(8) RNF13 (Kr.3q25.1) , RZF, PA-TM-RING RNF alaryhmä

RNF13, RZF , PA-TM-RING RNF-alaryhmä
Tässä PA-TM-RING _RNF proteiinissa oleva PA-ryhmä on tyyppiä PA-C-RZF ( siise i GRAIL tyyppiä), joten nämä kolme  tällaisen  PA-C-RZF tyyppisen domanin omaavat  ovat funktiotlaan myös erilaisia. tämä  RNF13 on  tarkemmin tunnettu kymmenisen vuotta ja  kiinnitti varmaan eniten huomiota siksi että se oli säätynyt ylös haimasyövässä. Vuonna 2010 havaittiin , että sillä on  tumaan kohdentava signaali .  Vuodelta 2013 on  artikkeli, jossa mainitaan, että RNF13  välittää  endoplasmisen stressin indusoimaa apoptoosia IRE1alfa/ JNK- tien  välityksellä. IRE1  on inositolia vaativa entsyymi ja ER stressisensori ja solukohtalon  päättäjä.
 IRE1alfa kuuluu proteiinikvaliteettikontrolliin  ER.ssä, jossa se tunnistaa  laskostumattomat proteiinit ja aktivoituu, mikä johtaa sen signaalitiehen ja väärinlaskostuneiden proteiinien hajoittamiseen UPR= Unfolded Protein Response.
 https://www.frontiersin.org/files/Articles/87464/fgene-05-00076-HTML/image_m/fgene-05-00076-g001.jpg 
Huom linkin kuvassa ei kuitenkaan piirretty esiin  RNF vaikutuskohtaa  tähän IRE1 signalointijärjestelmään ja sen nopeuttamiseen. 
RNF13 on siis  kriittinen välittäjä nopeuttamassa endoplasmisen retikulumin stressin indusoimaa apoptoosia. Siinä tapahtuvat mutaatiot assosioituvat  joihinkin tuumoreihin. Sekä RNF167 että RNF13 liittyviä mutaatioita on havaittu assosioituneena tuumoreihin

• https://www.ncbi.nlm.nih.gov/gene/11342

• Also known as RZF
• Summary- The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. The specific function of this gene has not yet been determined. Alternatively spliced transcript variants that encode the same protein have been reported. A pseudogene, which is also located on chromosome 3, has been defined for this gene. [provided by RefSeq, Jul 2008] Expression . Ubiquitous expression in thyroid (RPKM 22.1), brain (RPKM 22.0) and 25 other tissues See more Orthologs mouse all

Related articles in PubMed

1. RNF13: a novel RING-type ubiquitin ligase over-expressed in pancreatic cancer. Zhang Q, et al. Cell Res, 2009 Mar. PMID 18794910  Suomennosta. E3 ubikitiiniligaaseilla on tärkä osuus syövän kehittymisessä. RNF13 on ER/Golgi klvoon assosioitunut E3 ubikitiiniligaasi, jonka RING-domeeni  on tarpeen ubikitiiniligaasiaktiivisuudelle. RNF yli-ilmentymää havaittiin useissa  haiman alueen syöpänäyteissä, myös  syövän esiasteissa, kroonisessa pankreatiitissa ja haiman intraepiteliaalisessa neoplasiassa.  RNF13 värjäys korreloi tenaskiini-C ilmenemään.  haimatiehyeen adenokarsinoomassa, siis syövän progressioon.  Normaalin RNF13:n yliesiintymä lisäsi invasiivista potentiaalia ja gelatinolyysiaktiivisuutta MMP-9:llä.  Yhteenvetona RN13 osallistuu haiman karsinogeneesiin. Sen tekemät ubikitiiniväliteiset proteiinimodifikaatiot voivat  osllistua syövän kehittymsieen.
   

