Q9NTX7 (RN146_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase RNF146
EC=6.3.2.-

Alternative name(s):
Dactylidin
Iduna
RING finger protein 146

Gene names

Name:

RNF146

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	359 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation. May regulate many important biological processes, such as cell survival and DNA damage response. Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex. Acts in cooperation with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CASC3, TNKS and TNKS2. Recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain and mediates their ubiquitination, leading to their degradation. Different ubiquitin linkage types have been observed: TNKS2 undergoes ubiquination at 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys-48'. May regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location. Neuroprotective protein. Protects the brain against N-methyl-D-aspartate (NMDA) receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos. Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner. Does not affect PARP1 activation By similarity. Protects against cell death induced by DNA damaging agents, such as N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest. Promotes cell survival after gamma-irradiation. Facilitates DNA repair. Ref.12 Ref.13 Ref.14 Ref.15 Ref.17
Pathway	Protein modification; protein ubiquitination. Ref.12
Subunit structure	Can form homooligomers. Interacts with PARsylated AXIN1, AXIN2, BLZF1, CASC3, HIST1H1C, IPO7, LIG3, NCL, PARP1, XRCC1, XRCC5 and XRCC6. Interacts with DDB1, DHX15, IQGAP1, LRPPRC, PARP2, PRKDC, RUVBL2, TNKS1 and TNKS2. Binding often leads to interactor ubiquitination, in the presence of the appropriate E1 and E2 enzymes, and proteasomal degradation. Ref.12 Ref.14 Ref.15
Subcellular location	Cytoplasm › cytosol. Nucleus. Note: Translocates to the nucleus after DNA damage, such as laser-induced DNA breaks, and concentrates at DNA breaks. This translocation requires PARP1 activation and PAR-binding. Ref.1 Ref.14 Ref.15
Tissue specificity	Ubiquitously expressed. Up-regulated in brains from patients with Alzheimer disease.
Domain	The WWE domain mediates non-covalent PAR-binding. Ref.12
Post-translational modification	Ubiquitinated; autoubiquitinated. Polyubiquitinated in the presence of UBE2D1, UBE2D2 and UBE2D3. Multimonoubiquitinated in the presence of UBE2E1. Not ubiquinated in the presence of UBE2H, CDC34, UBE2L3, UBE2L6, nor UBE2C. In the absence of PAR, autoubiquitination occurs on Lys-85, Lys-95 and Lys-176 via 'Lys-11' and 'Lys-48' ubiquitin linkages. In the presence of PAR, Lys-131 and Lys-176 are ubiquitinated via 'Lys-6', 'Lys-33' and 'Lys-48' ubiquitin linkages. Autoubiquitination is enhanced upon PAR-binding. Ref.12 Ref.14 Ref.15
Involvement in disease	Defects in RNF146 are a cause of susceptibility to breast cancer.
Miscellaneous	Was named dactylidin after the Greek term 'daktylidi' for ring, 'the thing around the finger' (Ref.1). Was named Iduna after the Norse goddess of protection and eternal youth (Ref.13).
Sequence similarities	Contains 1 RING-type zinc finger. Contains 1 WWE domain.

Ontologies

Keywords
Biological process	Ubl conjugation pathway Wnt signaling pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Isopeptide bond Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of canonical Wnt receptor signaling pathway Inferred from mutant phenotype Ref.12. Source: UniProtKB protein K48-linked ubiquitination Inferred from mutant phenotype Ref.12. Source: UniProtKB protein autoubiquitination Inferred from direct assay Ref.12. Source: UniProtKB protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.12. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay Ref.1. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	poly-ADP-D-ribose binding Inferred from direct assay Ref.12. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.12. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NTX7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9NTX7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 359

359

E3 ubiquitin-protein ligase RNF146

PRO_0000056107

Regions

Domain

92 – 168

77

WWE

Zinc finger

37 – 75

39

RING-type

Sites

Binding site

108

1

iso-ADP-ribose adenine ring group

Binding site

111

1

iso-ADP-ribose 5'-phosphate group

Binding site

115

1

iso-ADP-ribose 5'-phosphate group

Binding site

145

1

iso-ADP-ribose 1'-phosphate group

Binding site

154

1

iso-ADP-ribose adenine ring group

Binding site

164

1

iso-ADP-ribose 1'-phosphate group

Binding site

176

1

iso-ADP-ribose 5'-phosphate group

Amino acid modifications

Cross-link

85

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.15

Cross-link

95

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.15

Cross-link

131

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.15

Cross-link

176

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.15

Natural variations

Alternative sequence

1

1

Missing in isoform 2.

