USB1_HUMAN
ID USB1_HUMAN Reviewed; 265 AA.
AC Q9BQ65; B4DWE3; B4DZW5; Q96FZ9; Q9H8X8;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=U6 snRNA phosphodiesterase 1 {ECO:0000305};
DE Short=hUsb1 {ECO:0000303|PubMed:22899009};
DE AltName: Full=3'-5' RNA exonuclease USB1 {ECO:0000305|PubMed:23022480};
DE EC=4.6.1.- {ECO:0000269|PubMed:23022480, ECO:0000269|PubMed:23190533, ECO:0000269|PubMed:28887445, ECO:0000269|PubMed:30215753};
DE AltName: Full=Mutated in poikiloderma with neutropenia protein 1 {ECO:0000303|PubMed:23022480};
DE Short=Mutated in PN protein 1 {ECO:0000303|PubMed:23022480};
DE Short=hMpn1 {ECO:0000303|PubMed:23022480};
GN Name=USB1 {ECO:0000255|HAMAP-Rule:MF_03040, ECO:0000312|HGNC:HGNC:25792};
GN Synonyms=C16orf57, Mpn1 {ECO:0000303|PubMed:23022480};
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] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Synovium, and Thymus;
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 GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney, Pancreas, Placenta, Skin, and Uterus;
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 INVOLVEMENT IN PN.
RX PubMed=20004881; DOI=10.1016/j.ajhg.2009.11.014;
RA Volpi L., Roversi G., Colombo E.A., Leijsten N., Concolino D., Calabria A.,
RA Mencarelli M.A., Fimiani M., Macciardi F., Pfundt R., Schoenmakers E.F.,
RA Larizza L.;
RT "Targeted next-generation sequencing appoints c16orf57 as clericuzio-type
RT poikiloderma with neutropenia gene.";
RL Am. J. Hum. Genet. 86:72-76(2010).
RN [5]
RP INVOLVEMENT IN PN.
RX PubMed=20503306; DOI=10.1002/ajmg.a.33455;
RA Tanaka A., Morice-Picard F., Lacombe D., Nagy N., Hide M., Taieb A.,
RA McGrath J.;
RT "Identification of a homozygous deletion mutation in C16orf57 in a family
RT with Clericuzio-type poikiloderma with neutropenia.";
RL Am. J. Med. Genet. A 152:1347-1348(2010).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH PLRG1;
RP CDC5L AND PRPF19, AND MUTAGENESIS OF HIS-120 AND HIS-208.
RX PubMed=23022480; DOI=10.1016/j.celrep.2012.08.031;
RA Shchepachev V., Wischnewski H., Missiaglia E., Soneson C., Azzalin C.M.;
RT "Mpn1, mutated in poikiloderma with neutropenia protein 1, is a conserved
RT 3'-to-5' RNA exonuclease processing U6 small nuclear RNA.";
RL Cell Rep. 2:855-865(2012).
RN [7]
RP SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF HIS-208, AND CATALYTIC
RP ACTIVITY.
RX PubMed=22899009; DOI=10.1101/gad.193169.112;
RA Mroczek S., Krwawicz J., Kutner J., Lazniewski M., Kucinski I.,
RA Ginalski K., Dziembowski A.;
RT "C16orf57, a gene mutated in poikiloderma with neutropenia, encodes a
RT putative phosphodiesterase responsible for the U6 snRNA 3' end
RT modification.";
RL Genes Dev. 26:1911-1925(2012).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-120 AND HIS-208.
RX PubMed=26213367; DOI=10.1016/j.febslet.2015.06.046;
RA Shchepachev V., Wischnewski H., Soneson C., Arnold A.W., Azzalin C.M.;
RT "Human Mpn1 promotes post-transcriptional processing and stability of
RT U6atac.";
RL FEBS Lett. 589:2417-2423(2015).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31832688; DOI=10.1093/nar/gkz1177;
RA Nomura Y., Montemayor E.J., Virta J.M., Hayes S.M., Butcher S.E.;
RT "Structural basis for the evolution of cyclic phosphodiesterase activity in
RT the U6 snRNA exoribonuclease Usb1.";
RL Nucleic Acids Res. 48:1423-1434(2020).
