ID TIRR_HUMAN Reviewed; 211 AA.
AC Q9BRJ7; Q8NAI2;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 10-MAY-2017, entry version 117.
DE RecName: Full=Tudor-interacting repair regulator protein {ECO:0000303|PubMed:28241136};
DE AltName: Full=NUDT16-like protein 1 {ECO:0000312|HGNC:HGNC:28154};
DE AltName: Full=Protein syndesmos {ECO:0000303|PubMed:18820299};
GN Name=NUDT16L1 {ECO:0000312|HGNC:HGNC:28154};
GN Synonyms=SDOS {ECO:0000250|UniProtKB:Q8VHN8},
GN TIRR {ECO:0000303|PubMed:28241136};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Prostate;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP RNA-BINDING, GENE EVOLUTION, AND GENE FAMILY ORGANIZATION.
RX PubMed=18820299; DOI=10.1093/nar/gkn605;
RA Taylor M.J., Peculis B.A.;
RT "Evolutionary conservation supports ancient origin for Nudt16, a
RT nuclear-localized, RNA-binding, RNA-decapping enzyme.";
RL Nucleic Acids Res. 36:6021-6034(2008).
RN [4]
RP LACK OF FUNCTION AS A DECAPPING ENZYME.
RX PubMed=21070968; DOI=10.1016/j.molcel.2010.10.010;
RA Song M.G., Li Y., Kiledjian M.;
RT "Multiple mRNA decapping enzymes in mammalian cells.";
RL Mol. Cell 40:423-432(2010).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH TP53BP1,
RP UBIQUITINATION AT LYS-10 AND LYS-151, AND MUTAGENESIS OF LYS-10 AND
RP LYS-151.
RX PubMed=28241136; DOI=10.1038/nature21358;
RA Drane P., Brault M.E., Cui G., Meghani K., Chaubey S., Detappe A.,
RA Parnandi N., He Y., Zheng X.F., Botuyan M.V., Kalousi A.,
RA Yewdell W.T., Muench C., Harper J.W., Chaudhuri J., Soutoglou E.,
RA Mer G., Chowdhury D.;
RT "TIRR regulates 53BP1 by masking its histone methyl-lysine binding
RT function.";
RL Nature 543:211-216(2017).
RN [7] {ECO:0000244|PDB:3KVH}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 6-211.
RA Tresaugues L., Siponen M.I., Arrowsmith C.H., Berglund H., Bountra C.,
RA Collins R., Edwards A.M., Flodin S., Flores A., Graslund S.,
RA Hammarstrom M., Johansson A., Johansson I., Kallas A., Karlberg T.,
RA Kotenyova T., Kotzsch A., Kraulis P., Moche M., Nielsen T.K.,
RA Nyman T., Persson C., Roos A.K., Schuler H., Schutz P., Thorsell A.G.,
RA Van Den Berg S., Weigelt J., Welin M., Wisniewska M., Nordlund P.;
RT "Crystal structure of human protein syndesmos (NUDT16L1).";
RL Submitted (NOV-2009) to the PDB data bank.
CC -!- FUNCTION: Key regulator of TP53BP1 required to stabilize TP53BP1
CC and regulate its recruitment to chromatin (PubMed:28241136). In
CC absence of DNA damage, interacts with the tandem Tudor-like domain
CC of TP53BP1, masking the region that binds histone H4 dimethylated
CC at 'Lys-20' (H4K20me2), thereby preventing TP53BP1 recruitment to
CC chromatin and maintaining TP53BP1 localization to the nucleus
CC (PubMed:28241136). Following DNA damage, ATM-induced
CC phosphorylation of TP53BP1 and subsequent recruitment of RIF1
CC leads to dissociate NUDT16L1/TIRR from TP53BP1, unmasking the
CC tandem Tudor-like domain and allowing recruitment of TP53BP1 to
CC DNA double strand breaks (DSBs) (PubMed:28241136). Binds U8 snoRNA
CC (PubMed:18820299). {ECO:0000269|PubMed:18820299,
CC ECO:0000269|PubMed:28241136}.
