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   27-MAR-2024, entry version 157.
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   GlyCosmos; Q9D304; 3 sites, No reported glycans.
DR   GlyGen; Q9D304; 3 sites.
DR   iPTMnet; Q9D304; -.
DR   PhosphoSitePlus; Q9D304; -.
DR   MaxQB; Q9D304; -.
DR   PaxDb; 10090-ENSMUSP00000108649; -.
DR   ProteomicsDB; 300412; -.
DR   Antibodypedia; 15043; 204 antibodies from 27 providers.
DR   DNASU; 66889; -.
DR   Ensembl; ENSMUST00000113026.2; ENSMUSP00000108649.2; ENSMUSG00000031438.12.
DR   GeneID; 66889; -.
DR   KEGG; mmu:66889; -.
DR   UCSC; uc009uki.2; mouse.
DR   AGR; MGI:1914139; -.
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   OMA; NKSRFFW; -.
DR   OrthoDB; 5474929at2759; -.
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 78 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 245 other cell types or tissues.
DR   ExpressionAtlas; Q9D304; baseline and differential.
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:0005770; C:late endosome; IDA:MGI.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
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:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
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   CDD; cd02122; PA_GRAIL_like; 1.
DR   CDD; cd16802; RING-H2_RNF128-like; 1.
DR   Gene3D; 3.50.30.30; -; 1.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   InterPro; IPR046450; PA_dom_sf.
DR   InterPro; IPR003137; PA_domain.
DR   InterPro; IPR001841; Znf_RING.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   PANTHER; PTHR46539; E3 UBIQUITIN-PROTEIN LIGASE ATL42; 1.
DR   PANTHER; PTHR46539:SF2; RING FINGER PROTEIN 150 ISOFORM X1; 1.
DR   Pfam; PF02225; PA; 1.
DR   Pfam; PF13639; zf-RING_2; 1.
DR   SMART; SM00184; RING; 1.
DR   SUPFAM; SSF52025; PA domain; 1.
DR   SUPFAM; SSF57850; RING/U-box; 1.
DR   PROSITE; PS50089; ZF_RING_2; 1.
DR   Genevisible; Q9D304; MM.
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
//