TAP45_TETTS
ID TAP45_TETTS Reviewed; 373 AA.
AC Q6JXI5; Q237B3;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 17-JUN-2020, sequence version 2.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=Telomerase-associated protein of 45 kDa {ECO:0000303|PubMed:15131081};
DE Short=p45 {ECO:0000303|PubMed:15131081};
GN Name=TAP45 {ECO:0000303|PubMed:15131081};
GN ORFNames=TTHERM_00083360 {ECO:0000312|EMBL:EAR92337.1};
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], AND DISRUPTION 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 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 [4]
RP SITE.
RX PubMed=21549126; DOI=10.1016/j.jmb.2011.04.040;
RA Rosenfeld K.K., Ziv T., Goldin S., Glaser F., Manor H.;
RT "Mapping of DNA binding sites in the Tetrahymena telomerase holoenzyme
RT proteins by UV cross-linking and mass spectrometry.";
RL J. Mol. Biol. 410:77-92(2011).
RN [5]
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 [6] {ECO:0007744|PDB:5DOI, ECO:0007744|PDB:5DOK}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 2-129 IN COMPLEX WITH TAP19;
RP TAP75 AND MAGNESIUM, FUNCTION, IDENTIFICATION IN THE TELOMERASE HOLOENZYME,
RP AND MUTAGENESIS OF ALA-109; GLU-112 AND MET-113.
RX PubMed=26551074; DOI=10.1038/nsmb.3126;
RA Wan B., Tang T., Upton H., Shuai J., Zhou Y., Li S., Chen J.,
RA Brunzelle J.S., Zeng Z., Collins K., Wu J., Lei M.;
RT "The Tetrahymena telomerase p75-p45-p19 subcomplex is a unique CST
RT complex.";
RL Nat. Struct. Mol. Biol. 22:1023-1026(2015).
RN [7] {ECO:0007744|PDB:5DFN}
RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 161-373, AND STRUCTURE BY
RP 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).
CC -!- FUNCTION: Component of a CST-like subcomplex of the holoenzyme
CC telomerase ribonucleoprotein complex, which stimulates telomerase
CC complementary-strand synthesis (PubMed:26551074). Telomerase is an
CC essential ribonucleoprotein enzyme that copies new telomeric repeats
CC onto chromosome ends by repetitively synthesizing the short telomere-
CC repeat sequence 5'-TTGGGG-3' using an RNA template component TER
CC (PubMed:26551074). The CST-like subcomplex (also named 7-4-1) binds
CC telomeric single-stranded DNA and coordinates telomere G-strand and C-
CC strand synthesis (PubMed:26551074). {ECO:0000269|PubMed:26551074}.
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:19941821, PubMed:23552895, PubMed:26551074, PubMed:26472759).
CC TEB1 and the CST-like subcomplex are tethered to the catalytic core by
CC TAP50/p50 (PubMed:19941821, PubMed:23552895, PubMed:26472759).
CC {ECO:0000269|PubMed:19941821, ECO:0000269|PubMed:23552895,
CC ECO:0000269|PubMed:26472759, ECO:0000269|PubMed:26551074}.
CC -!- INTERACTION:
CC Q6JXI5; D2CVN7: TAP19; NbExp=9; IntAct=EBI-16181547, EBI-16181555;
CC -!- SUBCELLULAR LOCATION: Chromosome, telomere {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Critically short telomeres.
CC {ECO:0000269|PubMed:15131081}.
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DR EMBL; AY280525; AAQ21363.1; -; mRNA.
DR EMBL; GG662749; EAR92337.1; -; Genomic_DNA.
DR RefSeq; XP_001012582.1; XM_001012582.3.
DR PDB; 5DFN; X-ray; 2.38 A; A/B=161-373.
DR PDB; 5DOI; X-ray; 2.20 A; E/F/G/H=2-129.
DR PDB; 5DOK; X-ray; 2.30 A; A/B=170-373.
DR PDBsum; 5DFN; -.
DR PDBsum; 5DOI; -.
DR PDBsum; 5DOK; -.
DR AlphaFoldDB; Q6JXI5; -.
DR SMR; Q6JXI5; -.
DR DIP; DIP-60205N; -.
DR DIP; DIP-61867N; -.
DR IntAct; Q6JXI5; 5.