   • Abstract Protein ubiquitination by E3 ubiquitin ligases plays an important role in cancer development. In this study, we provide experimental evidence that a RING-finger-containing protein RNF13 is an ER/Golgi membrane-associated E3 ubiquitin ligase and its RING finger domain is required for the ubiquitin ligase activity. Immunohistochemical analysis of pancreatic ductal adenocarcinoma (PDAC) and paracancerous normal tissues from 72 patients documented RNF13 over-expression in 30 tumor samples (41.7%, 30/72), and its expression was significantly associated with histological grading (P = 0.024). In addition, RNF13 was detected in precancerous lesions: tubular complexes in chronic pancreatitis (CP) and pancreatic intraepithelial neoplasia (PanIN) (79.3%, 23/29 and 62.8%, 22/35, respectively). Moreover, RNF13 staining was significantly correlated with Tenascin-C expression (P = 0.004) in PDAC samples, further supporting the role of RNF13 in cancer progression. Over-expression of wild type but not RING domain-mutant RNF13 in pancreatic MiaPaca-2 cancer cells increased invasive potential and gelatinolytic activity by matrix metalloproteinase-9. Taken together, these findings reveal that RNF13 is a novel E3 ubiquitin ligase involved in pancreatic carcinogenesis; ubiquitin-mediated modification of proteins by RNF13 may participate in pancreatic cancer development.
2. Tumour-associated mutations of PA-TM-RING ubiquitin ligases RNF167/RNF13 identify the PA domain as a determinant for endosomal localization. van Dijk JR, et al. Biochem J, 2014 Apr 1. PMID 24387786 Jos RING- domeeni saa pistemutaation RNF13  tai RNF167  proteiinissa, niiden ligasiaktiivisuus vaikuttuu.  Jos PA domeeni saa pistemutaation näiden proteiinien endosomaalinen lokalisoituminen vaikuttuu.  Tuumoreissa nämä RNF13 ja 167 voivat eisintyö ligaasikykyisinä ja silloin  ubikittinoidut  vialliset proteiinie jäävät sijaitsemaan väärään kohtaan. Solusubstraattien  normaalin degradaatioon vaaditaan  toimiva PA ja RING- domeeni näissä PA-TM-RING RNF molekyyleissä.
   

   •  Diverse cellular processes depend on endocytosis, intracellular vesicle trafficking, sorting and exocytosis, and processes that are regulated post-transcriptionally by modifications such as phosphorylation and ubiquitylation. The PA (protease-associated) domain E3 ligases, such as GodzillaCG10277 in Drosophila melanogaster and RNF167 (RING finger protein 167) in humans, have been implicated in the regulation of cellular endosome trafficking. In the present study, we have characterized point mutations in the RING (really interesting new gene) domain of human RNF13 and RNF167, which have been identified in human tumour samples, that abrogate ubiquitin ligase activity as well as function. In the present study, we have also identified a functional role for the PA domain, which is required for endosomal localization of these proteins. Although the PA domain point mutations of RNF13 and RNF167 identified in human tumours are ligase active, the resultant mutant proteins are mislocalized within the cell. Thus the PA domain E3 ligases examined in the present study appear to require both E3 ligase activity as well as an intact PA domain to efficiently target and ubiquitylate their cellular substrates.
3. Identification and characterization of a RING zinc finger gene (C-RZF) expressed in chicken embryo cells. Tranque P, et al. Proc Natl Acad Sci U S A, 1996 Apr 2. PMID 8610176, Free PMC Article
4. RNF13, a RING finger protein, mediates endoplasmic reticulum stress-induced apoptosis through the inositol-requiring enzyme (IRE1α)/c-Jun NH2-terminal kinase pathway. Arshad M, et al. J Biol Chem, 2013 Mar 22. PMID 23378536, Free PMC Article
   link:  https://www.frontiersin.org/files/Articles/87464/fgene-05-00076-HTML/image_m/fgene-05-00076-g001.jpg

