TIRR_HUMAN
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 03-AUG-2022, entry version 146.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., 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 [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 project:
RT 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 nuclear-
RT 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., Buerckstuemmer T.,
RA 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., Yewdell W.T.,
RA Muench C., Harper J.W., Chaudhuri J., Soutoglou E., 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:0007744|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., Nyman T.,
RA 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 and
CC regulate its recruitment to chromatin (PubMed:28241136). In absence of
CC DNA damage, interacts with the tandem Tudor-like domain of TP53BP1,
CC masking the region that binds histone H4 dimethylated at 'Lys-20'
CC (H4K20me2), thereby preventing TP53BP1 recruitment to chromatin and
CC maintaining TP53BP1 localization to the nucleus (PubMed:28241136).
CC Following DNA damage, ATM-induced phosphorylation of TP53BP1 and
CC subsequent recruitment of RIF1 leads to dissociate NUDT16L1/TIRR from
CC TP53BP1, unmasking the tandem Tudor-like domain and allowing
CC recruitment of TP53BP1 to DNA double strand breaks (DSBs)
CC (PubMed:28241136). Binds U8 snoRNA (PubMed:18820299).
CC {ECO:0000269|PubMed:18820299, ECO:0000269|PubMed:28241136}.
CC -!- SUBUNIT: Homodimer (PubMed:28241136). Interacts with TP53BP1 (via the
CC Tudor-like domain); interaction is abolished following DNA damage and
CC TP53BP1 phosphorylation by ATM (PubMed:28241136). Interacts (via the
CC cytoplasmic part) with SDC4 (By similarity). Interacts with TGFB1I1 and
CC PXN (By similarity). {ECO:0000250|UniProtKB:Q8VHN8,
CC ECO:0000269|PubMed:28241136}.
CC -!- INTERACTION:
CC Q9BRJ7; Q9NPB3: CABP2; NbExp=3; IntAct=EBI-2949792, EBI-12011224;
CC Q9BRJ7; P52597: HNRNPF; NbExp=3; IntAct=EBI-2949792, EBI-352986;
CC Q9BRJ7; P31943: HNRNPH1; NbExp=3; IntAct=EBI-2949792, EBI-351590;
CC Q9BRJ7; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-2949792, EBI-747204;
CC Q9BRJ7; Q0VD86: INCA1; NbExp=3; IntAct=EBI-2949792, EBI-6509505;
CC Q9BRJ7; Q15323: KRT31; NbExp=3; IntAct=EBI-2949792, EBI-948001;
CC Q9BRJ7; Q9H7H0-2: METTL17; NbExp=3; IntAct=EBI-2949792, EBI-11098807;
CC Q9BRJ7; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-2949792, EBI-11750983;
CC Q9BRJ7; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-2949792, EBI-741158;
CC Q9BRJ7; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-2949792, EBI-302345;
CC Q9BRJ7; Q6P9E2: RECK; NbExp=3; IntAct=EBI-2949792, EBI-10253121;
CC Q9BRJ7; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-2949792, EBI-358489;
CC Q9BRJ7; Q12933: TRAF2; NbExp=6; IntAct=EBI-2949792, EBI-355744;
CC Q9BRJ7; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-2949792, EBI-3650647;
CC Q9BRJ7; Q6AZZ1: TRIM68; NbExp=3; IntAct=EBI-2949792, EBI-2130449;
CC Q9BRJ7; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-2949792, EBI-527853;
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 -!- SIMILARITY: Belongs to the Nudix hydrolase family. TIRR subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Although strongly related to the nudix NUDT16 protein, lacks
CC the Nudix box and is therefore not related to the rest of the family
CC (PubMed:18820299, PubMed:21070968). Gene organization and evolutionary
CC distribution suggest that syndesmos NUDT16L1 probably originated as a
CC gene duplication event of the more ancient U8 snoRNA-decapping enzyme
CC NUDT16 (PubMed:18820299). Although similar to U8 snoRNA-decapping
CC enzyme NUDT16, lacks a number of residues which are necessary for
CC hydrolase activity and does not play a role in U8 snoRNA decapping
CC activity (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 PDB; 3KVH; X-ray; 1.70 A; A=6-211.
DR PDB; 5ZCJ; X-ray; 2.00 A; A/B=6-211.
DR PDB; 6CO1; X-ray; 2.18 A; A/B/C/D=6-211.
DR PDB; 6D0L; X-ray; 1.97 A; A/B=6-211.
DR PDBsum; 3KVH; -.
DR PDBsum; 5ZCJ; -.
DR PDBsum; 6CO1; -.
DR PDBsum; 6D0L; -.
DR AlphaFoldDB; Q9BRJ7; -.
DR SMR; Q9BRJ7; -.
DR BioGRID; 124035; 92.
DR IntAct; Q9BRJ7; 33.
DR MINT; Q9BRJ7; -.
DR STRING; 9606.ENSP00000306670; -.
DR iPTMnet; Q9BRJ7; -.
DR PhosphoSitePlus; Q9BRJ7; -.
DR BioMuta; NUDT16L1; -.
DR DMDM; 68566060; -.
DR EPD; Q9BRJ7; -.
DR jPOST; Q9BRJ7; -.
DR MassIVE; Q9BRJ7; -.
DR MaxQB; Q9BRJ7; -.
DR PaxDb; Q9BRJ7; -.
DR PeptideAtlas; Q9BRJ7; -.
DR PRIDE; Q9BRJ7; -.
DR ProteomicsDB; 78771; -. [Q9BRJ7-1]
DR ProteomicsDB; 78772; -. [Q9BRJ7-2]
DR Antibodypedia; 24391; 60 antibodies from 17 providers.
DR CPTC; Q9BRJ7; 1 antibody.
DR DNASU; 84309; -.
DR Ensembl; ENST00000304301.10; ENSP00000306670.5; ENSG00000168101.14. [Q9BRJ7-1]
DR Ensembl; ENST00000405142.1; ENSP00000458144.1; ENSG00000168101.14. [Q9BRJ7-2]
DR GeneID; 84309; -.
DR KEGG; hsa:84309; -.
DR MANE-Select; ENST00000304301.11; ENSP00000306670.5; NM_032349.4; NP_115725.1.
DR UCSC; uc002cxe.4; human. [Q9BRJ7-1]
DR CTD; 84309; -.
DR DisGeNET; 84309; -.
DR GeneCards; NUDT16L1; -.
DR HGNC; HGNC:28154; NUDT16L1.
DR HPA; ENSG00000168101; Low tissue specificity.
DR MIM; 617338; gene.
DR neXtProt; NX_Q9BRJ7; -.
DR PharmGKB; PA134977238; -.
DR VEuPathDB; HostDB:ENSG00000168101; -.
DR eggNOG; ENOG502S20E; Eukaryota.
DR GeneTree; ENSGT00390000016224; -.
DR HOGENOM; CLU_1212251_0_0_1; -.
DR InParanoid; Q9BRJ7; -.
DR OMA; PHREVAH; -.
DR OrthoDB; 1385294at2759; -.
DR PhylomeDB; Q9BRJ7; -.
DR PathwayCommons; Q9BRJ7; -.
DR SignaLink; Q9BRJ7; -.
DR BioGRID-ORCS; 84309; 65 hits in 1074 CRISPR screens.
DR ChiTaRS; NUDT16L1; human.
DR EvolutionaryTrace; Q9BRJ7; -.
DR GenomeRNAi; 84309; -.
DR Pharos; Q9BRJ7; Tbio.
DR PRO; PR:Q9BRJ7; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9BRJ7; protein.
DR Bgee; ENSG00000168101; Expressed in mucosa of transverse colon and 98 other tissues.
DR ExpressionAtlas; Q9BRJ7; baseline and differential.
DR Genevisible; Q9BRJ7; HS.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0030515; F:snoRNA binding; IDA:UniProtKB.
DR GO; GO:2001033; P:negative regulation of double-strand break repair via nonhomologous end joining; IDA:UniProtKB.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR SUPFAM; SSF55811; SSF55811; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Isopeptide bond; Nucleus;
KW Reference proteome; RNA-binding; Ubl conjugation.
FT CHAIN 1..211
FT /note="Tudor-interacting repair regulator protein"
FT /id="PRO_0000097648"
FT REGION 118..205
FT /note="Interaction with PXN"
FT /evidence="ECO:0000250|UniProtKB:Q8VHN8"
FT SITE 10
FT /note="Required for interaction with TP53BP1"
FT /evidence="ECO:0000269|PubMed:28241136"
FT CROSSLNK 10
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:28241136"
FT CROSSLNK 151
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:28241136"
FT VAR_SEQ 140..211
FT /note="LGLVRVPLYTQKDRVGGFPNFLSNAFVSTAKCQLLFALKVLNMMPEEKLVEA
FT LAAATEKQKKALEKLLPASS -> GPPPGPRPPPRGLALAPWKAPMGNTSPEGPLAGLG
FT RVSLSPAMGWGEGSGAGRPGKEGRGWGPALGLPQGCVTSALLPAIANPGSGGVGSVGRK
FT GWGRSGDCLGSWET (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014276"
FT MUTAGEN 10
FT /note="K->E: Abolishes interaction with TP53BP1."
FT /evidence="ECO:0000269|PubMed:28241136"
FT MUTAGEN 151
FT /note="K->E: Still able to interact with TP53BP1."
FT /evidence="ECO:0000269|PubMed:28241136"
FT STRAND 10..12
FT /evidence="ECO:0007829|PDB:6D0L"
FT HELIX 14..17
FT /evidence="ECO:0007829|PDB:3KVH"
FT STRAND 25..40
FT /evidence="ECO:0007829|PDB:3KVH"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:3KVH"
FT STRAND 44..55
FT /evidence="ECO:0007829|PDB:3KVH"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:3KVH"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:3KVH"
FT HELIX 74..80
FT /evidence="ECO:0007829|PDB:3KVH"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:3KVH"
FT STRAND 96..101
FT /evidence="ECO:0007829|PDB:3KVH"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:5ZCJ"
FT STRAND 108..116
FT /evidence="ECO:0007829|PDB:3KVH"
FT HELIX 119..130
FT /evidence="ECO:0007829|PDB:3KVH"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:3KVH"
FT STRAND 139..145
FT /evidence="ECO:0007829|PDB:3KVH"
FT HELIX 157..161
FT /evidence="ECO:0007829|PDB:3KVH"
FT HELIX 169..179
FT /evidence="ECO:0007829|PDB:3KVH"
FT HELIX 185..206
FT /evidence="ECO:0007829|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
