DBR1_HUMAN
ID DBR1_HUMAN Reviewed; 544 AA.
AC Q9UK59; Q96GH0; Q9NXQ6;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2006, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Lariat debranching enzyme;
DE EC=3.1.-.-;
GN Name=DBR1;
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 1), AND FUNCTION.
RX PubMed=10982890; DOI=10.1093/nar/28.18.3666;
RA Kim J.-W., Kim H.-C., Kim G.-M., Yang J.-M., Boeke J.D., Nam K.;
RT "Human RNA lariat debranching enzyme cDNA complements the phenotypes of
RT Saccharomyces cerevisiae dbr1 and Schizosaccharomyces pombe dbr1 mutants.";
RL Nucleic Acids Res. 28:3666-3673(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=2435736; DOI=10.1016/s0021-9258(18)61343-2;
RA Arenas J., Hurwitz J.;
RT "Purification of a RNA debranching activity from HeLa cells.";
RL J. Biol. Chem. 262:4274-4279(1987).
RN [5]
RP FUNCTION.
RX PubMed=16232320; DOI=10.1186/1742-4690-2-63;
RA Ye Y., De Leon J., Yokoyama N., Naidu Y., Camerini D.;
RT "DBR1 siRNA inhibition of HIV-1 replication.";
RL Retrovirology 2:63-63(2005).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-514, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-474; SER-478 AND SER-479, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-128, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-514, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-514, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-514, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-464, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP INVOLVEMENT IN IIAE11, VARIANTS IIAE11 GLY-13; HIS-17; THR-120 AND
RP 197-ARG--ALA-544 DEL, CHARACTERIZATION OF VARIANTS IIAE11 GLY-13; HIS-17;
RP THR-120 AND 197-ARG--ALA-544 DEL, FUNCTION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF HIS-85.
RX PubMed=29474921; DOI=10.1016/j.cell.2018.02.019;
RA Zhang S.Y., Clark N.E., Freije C.A., Pauwels E., Taggart A.J., Okada S.,
RA Mandel H., Garcia P., Ciancanelli M.J., Biran A., Lafaille F.G.,
RA Tsumura M., Cobat A., Luo J., Volpi S., Zimmer B., Sakata S., Dinis A.,
RA Ohara O., Garcia Reino E.J., Dobbs K., Hasek M., Holloway S.P.,
RA McCammon K., Hussong S.A., DeRosa N., Van Skike C.E., Katolik A.,
RA Lorenzo L., Hyodo M., Faria E., Halwani R., Fukuhara R., Smith G.A.,
RA Galvan V., Damha M.J., Al-Muhsen S., Itan Y., Boeke J.D., Notarangelo L.D.,
RA Studer L., Kobayashi M., Diogo L., Fairbrother W.G., Abel L.,
RA Rosenberg B.R., Hart P.J., Etzioni A., Casanova J.L.;
RT "Inborn Errors of RNA Lariat Metabolism in Humans with Brainstem Viral
RT Infection.";
RL Cell 172:952.e18-965.e18(2018).
CC -!- FUNCTION: Cleaves the 2'-5' phosphodiester linkage at the branch point
CC of excised lariat intron RNA and converts them into linear molecules
CC that can be subsequently degraded, thereby facilitating ribonucleotide
CC turnover (PubMed:10982890, PubMed:16232320). Linked to its role in pre-
CC mRNA processing mechanism, may also participate in retrovirus
CC replication via an RNA lariat intermediate in cDNA synthesis and have
CC an antiviral cell-intrinsic defense function in the brainstem
CC (PubMed:16232320, PubMed:29474921). {ECO:0000269|PubMed:10982890,
CC ECO:0000269|PubMed:16232320, ECO:0000269|PubMed:29474921}.
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000269|PubMed:2435736};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0. {ECO:0000269|PubMed:2435736};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UK59-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UK59-2; Sequence=VSP_020631, VSP_020632;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, strongest expression in the
CC spinal cord and brainstem. {ECO:0000269|PubMed:29474921}.
CC -!- DISEASE: Encephalitis, acute, infection (viral)-induced, 11 (IIAE11)
CC [MIM:619441]: An autosomal recessive disorder characterized by
CC increased susceptibility to viral encephalitis affecting the brainstem
CC and induced by neurotropic viruses, such as herpes simplex virus-1,
CC influenza B virus or norovirus. {ECO:0000269|PubMed:29474921}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the lariat debranching enzyme family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD53327.2; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF180919; AAD53327.2; ALT_FRAME; mRNA.
DR EMBL; AK000116; BAA90954.1; -; mRNA.
DR EMBL; BC009472; AAH09472.1; -; mRNA.
DR CCDS; CCDS33863.1; -. [Q9UK59-1]
DR RefSeq; NP_057300.2; NM_016216.3. [Q9UK59-1]
DR AlphaFoldDB; Q9UK59; -.
DR SMR; Q9UK59; -.
DR BioGRID; 119344; 24.
DR IntAct; Q9UK59; 14.
DR STRING; 9606.ENSP00000260803; -.
DR GlyGen; Q9UK59; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UK59; -.
DR PhosphoSitePlus; Q9UK59; -.
DR BioMuta; DBR1; -.
DR DMDM; 115311701; -.
DR EPD; Q9UK59; -.
DR jPOST; Q9UK59; -.
DR MassIVE; Q9UK59; -.
DR MaxQB; Q9UK59; -.
DR PaxDb; Q9UK59; -.
DR PeptideAtlas; Q9UK59; -.
DR PRIDE; Q9UK59; -.
DR ProteomicsDB; 84727; -. [Q9UK59-1]
DR ProteomicsDB; 84728; -. [Q9UK59-2]
DR Antibodypedia; 33423; 161 antibodies from 19 providers.
