GAR1_HUMAN
ID GAR1_HUMAN Reviewed; 217 AA.
AC Q9NY12; Q5MJQ2;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=H/ACA ribonucleoprotein complex subunit 1;
DE AltName: Full=Nucleolar protein family A member 1;
DE AltName: Full=snoRNP protein GAR1;
GN Name=GAR1; Synonyms=NOLA1;
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), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10757788; DOI=10.1128/mcb.20.9.3037-3048.2000;
RA Dragon F., Pogacic V., Filipowicz W.;
RT "In vitro assembly of human H/ACA small nucleolar RNPs reveals unique
RT features of U17 and telomerase RNAs.";
RL Mol. Cell. Biol. 20:3037-3048(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Li H., Nong W., Ke R., Zhong G., Xiao W., Shen C., Zhou G., Lin L.,
RA Yang S.;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 INTERACTION WITH THE SMN COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=11509230; DOI=10.1016/s0960-9822(01)00316-5;
RA Pellizzoni L., Baccon J., Charroux B., Dreyfuss G.;
RT "The survival of motor neurons (SMN) protein interacts with the snoRNP
RT proteins fibrillarin and GAR1.";
RL Curr. Biol. 11:1079-1088(2001).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=11790298; DOI=10.1016/s0960-9822(01)00650-9;
RA Andersen J.S., Lyon C.E., Fox A.H., Leung A.K.L., Lam Y.W., Steen H.,
RA Mann M., Lamond A.I.;
RT "Directed proteomic analysis of the human nucleolus.";
RL Curr. Biol. 12:1-11(2002).
RN [6]
RP INTERACTION WITH THE SMN COMPLEX.
RX PubMed=12244096; DOI=10.1074/jbc.m204551200;
RA Whitehead S.E., Jones K.W., Zhang X., Cheng X., Terns R.M., Terns M.P.;
RT "Determinants of the interaction of the spinal muscular atrophy disease
RT protein SMN with the dimethylarginine-modified box H/ACA small nucleolar
RT ribonucleoprotein GAR1.";
RL J. Biol. Chem. 277:48087-48093(2002).
RN [7]
RP FUNCTION, AND CHARACTERIZATION OF THE H/ACA SNORNP COMPLEX.
RX PubMed=15044956; DOI=10.1038/sj.emboj.7600181;
RA Wang C., Meier U.T.;
RT "Architecture and assembly of mammalian H/ACA small nucleolar and
RT telomerase ribonucleoproteins.";
RL EMBO J. 23:1857-1867(2004).
RN [8]
RP IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX.
RX PubMed=19179534; DOI=10.1126/science.1165357;
RA Venteicher A.S., Abreu E.B., Meng Z., McCann K.E., Terns R.M.,
RA Veenstra T.D., Terns M.P., Artandi S.E.;
RT "A human telomerase holoenzyme protein required for Cajal body localization
RT and telomere synthesis.";
RL Science 323:644-648(2009).
RN [9]
RP IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX.
RX PubMed=20351177; DOI=10.1128/mcb.00151-10;
RA Egan E.D., Collins K.;
RT "Specificity and stoichiometry of subunit interactions in the human
RT telomerase holoenzyme assembled in vivo.";
RL Mol. Cell. Biol. 30:2775-2786(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 SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-134, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [12]
RP STRUCTURE BY ELECTRON MICROSCOPY (7.7 ANGSTROMS) OF THE TELOMERASE
RP HOLOENZYME COMPLEX.
RX PubMed=29695869; DOI=10.1038/s41586-018-0062-x;
RA Nguyen T.H.D., Tam J., Wu R.A., Greber B.J., Toso D., Nogales E.,
RA Collins K.;
RT "Cryo-EM structure of substrate-bound human telomerase holoenzyme.";
RL Nature 557:190-195(2018).
CC -!- FUNCTION: Required for ribosome biogenesis and telomere maintenance.
CC Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP)
CC complex, which catalyzes pseudouridylation of rRNA. This involves the
CC isomerization of uridine such that the ribose is subsequently attached
CC to C5, instead of the normal N1. Each rRNA can contain up to 100
CC pseudouridine ('psi') residues, which may serve to stabilize the
CC conformation of rRNAs. May also be required for correct processing or
CC intranuclear trafficking of TERC, the RNA component of the telomerase
CC reverse transcriptase (TERT) holoenzyme. {ECO:0000269|PubMed:10757788,
CC ECO:0000269|PubMed:15044956}.
