ID GLD2_HUMAN Reviewed; 484 AA. AC Q6PIY7; Q86WZ2; Q8N927; DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 27-MAR-2024, entry version 139. DE RecName: Full=Poly(A) RNA polymerase GLD2 {ECO:0000305}; DE Short=hGLD-2 {ECO:0000305}; DE EC=2.7.7.19 {ECO:0000269|PubMed:15070731, ECO:0000269|PubMed:23200856, ECO:0000269|PubMed:31792053}; DE AltName: Full=PAP-associated domain-containing protein 4; DE AltName: Full=Terminal nucleotidyltransferase 2 {ECO:0000312|HGNC:HGNC:26776}; DE AltName: Full=Terminal uridylyltransferase 2; DE Short=TUTase 2; GN Name=TENT2 {ECO:0000312|HGNC:HGNC:26776}; GN Synonyms=GLD2 {ECO:0000312|HGNC:HGNC:26776}, PAPD4 GN {ECO:0000312|HGNC:HGNC:26776}; 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] (ISOFORM 1). RC TISSUE=Smooth muscle; 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]. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Pancreas; 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 ENZYME ACTIVITY. RX PubMed=15070731; DOI=10.1073/pnas.0400779101; RA Kwak J.E., Wang L., Ballantyne S., Kimble J., Wickens M.; RT "Mammalian GLD-2 homologs are poly(A) polymerases."; RL Proc. Natl. Acad. Sci. U.S.A. 101:4407-4412(2004). RN [5] RP TISSUE SPECIFICITY. RX PubMed=15987818; DOI=10.1261/rna.2630205; RA Rouhana L., Wang L., Buter N., Kwak J.E., Schiltz C.A., Gonzalez T., RA Kelley A.E., Landry C.F., Wickens M.; RT "Vertebrate GLD2 poly(A) polymerases in the germline and the brain."; RL RNA 11:1117-1130(2005). RN [6] 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-69, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [9] RP FUNCTION, MUTAGENESIS OF ASP-215, AND CATALYTIC ACTIVITY. RX PubMed=23200856; DOI=10.1016/j.celrep.2012.10.023; RA D'Ambrogio A., Gu W., Udagawa T., Mello C.C., Richter J.D.; RT "Specific miRNA stabilization by Gld2-catalyzed monoadenylation."; RL Cell Rep. 2:1537-1545(2012). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [11] RP FUNCTION, AND INTERACTION WITH QKI. RX PubMed=31792053; DOI=10.1074/jbc.ra119.011617; RA Hojo H., Yashiro Y., Noda Y., Ogami K., Yamagishi R., Okada S., RA Hoshino S.I., Suzuki T.; RT "The RNA-binding protein QKI-7 recruits the poly(A) polymerase GLD-2 for 3' RT adenylation and selective stabilization of microRNA-122."; RL J. Biol. Chem. 295:390-402(2020). CC -!- FUNCTION: Cytoplasmic poly(A) RNA polymerase that adds successive AMP CC monomers to the 3'-end of specific RNAs, forming a poly(A) tail CC (PubMed:15070731, PubMed:31792053). In contrast to the canonical CC nuclear poly(A) RNA polymerase, it only adds poly(A) to selected CC cytoplasmic mRNAs (PubMed:15070731). Does not play a role in CC replication-dependent histone mRNA degradation (PubMed:18172165). Adds CC a single nucleotide to the 3' end of specific miRNAs, monoadenylation CC stabilizes and prolongs the activity of some but not all miRNAs CC (PubMed:23200856, PubMed:31792053). {ECO:0000269|PubMed:15070731, CC ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:23200856, CC ECO:0000269|PubMed:31792053}. 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 Evidence={ECO:0000269|PubMed:15070731, ECO:0000269|PubMed:23200856, CC ECO:0000269|PubMed:31792053}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:O13833}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:O13833}; CC -!