RN145_MOUSE
ID RN145_MOUSE Reviewed; 663 AA.
AC Q5SWK7; Q8BXX5; Q9CXG1;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=RING finger protein 145 {ECO:0000303|PubMed:29374057};
DE EC=2.3.2.27 {ECO:0000269|PubMed:29068315, ECO:0000269|PubMed:29374057};
GN Name=Rnf145 {ECO:0000312|MGI:MGI:1921565};
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; 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).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26194095; DOI=10.1038/ncomms8838;
RA Graham D.B., Becker C.E., Doan A., Goel G., Villablanca E.J., Knights D.,
RA Mok A., Ng A.C., Doench J.G., Root D.E., Clish C.B., Xavier R.J.;
RT "Functional genomics identifies negative regulatory nodes controlling
RT phagocyte oxidative burst.";
RL Nat. Commun. 6:7838-7838(2015).
RN [5]
RP CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY
RP CHOLESTEROL, DISRUPTION PHENOTYPE, ACTIVE SITE, AND MUTAGENESIS OF CYS-537.
RX PubMed=29068315; DOI=10.7554/elife.28766;
RA Zhang L., Rajbhandari P., Priest C., Sandhu J., Wu X., Temel R.,
RA Castrillo A., de Aguiar Vallim T.Q., Sallam T., Tontonoz P.;
RT "Inhibition of cholesterol biosynthesis through RNF145-dependent
RT ubiquitination of SCAP.";
RL Elife 6:0-0(2017).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH INSIG1
RP AND INSIG2, AND MUTAGENESIS OF 81-TYR--PHE-84 AND CYS-537.
RX PubMed=29374057; DOI=10.1074/jbc.ra117.001260;
RA Jiang L.Y., Jiang W., Tian N., Xiong Y.N., Liu J., Wei J., Wu K.Y., Luo J.,
RA Shi X.J., Song B.L.;
RT "Ring finger protein 145 (RNF145) is a ubiquitin ligase for sterol-induced
RT degradation of HMG-CoA reductase.";
RL J. Biol. Chem. 293:4047-4055(2018).
CC -!- FUNCTION: E3 ubiquitin ligase that catalyzes the direct transfer of
CC ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate.
CC In response to bacterial infection, negatively regulates the phagocyte
CC oxidative burst by controlling the turnover of the NADPH oxidase
CC complex subunits. Promotes monoubiquitination of CYBA and 'Lys-48'-
CC linked polyubiquitination and degradation of CYBB NADPH oxidase
CC catalytic subunits, both essential for the generation of antimicrobial
CC reactive oxygen species (PubMed:26194095). Involved in the maintenance
CC of cholesterol homeostasis. In response to high sterol concentrations
CC ubiquitinates HMGCR, a rate-limiting enzyme in cholesterol
CC biosynthesis, and targets it for degradation. The interaction with
CC INSIG1 is required for this function (PubMed:29374057). In addition,
CC triggers ubiquitination of SCAP, likely inhibiting its transport to the
CC Golgi apparatus and the subsequent processing/maturation of SREBPF2,
CC ultimately down-regulating cholesterol biosynthesis (PubMed:29068315).
CC {ECO:0000269|PubMed:26194095, ECO:0000269|PubMed:29068315,
CC ECO:0000269|PubMed:29374057}.
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; Evidence={ECO:0000269|PubMed:29068315,
CC ECO:0000269|PubMed:29374057};
CC -!- SUBUNIT: Interacts (via YLYF motif) with INSIG1 and INSIG2.
CC {ECO:0000269|PubMed:29374057}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:26194095, ECO:0000269|PubMed:29068315,
CC ECO:0000269|PubMed:29374057}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: By high-cholesterol diet. {ECO:0000269|PubMed:29068315}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice generated by CRISPR-Cas9-mediated
CC gene editing are born at the expected Mendelian rate. Compared to wild-
CC type littermates, mutant mice show slightly reduced body weight and
CC increased serum cholesterol levels. {ECO:0000269|PubMed:29068315}.
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DR EMBL; AK014408; BAB29332.1; -; mRNA.
DR EMBL; AK043002; BAC31431.1; -; mRNA.
DR EMBL; AL603913; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC040799; AAH40799.1; -; mRNA.
DR CCDS; CCDS24565.1; -.
DR RefSeq; NP_083138.2; NM_028862.3.
DR RefSeq; XP_006534419.1; XM_006534356.2.
DR RefSeq; XP_006534420.1; XM_006534357.1.
DR RefSeq; XP_006534421.1; XM_006534358.3.
DR AlphaFoldDB; Q5SWK7; -.
DR STRING; 10090.ENSMUSP00000019333; -.
DR iPTMnet; Q5SWK7; -.
DR PhosphoSitePlus; Q5SWK7; -.
DR EPD; Q5SWK7; -.
DR MaxQB; Q5SWK7; -.
DR PaxDb; Q5SWK7; -.