VSP_012968

Natural variant

25

1

C → R.
Corresponds to variant rs10081141 [ dbSNP | Ensembl ].

VAR_065249

Experimental info

Mutagenesis

54

1

H → A: Partially suppression of WNT3A signaling and stabilization of AXIN1, TNKS and TNKS2 with or without WNT3A induction. No effect on TNKS1-binding. Ref.14

Mutagenesis

106

1

W → A: No effect on Wnt signaling pathway. Ref.14

Mutagenesis

108

1

Y → A: Loss of iso-ADP-ribose-binding. Ref.17

Mutagenesis

111

1

R → A: Minor effect on iso-ADP-ribose-binding. Ref.17

Mutagenesis

115

1

W → A: Strong decrease in iso-ADP-ribose-binding affinity. Ref.17

Mutagenesis

145

1

Y → A: Loss of iso-ADP-ribose-binding. Ref.17

Mutagenesis

154

1

Q → A: Loss of iso-ADP-ribose-binding affinity. Ref.17

Mutagenesis

163

1

R → A: Abolishes the ability to recognize and bind PARsylated proteins. Ref.12

Mutagenesis

164

1

R → A: Loss of iso-ADP-ribose-binding. Ref.17

Mutagenesis

176

1

K → A: Minor effect on iso-ADP-ribose-binding. Ref.17

Sequence conflict

69

1

K → R in BAB55359. Ref.3

Sequence conflict

74

1

C → R in BAB55108. Ref.3

Sequence conflict

100

1

G → E in CAG38545. Ref.4

Sequence conflict

166

1

I → V in CAG38545. Ref.4

Sequence conflict

229

1

L → S in BAB55108. Ref.3

Sequence conflict

329

1

S → L in BAB55108. Ref.3

Secondary structure

1

.

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.

359

Helix Strand Turn

Details...

