Q9D304 (RN128_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase RNF128
EC=6.3.2.-

Alternative name(s):
Gene related to anergy in lymphocytes protein
Goliath-related E3 ubiquitin-protein ligase 1
RING finger protein 128

Gene names

Name:	Rnf128
Synonyms:	Grail, Greul1
ORF Names:	MNCb-3816

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	428 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase that catalyzes polyubiquitin chains. Functions as an inhibitor of cytokine gene transcription. Inhibits IL2 and IL4 transcription and this activity is likely to be mediated by E3 ligase activity. Plays an important role in the induction of the anergic phenotype. Functions in the patterning of the dorsal ectoderm; sensitizes ectoderm to respond to neural-inducing signals By similarity. Ref.1 Ref.2
Pathway	Protein modification; protein ubiquitination.
Subcellular location	Endomembrane system; Single-pass membrane protein By similarity. Cytoplasm › perinuclear region By similarity. Note: Localized in an asymmetric perinuclear punctate manner. Localizes to the internal pool of the transferrin recycling endosomal pathway. Partially colocalized with the endoplasmic reticulum resident HSPA5, with Golgi resident STX5, and with the late endosomal GTPase RAB7A By similarity.
Tissue specificity	Expressed in brain, kidney, heart, liver, ovary, testis and thymus. Expression increased as early as 4 hours by 5- to 7-fold in anergized cultures as compared to resting or activated cells. Ref.2
Developmental stage	At E6.0, expressed in both the extraembryonic endoderm and extraembryonic ectoderm. After the beginning of gastrulation, expression remains extraembryonic, and is mostly confined to the visceral endoderm. At E8.5, expression appears within the mesodermally derived allantois, and is highly expressed in the epithelial layer of the yolk sac. At E9.5, expressed in the hindgut and adjoining yolk sac. At stage E10, appears to be widely expressed throughout the embryo with higher expression within the branchial arches and within intersomitic endothelial cells. Ref.2
Induction	Induced under anergic conditions. Up-regulated during T-cell anergy induction following signaling through the T-cell antigen receptor By similarity.
Domain	Binding to E2 ubiquitin-conjugating enzyme requires an intact RING finger domain By similarity.
Post-translational modification	Auto-ubiquitinated. Controls the development of T-cell clonal anergy by ubiquitination By similarity.
Sequence similarities	Contains 1 PA (protease associated) domain. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Membrane
Domain	Signal Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Glycoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of cytokine biosynthetic process Inferred from direct assay Ref.2. Source: MGI
Cellular_component	Golgi apparatus Inferred from direct assay Ref.2. Source: MGI endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum Inferred from direct assay Ref.2. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW late endosome Inferred from direct assay Ref.2. Source: MGI perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ubiquitin-protein ligase activity Inferred from direct assay Ref.1. Source: MGI zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 38	38	Potential
	Chain	39 – 428	390	E3 ubiquitin-protein ligase RNF128		PRO_0000261413
Regions
	Transmembrane	208 – 228	21	Helical; Potential
	Domain	75 – 183	109	PA
	Zinc finger	277 – 318	42	RING-type; atypical
Amino acid modifications
	Glycosylation	48	1	N-linked (GlcNAc...) Potential
	Glycosylation	59	1	N-linked (GlcNAc...) Potential
	Glycosylation	101	1	N-linked (GlcNAc...) Potential
Experimental info
	Mutagenesis	277	1	C → G: Loss of ubiquitination activity. Ref.1
	Mutagenesis	280	1	C → G: Loss of ubiquitination activity. Ref.1
	Sequence conflict	125	1	G → S in BAB23613. Ref.4