RN [10] {ECO:0007744|PDB:4H7W}
RP X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) OF 73-265, CATALYTIC ACTIVITY,
RP FUNCTION, ACTIVE SITE, MUTAGENESIS OF HIS-120 AND HIS-208, AND ACTIVITY
RP REGULATION.
RX PubMed=23190533; DOI=10.1182/blood-2012-10-461491;
RA Hilcenko C., Simpson P.J., Finch A.J., Bowler F.R., Churcher M.J., Jin L.,
RA Packman L.C., Shlien A., Campbell P., Kirwan M., Dokal I., Warren A.J.;
RT "Aberrant 3' oligoadenylation of spliceosomal U6 small nuclear RNA in
RT poikiloderma with neutropenia.";
RL Blood 121:1028-1038(2013).
RN [11] {ECO:0007744|PDB:5V1M}
RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) OF 79-265 IN COMPLEX WITH UMP,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, REGION, AND
RP ACTIVITY REGULATION.
RX PubMed=28887445; DOI=10.1038/s41467-017-00484-w;
RA Didychuk A.L., Montemayor E.J., Carrocci T.J., DeLaitsch A.T.,
RA Lucarelli S.E., Westler W.M., Brow D.A., Hoskins A.A., Butcher S.E.;
RT "Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic
RT phosphodiesterase activities.";
RL Nat. Commun. 8:497-497(2017).
RN [12] {ECO:0007744|PDB:6D2Z, ECO:0007744|PDB:6D30, ECO:0007744|PDB:6D31}
RP X-RAY CRYSTALLOGRAPHY (1.17 ANGSTROMS) OF 79-265 OF MUTANT HIS-208 IN
RP COMPLEX WITH AMP; 3'-TERMINAL PUPU RESIDUE AND 3'-TERMINAL PUPA RESIDUE,
RP MUTAGENESIS OF HIS-120; SER-122; TYR-202; HIS-208 AND SER-210, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, REGION, AND ACTIVE SITE.
RX PubMed=30215753; DOI=10.1093/nar/gky812;
RA Nomura Y., Roston D., Montemayor E.J., Cui Q., Butcher S.E.;
RT "Structural and mechanistic basis for preferential deadenylation of U6
RT snRNA by Usb1.";
RL Nucleic Acids Res. 46:11488-11501(2018).
CC -!- FUNCTION: 3'-5' RNA exonuclease that trims the 3' end of oligo(U) and
CC oligo(A) tracts of the pre-U6 small nuclear RNA (snRNA) molecule,
CC leading to the formation of a mature U6 snRNA 3' end-terminated with a
CC 2',3'-cyclic phosphate (PubMed:23022480, PubMed:22899009,
CC PubMed:26213367, PubMed:31832688, PubMed:23190533, PubMed:28887445,
CC PubMed:30215753). Participates in the U6 snRNA 3' end processing that
CC prevents U6 snRNA degradation (PubMed:23022480, PubMed:22899009,
CC PubMed:26213367, PubMed:31832688, PubMed:23190533, PubMed:28887445,
CC PubMed:30215753). In addition also removes uridines from the 3' end of
CC U6atac snRNA and possibly the vault RNA VTRNA1-1 (PubMed:26213367).
