RN146_HUMAN
ID RN146_HUMAN Reviewed; 359 AA.
AC Q9NTX7; E1P572; Q6FIB2; Q7L8H4; Q96K03; Q96T06; Q9NTX6;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=E3 ubiquitin-protein ligase RNF146;
DE EC=2.3.2.27;
DE AltName: Full=Dactylidin;
DE AltName: Full=Iduna;
DE AltName: Full=RING finger protein 146;
DE AltName: Full=RING-type E3 ubiquitin transferase RNF146 {ECO:0000305};
GN Name=RNF146;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=15813938; DOI=10.1111/j.1460-9568.2005.03977.x;
RA von Rotz R.C., Kins S., Hipfel R., von der Kammer H., Nitsch R.M.;
RT "The novel cytosolic RING finger protein dactylidin is up-regulated in
RT brains of patients with Alzheimer's disease.";
RL Eur. J. Neurosci. 21:1289-1298(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Eye;
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 [8]
RP POSSIBLE INVOLVEMENT IN BREAST CANCER.
RX PubMed=18326623; DOI=10.1073/pnas.0800441105;
RA Gold B., Kirchhoff T., Stefanov S., Lautenberger J., Viale A., Garber J.,
RA Friedman E., Narod S., Olshen A.B., Gregersen P., Kosarin K., Olsh A.,
RA Bergeron J., Ellis N.A., Klein R.J., Clark A.G., Norton L., Dean M.,
RA Boyd J., Offit K.;
RT "Genome-wide association study provides evidence for a breast cancer risk
RT locus at 6q22.33.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:4340-4345(2008).
RN [9]
RP POSSIBLE INVOLVEMENT IN BREAST CANCER.
RX PubMed=19690183; DOI=10.1158/1055-9965.epi-09-0151;
RA Kirchhoff T., Chen Z.Q., Gold B., Pal P., Gaudet M.M., Kosarin K.,
RA Levine D.A., Gregersen P., Spencer S., Harlan M., Robson M., Klein R.J.,
RA Hudis C.A., Norton L., Dean M., Offit K.;
RT "The 6q22.33 locus and breast cancer susceptibility.";
RL Cancer Epidemiol. Biomarkers Prev. 18:2468-2475(2009).
RN [10]
RP POSSIBLE INVOLVEMENT IN BREAST CANCER.
RX PubMed=19517271; DOI=10.1007/s10689-009-9255-7;
RA Menachem T.D., Laitman Y., Kaufman B., Friedman E.;
RT "The RNF146 and ECHDC1 genes as candidates for inherited breast and ovarian
RT cancer in Jewish Ashkenazi women.";
RL Fam. Cancer 8:399-402(2009).
RN [11]
RP POSSIBLE INVOLVEMENT IN BREAST CANCER.
RX PubMed=21445572; DOI=10.1007/s10549-011-1459-5;
RA Peng S., Lu B., Ruan W., Zhu Y., Sheng H., Lai M.;
RT "Genetic polymorphisms and breast cancer risk: evidence from meta-analyses,
RT pooled analyses, and genome-wide association studies.";
RL Breast Cancer Res. Treat. 127:309-324(2011).
RN [12]
RP FUNCTION, PATHWAY, DOMAIN WWE, UBIQUITINATION, INTERACTION WITH AXIN1;
RP AXIN2; CASC3 AND BLZF1, AND MUTAGENESIS OF ARG-163.
RX PubMed=21478859; DOI=10.1038/ncb2222;
RA Zhang Y., Liu S., Mickanin C., Feng Y., Charlat O., Michaud G.A.,
RA Schirle M., Shi X., Hild M., Bauer A., Myer V.E., Finan P.M., Porter J.A.,
RA Huang S.M., Cong F.;
RT "RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin
RT degradation and Wnt signalling.";
RL Nat. Cell Biol. 13:623-629(2011).
RN [13]
RP FUNCTION IN NEUROPROTECTION.
RX PubMed=21602803; DOI=10.1038/nm.2387;
RA Andrabi S.A., Kang H.C., Haince J.F., Lee Y.I., Zhang J., Chi Z.,
RA West A.B., Koehler R.C., Poirier G.G., Dawson T.M., Dawson V.L.;
RT "Iduna protects the brain from glutamate excitotoxicity and stroke by
RT interfering with poly(ADP-ribose) polymer-induced cell death.";
RL Nat. Med. 17:692-699(2011).
RN [14]
RP FUNCTION IN WNT SIGNALING, INTERACTION WITH AXIN1; DDB1; DHX15; IQGAP1;
RP LRPPRC; PARP1; PARP2; PRKDC; RUVBL2; TNKS1 AND TNKS2, UBIQUITINATION,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-54 AND TRP-106.
RX PubMed=21799911; DOI=10.1371/journal.pone.0022595;
RA Callow M.G., Tran H., Phu L., Lau T., Lee J., Sandoval W.N., Liu P.S.,
RA Bheddah S., Tao J., Lill J.R., Hongo J.A., Davis D., Kirkpatrick D.S.,
RA Polakis P., Costa M.;
RT "Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt
RT signaling.";
RL PLoS ONE 6:E22595-E22595(2011).
RN [15]
RP FUNCTION IN DNA DAMAGE RESPONSE, HOMOOLIGOMERIZATION, INTERACTION WITH
RP H1-2; IPO7; LIG3; NCL; PARP1; XRCC1; XRCC5 AND XRCC6, SUBCELLULAR LOCATION,
RP AND AUTOUBIQUITINATION AT LYS-85; LYS-95; LYS-131 AND LYS-176.
RX PubMed=21825151; DOI=10.1073/pnas.1108799108;
RA Kang H.C., Lee Y.I., Shin J.H., Andrabi S.A., Chi Z., Gagne J.P., Lee Y.,
RA Ko H.S., Lee B.D., Poirier G.G., Dawson V.L., Dawson T.M.;
RT "Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that
RT regulates DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:14103-14108(2011).
RN [16]
RP STRUCTURE BY NMR OF 24-84.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the RING domain of the human RING finger protein
RT 146.";
RL Submitted (JUN-2006) to the PDB data bank.
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 100-184 IN COMPLEX WITH
RP ISO-ADP-RIBOSE, FUNCTION, AND MUTAGENESIS OF TYR-108; ARG-111; TRP-115;
RP TYR-145; GLN-154; ARG-164 AND LYS-176.
RX PubMed=22267412; DOI=10.1101/gad.182618.111;
RA Wang Z., Michaud G.A., Cheng Z., Zhang Y., Hinds T.R., Fan E., Cong F.,
RA Xu W.;
RT "Recognition of the iso-ADP-ribose moiety in poly(ADP-ribose) by WWE
RT domains suggests a general mechanism for poly(ADP-ribosyl)ation-dependent
RT ubiquitination.";
RL Genes Dev. 26:235-240(2012).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that specifically binds poly-ADP-
CC ribosylated (PARsylated) proteins and mediates their ubiquitination and
CC subsequent degradation. May regulate many important biological
CC processes, such as cell survival and DNA damage response. Acts as an
CC activator of the Wnt signaling pathway by mediating the ubiquitination
CC of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin
CC destruction complex. Acts in cooperation with tankyrase proteins (TNKS
CC and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2,
CC BLZF1, CASC3, TNKS and TNKS2. Recognizes and binds tankyrase-dependent
CC PARsylated proteins via its WWE domain and mediates their
CC ubiquitination, leading to their degradation. Different ubiquitin
CC linkage types have been observed: TNKS2 undergoes ubiquitination at
CC 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys-48'.
CC May regulate TNKS and TNKS2 subcellular location, preventing
CC aggregation at a centrosomal location. Neuroprotective protein.
CC Protects the brain against N-methyl-D-aspartate (NMDA) receptor-
CC mediated glutamate excitotoxicity and ischemia, by interfering with
CC PAR-induced cell death, called parthanatos. Prevents nuclear
CC translocation of AIFM1 in a PAR-binding dependent manner. Does not
CC affect PARP1 activation (By similarity). Protects against cell death
CC induced by DNA damaging agents, such as N-methyl-N-nitro-N-
CC nitrosoguanidine (MNNG) and rescues cells from G1 arrest. Promotes cell
CC survival after gamma-irradiation. Facilitates DNA repair. {ECO:0000250,
CC ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:21602803,
CC ECO:0000269|PubMed:21799911, ECO:0000269|PubMed:21825151,
CC ECO:0000269|PubMed:22267412}.
