 

       430        440        450        460        470        480 
SDTTSTVASS QPSTVSETEA TLTSNSATGS SVGDDVRRTA SSAVPESGPP AMPRLPSCCP 

       490        500        510        520        530        540 
QHSPCGGTSQ SHHALAHPHS SCFQQHGHHF QHHHHHHHTP HPAVPVSPSF SDPACPVERP 

       550        560        570        580        590        600 
QVQAPCGANS SSGSSYHDQQ ALPVDLSNSA LRTHGSGGFH GASAFDPCCP VTSSRAAVFG 

       610        620        630        640        650        660 
HQAAAAPTQP LSIDGYGSSM VAQPQPQPPP QPSLSSCRHY MPPPYASLTR PLHHQASACH 

       670        680        690        700        710        720 
HSHGNAPPQT QPPPQVDYVI PHPVHAFHSQ ISSHAASHPV APPPPTHLGS TAAPIPQHLP 

       730        740        750        760        770        780 
PAHQPISHHI PAPAPSAQRL HPHEVMQRME VQRRRMMQHP TRAHERPPPH PHRMHPNYGH 

       790        800        810        820        830        840 
GHHIHVPQTM SSHPRQAPER TAWELGIEAG VTAATYTPGA LHPHLAHYHA PPRLHHLQLG 

       850        860        870        880        890        900 
ALPLMVPDMA GYPHIRYISS GLDGASFRGP FRGNFEELIH LEERLGNVNR GASQGTIERC 

       910        920        930        940        950        960 
TYPHKYKKVT TDWFSQRKLH CKQDGEEGTE EDTEEKCTIC LSILEEGEDV RRLPCMHLFH 

       970        980 
QVCVDQWLIT NKKCPICRVD IEAQLPSES 

« Hide

Isoform 2 [UniParc].

Checksum: 4BC421580AB2ACEB
Show »

FASTA981106,931

References

« Hide 'large scale' references
[1]"Induction of the mammalian node requires Arkadia function in the extraembryonic lineages."
Episkopou V., Arkell R., Timmons P.M., Walsh J.J., Andrew R.L., Swan D.
Nature 410:825-830(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
Strain: 129/Sv.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: C57BL/6J.
Tissue: Cerebellum, Head and Urinary bladder.
[3]"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 805-989 (ISOFORM 1).
Strain: CD-1 and FVB/N-3.
Tissue: Mammary tumor and Neural stem cell.
[4]"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, MUTAGENESIS OF CYS-937, INTERACTION WITH SMAD6 AND SMAD7, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF330197 mRNA. Translation: AAK38272.1.
AK048110 mRNA. Translation: BAC33245.1.
AK036351 mRNA. Translation: BAC29394.1.
AK137148 mRNA. Translation: BAE23252.1.
BC054842 mRNA. Translation: AAH54842.1.
BC069835 mRNA. Translation: AAH69835.1.
RefSeqNP_291082.1. NM_033604.2.
XP_006511648.1. XM_006511585.1.
XP_006511649.1. XM_006511586.1.
UniGeneMm.29783.

3D structure databases

ProteinModelPortalQ99ML9.
SMRQ99ML9. Positions 893-989.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid220311. 10 interactions.
IntActQ99ML9. 7 interactions.
MINTMINT-1899537.

PTM databases

PhosphoSiteQ99ML9.

Proteomic databases

PRIDEQ99ML9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034739; ENSMUSP00000034739; ENSMUSG00000032217. [Q99ML9-1]
ENSMUST00000113595; ENSMUSP00000109225; ENSMUSG00000032217. [Q99ML9-1]
GeneID93836.
KEGGmmu:93836.
UCSCuc009qoa.1. mouse. [Q99ML9-2]
uc009qoe.1. mouse. [Q99ML9-1]

Organism-specific databases

CTD54778.
MGIMGI:1934919. Rnf111.

Phylogenomic databases

eggNOGNOG291583.
GeneTreeENSGT00730000110863.
HOGENOMHOG000154152.
HOVERGENHBG093884.
InParanoidQ99ML9.
KOK10635.
OMAPCRKRFV.
OrthoDBEOG7WHH9N.
PhylomeDBQ99ML9.
TreeFamTF331862.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

BgeeQ99ML9.
CleanExMM_RNF111.
GenevestigatorQ99ML9.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
[Graphical view]
PROSITEPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio351685.
PROQ99ML9.
SOURCESearch...

Entry information

Entry nameRN111_MOUSE
AccessionPrimary (citable) accession number: Q99ML9
Secondary accession number(s): Q3UVL7 expand/collapse secondary AC list , Q6NSW2, Q7TMR3, Q8C881, Q8CBC0
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: June 1, 2001
Last modified: April 16, 2014
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot