PAPD7_HUMAN
ID PAPD7_HUMAN Reviewed; 772 AA.
AC Q5XG87; A8K1E2; M1JCE6; O43289; Q17RZ1; Q9Y6C1;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Terminal nucleotidyltransferase 4A {ECO:0000305};
DE AltName: Full=DNA polymerase sigma;
DE AltName: Full=LAK-1;
DE AltName: Full=Non-canonical poly(A) RNA polymerase PAPD7 {ECO:0000305};
DE EC=2.7.7.19;
DE AltName: Full=PAP-associated domain-containing protein 7;
DE AltName: Full=TRAMP-like complex polyadenylate polymerase;
DE AltName: Full=Terminal guanylyltransferase {ECO:0000305};
DE EC=2.7.7.- {ECO:0000269|PubMed:30026317};
DE AltName: Full=Terminal uridylyltransferase 5;
DE Short=TUTase 5;
DE AltName: Full=Topoisomerase-related function protein 4-1;
DE Short=TRF4-1;
GN Name=TENT4A {ECO:0000312|HGNC:HGNC:16705};
GN Synonyms=PAPD7 {ECO:0000303|PubMed:23376078},
GN POLS {ECO:0000312|HGNC:HGNC:16705}, TRF4 {ECO:0000303|PubMed:10066793};
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 2).
RX PubMed=10066793; DOI=10.1074/jbc.274.11.7302;
RA Walowsky C., Fitzhugh D.J., Castano I.B., Ju J.Y., Levin N.A.,
RA Christman M.F.;
RT "The topoisomerase-related function gene TRF4 affects cellular sensitivity
RT to the antitumor agent camptothecin.";
RL J. Biol. Chem. 274:7302-7308(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP MUTAGENESIS OF 167-ARG--PHE-230, AND ALTERNATIVE SPLICING.
RX PubMed=23376078; DOI=10.1016/j.bbrc.2013.01.072;
RA Ogami K., Cho R., Hoshino S.;
RT "Molecular cloning and characterization of a novel isoform of the non-
RT canonical poly(A) polymerase PAPD7.";
RL Biochem. Biophys. Res. Commun. 432:135-140(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Abe Y., Takaoka Y.;
RT "mLT positive LAK-cell clone No. 1.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-556 AND SER-626.
RG NIEHS SNPs program;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum, and Lung;
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 [8]
RP PRELIMINARY FUNCTION.
RX PubMed=10926539; DOI=10.1126/science.289.5480.774;
RA Wang Z., Castano I.B., De Las Penas A., Adams C., Christman M.F.;
RT "Pol kappa: a DNA polymerase required for sister chromatid cohesion.";
RL Science 289:774-779(2000).
RN [9]
RP REVIEW.
RX PubMed=11459963; DOI=10.1073/pnas.131022798;
RA Carson D.R., Christman M.F.;
RT "Evidence that replication fork components catalyze establishment of
RT cohesion between sister chromatids.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8270-8275(2001).
RN [10]
RP ABSENCE OF FUNCTION IN HISTONE MRNA DEGRADATION ACTIVITY.
RX PubMed=18172165; DOI=10.1101/gad.1622708;
RA Mullen T.E., Marzluff W.F.;
RT "Degradation of histone mRNA requires oligouridylation followed by
RT decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to
RT 5'.";
RL Genes Dev. 22:50-65(2008).
RN [11]
RP REVIEW ON RNA EXOSOMES.
RX PubMed=22817747; DOI=10.1042/bst20120061;
RA Sloan K.E., Schneider C., Watkins N.J.;
RT "Comparison of the yeast and human nuclear exosome complexes.";
RL Biochem. Soc. Trans. 40:850-855(2012).
RN [12]
RP FUNCTION.
RX PubMed=30026317; DOI=10.1126/science.aam5794;
RA Lim J., Kim D., Lee Y.S., Ha M., Lee M., Yeo J., Chang H., Song J., Ahn K.,
RA Kim V.N.;
RT "Mixed tailing by TENT4A and TENT4B shields mRNA from rapid
RT deadenylation.";
RL Science 361:701-704(2018).
CC -!- FUNCTION: Terminal nucleotidyltransferase that catalyzes preferentially
CC the transfert of ATP and GTP on RNA 3' poly(A) tail creating a
CC heterogeneous 3' poly(A) tail leading to mRNAs stabilization by
CC protecting mRNAs from active deadenylation (PubMed:23376078,
CC PubMed:30026317). Also functions as a catalytic subunit of a TRAMP-like
CC complex which has a poly(A) RNA polymerase activity and is involved in
CC a post-transcriptional quality control mechanism. Polyadenylation with
CC short oligo(A) tails is required for the degradative activity of the
CC exosome on several of its nuclear RNA substrates. Has no terminal
CC uridylyltransferase activity, and does not play a role in replication-
CC dependent histone mRNA degradation via uridylation (PubMed:23376078).