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 {ECO:0000269|PubMed:21478859}.
CC -!- SUBUNIT: Can form homooligomers. Interacts with PARsylated AXIN1,
CC AXIN2, BLZF1, CASC3, H1-2, IPO7, LIG3, NCL, PARP1, XRCC1, XRCC5 and
CC XRCC6. Interacts with DDB1, DHX15, IQGAP1, LRPPRC, PARP2, PRKDC,
CC RUVBL2, TNKS1 and TNKS2. Binding often leads to interactor
CC ubiquitination, in the presence of the appropriate E1 and E2 enzymes,
CC and proteasomal degradation. {ECO:0000269|PubMed:21478859,
CC ECO:0000269|PubMed:21799911, ECO:0000269|PubMed:21825151,
CC ECO:0000269|PubMed:22267412}.
CC -!- INTERACTION:
CC Q9NTX7; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-722397, EBI-749265;
CC Q9NTX7; P09874: PARP1; NbExp=4; IntAct=EBI-722397, EBI-355676;
CC Q9NTX7; O95271: TNKS; NbExp=6; IntAct=EBI-722397, EBI-1105254;
CC Q9NTX7; Q12933: TRAF2; NbExp=3; IntAct=EBI-722397, EBI-355744;
CC Q9NTX7; Q9UGJ1: TUBGCP4; NbExp=3; IntAct=EBI-722397, EBI-1052544;
CC Q9NTX7-2; Q8N6L0: KASH5; NbExp=7; IntAct=EBI-11750630, EBI-749265;
CC Q9NTX7-2; Q9BU61: NDUFAF3; NbExp=3; IntAct=EBI-11750630, EBI-2114801;
CC Q9NTX7-2; P49821: NDUFV1; NbExp=3; IntAct=EBI-11750630, EBI-748312;
CC Q9NTX7-2; Q12933: TRAF2; NbExp=3; IntAct=EBI-11750630, EBI-355744;
CC Q9NTX7-2; O76024: WFS1; NbExp=3; IntAct=EBI-11750630, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Nucleus. Note=Translocates to
CC the nucleus after DNA damage, such as laser-induced DNA breaks, and
CC concentrates at DNA breaks. This translocation requires PARP1
CC activation and PAR-binding.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NTX7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NTX7-2; Sequence=VSP_012968;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Up-regulated in brains from
CC patients with Alzheimer disease.
CC -!- DOMAIN: The WWE domain mediates non-covalent PAR-binding.
CC {ECO:0000269|PubMed:21478859}.
CC -!- PTM: Ubiquitinated; autoubiquitinated. Polyubiquitinated in the
CC presence of UBE2D1, UBE2D2 and UBE2D3. Multimonoubiquitinated in the
CC presence of UBE2E1. Not ubiquitinated in the presence of UBE2H, CDC34,
CC UBE2L3, UBE2L6, nor UBE2C. In the absence of PAR, autoubiquitination
CC occurs on Lys-85, Lys-95 and Lys-176 via 'Lys-11' and 'Lys-48'
CC ubiquitin linkages. In the presence of PAR, Lys-131 and Lys-176 are
CC ubiquitinated via 'Lys-6', 'Lys-33' and 'Lys-48' ubiquitin linkages.
CC Autoubiquitination is enhanced upon PAR-binding.
CC {ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:21799911,
CC ECO:0000269|PubMed:21825151}.
CC -!- DISEASE: Note=Defects in RNF146 are a cause of susceptibility to breast
CC cancer.
CC -!- MISCELLANEOUS: Was named dactylidin after the Greek term 'daktylidi'
CC for ring, 'the thing around the finger' (PubMed:15813938). Was named
CC Iduna after the Norse goddess of protection and eternal youth
CC (PubMed:21602803). {ECO:0000305|PubMed:15813938,
CC ECO:0000305|PubMed:21602803}.
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DR EMBL; AJ315122; CAC85986.1; -; mRNA.
DR EMBL; AL136829; CAB66763.1; -; mRNA.
DR EMBL; AK027558; BAB55196.1; -; mRNA.
DR EMBL; AK027436; BAB55108.1; -; mRNA.
