LARP7_TETTS
ID LARP7_TETTS Reviewed; 542 AA.
AC W7X6T2; Q6JXI6;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 41.
DE RecName: Full=La-related protein 7 homolog {ECO:0000305};
DE AltName: Full=Telomerase-associated protein of 65 kDa {ECO:0000303|PubMed:15131081};
DE Short=p65 {ECO:0000303|PubMed:15131081};
GN Name=TAP65 {ECO:0000303|PubMed:15131081};
GN ORFNames=TTHERM_000318539 {ECO:0000312|EMBL:EWS73087.1};
OS Tetrahymena thermophila (strain SB210).
OC Eukaryota; Sar; Alveolata; Ciliophora; Intramacronucleata;
OC Oligohymenophorea; Hymenostomatida; Tetrahymenina; Tetrahymenidae;
OC Tetrahymena.
OX NCBI_TaxID=312017;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, RNA-BINDING, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15131081; DOI=10.1101/gad.1201704;
RA Witkin K.L., Collins K.;
RT "Holoenzyme proteins required for the physiological assembly and activity
RT of telomerase.";
RL Genes Dev. 18:1107-1118(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SB210;
RX PubMed=16933976; DOI=10.1371/journal.pbio.0040286;
RA Eisen J.A., Coyne R.S., Wu M., Wu D., Thiagarajan M., Wortman J.R.,
RA Badger J.H., Ren Q., Amedeo P., Jones K.M., Tallon L.J., Delcher A.L.,
RA Salzberg S.L., Silva J.C., Haas B.J., Majoros W.H., Farzad M.,
RA Carlton J.M., Smith R.K. Jr., Garg J., Pearlman R.E., Karrer K.M., Sun L.,
RA Manning G., Elde N.C., Turkewitz A.P., Asai D.J., Wilkes D.E., Wang Y.,
RA Cai H., Collins K., Stewart B.A., Lee S.R., Wilamowska K., Weinberg Z.,
RA Ruzzo W.L., Wloga D., Gaertig J., Frankel J., Tsao C.-C., Gorovsky M.A.,
RA Keeling P.J., Waller R.F., Patron N.J., Cherry J.M., Stover N.A.,
RA Krieger C.J., del Toro C., Ryder H.F., Williamson S.C., Barbeau R.A.,
RA Hamilton E.P., Orias E.;
RT "Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a
RT model eukaryote.";
RL PLoS Biol. 4:1620-1642(2006).
RN [3]
RP FUNCTION, RNA-BINDING, AND IDENTIFICATION IN THE TELOMERASE HOLOENZYME
RP COMPLEX.
RX PubMed=15696174; DOI=10.1038/nsmb900;
RA Prathapam R., Witkin K.L., O'Connor C.M., Collins K.;
RT "A telomerase holoenzyme protein enhances telomerase RNA assembly with
RT telomerase reverse transcriptase.";
RL Nat. Struct. Mol. Biol. 12:252-257(2005).
RN [4]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=16507983; DOI=10.1128/mcb.26.6.2029-2036.2006;
RA O'Connor C.M., Collins K.;
RT "A novel RNA binding domain in tetrahymena telomerase p65 initiates
RT hierarchical assembly of telomerase holoenzyme.";
RL Mol. Cell. Biol. 26:2029-2036(2006).
RN [5]
RP FUNCTION, RNA-BINDING, AND IDENTIFICATION IN THE TELOMERASE HOLOENZYME
RP COMPLEX.
RX PubMed=17322903; DOI=10.1038/nature05600;
RA Stone M.D., Mihalusova M., O'connor C.M., Prathapam R., Collins K.,
RA Zhuang X.;
RT "Stepwise protein-mediated RNA folding directs assembly of telomerase
RT ribonucleoprotein.";
RL Nature 446:458-461(2007).
RN [6]
RP FUNCTION, RNA-BINDING, AND IDENTIFICATION IN THE TELOMERASE HOLOENZYME
RP COMPLEX.
RX PubMed=20713447; DOI=10.1128/mcb.00827-10;
RA Berman A.J., Gooding A.R., Cech T.R.;
RT "Tetrahymena telomerase protein p65 induces conformational changes
RT throughout telomerase RNA (TER) and rescues telomerase reverse
RT transcriptase and TER assembly mutants.";
RL Mol. Cell. Biol. 30:4965-4976(2010).