CC {ECO:0000269|PubMed:23376078, ECO:0000269|PubMed:30026317}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + RNA(n) = diphosphate + RNA(n)-3'-adenine ribonucleotide;
CC Xref=Rhea:RHEA:11332, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17347,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:140395,
CC ChEBI:CHEBI:173115; EC=2.7.7.19;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- SUBUNIT: Component of a nuclear TRAMP-like complex, an ATP-dependent
CC exosome regulatory complex consisting of a helicase (MTREX), an
CC oligadenylate polymerase (TENT4B or TENT4A), and a substrate specific
CC RNA-binding factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes
CC exist with specific compositions and are associated with nuclear, or
CC nucleolar RNA exosomes.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23376078}. Nucleus,
CC nucleoplasm {ECO:0000269|PubMed:23376078}. Note=Excluded from
CC nucleolus, weak staining detected in the cytoplasm.
CC {ECO:0000269|PubMed:23376078}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=l;
CC IsoId=Q5XG87-1; Sequence=Displayed;
CC Name=2; Synonyms=s;
CC IsoId=Q5XG87-2; Sequence=VSP_053732;
CC -!- MISCELLANEOUS: [Isoform 2]: Exhibits poor nucleotidyl transferase
CC activity. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the DNA polymerase type-B-like family.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to have DNA polymerase activity.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD45198.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/pols/";
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DR EMBL; AF089896; AAD45198.1; ALT_SEQ; mRNA.
DR EMBL; KC424495; AGE92663.1; -; mRNA.
DR EMBL; AB005754; BAA24434.2; -; mRNA.
DR EMBL; AY623114; AAT38110.1; -; Genomic_DNA.
DR EMBL; AK289857; BAF82546.1; -; mRNA.
DR EMBL; CH471102; EAX08101.1; -; Genomic_DNA.
DR EMBL; BC084567; AAH84567.2; -; mRNA.
DR EMBL; BC117137; AAI17138.1; -; mRNA.
DR EMBL; BC126106; AAI26107.1; -; mRNA.
DR RefSeq; NP_001165276.1; NM_001171805.1.
DR RefSeq; NP_001165277.1; NM_001171806.1.
DR RefSeq; NP_008930.1; NM_006999.4.
DR AlphaFoldDB; Q5XG87; -.
DR SMR; Q5XG87; -.
DR BioGRID; 116232; 9.
DR IntAct; Q5XG87; 4.
DR MINT; Q5XG87; -.
DR STRING; 9606.ENSP00000230859; -.
DR ChEMBL; CHEMBL4680033; -.
DR GlyGen; Q5XG87; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5XG87; -.
DR PhosphoSitePlus; Q5XG87; -.
DR BioMuta; PAPD7; -.
DR DMDM; 60392922; -.
DR EPD; Q5XG87; -.
DR jPOST; Q5XG87; -.
DR MassIVE; Q5XG87; -.
DR MaxQB; Q5XG87; -.
DR PaxDb; Q5XG87; -.
DR PeptideAtlas; Q5XG87; -.
DR PRIDE; Q5XG87; -.
DR ProteomicsDB; 65815; -. [Q5XG87-1]
DR Antibodypedia; 22404; 156 antibodies from 22 providers.
DR DNASU; 11044; -.
DR Ensembl; ENST00000631941.2; ENSP00000488642.1; ENSG00000112941.14. [Q5XG87-2]
DR GeneID; 11044; -.
DR KEGG; hsa:11044; -.
DR UCSC; uc003jdx.1; human. [Q5XG87-1]
DR CTD; 11044; -.
DR DisGeNET; 11044; -.
DR GeneCards; TENT4A; -.
DR HGNC; HGNC:16705; TENT4A.
DR HPA; ENSG00000112941; Low tissue specificity.
DR MIM; 605198; gene.
DR neXtProt; NX_Q5XG87; -.
DR OpenTargets; ENSG00000112941; -.
DR PharmGKB; PA33523; -.
DR VEuPathDB; HostDB:ENSG00000112941; -.
DR eggNOG; KOG1906; Eukaryota.
DR GeneTree; ENSGT00940000157811; -.
DR HOGENOM; CLU_013572_3_0_1; -.
DR InParanoid; Q5XG87; -.
DR TreeFam; TF313939; -.
DR BRENDA; 2.7.7.19; 2681.
DR PathwayCommons; Q5XG87; -.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR SignaLink; Q5XG87; -.
DR BioGRID-ORCS; 11044; 10 hits in 1083 CRISPR screens.
DR ChiTaRS; PAPD7; human.
DR GenomeRNAi; 11044; -.
DR Pharos; Q5XG87; Tbio.
