Q99ML9 (RN111_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase Arkadia
EC=6.3.2.-

Alternative name(s):
RING finger protein 111

Gene names

Name:

Rnf111

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	989 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 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 process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Developmental protein Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	pattern 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-dependent 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_component	cytoplasm Inferred from direct assay PubMed 16601693. Source: BHF-UCL nucleolus Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome protein complex Inferred from direct assay PubMed 16601693. Source: MGI
Molecular_function	SUMO 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...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 989	989	E3 ubiquitin-protein ligase Arkadia		PRO_0000280691
Regions
	Zinc finger	937 – 978	42	RING-type; atypical
	Region	240 – 402	163	Interaction with AXIN1 By similarity
	Motif	298 – 302	5	SUMO interaction motif 1 (SIM); mediates the binding to polysumoylated substrates By similarity
	Motif	323 – 329	7	SUMO interaction motif 2 (SIM); mediates the binding to polysumoylated substrates By similarity
	Motif	380 – 384	5	SUMO interaction motif 3 (SIM); mediates the binding to polysumoylated substrates By similarity
	Compositional bias	218 – 221	4	Poly-Ser
	Compositional bias	250 – 451	202	Ser-rich
	Compositional bias	492 – 521	30	His-rich
	Compositional bias	624 – 776	153	Pro-rich
Natural variations
	Alternative sequence	909 – 916	8	Missing in isoform 2.		VSP_023842
Experimental info
	Mutagenesis	937	1	C → A: No effect on TGF-beta and BMP signaling. Ref.4
	Sequence conflict	121	1	L → V in BAC29394. Ref.2
	Sequence conflict	219	1	S → G in BAC33245. Ref.2
	Sequence conflict	256	1	S → N in BAC33245. Ref.2
	Sequence conflict	805	1	L → V in AAH54842. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 212E3C37BC70DCB5	FASTA	989	107,896
	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
	Isoform 2 [UniParc]. Checksum: 4BC421580AB2ACEB	FASTA	981	106,931
	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 TYPHKYKKRK LHCKQDGEEG TEEDTEEKCT ICLSILEEGE DVRRLPCMHL FHQVCVDQWL 970 980 ITNKKCPICR VDIEAQLPSE S

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00117820. IPI00830944.
RefSeq	NP_291082.1. NM_033604.2.
UniGene	Mm.29783.
3D structure databases
HSSP	HSSP built from PDB template 1IYM based on UniProtKB Q9LRB7.
ProteinModelPortal	Q99ML9.
SMR	Q99ML9. Positions 936-989.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99ML9. 2 interactions.
MINT	MINT-1899537.
PTM databases
PhosphoSite	Q99ML9.
Proteomic databases
PRIDE	Q99ML9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000034739; ENSMUSP00000034739; ENSMUSG00000032217. ENSMUST00000113595; ENSMUSP00000109225; ENSMUSG00000032217.
GeneID	93836.
KEGG	mmu:93836.
UCSC	uc009qoa.1. mouse. uc009qoe.1. mouse.
Organism-specific databases
CTD	54778.
MGI	MGI:1934919. Rnf111.
Phylogenomic databases
eggNOG	NOG291583.
GeneTree	ENSGT00670000097625.
HOGENOM	HOG000154152.
HOVERGEN	HBG093884.
InParanoid	Q99ML9.
KO	K10635.
OMA	CDDSQKQ.
OrthoDB	EOG4MSCXR.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
Bgee	Q99ML9.
CleanEx	MM_RNF111.
Genevestigator	Q99ML9.
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
NextBio	351685.
SOURCE	Search...

Entry information

Entry name

RN111_MOUSE

Accession

Primary (citable) accession number: Q99ML9
Secondary accession number(s): Q3UVL7 , Q6NSW2, Q7TMR3, Q8C881, Q8CBC0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 2007
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program