RN128_MOUSE
ID RN128_MOUSE Reviewed; 428 AA.
AC Q9D304; Q3UJY0; Q9CVG1; Q9DBN3; Q9JJF8;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=E3 ubiquitin-protein ligase RNF128;
DE EC=2.3.2.27;
DE AltName: Full=Gene related to anergy in lymphocytes protein;
DE AltName: Full=Goliath-related E3 ubiquitin-protein ligase 1;
DE AltName: Full=RING finger protein 128;
DE AltName: Full=RING-type E3 ubiquitin transferase RNF128 {ECO:0000305};
DE Flags: Precursor;
GN Name=Rnf128; Synonyms=Grail, Greul1; ORFNames=MNCb-3816;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF CYS-277 AND
RP CYS-280.
RC STRAIN=CD-1;
RX PubMed=12435366; DOI=10.1006/dbio.2002.0814;
RA Borchers A.G.M., Hufton A.L., Eldridge A.G., Jackson P.K., Harland R.M.,
RA Baker J.C.;
RT "The E3 ubiquitin ligase GREUL1 anteriorizes ectoderm during Xenopus
RT development.";
RL Dev. Biol. 251:395-408(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN UBIQUITINATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND MUTAGENESIS.
RX PubMed=12705856; DOI=10.1016/s1074-7613(03)00084-0;
RA Anandasabapathy N., Ford G.S., Bloom D., Holness C., Paragas V.,
RA Seroogy C., Skrenta H., Hollenhorst M., Fathman C.G., Soares L.;
RT "GRAIL: an E3 ubiquitin ligase that inhibits cytokine gene transcription is
RT expressed in anergic CD4+ T cells.";
RL Immunity 18:535-547(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Osada N., Kusuda J., Tanuma R., Ito A., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation of full-length cDNA clones from mouse brain cDNA library made by
RT oligo-capping method.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cecum, Liver, and Small intestine;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that catalyzes 'Lys-48'- and
CC 'Lys-63'-linked polyubiquitin chains formation. Functions as an
CC inhibitor of cytokine gene transcription. Inhibits IL2 and IL4
CC transcription, thereby playing an important role in the induction of
CC the anergic phenotype, a long-term stable state of T-lymphocyte
CC unresponsiveness to antigenic stimulation associated with the blockade
CC of interleukin production. Ubiquitinates ARPC5 with 'Lys-48' linkages
CC and COR1A with 'Lys-63' linkages leading to their degradation, down-
CC regulation of these cytosleletal components results in impaired
CC lamellipodium formation and reduced accumulation of F-actin at the
CC immunological synapse. Functions in the patterning of the dorsal
CC ectoderm; sensitizes ectoderm to respond to neural-inducing signals (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:12435366,
CC ECO:0000269|PubMed:12705856}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000250}; Single-pass
CC membrane protein {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}.
CC Cytoplasm, perinuclear region {ECO:0000250}. Note=Localized in an
CC asymmetric perinuclear punctate manner. Localizes to the internal pool
CC of the transferrin recycling endosomal pathway. Partially colocalized
CC with the endoplasmic reticulum resident HSPA5, with Golgi resident
CC STX5, and with the late endosomal GTPase RAB7A. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, kidney, heart, liver, ovary,
CC testis and thymus. Expression increased as early as 4 hours by 5- to 7-
CC fold in anergized cultures as compared to resting or activated cells.
CC {ECO:0000269|PubMed:12705856}.
CC -!- DEVELOPMENTAL STAGE: At 6.0 dpc, expressed in both the extraembryonic
CC endoderm and extraembryonic ectoderm. After the beginning of
CC gastrulation, expression remains extraembryonic, and is mostly confined
CC to the visceral endoderm. At 8.5 dpc, expression appears within the
CC mesodermally derived allantois, and is highly expressed in the
CC epithelial layer of the yolk sac. At 9.5 dpc, expressed in the hindgut
CC and adjoining yolk sac. At stage 10 dpc, appears to be widely expressed
CC throughout the embryo with higher expression within the branchial
CC arches and within intersomitic endothelial cells.
CC {ECO:0000269|PubMed:12705856}.
CC -!- INDUCTION: Induced under anergic conditions. Up-regulated during T-cell
CC anergy induction following signaling through the T-cell antigen
CC receptor. {ECO:0000250|UniProtKB:Q8TEB7}.
CC -!- DOMAIN: Binding to E2 ubiquitin-conjugating enzyme requires an intact
CC RING finger domain. {ECO:0000250|UniProtKB:Q8TEB7}.
CC -!- PTM: Auto-ubiquitinated. Controls the development of T-cell clonal
CC anergy by ubiquitination. {ECO:0000250|UniProtKB:Q8TEB7}.
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DR EMBL; AY112656; AAM51876.1; -; mRNA.