CC {ECO:0000269|PubMed:22899009, ECO:0000269|PubMed:23022480,
CC ECO:0000269|PubMed:23190533, ECO:0000269|PubMed:26213367,
CC ECO:0000269|PubMed:28887445, ECO:0000269|PubMed:30215753,
CC ECO:0000269|PubMed:31832688}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3'-end uridylyl-uridine-RNA = a 3'-end 2',3'-cyclophospho-
CC uridine-RNA + uridine; Xref=Rhea:RHEA:46052, Rhea:RHEA-COMP:17384,
CC Rhea:RHEA-COMP:17385, ChEBI:CHEBI:16704, ChEBI:CHEBI:85643,
CC ChEBI:CHEBI:85644; Evidence={ECO:0000269|PubMed:23022480,
CC ECO:0000269|PubMed:23190533, ECO:0000269|PubMed:28887445,
CC ECO:0000269|PubMed:31832688, ECO:0000305|PubMed:22899009};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46053;
CC Evidence={ECO:0000305|PubMed:22899009, ECO:0000305|PubMed:23022480};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3'-end uridylyl-adenosine-RNA = a 3'-end 2',3'-cyclophospho-
CC uridine-RNA + adenosine; Xref=Rhea:RHEA:67896, Rhea:RHEA-COMP:17385,
CC Rhea:RHEA-COMP:17386, ChEBI:CHEBI:16335, ChEBI:CHEBI:85644,
CC ChEBI:CHEBI:176518; Evidence={ECO:0000269|PubMed:23190533,
CC ECO:0000269|PubMed:30215753};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67897;
CC Evidence={ECO:0000269|PubMed:23190533};
CC -!- ACTIVITY REGULATION: 3'-5' RNA exonuclease activity is inhibited by a
CC 3' phosphate terminated RNA. {ECO:0000269|PubMed:23190533,
CC ECO:0000269|PubMed:28887445}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.58 uM for UAUUUdUUU {ECO:0000269|PubMed:30215753};
CC KM=9.75 uM for UAUUUdUAU {ECO:0000269|PubMed:30215753};
CC KM=3.12 uM for UAUUUdUAU {ECO:0000269|PubMed:30215753};
CC KM=7.17 uM for UAUUUdUAA {ECO:0000269|PubMed:30215753};
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:28887445,
CC ECO:0000269|PubMed:30215753};
CC -!- SUBUNIT: Interacts with PLRG1, CDC5L AND PRPF19.
CC {ECO:0000269|PubMed:23022480}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03040,
CC ECO:0000269|PubMed:22899009, ECO:0000269|PubMed:23022480}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9BQ65-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BQ65-2; Sequence=VSP_042878;
CC Name=3;
CC IsoId=Q9BQ65-3; Sequence=VSP_042936;
CC -!- DISEASE: Poikiloderma with neutropenia (PN) [MIM:604173]: A
CC genodermatosis characterized by poikiloderma, pachyonychia and chronic
CC neutropenia. The disorder starts as a papular erythematous rash on the
CC limbs during the first year of life. It gradually spreads centripetally
CC and, as the papular rash resolves, hypo- and hyperpigmentation result,
CC with development of telangiectasias. Another skin manifestation is
CC pachyonychia, but alopecia and leukoplakia are distinctively absent.
CC Patients have recurrent pneumonias that usually result in reactive
CC airway disease and/or chronic cough. One of the most important
CC extracutaneous symptoms is an increased susceptibility to infections,
CC mainly affecting the respiratory system, primarily due to a chronic
CC neutropenia and to neutrophil functional defects. Bone marrow
CC abnormalities account for neutropenia and may evolve into
CC myelodysplasia associated with the risk of leukemic transformation.
CC Poikiloderma with neutropenia shows phenotypic overlap with Rothmund-
CC Thomson syndrome. {ECO:0000269|PubMed:20004881,
CC ECO:0000269|PubMed:20503306}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the 2H phosphoesterase superfamily. USB1 family.
CC {ECO:0000255|HAMAP-Rule:MF_03040}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK023216; BAB14469.1; -; mRNA.
DR EMBL; AK301494; BAG63005.1; -; mRNA.
DR EMBL; AK303121; BAG64227.1; -; mRNA.
DR EMBL; AC010543; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC012182; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004415; AAH04415.1; -; mRNA.
DR EMBL; BC006291; AAH06291.1; -; mRNA.
DR EMBL; BC007774; AAH07774.1; -; mRNA.