DR STRING; 5911.EAR92337; -.
DR EnsemblProtists; EAR92337; EAR92337; TTHERM_00083360.
DR GeneID; 7839348; -.
DR KEGG; tet:TTHERM_00083360; -.
DR HOGENOM; CLU_742904_0_0_1; -.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IMP:UniProtKB.
PE 1: Evidence at protein level;
KW 3D-structure; Chromosome; Magnesium; Metal-binding; Reference proteome;
KW Telomere.
FT CHAIN 1..373
FT /note="Telomerase-associated protein of 45 kDa"
FT /id="PRO_0000449909"
FT BINDING 187
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:26551074,
FT ECO:0000312|PDB:5DOK"
FT BINDING 188
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:26551074,
FT ECO:0000312|PDB:5DOK"
FT BINDING 191
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:26551074,
FT ECO:0000312|PDB:5DOK"
FT BINDING 339
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:26551074,
FT ECO:0000312|PDB:5DOK"
FT SITE 351
FT /note="Minor DNA-binding site"
FT /evidence="ECO:0000305|PubMed:21549126"
FT MUTAGEN 109
FT /note="A->R,W: Abolished interaction with TAP19/p19."
FT /evidence="ECO:0000269|PubMed:26551074"
FT MUTAGEN 112
FT /note="E->R: Abolished interaction with TAP19/p19."
FT /evidence="ECO:0000269|PubMed:26551074"
FT MUTAGEN 113
FT /note="M->W: Abolished interaction with TAP19/p19."
FT /evidence="ECO:0000269|PubMed:26551074"
FT CONFLICT 178
FT /note="T -> S (in Ref. 1; AAQ21363)"
FT TURN 10..12
FT /evidence="ECO:0007829|PDB:5DOI"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:5DOI"
FT STRAND 21..31
FT /evidence="ECO:0007829|PDB:5DOI"
FT STRAND 49..53
FT /evidence="ECO:0007829|PDB:5DOI"
FT STRAND 58..62
FT /evidence="ECO:0007829|PDB:5DOI"
FT STRAND 78..86
FT /evidence="ECO:0007829|PDB:5DOI"
FT STRAND 97..106
FT /evidence="ECO:0007829|PDB:5DOI"
FT HELIX 109..124
FT /evidence="ECO:0007829|PDB:5DOI"
FT HELIX 179..203
FT /evidence="ECO:0007829|PDB:5DOK"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:5DOK"
FT HELIX 233..236
FT /evidence="ECO:0007829|PDB:5DOK"
FT HELIX 240..247
FT /evidence="ECO:0007829|PDB:5DOK"
FT HELIX 255..271
FT /evidence="ECO:0007829|PDB:5DOK"
FT STRAND 274..281
FT /evidence="ECO:0007829|PDB:5DOK"
FT STRAND 284..289
FT /evidence="ECO:0007829|PDB:5DOK"
FT HELIX 291..308
FT /evidence="ECO:0007829|PDB:5DOK"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:5DOK"
FT HELIX 315..326
FT /evidence="ECO:0007829|PDB:5DOK"
FT TURN 329..331
FT /evidence="ECO:0007829|PDB:5DOK"
FT HELIX 338..350
FT /evidence="ECO:0007829|PDB:5DOK"
SQ SEQUENCE 373 AA; 43632 MW; 00A007C762EC66E5 CRC64;
MEDNFELVFL KELPSLPDFS KVCFTGLILS FSNFPSSEQN QQKDVPHKIA IIQDSTGEAE
LFLDMYKFCQ EEISVFKAIT GIGVLKKKNI GAGQVCKIIV ERFRIIHSAD EEMLQYLLIQ
KYKLSKTLNE QQQIKQKEQQ INQQKIDKVV QDKESKEHLL WKQQQIPQIK SNQENINTLK
YKELIAGELM RITHKLLIQK LQQQQPANNN KQINEMDVES NELAEKKEVI IKIQEIAKDQ
QLYDTLSIQY QVDQKEQYYA KIAQSLEDFV SISALKMVSY IYPNISYQVS IGFFQNILDI
ATKTVKDRGA LGCNYKYLKD KLTKALNLQQ ISYPLISESY ISYLVHLFQD FNIIEIENEH
KFYYKQAFQY DDS