RN [7]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=22315458; DOI=10.1261/rna.031377.111;
RA Akiyama B.M., Loper J., Najarro K., Stone M.D.;
RT "The C-terminal domain of Tetrahymena thermophila telomerase holoenzyme
RT protein p65 induces multiple structural changes in telomerase RNA.";
RL RNA 18:653-660(2012).
RN [8]
RP IDENTIFICATION IN THE TELOMERASE HOLOENZYME.
RX PubMed=19941821; DOI=10.1016/j.molcel.2009.09.041;
RA Min B., Collins K.;
RT "An RPA-related sequence-specific DNA-binding subunit of telomerase
RT holoenzyme is required for elongation processivity and telomere
RT maintenance.";
RL Mol. Cell 36:609-619(2009).
RN [9] {ECO:0007744|PDB:2LSL, ECO:0007744|PDB:4ERD, ECO:0007744|PDB:4EYT}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 375-542 IN COMPLEX WITH TER RNA,
RP FUNCTION, RNA-BINDING, DOMAIN, AND MUTAGENESIS OF TYR-407 AND ARG-465.
RX PubMed=22705372; DOI=10.1016/j.molcel.2012.05.018;
RA Singh M., Wang Z., Koo B.K., Patel A., Cascio D., Collins K., Feigon J.;
RT "Structural basis for telomerase RNA recognition and RNP assembly by the
RT holoenzyme La family protein p65.";
RL Mol. Cell 47:16-26(2012).
RN [10]
RP STRUCTURE BY ELECTRON MICROSCOPY OF THE TELOMERASE HOLOENZYME.
RX PubMed=23552895; DOI=10.1038/nature12062;
RA Jiang J., Miracco E.J., Hong K., Eckert B., Chan H., Cash D.D., Min B.,
RA Zhou Z.H., Collins K., Feigon J.;
RT "The architecture of Tetrahymena telomerase holoenzyme.";
RL Nature 496:187-192(2013).
RN [11]
RP STRUCTURE BY ELECTRON MICROSCOPY OF THE TELOMERASE HOLOENZYME.
RX PubMed=26472759; DOI=10.1126/science.aab4070;
RA Jiang J., Chan H., Cash D.D., Miracco E.J., Ogorzalek Loo R.R., Upton H.E.,
RA Cascio D., O'Brien Johnson R., Collins K., Loo J.A., Zhou Z.H., Feigon J.;
RT "Structure of Tetrahymena telomerase reveals previously unknown subunits,
RT functions, and interactions.";
RL Science 350:AAB4070-AAB4070(2015).
RN [12] {ECO:0007744|PDB:6D6V}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.80 ANGSTROMS) OF THE TELOMERASE
RP HOLOENZYME IN COMPLEX WITH TELOMERIC DNA AND TER RNA.
RX PubMed=29775593; DOI=10.1016/j.cell.2018.04.038;
RA Jiang J., Wang Y., Susac L., Chan H., Basu R., Zhou Z.H., Feigon J.;
RT "Structure of telomerase with telomeric DNA.";
RL Cell 173:1179-1190(2018).
CC -!- FUNCTION: RNA-binding protein required for assembly of the holoenzyme
CC telomerase ribonucleoprotein (RNP) complex (PubMed:15131081,
CC PubMed:15696174, PubMed:16507983, PubMed:17322903, PubMed:20713447,
CC PubMed:22315458, PubMed:22705372). Telomerase is an essential
CC ribonucleoprotein enzyme that copies new telomeric repeats onto
CC chromosome ends by repetitively synthesizing the short telomere-repeat
CC sequence 5'-TTGGGG-3' using an RNA template component TER
CC (PubMed:15696174, PubMed:17322903, PubMed:20713447). TAP65/p65
CC specifically binds telomerase RNA template TER and is required for
CC biogenesis and placement of the TER stem-terminus element: TAP65/p65
CC first protects the 3'-end of TER from degradation and acts as a
CC chaperone to correctly fold TER for protein binding; it then bends TER
CC stem-loop IV to position it for interaction of stem-loop IV with
CC catalytic TERT RNA-binding domain (PubMed:15696174, PubMed:17322903,
CC PubMed:20713447, PubMed:22315458, PubMed:22705372).