DR EMBL; BC010099; AAH10099.1; -; mRNA.
DR EMBL; BC021554; AAH21554.1; -; mRNA.
DR CCDS; CCDS10791.1; -. [Q9BQ65-1]
DR CCDS; CCDS55997.1; -. [Q9BQ65-3]
DR CCDS; CCDS55998.1; -. [Q9BQ65-2]
DR RefSeq; NP_001182231.1; NM_001195302.1. [Q9BQ65-2]
DR RefSeq; NP_001191840.1; NM_001204911.1. [Q9BQ65-3]
DR RefSeq; NP_001317497.1; NM_001330568.1.
DR RefSeq; NP_078874.2; NM_024598.3. [Q9BQ65-1]
DR PDB; 4H7W; X-ray; 1.10 A; A=73-265.
DR PDB; 5V1M; X-ray; 1.47 A; A=79-265.
DR PDB; 6D2Z; X-ray; 1.18 A; A=79-265.
DR PDB; 6D30; X-ray; 1.17 A; A=79-265.
DR PDB; 6D31; X-ray; 1.20 A; A=79-265.
DR PDBsum; 4H7W; -.
DR PDBsum; 5V1M; -.
DR PDBsum; 6D2Z; -.
DR PDBsum; 6D30; -.
DR PDBsum; 6D31; -.
DR AlphaFoldDB; Q9BQ65; -.
DR SMR; Q9BQ65; -.
DR BioGRID; 122778; 49.
DR IntAct; Q9BQ65; 25.
DR MINT; Q9BQ65; -.
DR STRING; 9606.ENSP00000219281; -.
DR iPTMnet; Q9BQ65; -.
DR PhosphoSitePlus; Q9BQ65; -.
DR BioMuta; USB1; -.
DR DMDM; 74732815; -.
DR EPD; Q9BQ65; -.
DR jPOST; Q9BQ65; -.
DR MassIVE; Q9BQ65; -.
DR MaxQB; Q9BQ65; -.
DR PaxDb; Q9BQ65; -.
DR PeptideAtlas; Q9BQ65; -.
DR PRIDE; Q9BQ65; -.
DR ProteomicsDB; 78632; -. [Q9BQ65-1]
DR ProteomicsDB; 78633; -. [Q9BQ65-2]
DR ProteomicsDB; 78634; -. [Q9BQ65-3]
DR Antibodypedia; 29032; 136 antibodies from 24 providers.
DR DNASU; 79650; -.
DR Ensembl; ENST00000219281.8; ENSP00000219281.3; ENSG00000103005.12. [Q9BQ65-1]
DR Ensembl; ENST00000423271.7; ENSP00000409792.3; ENSG00000103005.12. [Q9BQ65-3]
DR Ensembl; ENST00000539737.6; ENSP00000446143.2; ENSG00000103005.12. [Q9BQ65-2]
DR GeneID; 79650; -.
DR KEGG; hsa:79650; -.
DR MANE-Select; ENST00000219281.8; ENSP00000219281.3; NM_024598.4; NP_078874.2.
DR UCSC; uc002emz.4; human. [Q9BQ65-1]
DR CTD; 79650; -.
DR DisGeNET; 79650; -.
DR GeneCards; USB1; -.
DR GeneReviews; USB1; -.
DR HGNC; HGNC:25792; USB1.
DR HPA; ENSG00000103005; Low tissue specificity.
DR MalaCards; USB1; -.
DR MIM; 604173; phenotype.
DR MIM; 613276; gene.
DR neXtProt; NX_Q9BQ65; -.
DR OpenTargets; ENSG00000103005; -.
DR Orphanet; 1775; Dyskeratosis congenita.
DR Orphanet; 221046; Poikiloderma with neutropenia.
DR PharmGKB; PA143485394; -.
DR VEuPathDB; HostDB:ENSG00000103005; -.
DR eggNOG; KOG3102; Eukaryota.