• Nuclear targeting of an endosomal E3 ubiquitin ligase. Bocock JP, et al. Traffic, 2010 Jun. PMID 20230530 Suom. huom. Tällä RNF13 ubikitiiniligaasilla on tumaan kohdentava signaalikohta ja se  voi  päästä tuman sisäkalvoon kiertävien endosomien avulla  ja sillä on potentiaalia suorittaa  avainasemassa olevien tumaproteiinin  turn over vasteena plasmakalvon saamiin signaaleihin.  Ring finger protein 13 (RNF13) is an E3 ubiquitin ligase embedded in endosome membranes. The protein undergoes constitutive post-translational proteolysis, making its detection difficult unless cells are incubated with a proteasome inhibitor to allow biosynthetic forms to accumulate. When cells were treated with phorbol 12-myristate 13-acetate (PMA), RNF13 avoided proteolysis. A similar stabilization was seen on ionomycin treatment of cells. Drug treatment stabilized both the full-length protein and a membrane-embedded C-terminal fragment generated following ectodomain shedding. Immunofluorescence staining revealed that PMA treatment caused the protein to accumulate in recycling endosomes, where it colocalized with transferrin receptor, and on the inner nuclear membrane, where it colocalized with lamin B. Expression of dominant-negative Rab11 inhibited nuclear localization, suggesting RNF13 was targeted to the inner nuclear membrane through recycling endosomes. New protein synthesis was necessary for this targeting. Nuclear localization was confirmed by immunoelectron microscopy and by purification of the inner nuclear membrane. Stress-induced transport of an endosomal protein to the inner nuclear membrane is a novel mechanism for introduction of regulatory proteins to the DNA environment. RNF13, with its ubiquitin ligase-active RING domain, has the potential to turn over key nuclear proteins in response to signals received at the plasma membrane.

See all (24) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Protease-activated point mutations are identified in RNF13 and RNF167.
2. RNF13 is a critical mediator for facilitating endoplasmic reticulum stress-induced apoptosis through the activation of the IRE1alpha-TRAF2-JNK signaling pathway.
3. analysis of nuclear targeting of Nuclear targeting of RNF13 endosomal E3 ubiquitin ligase
4. RNF13 is a novel E3 ubiquitin ligase involved in pancreatic carcinogenesis.
5. Mice lacking Mt1/2 have a rapid decrease in Rnf13 during acute lung injury
    Thus, MT ultimately improves survival in the progression of acute lung injury in mice. Transcriptome-wide analysis suggests that this survival may be mediated through changes in the destabilization of transcripts associated with protein processing, the subsequent augmentation of transcripts controlling inflammation, extracellular matrix regulation, coagulation/fibrinolysis, and disruption of surfactant homeostasis.
    https://res.mdpi.com/ijms/ijms-17-00336/article_deploy/html/images/ijms-17-00336-g001.png
6. Cloning report of the chicken homolog
   

Preferred Names

E3 ubiquitin-protein ligase RNF13

Names

RING zinc finger protein

RING-type E3 ubiquitin transferase RNF13

Conserved Domains (2) summary

cd02123
Location:23 → 180

PA_C_RZF_like; PA_C-RZF_ like: Protease-associated (PA) domain C_RZF-like. This group includes various PA domain-containing proteins similar to C-RZF (chicken embryo RING zinc finger) protein. These proteins contain a C3H2C3 RING finger. C-RZF is expressed in embryo …

AMINOACIDS: .. lfaflnll pveadilayn fenasqtfdd lparfgyrlp

61 aeglkgflin skpenacepi vpppvkdnss gtfivlirrl dcnfdikvln aqragykaai 121 vhnvdsddli smgsndievl kkidipsvfi gessanslkd eftyekgghl ilvpefslpl

cd16797
Location:238 → 283

RING-H2_RNF167; RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins

Peptide history and isoform 1 sequence:

https://www.ncbi.nlm.nih.gov/protein/NP_009213.1

E3 ubiquitin-protein ligase RNF13 isoform 1 [Homo sapiens]