DR PRO; PR:Q5XG87; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q5XG87; protein.
DR Bgee; ENSG00000112941; Expressed in secondary oocyte and 198 other tissues.
DR ExpressionAtlas; Q5XG87; baseline and differential.
DR Genevisible; Q5XG87; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031499; C:TRAMP complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0070568; F:guanylyltransferase activity; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004652; F:polynucleotide adenylyltransferase activity; IBA:GO_Central.
DR GO; GO:0043221; F:SMC family protein binding; TAS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; NAS:UniProtKB.
DR GO; GO:0007076; P:mitotic chromosome condensation; NAS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0060212; P:negative regulation of nuclear-transcribed mRNA poly(A) tail shortening; IMP:UniProtKB.
DR GO; GO:1905870; P:positive regulation of 3'-UTR-mediated mRNA stabilization; IMP:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:UniProtKB.
DR GO; GO:0071076; P:RNA 3' uridylation; IMP:UniProtKB.
DR GO; GO:0031123; P:RNA 3'-end processing; IBA:GO_Central.
DR GO; GO:0043631; P:RNA polyadenylation; IEA:InterPro.
DR GO; GO:0007062; P:sister chromatid cohesion; TAS:UniProtKB.
DR Gene3D; 3.30.460.10; -; 1.
DR InterPro; IPR043519; NT_sf.
DR InterPro; IPR002058; PAP_assoc.
DR InterPro; IPR002934; Polymerase_NTP_transf_dom.
DR InterPro; IPR040137; TENT4A.
DR InterPro; IPR045862; Trf4-like.
DR PANTHER; PTHR23092; PTHR23092; 1.
DR PANTHER; PTHR23092:SF24; PTHR23092:SF24; 1.
DR Pfam; PF01909; NTP_transf_2; 1.
DR Pfam; PF03828; PAP_assoc; 1.
DR SUPFAM; SSF81301; SSF81301; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Magnesium; Manganese;
KW Metal-binding; mRNA processing; Nucleotide-binding; Nucleotidyltransferase;
KW Nucleus; Reference proteome; Transferase.
FT CHAIN 1..772
FT /note="Terminal nucleotidyltransferase 4A"
FT /id="PRO_0000120308"
FT DOMAIN 408..468
FT /note="PAP-associated"
FT REGION 35..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 581..612
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 717..772
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..63
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 84..119
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 277
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 279
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..230
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10066793,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|Ref.3"
FT /id="VSP_053732"
FT VARIANT 556
FT /note="N -> S (in dbSNP:rs28381415)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021175"
FT VARIANT 626
FT /note="G -> S (in dbSNP:rs28381418)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021176"
FT MUTAGEN 167..230
FT /note="Missing: Localizes to cytoplasm."
FT /evidence="ECO:0000269|PubMed:23376078"
SQ SEQUENCE 772 AA; 82360 MW; A5EBEC15CA37689C CRC64;
MQIWETSQGV GRGGSGFASY FCLNSPALDT AAAAGAAGRG SGGLGPALPA ASPPPPGPTA
PAALPPALLT ALGPAAEGAR RLHKSPSLSS SSSSSSSNAE SGTESPGCSS SSSSSASLGR
PGGGRGGAFF NFADGAPSAP GTANGHPGPR GPAPAGSPSQ HQFHPGRRKR ENKASTYGLN
YLLSGSRAAA LSGGGGPGAQ APRPGTPWKS RAYSPGIQGL HEEIIDFYNF MSPCPEEAAM
RREVVKRIET VVKDLWPTAD VQIFGSFSTG LYLPTSDIDL VVFGKWERPP LQLLEQALRK
HNVAEPCSIK VLDKATVPII KLTDQETEVK VDISFNMETG VRAAEFIKNY MKKYSLLPYL
ILVLKQFLLQ RDLNEVFTGG ISSYSLILMA ISFLQLHPRI DARRADENLG MLLVEFFELY
GRNFNYLKTG IRIKEGGAYI AKEEIMKAMT SGYRPSMLCI EDPLLPGNDV GRSSYGAMQV
KQVFDYAYIV LSHAVSPLAR SYPNRDAEST LGRIIKVTQE VIDYRRWIKE KWGSKAHPSP
GMDSRIKIKE RIATCNGEQT QNREPESPYG QRLTLSLSSP QLLSSGSSAS SVSSLSGSDV
DSDTPPCTTP SVYQFSLQAP APLMAGLPTA LPMPSGKPQP TTSRTLIMTT NNQTRFTIPP
PTLGVAPVPC RQAGVEGTAS LKAVHHMSSP AIPSASPNPL SSPHLYHKQH NGMKLSMKGS
HGHTQGGGYS SVGSGGVRPP VGNRGHHQYN RTGWRRKKHT HTRDSLPVSL SR