DR DNASU; 51163; -.
DR Ensembl; ENST00000260803.9; ENSP00000260803.4; ENSG00000138231.13. [Q9UK59-1]
DR GeneID; 51163; -.
DR KEGG; hsa:51163; -.
DR MANE-Select; ENST00000260803.9; ENSP00000260803.4; NM_016216.4; NP_057300.2.
DR UCSC; uc003erv.4; human. [Q9UK59-1]
DR CTD; 51163; -.
DR DisGeNET; 51163; -.
DR GeneCards; DBR1; -.
DR HGNC; HGNC:15594; DBR1.
DR HPA; ENSG00000138231; Low tissue specificity.
DR MIM; 607024; gene.
DR MIM; 619441; phenotype.
DR neXtProt; NX_Q9UK59; -.
DR OpenTargets; ENSG00000138231; -.
DR PharmGKB; PA27166; -.
DR VEuPathDB; HostDB:ENSG00000138231; -.
DR eggNOG; KOG2863; Eukaryota.
DR GeneTree; ENSGT00510000047481; -.
DR HOGENOM; CLU_005893_0_2_1; -.
DR InParanoid; Q9UK59; -.
DR OMA; GIDDPLC; -.
DR OrthoDB; 1047278at2759; -.
DR PhylomeDB; Q9UK59; -.
DR TreeFam; TF313221; -.
DR PathwayCommons; Q9UK59; -.
DR SignaLink; Q9UK59; -.
DR BioGRID-ORCS; 51163; 800 hits in 1071 CRISPR screens.
DR GeneWiki; DBR1; -.
DR GenomeRNAi; 51163; -.
DR Pharos; Q9UK59; Tbio.
DR PRO; PR:Q9UK59; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9UK59; protein.
DR Bgee; ENSG00000138231; Expressed in buccal mucosa cell and 172 other tissues.
DR ExpressionAtlas; Q9UK59; baseline and differential.
DR Genevisible; Q9UK59; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0008419; F:RNA lariat debranching enzyme activity; IMP:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IBA:GO_Central.
DR GO; GO:0000375; P:RNA splicing, via transesterification reactions; IMP:UniProtKB.
DR CDD; cd00844; MPP_Dbr1_N; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR007708; DBR1_C.
DR InterPro; IPR041816; Dbr1_N.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR Pfam; PF05011; DBR1; 1.
DR Pfam; PF00149; Metallophos; 1.
DR SMART; SM01124; DBR1; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Disease variant; Hydrolase;
KW Metal-binding; mRNA processing; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..544
FT /note="Lariat debranching enzyme"
FT /id="PRO_0000250358"
FT REGION 395..463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..544
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 411..425
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 442..463
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..535
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 464
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 474
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 479
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 485
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q923B1"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q923B1"
FT MOD_RES 514
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..232
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020631"
FT VAR_SEQ 233..237
FT /note="ALMQH -> MIHIV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020632"
FT VARIANT 13
FT /note="L -> G (in IIAE11; requires 2 nucleotide
FT substitutions; decreased protein abundance; decreased RNA
FT lariat debranching enzyme activity)"
FT /evidence="ECO:0000269|PubMed:29474921"
FT /id="VAR_086073"
FT VARIANT 17
FT /note="Y -> H (in IIAE11; decreased protein abundance;
FT decreased RNA lariat debranching enzyme activity)"
FT /evidence="ECO:0000269|PubMed:29474921"
FT /id="VAR_086074"
FT VARIANT 120
FT /note="I -> T (in IIAE11; decreased protein abundance;
FT decreased RNA lariat debranching enzyme activity)"
FT /evidence="ECO:0000269|PubMed:29474921"
FT /id="VAR_086075"
FT VARIANT 197..544
FT /note="Missing (in IIAE11; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:29474921"
FT /id="VAR_086076"
FT MUTAGEN 85
FT /note="H->N: No effect on protein abundance. Loss of RNA
FT lariat debranching enzyme activity."
FT /evidence="ECO:0000269|PubMed:29474921"
FT CONFLICT 308
FT /note="N -> S (in Ref. 2; BAA90954)"
FT /evidence="ECO:0000305"
FT CONFLICT 496
FT /note="T -> L (in Ref. 1; AAD53327)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 544 AA; 61555 MW; DDA5F4FADA194BAA CRC64;
MRVAVAGCCH GELDKIYETL ALAERRGPGP VDLLLCCGDF QAVRNEADLR CMAVPPKYRH
MQTFYRYYSG EKKAPVLTLF IGGNHEASNH LQELPYGGWV APNIYYLGLA GVVKYRGVRI
GGISGIFKSH DYRKGHFECP PYNSSTIRSI YHVRNIEVYK LKQLKQPIDI FLSHDWPRSI
YHYGNKKQLL KTKSFFRQEV ENNTLGSPAA SELLEHLKPT YWFSAHLHVK FAALMQHQAK
DKGQTARATK FLALDKCLPH RDFLQILEIE HDPSAPDYLE YDIEWLTILR ATDDLINVTG
RLWNMPENNG LHARWDYSAT EEGMKEVLEK LNHDLKVPCN FSVTAACYDP SKPQTQMQLI
HRINPQTTEF CAQLGIIDIN VRLQKSKEEH HVCGEYEEQD DVESNDSGED QSEYNTDTSA
LSSINPDEIM LDEEEDEDSI VSAHSGMNTP SVEPSDQASE FSASFSDVRI LPGSMIVSSD
DTVDSTIDRE GKPGGTVESG NGEDLTKVPL KRLSDEHEPE QRKKIKRRNQ AIYAAVDDDD
DDAA