DR EMBL; AF426411; AAL34514.1; -; mRNA.
DR EMBL; AB041548; BAA95033.1; -; mRNA.
DR EMBL; AK004847; BAB23613.1; -; mRNA.
DR EMBL; AK008312; BAB25595.3; -; mRNA.
DR EMBL; AK018582; BAB31291.1; -; mRNA.
DR EMBL; AK146266; BAE27025.1; -; mRNA.
DR EMBL; AK167031; BAE39203.1; -; mRNA.
DR EMBL; BC010477; AAH10477.1; -; mRNA.
DR CCDS; CCDS30435.1; -.
DR RefSeq; NP_001241690.1; NM_001254761.1.
DR RefSeq; NP_075759.3; NM_023270.5.
DR AlphaFoldDB; Q9D304; -.
DR SMR; Q9D304; -.
DR BioGRID; 211790; 5.
DR STRING; 10090.ENSMUSP00000108649; -.
DR GlyGen; Q9D304; 3 sites.
DR iPTMnet; Q9D304; -.
DR PhosphoSitePlus; Q9D304; -.
DR MaxQB; Q9D304; -.
DR PaxDb; Q9D304; -.
DR PRIDE; Q9D304; -.
DR ProteomicsDB; 300412; -.
DR Antibodypedia; 15043; 156 antibodies from 26 providers.
DR DNASU; 66889; -.
DR Ensembl; ENSMUST00000113026; ENSMUSP00000108649; ENSMUSG00000031438.
DR GeneID; 66889; -.
DR KEGG; mmu:66889; -.
DR UCSC; uc009uki.2; mouse.
DR CTD; 79589; -.
DR MGI; MGI:1914139; Rnf128.
DR VEuPathDB; HostDB:ENSMUSG00000031438; -.
DR eggNOG; KOG4628; Eukaryota.
DR GeneTree; ENSGT00940000158347; -.
DR HOGENOM; CLU_049885_0_0_1; -.
DR InParanoid; Q9D304; -.
DR OrthoDB; 1487241at2759; -.
DR PhylomeDB; Q9D304; -.
DR TreeFam; TF317486; -.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 66889; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Rnf128; mouse.
DR PRO; PR:Q9D304; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9D304; protein.
DR Bgee; ENSMUSG00000031438; Expressed in urinary bladder urothelium and 242 other tissues.
DR ExpressionAtlas; Q9D304; baseline and differential.
DR Genevisible; Q9D304; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0001818; P:negative regulation of cytokine production; IDA:MGI.
DR GO; GO:0031647; P:regulation of protein stability; ISO:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR003137; PA_domain.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF02225; PA; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Cytoskeleton; Glycoprotein; Membrane; Metal-binding;
KW Reference proteome; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT SIGNAL 1..38
FT /evidence="ECO:0000255"
FT CHAIN 39..428
FT /note="E3 ubiquitin-protein ligase RNF128"
FT /id="PRO_0000261413"
FT TRANSMEM 208..228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 75..183
FT /note="PA"
FT ZN_FING 277..318
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 342..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 59
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 277
FT /note="C->G: Loss of ubiquitination activity."
FT /evidence="ECO:0000269|PubMed:12435366"
FT MUTAGEN 280
FT /note="C->G: Loss of ubiquitination activity."
FT /evidence="ECO:0000269|PubMed:12435366"
FT CONFLICT 125
FT /note="G -> S (in Ref. 4; BAB23613)"
FT /evidence="ECO:0000305"
FT CONFLICT 131
FT /note="K -> N (in Ref. 4; BAB23613)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="I -> V (in Ref. 3; BAA95033)"
FT /evidence="ECO:0000305"
FT CONFLICT 352
FT /note="P -> H (in Ref. 4; BAE27025)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 428 AA; 46276 MW; 480DCF46C75E238F CRC64;
MGPPPGIGVY CRGGCGAARL LAWCFLLALS PHAPGSRGAE AVWTAYLNVS WRVPHTGVNR
TVWELSEEGV YGQDSPLEPV SGVLVPPDGP GALNACNPHT NFTVPTVWGS TVQVSWLALI
QRGGGCTFAD KIHLASERGA SGAVIFNFPG TRNEVIPMSH PGAGDIVAIM IGNLKGTKIL
QSIQRGIQVT MVIEVGKKHG PWVNHYSIFF VSVSFFIITA ATVGYFIFYS ARRLRNARAQ
SRKQRQLKAD AKKAIGKLQL RTLKQGDKEI GPDGDSCAVC IELYKPNDLV RILTCNHIFH
KTCVDPWLLE HRTCPMCKCD ILKALGIEVD VEDGSVSLQV PVSNEASNTA SPHEEDSRSE
TASSGYASVQ GADEPPLEEH AQSANENLQL VNHEANSVAV DVVPHVDNPT FEEDETPDQE
AAVREIKS