CC {ECO:0000269|PubMed:15131081, ECO:0000269|PubMed:15696174,
CC ECO:0000269|PubMed:16507983, ECO:0000269|PubMed:17322903,
CC ECO:0000269|PubMed:20713447, ECO:0000269|PubMed:22315458,
CC ECO:0000269|PubMed:22705372}.
CC -!- SUBUNIT: Component of the telomerase holoenzyme complex, composed of
CC the catalytic core (the catalytic subunit TERT, the telomerase RNA
CC template component TER and TAP65/p65), which is associated with two
CC heterotrimeric subcomplexes: (i) the replication protein A (RPA)-
CC related subcomplex, composed of TEB1, RPA2/TEB2 and RPA3/TEB3 and (ii)
CC the CST-like subcomplex, composed of TAP75/p75, TAP45/p45 and TAP19/p19
CC (PubMed:15696174, PubMed:17322903, PubMed:20713447, PubMed:19941821,
CC PubMed:22705372, PubMed:23552895, PubMed:26472759, PubMed:29775593).
CC TEB1 and the CST-like subcomplex are tethered to the catalytic core by
CC TAP50/p50 (PubMed:19941821, PubMed:23552895, PubMed:26472759,
CC PubMed:29775593). {ECO:0000269|PubMed:15696174,
CC ECO:0000269|PubMed:17322903, ECO:0000269|PubMed:19941821,
CC ECO:0000269|PubMed:20713447, ECO:0000269|PubMed:22705372,
CC ECO:0000269|PubMed:23552895, ECO:0000269|PubMed:26472759,
CC ECO:0000269|PubMed:29775593}.
CC -!- SUBCELLULAR LOCATION: Chromosome, telomere {ECO:0000305}.
CC -!- DOMAIN: The HTH La-type RNA-binding and RRM domains cooperatively bind
CC to TER RNA UUU-3'OH sequence after it is transcribed by Polymerase III
CC (PubMed:22705372). UUU-3'OH-binding by the HTH La-type RNA-binding and
CC RRM domains positions the xRRM domain to bind to the adjacent proximal
CC stem-loop IV and central dinucleotide GA bulge (PubMed:22705372).
CC {ECO:0000269|PubMed:22705372}.
CC -!- DISRUPTION PHENOTYPE: Critically short telomeres (PubMed:15131081).
CC Reduced accumulation of telomerase RNA TER (PubMed:15131081).
CC {ECO:0000269|PubMed:15131081}.
CC -!- SIMILARITY: Belongs to the LARP7 family. {ECO:0000305}.
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DR EMBL; AY280524; AAQ21362.1; -; Genomic_DNA.
DR EMBL; GG662605; EWS73087.1; -; Genomic_DNA.
DR RefSeq; XP_012654396.1; XM_012798942.1.
DR PDB; 2LSL; NMR; -; A=369-519.
DR PDB; 4ERD; X-ray; 2.59 A; A/B=375-542.
DR PDB; 4EYT; X-ray; 2.50 A; A/B/C/D/E/F=375-542.
DR PDB; 6D6V; EM; 4.80 A; H=1-542.
DR PDB; 7LMA; EM; 3.30 A; H=1-542.
DR PDB; 7LMB; EM; 3.80 A; H=1-542.
DR PDBsum; 2LSL; -.
DR PDBsum; 4ERD; -.
DR PDBsum; 4EYT; -.
DR PDBsum; 6D6V; -.
DR PDBsum; 7LMA; -.
DR PDBsum; 7LMB; -.
DR AlphaFoldDB; W7X6T2; -.
DR SMR; W7X6T2; -.
DR DIP; DIP-60203N; -.
DR DIP; DIP-61864N; -.
DR IntAct; W7X6T2; 8.
DR STRING; 5911.EAS01190; -.
DR GeneID; 24438417; -.
DR KEGG; tet:TTHERM_000318539; -.
DR eggNOG; KOG0118; Eukaryota.
DR eggNOG; KOG3525; Eukaryota.
DR OrthoDB; 1499213at2759; -.
DR Proteomes; UP000009168; Unassembled WGS sequence.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IDA:UniProtKB.
DR GO; GO:0070034; F:telomerase RNA binding; IDA:UniProtKB.
DR GO; GO:1904868; P:telomerase catalytic core complex assembly; IDA:UniProtKB.
