RNF122 (Kr.8p12) poikkeusjäsen PA-(sine PA)-TM-RING RNF alaryhmä . RIG-1 signaloinnin negatiivinen säätelijä

RNF122 (Kr.8p12).

Poikkeusjäsen PA-TM-RING RNF-proteiinien ryhmässä, koska ei omaa PA- eikä signaalipeptididomaaneja. Geeniä ilmenee yleisesti, eniten sappirakossa, lisämunuaisessa ja 25 muussa kudoksessa. Proteiinia sijaitsee endoplasmisessa verkostossa ja Golgin laiteessa ja se saattaa liittyä solun elinkykyisyyteen, vuoden 2013 päivityksen mukaan. Geenistä on saatu ensimmäisiä tarkkoja tietoja 2006 aikaan

Related articles in PubMed

1. [Cloning, expression and subcellular localization of a novel human gene-RNF122]. Wang L, et al. Beijing Da Xue Xue Bao Yi Xue Ban, 2006 Jun 18. PMID 16778963
2. Cell-based screening and validation of human novel genes associated with cell viability. Wang L, et al. J Biomol Screen, 2006 Jun. PMID 16751333
3. Isolation of 115 human chromosome 8-specific expressed-sequence tags by exon amplification. Koyama K, et al. Genomics, 1995 Mar 20. PMID 7601449

• RNF122 suppresses antiviral type I interferon production by targeting RIG-I CARDs to mediate RIG-I degradation. Wang W, et al. Proc Natl Acad Sci U S A, 2016 Aug 23. PMID 27506794, Free PMC Article

Suomennosta: RIG-1 on sytoplasminen luonnollisen immuniteetin virus-RNA:ta tunnistava sensori ja se on tiukasti säädelty, jotta immuunihomeostaasi pysyisi asianmukaisena ja ennaltaestyisi myös ylisuuret tulehdukselliset reaktiot, joita aiheutuu muista alkusyistä kuin antivirusvasteesta eliminoitaessa tehokkaasti virus-RNA:ta. RIG-I-aktiviteetin säätelyssä on ratkaisevaa posttranslationaaliset modifikaatiot, erityisesti ubikitinaatio. On lisääntyvää näyttöä siitä, että E3-ubikitiiniligaseilla on tärkä osa monissa soluprosesseissa kuten solun prolioferaatiossa ja antiviraalissa luonnollisen immuniteetin siganloinnissa.Tutkijat etsiessään RNA:lla infektoituneista soluista RIG-I:n kanssa interaktion tekeviä proteiineja tunnistivat E3 ubikitiiniligaasin RNF122, kun se teki suoraa interaktiota hiiren RIG-1 kanssa. RNF122 TM-domeeni liittyi RIG-I:n CARD-domeeneihin.(CARD= Kaspaasiaktivaatio ja rekrytointidommaani). Tästä interaktiosta triggeröityi tehokkaasti RNF122:n suorittamat K48-ubikitinaatiot RIG-I-CARD proteiinin lysiineihin K115 ja K146, mikä edisti RIG-I hajoittamista ja tästä taas RIG-I alavirran signalointiin seurasi huomattava inhibitio.RNF122 esiintyy laajalti eri immuunisoluissa, eriotyisesti makrofageissa.

RNF122-vajeinen hiiri lisäsi selektiivisesti RIG-I-triggeröityvää I-tyypin interferonin ja makrofagiperäisten proinflammatoristen sytokiinien tuottoa. RNF122-vajeinen hiiri oli resistentimpi RNA-viruksen aiheuttamaa letaalia infektiota kohtaan ja IFN I- tuotanto lisääntyi. Täten tutkijat osoittivat, että RNF122 toimii selektiivisenä negatiivisena säätelijänä RIG-I:n triggeröimälle luonnolliselle antivirusvasteelle kohdentamalla ubikitinaation RIG-I:n CARD-domeeneihin ja välittämällä RIG-I:n proteosomaalisen hajoitukseen.