DR PRIDE; Q5SWK7; -.
DR ProteomicsDB; 301613; -.
DR Antibodypedia; 28490; 88 antibodies from 17 providers.
DR DNASU; 74315; -.
DR Ensembl; ENSMUST00000019333; ENSMUSP00000019333; ENSMUSG00000019189.
DR GeneID; 74315; -.
DR KEGG; mmu:74315; -.
DR UCSC; uc007inh.2; mouse.
DR CTD; 153830; -.
DR MGI; MGI:1921565; Rnf145.
DR VEuPathDB; HostDB:ENSMUSG00000019189; -.
DR eggNOG; KOG0802; Eukaryota.
DR GeneTree; ENSGT00940000157281; -.
DR HOGENOM; CLU_016467_1_0_1; -.
DR InParanoid; Q5SWK7; -.
DR OMA; NECIATR; -.
DR OrthoDB; 897451at2759; -.
DR PhylomeDB; Q5SWK7; -.
DR TreeFam; TF318635; -.
DR BioGRID-ORCS; 74315; 5 hits in 73 CRISPR screens.
DR ChiTaRS; Rnf145; mouse.
DR PRO; PR:Q5SWK7; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q5SWK7; protein.
DR Bgee; ENSMUSG00000019189; Expressed in superior cervical ganglion and 257 other tissues.
DR ExpressionAtlas; Q5SWK7; baseline and differential.
DR Genevisible; Q5SWK7; MM.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR025754; TRC8_N_dom.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR011016; Znf_RING-CH.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13705; TRC8_N; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00744; RINGv; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Membrane; Metal-binding; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..663
FT /note="RING finger protein 145"
FT /id="PRO_0000294025"
FT TRANSMEM 53..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..97
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 205..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 275..295
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 316..336
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 340..360
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 384..404
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 460..480
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 482..502
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 537..575
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 587..663
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 81..84
FT /note="YLYF motif"
FT /evidence="ECO:0000269|PubMed:29374057"
FT COMPBIAS 619..637
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 537
FT /evidence="ECO:0000269|PubMed:29068315"
FT MUTAGEN 81..84
FT /note="YLYF->AAAA: Impairs interaction with INSIG1."
FT /evidence="ECO:0000269|PubMed:29374057"
FT MUTAGEN 537
FT /note="C->A: Abolishes E3 ubiquitin ligase activity.
FT Impairs ubiquitination of SCAP and functional regulation of
FT cholesterol biosynthesis. Impairs sterol-induced
FT ubiquitination and degradation of HMGCR."
FT /evidence="ECO:0000269|PubMed:29068315,
FT ECO:0000269|PubMed:29374057"
FT CONFLICT 38
FT /note="I -> V (in Ref. 1; BAB29332)"
FT /evidence="ECO:0000305"
FT CONFLICT 68
FT /note="V -> G (in Ref. 1; BAC31431)"
FT /evidence="ECO:0000305"
FT CONFLICT 91
FT /note="Y -> C (in Ref. 1; BAB29332)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="F -> S (in Ref. 1; BAB29332)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="V -> I (in Ref. 1; BAB29332)"
FT /evidence="ECO:0000305"
FT CONFLICT 448
FT /note="D -> E (in Ref. 1; BAB29332)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 663 AA; 74648 MW; 51704F91EE4F8F34 CRC64;
MAAKEKLEAV LNVALRVPSI MLLDVLYRWD VSSFFQQIQR SSLNNNPLFQ YKYLALNMHY
VGYILSVVLL TLPRQHLVQL YLYFVTALLL YAGHQISRDY VRSELESAYE GPMYLEPLSM
NRFTTALIGQ LVVCTLCSCV MKTKQIWLFS AHMLPLLARL CLVPLETIVI INKFAMIFTG
LEVLYFLGSN LLVPYNLAKS AYRELVQVVE VYGLLALGMS LWNQLVVPVL FMVFWLVLFA
LQIYSYFSTR DQPASRERLL FLFLTSIAEC CSTPYSLLGL VFTVSFVALG VLTLCKFYLQ
GYRAFMNDPA MNRGMTEGVT LLILAVQTGL IELQVVHRAF LLSIILFIVV ASILQSMLEI
ADPIVLALGA SRDKSLWKHF RAVSLCLFLL VFPAYMAYMI CQFFHMDFWL LIIISSSILT
SLQVLGTLFI YVLFMVEEFR KEPVENMDDV IYYVNGTYRL LEFVVALCVV AYGVSETIFG
EWTVMGSMII FIHSYYNVWL RAQLGWKSFL LRRDAVNKIK SLPVATQEQL EKHNDICAIC
YQDMKSAVIT PCSHFFHAGC LKKWLYVQDT CPLCHCHLKN SSQLPGLGTE AAPQPPAGAE
QNIVLQEGPE PPDHESPPGT GTQEGSGDSS EHINRGSASQ EGAADAGEGP QIPEGEVCPV
ESA