Beta strand

30 – 33

4

Beta strand

38 – 43

6

Beta strand

45 – 50

6

Turn

51 – 53

3

Beta strand

54 – 57

4

Helix

58 – 63

6

Beta strand

68 – 70

3

Beta strand

72 – 74

3

Helix

80 – 83

4

Beta strand

104 – 109

6

Beta strand

111 – 116

6

Helix

119 – 130

12

Beta strand

134 – 140

7

Beta strand

143 – 148

6

Turn

149 – 152

4

Beta strand

153 – 159

7

Beta strand

164 – 173

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 7337C410EDA30A7E	FASTA	359	38,950
	10 20 30 40 50 60 MMAGCGEIDH SINMLPTNRK ANESCSNTAP SLTVPECAIC LQTCVHPVSL PCKHVFCYLC 70 80 90 100 110 120 VKGASWLGKR CALCRQEIPE DFLDKPTLLS PEELKAASRG NGEYAWYYEG RNGWWQYDER 130 140 150 160 170 180 TSRELEDAFS KGKKNTEMLI AGFLYVADLE NMVQYRRNEH GRRRKIKRDI IDIPKKGVAG 190 200 210 220 230 240 LRLDCDANTV NLARESSADG ADSVSAQSGA SVQPLVSSVR PLTSVDGQLT SPATPSPDAS 250 260 270 280 290 300 TSLEDSFAHL QLSGDNTAER SHRGEGEEDH ESPSSGRVPA PDTSIEETES DASSDSEDVS 310 320 330 340 350 AVVAQHSLTQ QRLLVSNANQ TVPDRSDRSG TDRSVAGGGT VSVSVRSRRP DGQCTVTEV
	Isoform 2 [UniParc]. Checksum: E46AA6522DA8D48B	FASTA	358	38,819
	10 20 30 40 50 60 MAGCGEIDHS INMLPTNRKA NESCSNTAPS LTVPECAICL QTCVHPVSLP CKHVFCYLCV 70 80 90 100 110 120 KGASWLGKRC ALCRQEIPED FLDKPTLLSP EELKAASRGN GEYAWYYEGR NGWWQYDERT 130 140 150 160 170 180 SRELEDAFSK GKKNTEMLIA GFLYVADLEN MVQYRRNEHG RRRKIKRDII DIPKKGVAGL 190 200 210 220 230 240 RLDCDANTVN LARESSADGA DSVSAQSGAS VQPLVSSVRP LTSVDGQLTS PATPSPDAST 250 260 270 280 290 300 SLEDSFAHLQ LSGDNTAERS HRGEGEEDHE SPSSGRVPAP DTSIEETESD ASSDSEDVSA 310 320 330 340 350 VVAQHSLTQQ RLLVSNANQT VPDRSDRSGT DRSVAGGGTV SVSVRSRRPD GQCTVTEV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The novel cytosolic RING finger protein dactylidin is up-regulated in brains of patients with Alzheimer's disease." von Rotz R.C., Kins S., Hipfel R., von der Kammer H., Nitsch R.M. Eur. J. Neurosci. 21:1289-1298(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION. Tissue: Brain.
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Placenta and Teratocarcinoma.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Eye.
[8]	"Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33." Gold B., Kirchhoff T., Stefanov S., Lautenberger J., Viale A., Garber J., Friedman E., Narod S., Olshen A.B., Gregersen P., Kosarin K., Olsh A., Bergeron J., Ellis N.A., Klein R.J., Clark A.G., Norton L., Dean M., Boyd J., Offit K. Proc. Natl. Acad. Sci. U.S.A. 105:4340-4345(2008) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN BREAST CANCER.
[9]	"The 6q22.33 locus and breast cancer susceptibility." Kirchhoff T., Chen Z.Q., Gold B., Pal P., Gaudet M.M., Kosarin K., Levine D.A., Gregersen P., Spencer S., Harlan M., Robson M., Klein R.J., Hudis C.A., Norton L., Dean M., Offit K. Cancer Epidemiol. Biomarkers Prev. 18:2468-2475(2009) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN BREAST CANCER.
[10]	"The RNF146 and ECHDC1 genes as candidates for inherited breast and ovarian cancer in Jewish Ashkenazi women." Menachem T.D., Laitman Y., Kaufman B., Friedman E. Fam. Cancer 8:399-402(2009) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN BREAST CANCER.
[11]	"Genetic polymorphisms and breast cancer risk: evidence from meta-analyses, pooled analyses, and genome-wide association studies." Peng S., Lu B., Ruan W., Zhu Y., Sheng H., Lai M. Breast Cancer Res. Treat. 127:309-324(2011) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN BREAST CANCER.
[12]	"RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling." Zhang Y., Liu S., Mickanin C., Feng Y., Charlat O., Michaud G.A., Schirle M., Shi X., Hild M., Bauer A., Myer V.E., Finan P.M., Porter J.A., Huang S.M., Cong F. Nat. Cell Biol. 13:623-629(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PATHWAY, DOMAIN WWE, UBIQUITINATION, INTERACTION WITH AXIN1; AXIN2; CASC3 AND BLZF1, MUTAGENESIS OF ARG-163.
[13]	"Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death." Andrabi S.A., Kang H.C., Haince J.F., Lee Y.I., Zhang J., Chi Z., West A.B., Koehler R.C., Poirier G.G., Dawson T.M., Dawson V.L. Nat. Med. 17:692-699(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NEUROPROTECTION.
[14]	"Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling." Callow M.G., Tran H., Phu L., Lau T., Lee J., Sandoval W.N., Liu P.S., Bheddah S., Tao J., Lill J.R., Hongo J.A., Davis D., Kirkpatrick D.S., Polakis P., Costa M. PLoS ONE 6:E22595-E22595(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN WNT SIGNALING, INTERACTION WITH AXIN1; DDB1; DHX15; IQGAP1; LRPPRC; PARP1; PARP2; PRKDC; RUVBL2; TNKS1 AND TNKS2, UBIQUITINATION, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-54 AND TRP-106.
[15]	"Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage." Kang H.C., Lee Y.I., Shin J.H., Andrabi S.A., Chi Z., Gagne J.P., Lee Y., Ko H.S., Lee B.D., Poirier G.G., Dawson V.L., Dawson T.M. Proc. Natl. Acad. Sci. U.S.A. 108:14103-14108(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DNA DAMAGE RESPONSE, HOMOOLIGOMERIZATION, INTERACTION WITH HIST1H1C; IPO7; LIG3; NCL; PARP1; XRCC1; XRCC5 AND XRCC6, SUBCELLULAR LOCATION, AUTOUBIQUITINATION AT LYS-85; LYS-95; LYS-131 AND LYS-176.
[16]	"Solution structure of the RING domain of the human RING finger protein 146." RIKEN structural genomics initiative (RSGI) Submitted (JUN-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 24-84.
[17]	"Recognition of the iso-ADP-ribose moiety in poly(ADP-ribose) by WWE domains suggests a general mechanism for poly(ADP-ribosyl)ation-dependent ubiquitination." Wang Z., Michaud G.A., Cheng Z., Zhang Y., Hinds T.R., Fan E., Cong F., Xu W. Genes Dev. 26:235-240(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 100-184 IN COMPLEX WITH ISO-ADP-RIBOSE, FUNCTION, MUTAGENESIS OF TYR-108; ARG-111; TRP-115; TYR-145; GLN-154; ARG-164 AND LYS-176.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ315122 mRNA. Translation: CAC85986.1.
AL136829 mRNA. Translation: CAB66763.1.
AK027558 mRNA. Translation: BAB55196.1.
AK027436 mRNA. Translation: BAB55108.1.
AK027776 mRNA. Translation: BAB55359.1.
CR533514 mRNA. Translation: CAG38545.1.
AL109939 Genomic DNA. Translation: CAB76254.1.
AL109939 Genomic DNA. Translation: CAB76255.1.
CH471051 Genomic DNA. Translation: EAW48109.1.
CH471051 Genomic DNA. Translation: EAW48111.1.
BC008235 mRNA. Translation: AAH08235.1.