• AbstractThe activation of retinoic acid-inducible gene 1 (RIG-I), a cytoplasmic innate sensor for viral RNA, is tightly regulated to maintain immune homeostasis properly and prevent excessive inflammatory reactions other than initiation of antiviral innate response to eliminate RNA virus effectively. Posttranslational modifications, particularly ubiquitination, are crucial for regulation of RIG-I activity. Increasing evidence suggests that E3 ligases play important roles in various cellular processes, including cell proliferation and antiviral innate signaling. Here we identify that E 3 ubiquitin ligase RING finger protein 122 (RNF122) directly interacts with mouse RIG-I through MS screening of RIG-I-interacting proteins in RNA virus-infected cells. The transmembrane domain of RNF122 associates with the caspase activation and recruitment domains (CARDs) of RIG-I; this interaction effectively triggers RING finger domain of RNF122 to deliver the Lys-48-linked ubiquitin to the Lys115 and Lys146 residues of RIG-I CARDs and promotes RIG-I degradation, resulting in a marked inhibition of RIG-I downstream signaling. RNF122 is widely expressed in various immune cells, with preferential expression in macrophages. Deficiency of RNF122 selectively increases RIG-I-triggered production of type I IFNs and proinflammatory cytokines in macrophages. RNF122-deficient mice exhibit more resistance against lethal RNA virus infection, with increased production of type I IFNs. Thus, we demonstrate that RNF122 acts as a selective negative regulator of RIG-I-triggered antiviral innate response by targeting CARDs of RIG-I and mediating proteasomal degradation of RIG-I. Our study outlines a way for E3 ligase to regulate innate sensor RIG-I for the control of antiviral innate immunity.

4. RNF122: a novel ubiquitin ligase associated with calcium-modulating cyclophilin ligand. Peng Z, et al. BMC Cell Biol, 2010 Jun 17. PMID 20553626, Free PMC Article Abstract BACKGROUND: RNF

Suomennosta.122 on äskettäin löydettyjä RING-finger proteiineja, jotka liittyvät solun elinkykyisyyteen ja sitä yli-ilmentää anaplastiset tyreoideakarsinoomasolut. RNF122 omaa RING finger -domeenin C-terminaalissa ja TM-domeenin N-terminaalissa. Tässä tutkimuksessa luonnehdittiin tätä RING finger proteiinia sen biologisen tehtävän ymmärtämiseksi. Havaittiin sen olevan ubikitiiniligaasi, joka pystyy autoubikitinoitumaan ja hajoittumaan RING finger domeenista riippuvalla tavalla. Löydettiin hiivahybdridiseulonnassa kalsiumia moduloiva syklofiliiniligandi CAML, joka on RNF122:n kanssa interaktion tekevä proteiini. Jatkotutkimuksissa havaittiin , että CAML ei ole ubikitiiniligaasin subtraatti, vaan se stabiloi RNF122:n ,

Yhteenveto: RNF122 voidaan luonnehtia C3H2C3-tyyppisen RING-finger domaanin omaavaksi E3 ubikitiiniligaasiksi, joka sijoittuu endoplasmiseen retikulumiin. Se säätelee itse omaa hajoamistaan RING finger domeenista ja proteosomista riippuvalla tavalla. RNF122 E3 ubikitiiniligaasi aktiivisuus on riippuvainen RING finger domeenista . RNF122 tekee interaktion CAML:n kanssa

• RNF122 is a recently discovered RING finger protein that is associated with HEK293T cell viability and is overexpressed in anaplastic thyroid cancer cells. RNF122 owns a RING finger domain in C terminus and transmembrane domain in N terminus. However, the biological mechanism underlying RNF122 action remains unknown. RESULTS: In this study, we characterized RNF122 both biochemically and intracellularly in order to gain an understanding of its biological role. RNF122 was identified as a new ubiquitin ligase that can ubiquitinate itself and undergoes degradation in a RING finger-dependent manner. From a yeast two-hybrid screen, we identified calcium-modulating cyclophilin ligand (CAML) as an RNF122-interacting protein. To examine the interaction between CAML and RNF122, we performed co-immunoprecipitation and colocalization experiments using intact cells. What is more, we found that CAML is not a substrate of ubiquitin ligase RNF122, but that, instead, it stabilizes RNF122. CONCLUSIONS: RNF122 can be characterized as a C3H2C3-type RING finger-containing E3 ubiquitin ligase localized to the ER. RNF122 promotes its own degradation in a RING finger-and proteasome-dependent manner. RNF122 interacts with CAML, and its E3 ubiquitin ligase activity was noted to be dependent on the RING finger domain.