DR EMBL; AK027776; BAB55359.1; -; mRNA.
DR EMBL; CR533514; CAG38545.1; -; mRNA.
DR EMBL; AL109939; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48109.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48111.1; -; Genomic_DNA.
DR EMBL; BC008235; AAH08235.1; -; mRNA.
DR CCDS; CCDS5136.1; -. [Q9NTX7-2]
DR CCDS; CCDS56449.1; -. [Q9NTX7-1]
DR RefSeq; NP_001229773.1; NM_001242844.1. [Q9NTX7-2]
DR RefSeq; NP_001229774.1; NM_001242845.1. [Q9NTX7-2]
DR RefSeq; NP_001229775.1; NM_001242846.1. [Q9NTX7-2]
DR RefSeq; NP_001229776.1; NM_001242847.1. [Q9NTX7-2]
DR RefSeq; NP_001229777.1; NM_001242848.1. [Q9NTX7-2]
DR RefSeq; NP_001229778.1; NM_001242849.1. [Q9NTX7-1]
DR RefSeq; NP_001229779.1; NM_001242850.1. [Q9NTX7-1]
DR RefSeq; NP_001229780.1; NM_001242851.1. [Q9NTX7-1]
DR RefSeq; NP_001229781.1; NM_001242852.1. [Q9NTX7-2]
DR RefSeq; NP_112225.2; NM_030963.3. [Q9NTX7-2]
DR RefSeq; XP_006715634.1; XM_006715571.3. [Q9NTX7-2]
DR RefSeq; XP_011534463.1; XM_011536161.2. [Q9NTX7-2]
DR RefSeq; XP_011534464.1; XM_011536162.2. [Q9NTX7-2]
DR RefSeq; XP_011534465.1; XM_011536163.2. [Q9NTX7-2]
DR RefSeq; XP_011534466.1; XM_011536164.2. [Q9NTX7-2]
DR RefSeq; XP_016866825.1; XM_017011336.1. [Q9NTX7-1]
DR RefSeq; XP_016866826.1; XM_017011337.1.
DR RefSeq; XP_016866827.1; XM_017011338.1. [Q9NTX7-2]
DR RefSeq; XP_016866828.1; XM_017011339.1. [Q9NTX7-2]
DR RefSeq; XP_016866829.1; XM_017011340.1. [Q9NTX7-2]
DR RefSeq; XP_016866830.1; XM_017011341.1. [Q9NTX7-2]
DR RefSeq; XP_016866831.1; XM_017011342.1. [Q9NTX7-2]
DR RefSeq; XP_016866832.1; XM_017011343.1. [Q9NTX7-2]
DR PDB; 2D8T; NMR; -; A=27-84.
DR PDB; 3V3L; X-ray; 1.65 A; A/B=100-184.
DR PDB; 6CF6; X-ray; 1.93 A; C/D=191-203.
DR PDBsum; 2D8T; -.
DR PDBsum; 3V3L; -.
DR PDBsum; 6CF6; -.
DR AlphaFoldDB; Q9NTX7; -.
DR SMR; Q9NTX7; -.
DR BioGRID; 123598; 66.
DR DIP; DIP-52730N; -.
DR IntAct; Q9NTX7; 49.
DR MINT; Q9NTX7; -.
DR STRING; 9606.ENSP00000357297; -.
DR GlyGen; Q9NTX7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NTX7; -.
DR PhosphoSitePlus; Q9NTX7; -.
DR BioMuta; RNF146; -.
DR DMDM; 60390653; -.
DR EPD; Q9NTX7; -.
DR jPOST; Q9NTX7; -.
DR MassIVE; Q9NTX7; -.
DR MaxQB; Q9NTX7; -.
DR PaxDb; Q9NTX7; -.
DR PeptideAtlas; Q9NTX7; -.
DR PRIDE; Q9NTX7; -.
DR ProteomicsDB; 82642; -. [Q9NTX7-1]
DR ProteomicsDB; 82643; -. [Q9NTX7-2]
DR Antibodypedia; 19579; 68 antibodies from 18 providers.
DR DNASU; 81847; -.