DR GeneTree; ENSGT00390000004596; -.
DR InParanoid; Q9BQ65; -.
DR OMA; KTVVLQY; -.
DR OrthoDB; 1282784at2759; -.
DR PhylomeDB; Q9BQ65; -.
DR TreeFam; TF324364; -.
DR PathwayCommons; Q9BQ65; -.
DR SignaLink; Q9BQ65; -.
DR BioGRID-ORCS; 79650; 63 hits in 1085 CRISPR screens.
DR ChiTaRS; USB1; human.
DR GenomeRNAi; 79650; -.
DR Pharos; Q9BQ65; Tbio.
DR PRO; PR:Q9BQ65; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9BQ65; protein.
DR Bgee; ENSG00000103005; Expressed in granulocyte and 178 other tissues.
DR ExpressionAtlas; Q9BQ65; baseline and differential.
DR Genevisible; Q9BQ65; HS.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:1990838; F:poly(U)-specific exoribonuclease activity, producing 3' uridine cyclic phosphate ends; IDA:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IMP:UniProtKB.
DR GO; GO:0034472; P:snRNA 3'-end processing; IMP:UniProtKB.
DR GO; GO:0034477; P:U6 snRNA 3'-end processing; IDA:UniProtKB.
DR HAMAP; MF_03040; USB1; 1.
DR InterPro; IPR027521; Usb1.
DR PANTHER; PTHR13522; PTHR13522; 1.
DR Pfam; PF09749; HVSL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Hydrolase; Lyase; Nuclease; Nucleus;
KW Reference proteome.
FT CHAIN 1..265
FT /note="U6 snRNA phosphodiesterase 1"
FT /id="PRO_0000274391"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..30
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 120
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03040,
FT ECO:0000269|PubMed:23190533, ECO:0000269|PubMed:30215753"
FT ACT_SITE 208
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03040,
FT ECO:0000269|PubMed:23190533, ECO:0000269|PubMed:30215753"
FT BINDING 120..122
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:30215753,
FT ECO:0007744|PDB:6D31"
FT BINDING 164
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000269|PubMed:28887445,
FT ECO:0007744|PDB:5V1M"
FT BINDING 202
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:30215753,
FT ECO:0007744|PDB:6D31"
FT BINDING 202
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000269|PubMed:28887445,
FT ECO:0007744|PDB:5V1M"
FT BINDING 204..210
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000269|PubMed:30215753,
FT ECO:0007744|PDB:6D31"
FT BINDING 206..210
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000269|PubMed:28887445,
FT ECO:0007744|PDB:5V1M"
FT VAR_SEQ 150..265
FT /note="RFFFTANQVKIYTNQEKTRTFIGLEVTSGHAQFLDLVSEVDRVMEEFNLTTF
FT YQDPSFHLSLAWCVGDARLQLEGQCLQELQAIVDGFEDAEVLLRVHTEQVRCKSGNKFF
FT SMPLK -> SPHPGPHCLIGTKDAPVTQEIPKDLGALRQEPGSQTR (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042936"
FT VAR_SEQ 150..167
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042878"
FT VARIANT 115
FT /note="R -> K (in dbSNP:rs35025252)"
FT /id="VAR_053822"
FT VARIANT 250
FT /note="Q -> E (in dbSNP:rs16959641)"
FT /id="VAR_030277"
FT MUTAGEN 120
FT /note="H->A: Abolishes exoribonuclease activity. Does not
FT restore U6 snRNA processing when expressed in deleted mpn1
FT yeast cells; when associated with A-208. Increases the
FT accumulation of unspliced pre-mRNAs when expressed in
FT deleted mpn1 yeast cells; when associated with A-208. Slows
FT growth in the cold when expressed in deleted mpn1 yeast
FT cells; when associated with A-208. Abolishes
FT exoribonuclease activity; when associated with A-208.
FT Decreases U6 and U6atac motility."