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RNF 122 peptide history and sequence

https://www.ncbi.nlm.nih.gov/protein/NP_079063.2

RING finger protein 122 [Homo sapiens]

NCBI Reference Sequence: NP_079063.2
Identical Proteins FASTA Graphics

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LOCUS       NP_079063                155 aa            linear   PRI 30-APR-2018
DEFINITION  RING finger protein 122 [Homo sapiens].
ACCESSION   NP_079063
VERSION     NP_079063.2
DBSOURCE    REFSEQ: accession NM_024787.3
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 155)
  AUTHORS   Wang L, Gao X, Gao P, Deng W, Yu P, Ma J, Guo J, Wang X, Cheng H,
            Zhang C, Yu C, Ma X, Lv B, Lu Y, Shi T and Ma D.
  TITLE     Cell-based screening and validation of human novel genes associated
            with cell viability
  JOURNAL   J Biomol Screen 11 (4), 369-376 (2006)
   PUBMED   16751333
REFERENCE   2  (residues 1 to 155)
  AUTHORS   Saurin AJ, Borden KL, Boddy MN and Freemont PS.
  TITLE     Does this have a familiar RING?
  JOURNAL   Trends Biochem. Sci. 21 (6), 208-214 (1996)
   PUBMED   8744354
REFERENCE   3  (residues 1 to 155)
  AUTHORS   Koyama K, Sudo K and Nakamura Y.
  TITLE     Isolation of 115 human chromosome 8-specific expressed-sequence
            tags by exon amplification
  JOURNAL   Genomics 26 (2), 245-253 (1995)
   PUBMED   7601449
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA610129.1, DA904646.1,
            BC093884.1 and AC013603.17.
            On Oct 30, 2003 this sequence version replaced NP_079063.1.
            
            Summary: The encoded protein contains a RING finger, a motif
            present in a variety of functionally distinct proteins and known to
            be involved in protein-protein and protein-DNA interactions. The
            encoded protein is localized to the endoplasmic reticulum and golgi
            apparatus, and may be associated with cell viability. [provided by
            RefSeq, Jul 2013].
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK022588.1, BC093884.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN03267760 [ECO:0000348]
            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..155
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8p12"
     Protein         1..155
                     /product="RING finger protein 122"
                     /calculated_mol_wt=17344
     Site            40..60
                     /site_type="transmembrane region"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9H9V4.2)"
     Region          91..137
                     /region_name="RING-H2_RNF24_like"
                     /note="RING finger, H2 subclass, found in RING finger
                     proteins RNF24, RNF122, and similar proteins; cd16469"
                     /db_xref="CDD:319383"
     Region          93..133
                     /region_name="RING-H2 finger (C3H2C3-type)"
                     /note="RING-H2 finger (C3H2C3-type) [structural motif]"
                     /db_xref="CDD:319383"
     Site            order(93,96,111,113,116,119,130,133)
                     /site_type="other"
                     /note="Zn binding site [ion binding]"
                     /db_xref="CDD:319383"
     CDS             1..155
                     /gene="RNF122"
                     /coded_by="NM_024787.3:406..873"
                     /db_xref="CCDS:CCDS6091.1"
                     /db_xref="GeneID:79845"
                     /db_xref="HGNC:HGNC:21147"
ORIGIN      
        1 mhpfqwcngc fcglglvstn kscsmppisf qdlplniymv ifgtgifvfm lslifccyfi
       61 sklrnqaqse rygykevvlk gdakklqlyg qtcavcledf kgkdelgvlp cqhafhrkcl
      121 vkwlevrcvc pmcnkpiasp seatqnigil ldelv
//