CC -!- SUBUNIT: Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA
CC snoRNP) complex, which contains NHP2/NOLA2, GAR1/NOLA1, NOP10/NOLA3,
CC and DKC1/NOLA4, which is presumed to be the catalytic subunit
CC (PubMed:11509230, PubMed:12244096). The complex contains a stable core
CC formed by binding of one or two NOP10-DKC1 heterodimers to NHP2; GAR1
CC subsequently binds to this core via DKC1 (PubMed:11509230,
CC PubMed:12244096). The complex binds a box H/ACA small nucleolar RNA
CC (snoRNA), which may target the specific site of modification within the
CC RNA substrate (PubMed:11509230, PubMed:12244096). The complex also
CC interacts with TERC, which contains a 3'-terminal domain related to the
CC box H/ACA snoRNAs (PubMed:11509230, PubMed:12244096). Specific
CC interactions with snoRNAs or TERC are mediated by GAR1 and NHP2
CC (PubMed:11509230, PubMed:12244096). Associates with NOLC1/NOPP140
CC (PubMed:11509230, PubMed:12244096). H/ACA snoRNPs interact with the SMN
CC complex, consisting of SMN1 or SMN2, GEMIN2/SIP1, DDX20/GEMIN3, and
CC GEMIN4 (PubMed:11509230, PubMed:12244096). This is mediated by
CC interaction between GAR1 and SMN1 or SMN2 (PubMed:11509230,
CC PubMed:12244096). The SMN complex may be required for correct assembly
CC of the H/ACA snoRNP complex (PubMed:11509230, PubMed:12244096).
CC Component of the telomerase holoenzyme complex composed of one molecule
CC of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA
CC ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a
CC telomerase RNA template component (TERC) (PubMed:19179534,
CC PubMed:20351177, PubMed:29695869). The telomerase holoenzyme complex is
CC associated with TEP1, SMG6/EST1A and POT1 (PubMed:19179534).
CC {ECO:0000269|PubMed:11509230, ECO:0000269|PubMed:12244096,
CC ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:20351177,
CC ECO:0000269|PubMed:29695869}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus. Nucleus, Cajal body.
CC Note=Also localized to Cajal bodies (coiled bodies).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NY12-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NY12-2; Sequence=VSP_014594;
CC -!- DOMAIN: Interaction with SMN1 requires at least one of the RGG-box
CC regions.
CC -!- SIMILARITY: Belongs to the GAR1 family. {ECO:0000305}.
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DR EMBL; AJ276003; CAB76563.1; -; mRNA.
DR EMBL; AY780787; AAV98357.1; -; mRNA.
DR EMBL; BC003413; AAH03413.1; -; mRNA.
DR CCDS; CCDS34050.1; -. [Q9NY12-1]
DR RefSeq; NP_061856.1; NM_018983.3. [Q9NY12-1]
DR RefSeq; NP_127460.1; NM_032993.2. [Q9NY12-1]
DR PDB; 7BGB; EM; 3.39 A; D/H=1-217.
DR PDB; 7V9A; EM; 3.94 A; D/H=1-217.
DR PDBsum; 7BGB; -.
DR PDBsum; 7V9A; -.
DR AlphaFoldDB; Q9NY12; -.
DR SMR; Q9NY12; -.
DR BioGRID; 119949; 199.
DR ComplexPortal; CPX-265; Telomerase holoenzyme complex.
DR CORUM; Q9NY12; -.
DR IntAct; Q9NY12; 89.
DR MINT; Q9NY12; -.
DR STRING; 9606.ENSP00000226796; -.
DR GlyGen; Q9NY12; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NY12; -.
DR PhosphoSitePlus; Q9NY12; -.
DR SwissPalm; Q9NY12; -.
DR BioMuta; GAR1; -.
DR DMDM; 51828015; -.
DR EPD; Q9NY12; -.
DR jPOST; Q9NY12; -.
DR MassIVE; Q9NY12; -.
DR MaxQB; Q9NY12; -.
DR PaxDb; Q9NY12; -.
DR PeptideAtlas; Q9NY12; -.
DR PRIDE; Q9NY12; -.
DR ProteomicsDB; 83147; -. [Q9NY12-1]
DR ProteomicsDB; 83148; -. [Q9NY12-2]
DR Antibodypedia; 26373; 134 antibodies from 24 providers.
DR DNASU; 54433; -.
DR Ensembl; ENST00000226796.7; ENSP00000226796.6; ENSG00000109534.17. [Q9NY12-1]
DR Ensembl; ENST00000394631.7; ENSP00000378127.3; ENSG00000109534.17. [Q9NY12-1]
DR GeneID; 54433; -.