	Sequence conflict	131	1	K → N in BAB23613. Ref.4
	Sequence conflict	132	1	I → V in BAA95033. Ref.3
	Sequence conflict	352	1	P → H in BAE27025. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q9D304 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 480DCF46C75E238F	FASTA	428	46,276
	10 20 30 40 50 60 MGPPPGIGVY CRGGCGAARL LAWCFLLALS PHAPGSRGAE AVWTAYLNVS WRVPHTGVNR 70 80 90 100 110 120 TVWELSEEGV YGQDSPLEPV SGVLVPPDGP GALNACNPHT NFTVPTVWGS TVQVSWLALI 130 140 150 160 170 180 QRGGGCTFAD KIHLASERGA SGAVIFNFPG TRNEVIPMSH PGAGDIVAIM IGNLKGTKIL 190 200 210 220 230 240 QSIQRGIQVT MVIEVGKKHG PWVNHYSIFF VSVSFFIITA ATVGYFIFYS ARRLRNARAQ 250 260 270 280 290 300 SRKQRQLKAD AKKAIGKLQL RTLKQGDKEI GPDGDSCAVC IELYKPNDLV RILTCNHIFH 310 320 330 340 350 360 KTCVDPWLLE HRTCPMCKCD ILKALGIEVD VEDGSVSLQV PVSNEASNTA SPHEEDSRSE 370 380 390 400 410 420 TASSGYASVQ GADEPPLEEH AQSANENLQL VNHEANSVAV DVVPHVDNPT FEEDETPDQE AAVREIKS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The E3 ubiquitin ligase GREUL1 anteriorizes ectoderm during Xenopus development." Borchers A.G.M., Hufton A.L., Eldridge A.G., Jackson P.K., Harland R.M., Baker J.C. Dev. Biol. 251:395-408(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, MUTAGENESIS OF CYS-277 AND CYS-280. Strain: CD-1.
[2]	"GRAIL: an E3 ubiquitin ligase that inhibits cytokine gene transcription is expressed in anergic CD4+ T cells." Anandasabapathy N., Ford G.S., Bloom D., Holness C., Paragas V., Seroogy C., Skrenta H., Hollenhorst M., Fathman C.G., Soares L. Immunity 18:535-547(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN UBIQUITINATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, MUTAGENESIS.
[3]	"Isolation of full-length cDNA clones from mouse brain cDNA library made by oligo-capping method." Osada N., Kusuda J., Tanuma R., Ito A., Hirata M., Sugano S., Hashimoto K. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
[4]	"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]. Strain: C57BL/6J. Tissue: Cecum, Liver and Small intestine.
[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]. Strain: 129. Tissue: Mammary tumor.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY112656 mRNA. Translation: AAM51876.1. AF426411 mRNA. Translation: AAL34514.1. AB041548 mRNA. Translation: BAA95033.1. AK004847 mRNA. Translation: BAB23613.1. AK008312 mRNA. Translation: BAB25595.3. AK018582 mRNA. Translation: BAB31291.1. AK146266 mRNA. Translation: BAE27025.1. AK167031 mRNA. Translation: BAE39203.1. BC010477 mRNA. Translation: AAH10477.1.
IPI	IPI00331363.
RefSeq	NP_001241690.1. NM_001254761.1. NP_075759.3. NM_023270.5.
UniGene	Mm.27764.
3D structure databases
ProteinModelPortal	Q9D304.
SMR	Q9D304. Positions 38-204, 277-320.
ModBase	Search...
PTM databases
PhosphoSite	Q9D304.
Proteomic databases
PRIDE	Q9D304.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000113026; ENSMUSP00000108649; ENSMUSG00000031438.
GeneID	66889.
KEGG	mmu:66889.
UCSC	uc009uki.2. mouse.
Organism-specific databases
CTD	79589.
MGI	MGI:1914139. Rnf128.
Phylogenomic databases
eggNOG	NOG271676.
GeneTree	ENSGT00700000104211.
HOGENOM	HOG000231432.
HOVERGEN	HBG057659.
InParanoid	Q9D304.
KO	K10629.
OrthoDB	EOG4JT06C.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q9D304.
Bgee	Q9D304.
CleanEx	MM_RNF128.
Genevestigator	Q9D304.
GermOnline	ENSMUSG00000031438. Mus musculus.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR003137. Protease-assoc_domain. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF02225. PA. 1 hit. 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	322937.
SOURCE	Search...

Entry information

Entry name

RN128_MOUSE

Accession

Primary (citable) accession number: Q9D304
Secondary accession number(s): Q3UJY0 , Q9CVG1, Q9DBN3, Q9JJF8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	June 1, 2001
Last modified:	May 29, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program