DR GO; GO:0090669; P:telomerase RNA stabilization; IDA:UniProtKB.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IDA:UniProtKB.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.30.70.330; -; 3.
DR InterPro; IPR045180; La_dom_prot.
DR InterPro; IPR006630; La_HTH.
DR InterPro; IPR014886; La_xRRM.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR22792; PTHR22792; 1.
DR Pfam; PF05383; La; 1.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00715; LA; 1.
DR SMART; SM00360; RRM; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50961; HTH_LA; 1.
DR PROSITE; PS50102; RRM; 1.
DR PROSITE; PS51939; XRRM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromosome; Reference proteome; RNA-binding; Telomere.
FT CHAIN 1..542
FT /note="La-related protein 7 homolog"
FT /id="PRO_0000449907"
FT DOMAIN 112..239
FT /note="HTH La-type RNA-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00332"
FT DOMAIN 247..335
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 374..542
FT /note="xRRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01288,
FT ECO:0000305|PubMed:22705372"
FT MUTAGEN 407
FT /note="Y->A: Decreased binding to TER RNA stem-loop IV."
FT /evidence="ECO:0000269|PubMed:22705372"
FT MUTAGEN 465
FT /note="R->A: Decreased binding to TER RNA stem-loop IV."
FT /evidence="ECO:0000269|PubMed:22705372"
FT HELIX 116..130
FT /evidence="ECO:0007829|PDB:7LMA"
FT HELIX 134..137
FT /evidence="ECO:0007829|PDB:7LMA"
FT HELIX 142..147
FT /evidence="ECO:0007829|PDB:7LMA"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:7LMA"
FT TURN 156..160
FT /evidence="ECO:0007829|PDB:7LMA"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:7LMA"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:7LMA"
FT HELIX 203..215
FT /evidence="ECO:0007829|PDB:7LMA"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:7LMA"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:7LMA"
FT STRAND 380..384
FT /evidence="ECO:0007829|PDB:4EYT"
FT HELIX 392..400
FT /evidence="ECO:0007829|PDB:4EYT"
FT TURN 401..403
FT /evidence="ECO:0007829|PDB:2LSL"
FT STRAND 406..410
FT /evidence="ECO:0007829|PDB:4EYT"
FT TURN 453..456
FT /evidence="ECO:0007829|PDB:2LSL"
FT STRAND 462..468
FT /evidence="ECO:0007829|PDB:4EYT"
FT HELIX 469..479
FT /evidence="ECO:0007829|PDB:4EYT"
FT TURN 482..485
FT /evidence="ECO:0007829|PDB:4EYT"
FT STRAND 486..491
FT /evidence="ECO:0007829|PDB:4EYT"
FT STRAND 494..499
FT /evidence="ECO:0007829|PDB:4EYT"
FT HELIX 504..517
FT /evidence="ECO:0007829|PDB:4EYT"
SQ SEQUENCE 542 AA; 64125 MW; 4ECB1A01A3D57417 CRC64;
MDEYLENTNL EELEQECFME DYQHEDVVEQ ENHQVDANDI YENQQMNDES QLNQDVKISQ
QKEQAVEMIE EQQQNNQDKF KQFQDCMAHI TELNFKRNYQ NLTEQSSSNN VVAEELDIKE
SLKLQMEYYF CDTNLTHDSY LRGIISKSPK NCVDIKVFLK FNKIQQILKQ IQDKQIVSTY
GIENQSQKKN HKNYKNQNAT FSKKDLIHLI RDSLKESKIL KVKMDSLKVK RRFPFNLEQA
LKNSKQRTLY IDFLPPKCSK QTLVSIFGNF RIININLPLQ KNSQLCQGFA FIEFFSEEEA
NQALITKNSS IPKELILLTE KKIGQGSIRI ITYKKWQEEK QSFKELSKNQ NEQKNKNMNQ
SRKASDEFVS IDVEIKQNCL IKIINIPQGT LKAEVVLAVR HLGYEFYCDY IDENSNQINS
NKISLSTQQQ NTAQCSNIQI ENNLIQQDQH PQLNDLLKEG QAMIRFQNSD EQRLAIQKLL
NHNNNKLQIE IRGQICDVIS TIPEDEEKNY WNYIKFKKNE FRKFFFMKKQ QKKQNITQNY
NK