DR KEGG; hsa:54433; -.
DR MANE-Select; ENST00000226796.7; ENSP00000226796.6; NM_018983.4; NP_061856.1.
DR UCSC; uc003hzt.4; human. [Q9NY12-1]
DR CTD; 54433; -.
DR DisGeNET; 54433; -.
DR GeneCards; GAR1; -.
DR HGNC; HGNC:14264; GAR1.
DR HPA; ENSG00000109534; Low tissue specificity.
DR MIM; 606468; gene.
DR neXtProt; NX_Q9NY12; -.
DR OpenTargets; ENSG00000109534; -.
DR PharmGKB; PA164720194; -.
DR VEuPathDB; HostDB:ENSG00000109534; -.
DR eggNOG; KOG3262; Eukaryota.
DR GeneTree; ENSGT00730000111223; -.
DR HOGENOM; CLU_080002_0_1_1; -.
DR InParanoid; Q9NY12; -.
DR OMA; HSCEGEM; -.
DR PhylomeDB; Q9NY12; -.
DR TreeFam; TF350747; -.
DR PathwayCommons; Q9NY12; -.
DR Reactome; R-HSA-171319; Telomere Extension By Telomerase.
DR Reactome; R-HSA-6790901; rRNA modification in the nucleus and cytosol.
DR SignaLink; Q9NY12; -.
DR SIGNOR; Q9NY12; -.
DR BioGRID-ORCS; 54433; 434 hits in 1084 CRISPR screens.
DR ChiTaRS; GAR1; human.
DR GeneWiki; Nucleolar_protein,_member_A1; -.
DR GenomeRNAi; 54433; -.
DR Pharos; Q9NY12; Tbio.
DR PRO; PR:Q9NY12; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9NY12; protein.
DR Bgee; ENSG00000109534; Expressed in tendon of biceps brachii and 212 other tissues.
DR Genevisible; Q9NY12; HS.
DR GO; GO:0072589; C:box H/ACA scaRNP complex; TAS:BHF-UCL.
DR GO; GO:0031429; C:box H/ACA snoRNP complex; IDA:BHF-UCL.
DR GO; GO:0090661; C:box H/ACA telomerase RNP complex; IDA:BHF-UCL.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IDA:UniProtKB.
DR GO; GO:0034513; F:box H/ACA snoRNA binding; IPI:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; IPI:BHF-UCL.
DR GO; GO:0070034; F:telomerase RNA binding; IPI:BHF-UCL.
DR GO; GO:0000454; P:snoRNA guided rRNA pseudouridine synthesis; IBA:GO_Central.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IDA:UniProtKB.
DR Gene3D; 2.40.10.230; -; 1.
DR InterPro; IPR038664; Gar1/Naf1_Cbf5-bd_sf.
DR InterPro; IPR007504; H/ACA_rnp_Gar1/Naf1.
DR InterPro; IPR009000; Transl_B-barrel_sf.
DR Pfam; PF04410; Gar1; 1.
DR SUPFAM; SSF50447; SSF50447; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Isopeptide bond; Nucleus;
KW Reference proteome; Repeat; Ribonucleoprotein; Ribosome biogenesis;
KW RNA-binding; rRNA processing; Ubl conjugation.
FT CHAIN 1..217
FT /note="H/ACA ribonucleoprotein complex subunit 1"
FT /id="PRO_0000208552"
FT REGION 1..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4..57
FT /note="RGG-box 1"
FT REGION 156..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 169..217
FT /note="RGG-box 2"
FT CROSSLNK 134
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 181..198
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_014594"
FT CONFLICT 39
FT /note="G -> D (in Ref. 2; AAV98357)"
FT /evidence="ECO:0000305"
FT STRAND 71..79
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 81..88
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 109..122
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:7BGB"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:7BGB"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:7BGB"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:7BGB"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:7BGB"
SQ SEQUENCE 217 AA; 22348 MW; 48CF04B78836EF91 CRC64;
MSFRGGGRGG FNRGGGGGGF NRGGSSNHFR GGGGGGGGGN FRGGGRGGFG RGGGRGGFNK
GQDQGPPERV VLLGEFLHPC EDDIVCKCTT DENKVPYFNA PVYLENKEQI GKVDEIFGQL
RDFYFSVKLS ENMKASSFKK LQKFYIDPYK LLPLQRFLPR PPGEKGPPRG GGRGGRGGGR
GGGGRGGGRG GGFRGGRGGG GGGFRGGRGG GFRGRGH