NCBI Reference Sequence: NP_009213.1
Identical Proteins FASTA Graphics

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LOCUS       NP_009213                381 aa            linear   PRI 03-JUN-2018
DEFINITION  E3 ubiquitin-protein ligase RNF13 isoform 1 [Homo sapiens].
ACCESSION   NP_009213
VERSION     NP_009213.1
DBSOURCE    REFSEQ: accession NM_007282.4
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 381)
  AUTHORS   Charlaftis N, Suddason T, Wu X, Anwar S, Karin M and Gallagher E.
  TITLE     The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to
            cytokines
  JOURNAL   EMBO J. 33 (21), 2581-2596 (2014)
   PUBMED   25260751
REFERENCE   2  (residues 1 to 381)
  AUTHORS   van Dijk JR, Yamazaki Y and Palmer RH.
  TITLE     Tumour-associated mutations of PA-TM-RING ubiquitin ligases
            RNF167/RNF13 identify the PA domain as a determinant for endosomal
            localization
  JOURNAL   Biochem. J. 459 (1), 27-36 (2014)
   PUBMED   24387786
  REMARK    GeneRIF: Protease-activated point mutations are identified in RNF13
            and RNF167.
REFERENCE   3  (residues 1 to 381)
  AUTHORS   Arshad M, Ye Z, Gu X, Wong CK, Liu Y, Li D, Zhou L, Zhang Y, Bay
            WP, Yu VC and Li P.
  TITLE     RNF13, a RING finger protein, mediates endoplasmic reticulum
            stress-induced apoptosis through the inositol-requiring enzyme
            (IRE1alpha)/c-Jun NH2-terminal kinase pathway
  JOURNAL   J. Biol. Chem. 288 (12), 8726-8736 (2013)
   PUBMED   23378536
  REMARK    GeneRIF: RNF13 is a critical mediator for facilitating endoplasmic
            reticulum stress-induced apoptosis through the activation of the
            IRE1alpha-TRAF2-JNK signaling pathway.
REFERENCE   4  (residues 1 to 381)
  AUTHORS   Bocock JP, Carmicle S, Madamba E and Erickson AH.
  TITLE     Nuclear targeting of an endosomal E3 ubiquitin ligase
  JOURNAL   Traffic 11 (6), 756-766 (2010)
   PUBMED   20230530
  REMARK    GeneRIF: analysis of nuclear targeting of Nuclear targeting of
            RNF13 endosomal E3 ubiquitin ligase
REFERENCE   5  (residues 1 to 381)
  AUTHORS   Zhang Q, Meng Y, Zhang L, Chen J and Zhu D.
  TITLE     RNF13: a novel RING-type ubiquitin ligase over-expressed in
            pancreatic cancer
  JOURNAL   Cell Res. 19 (3), 348-357 (2009)
   PUBMED   18794910
  REMARK    GeneRIF: RNF13 is a novel E3 ubiquitin ligase involved in
            pancreatic carcinogenesis.
REFERENCE   6  (residues 1 to 381)
  AUTHORS   van Wijk SJ, de Vries SJ, Kemmeren P, Huang A, Boelens R, Bonvin AM
            and Timmers HT.
  TITLE     A comprehensive framework of E2-RING E3 interactions of the human
            ubiquitin-proteasome system
  JOURNAL   Mol. Syst. Biol. 5, 295 (2009)
   PUBMED   19690564
  REMARK    Erratum:[Mol Syst Biol. 2009;5:317]
REFERENCE   7  (residues 1 to 381)
  AUTHORS   Schroder B, Wrocklage C, Pan C, Jager R, Kosters B, Schafer H,
            Elsasser HP, Mann M and Hasilik A.
  TITLE     Integral and associated lysosomal membrane proteins
  JOURNAL   Traffic 8 (12), 1676-1686 (2007)
   PUBMED   17897319
REFERENCE   8  (residues 1 to 381)
  AUTHORS   Wang AG, Yoon SY, Oh JH, Jeon YJ, Kim M, Kim JM, Byun SS, Yang JO,
            Kim JH, Kim DG, Yeom YI, Yoo HS, Kim YS and Kim NS.
  TITLE     Identification of intrahepatic cholangiocarcinoma related genes by
            comparison with normal liver tissues using expressed sequence tags
  JOURNAL   Biochem. Biophys. Res. Commun. 345 (3), 1022-1032 (2006)
   PUBMED   16712791
REFERENCE   9  (residues 1 to 381)
  AUTHORS   Wesselkamper SC, McDowell SA, Medvedovic M, Dalton TP, Deshmukh HS,
            Sartor MA, Case LM, Henning LN, Borchers MT, Tomlinson CR, Prows DR
            and Leikauf GD.
  TITLE     The role of metallothionein in the pathogenesis of acute lung
            injury
  JOURNAL   Am. J. Respir. Cell Mol. Biol. 34 (1), 73-82 (2006)
   PUBMED   16166738
  REMARK    GeneRIF: Mice lacking Mt1/2 have a rapid decrease in Rnf13 during
            acute lung injury
REFERENCE   10 (residues 1 to 381)
  AUTHORS   Tranque P, Crossin KL, Cirelli C, Edelman GM and Mauro VP.
  TITLE     Identification and characterization of a RING zinc finger gene
            (C-RZF) expressed in chicken embryo cells
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 93 (7), 3105-3109 (1996)
   PUBMED   8610176
  REMARK    GeneRIF: Cloning report of the chicken homolog
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA031838.1, BC009803.1,
            CB109037.1 and AC117395.5.
            