FT /evidence="ECO:0000269|PubMed:23022480,
FT ECO:0000269|PubMed:23190533, ECO:0000269|PubMed:26213367"
FT MUTAGEN 120
FT /note="H->N: Significantly decreases exonuclease activity."
FT /evidence="ECO:0000269|PubMed:30215753"
FT MUTAGEN 122
FT /note="S->C: Significantly decreases exonuclease activity."
FT /evidence="ECO:0000269|PubMed:30215753"
FT MUTAGEN 202
FT /note="Y->A: Significantly decreases exonuclease activity."
FT /evidence="ECO:0000269|PubMed:30215753"
FT MUTAGEN 208
FT /note="H->A: Abolishes exoribonuclease activity. Does not
FT rescue the molecular phenotype caused by USB1 depletion.
FT Does not restore U6 snRNA processing when expressed in
FT deleted mpn1 yeast cells; when associated with A-120.
FT Increases the accumulation of unspliced pre-mRNAs when
FT expressed in deleted mpn1 yeast cells; when associated with
FT A-120. Slows growth in the cold when expressed in deleted
FT mpn1 yeast cells; when associated with A-120. Abolishes
FT exoribonuclease activity; when associated with A-120.
FT Decreases U6 and U6atac motility."
FT /evidence="ECO:0000269|PubMed:22899009,
FT ECO:0000269|PubMed:23022480, ECO:0000269|PubMed:23190533,
FT ECO:0000269|PubMed:26213367"
FT MUTAGEN 208
FT /note="H->N: Loss of exonuclease activity."
FT /evidence="ECO:0000269|PubMed:30215753"
FT MUTAGEN 208
FT /note="H->Q: Loss of exonuclease activity."
FT /evidence="ECO:0000269|PubMed:30215753"
FT MUTAGEN 210
FT /note="S->C: Significantly decreases exonuclease activity."
FT /evidence="ECO:0000269|PubMed:30215753"
FT CONFLICT 89
FT /note="Y -> C (in Ref. 3; AAH10099)"
FT /evidence="ECO:0000305"
FT CONFLICT 209
FT /note="L -> P (in Ref. 1; BAB14469)"
FT /evidence="ECO:0000305"
FT STRAND 80..89
FT /evidence="ECO:0007829|PDB:4H7W"
FT HELIX 93..107
FT /evidence="ECO:0007829|PDB:4H7W"
FT STRAND 117..122
FT /evidence="ECO:0007829|PDB:4H7W"
FT STRAND 127..130
FT /evidence="ECO:0007829|PDB:4H7W"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:4H7W"
FT HELIX 134..145
FT /evidence="ECO:0007829|PDB:4H7W"
FT STRAND 155..162
FT /evidence="ECO:0007829|PDB:4H7W"
FT STRAND 166..175
FT /evidence="ECO:0007829|PDB:4H7W"
FT HELIX 179..195
FT /evidence="ECO:0007829|PDB:4H7W"
FT STRAND 208..216
FT /evidence="ECO:0007829|PDB:4H7W"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:4H7W"
FT HELIX 225..235
FT /evidence="ECO:0007829|PDB:4H7W"
FT HELIX 241..244
FT /evidence="ECO:0007829|PDB:4H7W"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:6D30"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:4H7W"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:4H7W"
SQ SEQUENCE 265 AA; 30268 MW; 75D8BF51DF8D353D CRC64;
MSAAPLVGYS SSGSEDESED GMRTRPGDGS HRRGQSPLPR QRFPVPDSVL NMFPGTEEGP
EDDSTKHGGR VRTFPHERGN WATHVYVPYE AKEEFLDLLD VLLPHAQTYV PRLVRMKVFH
LSLSQSVVLR HHWILPFVQA LKARMTSFHR FFFTANQVKI YTNQEKTRTF IGLEVTSGHA
QFLDLVSEVD RVMEEFNLTT FYQDPSFHLS LAWCVGDARL QLEGQCLQEL QAIVDGFEDA
EVLLRVHTEQ VRCKSGNKFF SMPLK