IPI

IPI00008911.
IPI00550283.

RefSeq

NP_001229773.1. NM_001242844.1.
NP_001229774.1. NM_001242845.1.
NP_001229775.1. NM_001242846.1.
NP_001229778.1. NM_001242849.1.
NP_001229779.1. NM_001242850.1.
NP_001229780.1. NM_001242851.1.
NP_001229781.1. NM_001242852.1.
NP_112225.2. NM_030963.3.

UniGene

Hs.267120.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2D8T	NMR	-	A	27-84	[»]
3V3L	X-ray	1.65	A/B	100-184	[»]

ProteinModelPortal

Q9NTX7.

ModBase

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Protein-protein interaction databases

IntAct

Q9NTX7. 4 interactions.

MINT

MINT-1370830.

STRING

9606.ENSP00000309365.

PTM databases

PhosphoSite

Q9NTX7.

Polymorphism databases

DMDM

60390653.

Proteomic databases

PaxDb

Q9NTX7.

PRIDE

Q9NTX7.

Protocols and materials databases

DNASU

81847.

StructuralBiologyKnowledgebase

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Genome annotation databases

Ensembl

ENST00000309649; ENSP00000309365; ENSG00000118518.
ENST00000356799; ENSP00000349253; ENSG00000118518.
ENST00000368314; ENSP00000357297; ENSG00000118518.

GeneID

81847.

KEGG

hsa:81847.

UCSC

uc003qat.3. human.

Organism-specific databases

CTD

81847.

GeneCards

GC06P127587.

HGNC

HGNC:21336. RNF146.

HPA

HPA027158.
HPA027209.

MIM

612137. gene.

neXtProt

NX_Q9NTX7.

PharmGKB

PA134910489.

GenAtlas

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Phylogenomic databases

eggNOG

NOG298024.

HOVERGEN

HBG057514.

InParanoid

Q9NTX7.

KO

K15700.

OMA

RMAGCGE.

OrthoDB

EOG4F7NM2.

Enzyme and pathway databases

UniPathway

UPA00143.

Gene expression databases

Bgee

Q9NTX7.

CleanEx

HS_RNF146.

Genevestigator

Q9NTX7.

GermOnline

ENSG00000118518. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR004170. WWE-dom.
IPR018123. WWE-dom_subgr.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

Pfam

PF02825. WWE. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view]

SMART

SM00184. RING. 1 hit.
SM00678. WWE. 1 hit.
[Graphical view]

PROSITE

PS50918. WWE. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

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Other

EvolutionaryTrace

Q9NTX7.

GenomeRNAi

81847.

NextBio

72150.

SOURCE

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Entry information

Entry name

RN146_HUMAN

Accession

Primary (citable) accession number: Q9NTX7
Secondary accession number(s): E1P572 , Q6FIB2, Q7L8H4, Q96K03, Q96T06, Q9NTX6

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2005
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.