DR Ensembl; ENST00000368314.6; ENSP00000357297.1; ENSG00000118518.17. [Q9NTX7-1]
DR Ensembl; ENST00000608991.5; ENSP00000477168.1; ENSG00000118518.17. [Q9NTX7-2]
DR Ensembl; ENST00000610153.1; ENSP00000476814.1; ENSG00000118518.17. [Q9NTX7-1]
DR GeneID; 81847; -.
DR KEGG; hsa:81847; -.
DR MANE-Select; ENST00000368314.6; ENSP00000357297.1; NM_001242850.2; NP_001229779.1.
DR UCSC; uc003qav.4; human. [Q9NTX7-1]
DR CTD; 81847; -.
DR DisGeNET; 81847; -.
DR GeneCards; RNF146; -.
DR HGNC; HGNC:21336; RNF146.
DR HPA; ENSG00000118518; Low tissue specificity.
DR MIM; 612137; gene.
DR neXtProt; NX_Q9NTX7; -.
DR OpenTargets; ENSG00000118518; -.
DR PharmGKB; PA134910489; -.
DR VEuPathDB; HostDB:ENSG00000118518; -.
DR eggNOG; KOG0824; Eukaryota.
DR GeneTree; ENSGT00390000000358; -.
DR HOGENOM; CLU_067425_0_0_1; -.
DR InParanoid; Q9NTX7; -.
DR OMA; KTNESCA; -.
DR OrthoDB; 1469576at2759; -.
DR PhylomeDB; Q9NTX7; -.
DR TreeFam; TF318925; -.
DR PathwayCommons; Q9NTX7; -.
DR Reactome; R-HSA-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-HSA-4641257; Degradation of AXIN.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity.
DR SignaLink; Q9NTX7; -.
DR SIGNOR; Q9NTX7; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 81847; 41 hits in 1138 CRISPR screens.
DR ChiTaRS; RNF146; human.
DR EvolutionaryTrace; Q9NTX7; -.
DR GeneWiki; RNF146; -.
DR GenomeRNAi; 81847; -.
DR Pharos; Q9NTX7; Tbio.
DR PRO; PR:Q9NTX7; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9NTX7; protein.
DR Bgee; ENSG00000118518; Expressed in cerebellar vermis and 192 other tissues.
DR ExpressionAtlas; Q9NTX7; baseline and differential.
DR Genevisible; Q9NTX7; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0072572; F:poly-ADP-D-ribose binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; TAS:Reactome.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd16546; RING-HC_RNF146; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.30.720.50; -; 1.
DR InterPro; IPR044110; RING-HC_RNF146.
DR InterPro; IPR033509; RNF146.
DR InterPro; IPR004170; WWE-dom.
DR InterPro; IPR018123; WWE-dom_subgr.
DR InterPro; IPR037197; WWE_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR13417:SF2; PTHR13417:SF2; 1.
DR Pfam; PF02825; WWE; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00678; WWE; 1.
DR SUPFAM; SSF117839; SSF117839; 1.
DR PROSITE; PS50918; WWE; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Wnt signaling pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..359
FT /note="E3 ubiquitin-protein ligase RNF146"
FT /id="PRO_0000056107"
FT DOMAIN 92..168
FT /note="WWE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT ZN_FING 37..75
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 254..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 256..275
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 295..325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 333..359
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 108
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:22267412"
FT BINDING 111
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:22267412"
FT BINDING 115
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:22267412"
FT BINDING 145
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:22267412"
FT BINDING 154
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:22267412"
FT BINDING 164
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:22267412"
FT BINDING 176
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_part="poly[(1''->2')-ADP-alpha-D-ribose] group"
FT /ligand_part_id="ChEBI:CHEBI:157741"
FT /evidence="ECO:0000269|PubMed:22267412"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5XIK5"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5XIK5"
FT CROSSLNK 85
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:21825151"
FT CROSSLNK 95
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:21825151"
FT CROSSLNK 131
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:21825151"
FT CROSSLNK 176
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:21825151"
FT VAR_SEQ 1
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11230166,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15813938, ECO:0000303|Ref.4"
FT /id="VSP_012968"
FT VARIANT 25
FT /note="C -> R (in dbSNP:rs10081141)"
FT /id="VAR_065249"
FT MUTAGEN 54
FT /note="H->A: Partially suppression of WNT3A signaling and
FT stabilization of AXIN1, TNKS and TNKS2 with or without
FT WNT3A induction. No effect on TNKS1-binding."