CC -!- SUBUNIT: Homodimer (PubMed:28241136). Interacts with TP53BP1 (via
CC the Tudor-like domain); interaction is abolished following DNA
CC damage and TP53BP1 phosphorylation by ATM (PubMed:28241136).
CC Interacts (via the cytoplasmic part) with SDC4 (By similarity).
CC Interacts with TGFB1I1 and PXN (By similarity).
CC {ECO:0000250|UniProtKB:Q8VHN8, ECO:0000269|PubMed:28241136}.
CC -!- INTERACTION:
CC Q8ND90:PNMA1; NbExp=3; IntAct=EBI-2949792, EBI-302345;
CC Q12933:TRAF2; NbExp=5; IntAct=EBI-2949792, EBI-355744;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28241136}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BRJ7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BRJ7-2; Sequence=VSP_014276;
CC Note=No experimental confirmation available.;
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. TIRR subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Although strongly related to the nudix NUDT16 protein,
CC lacks the Nudix box and is therefore not related to the rest of
CC the family (PubMed:18820299, PubMed:21070968). Gene organization
CC and evolutionary distribution suggest that syndesmos NUDT16L1
CC probably originated as a gene duplication event of the more
CC ancient U8 snoRNA-decapping enzyme NUDT16 (PubMed:18820299).
CC Although similar to U8 snoRNA-decapping enzyme NUDT16, lacks a
CC number of residues which are necessary for hydrolase activity and
CC does not play a role in U8 snoRNA decapping activity
CC (PubMed:21070968). {ECO:0000269|PubMed:18820299,
CC ECO:0000269|PubMed:21070968}.
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DR EMBL; AK092642; BAC03933.1; -; mRNA.
DR EMBL; BC006223; AAH06223.1; -; mRNA.
DR CCDS; CCDS10519.1; -. [Q9BRJ7-1]
DR RefSeq; NP_115725.1; NM_032349.3. [Q9BRJ7-1]
DR UniGene; Hs.513315; -.
DR PDB; 3KVH; X-ray; 1.70 A; A=6-211.
DR PDBsum; 3KVH; -.
DR ProteinModelPortal; Q9BRJ7; -.
DR SMR; Q9BRJ7; -.
DR BioGrid; 124035; 22.
DR IntAct; Q9BRJ7; 13.
DR MINT; MINT-5009616; -.
DR STRING; 9606.ENSP00000306670; -.
DR iPTMnet; Q9BRJ7; -.
DR PhosphoSitePlus; Q9BRJ7; -.
DR BioMuta; NUDT16L1; -.
DR DMDM; 68566060; -.
DR EPD; Q9BRJ7; -.
DR MaxQB; Q9BRJ7; -.
DR PaxDb; Q9BRJ7; -.
DR PeptideAtlas; Q9BRJ7; -.
DR PRIDE; Q9BRJ7; -.
DR DNASU; 84309; -.
DR Ensembl; ENST00000304301; ENSP00000306670; ENSG00000168101. [Q9BRJ7-1]
DR Ensembl; ENST00000405142; ENSP00000458144; ENSG00000168101. [Q9BRJ7-2]
DR GeneID; 84309; -.
DR KEGG; hsa:84309; -.
DR UCSC; uc002cxe.4; human. [Q9BRJ7-1]
DR CTD; 84309; -.
DR GeneCards; NUDT16L1; -.
DR HGNC; HGNC:28154; NUDT16L1.
DR HPA; HPA044186; -.
DR HPA; HPA063605; -.
DR MIM; 617338; gene.
DR neXtProt; NX_Q9BRJ7; -.
DR PharmGKB; PA134977238; -.
DR eggNOG; ENOG410IYGP; Eukaryota.
DR eggNOG; ENOG4111QA1; LUCA.
DR GeneTree; ENSGT00390000016224; -.
DR HOGENOM; HOG000007083; -.
DR HOVERGEN; HBG067297; -.
DR InParanoid; Q9BRJ7; -.
DR KO; K16867; -.
DR OMA; ISTAKYQ; -.
DR OrthoDB; EOG091G0XY4; -.
DR PhylomeDB; Q9BRJ7; -.