            Summary: The protein encoded by this gene contains a RING zinc
            finger, a motif known to be involved in protein-protein
            interactions. The specific function of this gene has not yet been
            determined. Alternatively spliced transcript variants that encode
            the same protein have been reported. A pseudogene, which is also
            located on chromosome 3, has been defined for this gene. [provided
            by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) represents the longer
            transcript. Both variants 1 and 4 encode the same protein.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660807.127260.1, BC009803.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..381
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3q25.1"
     Protein         1..381
                     /product="E3 ubiquitin-protein ligase RNF13 isoform 1"
                     /EC_number="2.3.2.27"
                     /note="RING zinc finger protein; E3 ubiquitin-protein
                     ligase RNF13; RING-type E3 ubiquitin transferase RNF13"
                     /calculated_mol_wt=42683
     Region          23..180
                     /region_name="PA_C_RZF_like"
                     /note="PA_C-RZF_ like: Protease-associated (PA) domain
                     C_RZF-like. This group includes various PA
                     domain-containing proteins similar to C-RZF (chicken
                     embryo RING zinc finger) protein. These proteins contain a
                     C3H2C3 RING finger. C-RZF is expressed in embryo...;
                     cd02123"
                     /db_xref="CDD:239038"
     Site            130..132
                     /site_type="other"
                     /note="PA/protease or protease-like domain interface
                     [polypeptide binding]"
                     /db_xref="CDD:239038"
     Site            183..203
                     /site_type="transmembrane region"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (O43567.1)"
     Region          238..283
                     /region_name="RING-H2_RNF167"
                     /note="RING finger, H2 subclass, found in RING finger
                     protein 167 (RNF167) and similar proteins; cd16797"
                     /db_xref="CDD:319711"
     Region          240..281
                     /region_name="RING-H2 finger (C3H2C3-type)"
                     /note="RING-H2 finger (C3H2C3-type) [structural motif]"
                     /db_xref="CDD:319711"
     Site            order(240,243,258,260,263,266,278,281)
                     /site_type="other"
                     /note="Zn binding site [ion binding]"
                     /db_xref="CDD:319711"
     CDS             1..381
                     /gene="RNF13"
                     /gene_synonym="RZF"
                     /coded_by="NM_007282.4:785..1930"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS3146.1"
                     /db_xref="GeneID:11342"
                     /db_xref="HGNC:HGNC:10057"
                     /db_xref="MIM:609247"
ORIGIN      
        1 mllsigmlml satqvytilt vqlfaflnll pveadilayn fenasqtfdd lparfgyrlp
       61 aeglkgflin skpenacepi vpppvkdnss gtfivlirrl dcnfdikvln aqragykaai
      121 vhnvdsddli smgsndievl kkidipsvfi gessanslkd eftyekgghl ilvpefslpl
      181 eyylipflii vgiclilivi fmitkfvqdr hrarrnrlrk dqlkklpvhk fkkgdeydvc
      241 aicldeyedg dklrilpcsh ayhckcvdpw ltktkktcpv ckqkvvpsqg dsdsdtdssq
      301 eenevtehtp llrplasvsa qsfgalsesr shqnmtessd yeeddnedtd ssdaeneine
      361 hdvvvqlqpn gerdyniant v
//