FT /evidence="ECO:0000269|PubMed:21799911"
FT MUTAGEN 106
FT /note="W->A: No effect on Wnt signaling pathway."
FT /evidence="ECO:0000269|PubMed:21799911"
FT MUTAGEN 108
FT /note="Y->A: Loss of iso-ADP-ribose-binding."
FT /evidence="ECO:0000269|PubMed:22267412"
FT MUTAGEN 111
FT /note="R->A: Minor effect on iso-ADP-ribose-binding."
FT /evidence="ECO:0000269|PubMed:22267412"
FT MUTAGEN 115
FT /note="W->A: Strong decrease in iso-ADP-ribose-binding
FT affinity."
FT /evidence="ECO:0000269|PubMed:22267412"
FT MUTAGEN 145
FT /note="Y->A: Loss of iso-ADP-ribose-binding."
FT /evidence="ECO:0000269|PubMed:22267412"
FT MUTAGEN 154
FT /note="Q->A: Loss of iso-ADP-ribose-binding affinity."
FT /evidence="ECO:0000269|PubMed:22267412"
FT MUTAGEN 163
FT /note="R->A: Abolishes the ability to recognize and bind
FT PARsylated proteins."
FT /evidence="ECO:0000269|PubMed:21478859"
FT MUTAGEN 164
FT /note="R->A: Loss of iso-ADP-ribose-binding."
FT /evidence="ECO:0000269|PubMed:22267412"
FT MUTAGEN 176
FT /note="K->A: Minor effect on iso-ADP-ribose-binding."
FT /evidence="ECO:0000269|PubMed:22267412"
FT CONFLICT 69
FT /note="K -> R (in Ref. 3; BAB55359)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="C -> R (in Ref. 3; BAB55108)"
FT /evidence="ECO:0000305"
FT CONFLICT 100
FT /note="G -> E (in Ref. 4; CAG38545)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="I -> V (in Ref. 4; CAG38545)"
FT /evidence="ECO:0000305"
FT CONFLICT 229
FT /note="L -> S (in Ref. 3; BAB55108)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="S -> L (in Ref. 3; BAB55108)"
FT /evidence="ECO:0000305"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:2D8T"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:2D8T"
FT STRAND 45..50
FT /evidence="ECO:0007829|PDB:2D8T"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:2D8T"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:2D8T"
FT HELIX 58..63
FT /evidence="ECO:0007829|PDB:2D8T"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:2D8T"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:2D8T"
FT HELIX 80..83
FT /evidence="ECO:0007829|PDB:2D8T"
FT STRAND 104..109
FT /evidence="ECO:0007829|PDB:3V3L"
FT STRAND 111..116
FT /evidence="ECO:0007829|PDB:3V3L"
FT HELIX 119..130
FT /evidence="ECO:0007829|PDB:3V3L"
FT STRAND 134..140
FT /evidence="ECO:0007829|PDB:3V3L"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:3V3L"
FT TURN 149..152
FT /evidence="ECO:0007829|PDB:3V3L"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:3V3L"
FT STRAND 164..173
FT /evidence="ECO:0007829|PDB:3V3L"
SQ SEQUENCE 359 AA; 38950 MW; 7337C410EDA30A7E CRC64;
MMAGCGEIDH SINMLPTNRK ANESCSNTAP SLTVPECAIC LQTCVHPVSL PCKHVFCYLC
VKGASWLGKR CALCRQEIPE DFLDKPTLLS PEELKAASRG NGEYAWYYEG RNGWWQYDER
TSRELEDAFS KGKKNTEMLI AGFLYVADLE NMVQYRRNEH GRRRKIKRDI IDIPKKGVAG
LRLDCDANTV NLARESSADG ADSVSAQSGA SVQPLVSSVR PLTSVDGQLT SPATPSPDAS
TSLEDSFAHL QLSGDNTAER SHRGEGEEDH ESPSSGRVPA PDTSIEETES DASSDSEDVS
AVVAQHSLTQ QRLLVSNANQ TVPDRSDRSG TDRSVAGGGT VSVSVRSRRP DGQCTVTEV