DR EvolutionaryTrace; Q9BRJ7; -.
DR GenomeRNAi; 84309; -.
DR PRO; PR:Q9BRJ7; -.
DR Proteomes; UP000005640; Chromosome 16.
DR Bgee; ENSG00000168101; -.
DR CleanEx; HS_NUDT16L1; -.
DR ExpressionAtlas; Q9BRJ7; baseline and differential.
DR Genevisible; Q9BRJ7; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016787; F:hydrolase activity; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0030515; F:snoRNA binding; IDA:UniProtKB.
DR InterPro; IPR015797; NUDIX_hydrolase_dom-like.
DR SUPFAM; SSF55811; SSF55811; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Isopeptide bond; Nucleus; Reference proteome; RNA-binding;
KW Ubl conjugation.
FT CHAIN 1 211 Tudor-interacting repair regulator
FT protein.
FT /FTId=PRO_0000097648.
FT REGION 118 205 Interaction with PXN.
FT {ECO:0000250|UniProtKB:Q8VHN8}.
FT SITE 10 10 Required for interaction with TP53BP1.
FT {ECO:0000269|PubMed:28241136}.
FT CROSSLNK 10 10 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT {ECO:0000269|PubMed:28241136}.
FT CROSSLNK 151 151 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT {ECO:0000269|PubMed:28241136}.
FT VAR_SEQ 140 211 LGLVRVPLYTQKDRVGGFPNFLSNAFVSTAKCQLLFALKVL
FT NMMPEEKLVEALAAATEKQKKALEKLLPASS -> GPPPGP
FT RPPPRGLALAPWKAPMGNTSPEGPLAGLGRVSLSPAMGWGE
FT GSGAGRPGKEGRGWGPALGLPQGCVTSALLPAIANPGSGGV
FT GSVGRKGWGRSGDCLGSWET (in isoform 2).
FT {ECO:0000303|PubMed:14702039}.
FT /FTId=VSP_014276.
FT MUTAGEN 10 10 K->E: Abolishes interaction with TP53BP1.
FT {ECO:0000269|PubMed:28241136}.
FT MUTAGEN 151 151 K->E: Still able to interact with
FT TP53BP1. {ECO:0000269|PubMed:28241136}.
FT HELIX 14 17 {ECO:0000244|PDB:3KVH}.
FT STRAND 25 40 {ECO:0000244|PDB:3KVH}.
FT TURN 41 43 {ECO:0000244|PDB:3KVH}.
FT STRAND 44 55 {ECO:0000244|PDB:3KVH}.
FT STRAND 63 67 {ECO:0000244|PDB:3KVH}.
FT TURN 69 71 {ECO:0000244|PDB:3KVH}.
FT HELIX 74 80 {ECO:0000244|PDB:3KVH}.
FT HELIX 93 95 {ECO:0000244|PDB:3KVH}.
FT STRAND 96 101 {ECO:0000244|PDB:3KVH}.
FT STRAND 108 116 {ECO:0000244|PDB:3KVH}.
FT HELIX 119 130 {ECO:0000244|PDB:3KVH}.
FT TURN 136 138 {ECO:0000244|PDB:3KVH}.
FT STRAND 139 145 {ECO:0000244|PDB:3KVH}.
FT HELIX 157 161 {ECO:0000244|PDB:3KVH}.
FT HELIX 169 179 {ECO:0000244|PDB:3KVH}.
FT HELIX 185 206 {ECO:0000244|PDB:3KVH}.
SQ SEQUENCE 211 AA; 23338 MW; B20AA5AE1E7F7C8C CRC64;
MSTAAVPELK QISRVEAMRL GPGWSHSCHA MLYAANPGQL FGRIPMRFSV LMQMRFDGLL
GFPGGFVDRR FWSLEDGLNR VLGLGLGCLR LTEADYLSSH LTEGPHRVVA HLYARQLTLE
QLHAVEISAV HSRDHGLEVL GLVRVPLYTQ KDRVGGFPNF LSNAFVSTAK CQLLFALKVL
NMMPEEKLVE ALAAATEKQK KALEKLLPAS S
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