- SUBUNIT: Interacts with CPEB1, CPEB2, CPSF1 and PABPC1 (By similarity). CC Interacts with QKI isoform QKI7; promoting recruitment to miRNA miR-122 CC and miR-122 stabilization (PubMed:31792053). CC {ECO:0000250|UniProtKB:Q91YI6, ECO:0000269|PubMed:31792053}. CC -!- INTERACTION: CC Q6PIY7; A2RRN7: CADPS; NbExp=3; IntAct=EBI-2802204, EBI-10179719; CC Q6PIY7; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-2802204, EBI-739580; CC Q6PIY7; Q86UW9: DTX2; NbExp=3; IntAct=EBI-2802204, EBI-740376; CC Q6PIY7; Q93062: RBPMS; NbExp=3; IntAct=EBI-2802204, EBI-740322; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q91YI6}. Nucleus CC {ECO:0000250|UniProtKB:Q91YI6}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q6PIY7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6PIY7-2; Sequence=VSP_034324; CC -!- TISSUE SPECIFICITY: Expressed in brain. Within brain, it is expressed CC in cerebellum, hippocampus and medulla. {ECO:0000269|PubMed:15987818}. CC -!- SIMILARITY: Belongs to the DNA polymerase type-B-like family. GLD2 CC subfamily. {ECO:0000305}. 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; AK095818; BAC04629.1; -; mRNA. DR EMBL; CH471084; EAW95837.1; -; Genomic_DNA. DR EMBL; BC026061; AAH26061.1; -; mRNA. DR EMBL; BC047581; AAH47581.1; -; mRNA. DR CCDS; CCDS4048.1; -. [Q6PIY7-1] DR CCDS; CCDS75266.1; -. [Q6PIY7-2] DR RefSeq; NP_001107865.1; NM_001114393.1. [Q6PIY7-1] DR RefSeq; NP_001107866.1; NM_001114394.1. [Q6PIY7-1] DR RefSeq; NP_001284673.1; NM_001297744.1. [Q6PIY7-2] DR RefSeq; NP_776158.2; NM_173797.3. [Q6PIY7-1] DR RefSeq; XP_016864642.1; XM_017009153.1. DR RefSeq; XP_016864643.1; XM_017009154.1. DR RefSeq; XP_016864644.1; XM_017009155.1. DR RefSeq; XP_016864645.1; XM_017009156.1. DR RefSeq; XP_016864646.1; XM_017009157.1. DR RefSeq; XP_016864647.1; XM_017009158.1. DR RefSeq; XP_016864648.1; XM_017009159.1. DR RefSeq; XP_016864649.1; XM_017009160.1. DR AlphaFoldDB; Q6PIY7; -. DR SMR; Q6PIY7; -. DR BioGRID; 127943; 43. DR IntAct; Q6PIY7; 9. DR MINT; Q6PIY7; -. DR STRING; 9606.ENSP00000397563; -. DR iPTMnet; Q6PIY7; -. DR PhosphoSitePlus; Q6PIY7; -. DR BioMuta; PAPD4; -. DR DMDM; 74737798; -. DR EPD; Q6PIY7; -. DR jPOST; Q6PIY7; -. DR MassIVE; Q6PIY7; -. DR MaxQB; Q6PIY7; -. DR PaxDb; 9606-ENSP00000397563; -. DR PeptideAtlas; Q6PIY7; -. DR ProteomicsDB; 67187; -. [Q6PIY7-1] DR ProteomicsDB; 67188; -. [Q6PIY7-2] DR Pumba; Q6PIY7; -. DR Antibodypedia; 24569; 127 antibodies from 20 providers. DR DNASU; 167153; -. DR Ensembl; ENST00000296783.7; ENSP00000296783.3; ENSG00000164329.15. [Q6PIY7-1] DR Ensembl; ENST00000423041.6; ENSP00000393412.2; ENSG00000164329.15. [Q6PIY7-2] DR Ensembl; ENST00000453514.6; ENSP00000397563.1; ENSG00000164329.15. [Q6PIY7-1] DR GeneID; 167153; -. DR KEGG; hsa:167153; -. DR MANE-Select; ENST00000453514.6; ENSP00000397563.1; NM_001114394.3; NP_001107866.1. DR UCSC; uc003kga.3; human. [Q6PIY7-1] DR AGR; HGNC:26776; -. DR CTD; 167153; -. DR DisGeNET; 167153; -. DR GeneCards; TENT2; -. DR HGNC; HGNC:26776; TENT2. DR HPA; ENSG00000164329; Low tissue specificity. DR MIM; 614121; gene. DR neXtProt; NX_Q6PIY7; -. DR OpenTargets; ENSG00000164329; -. DR PharmGKB; PA134918975; -. DR VEuPathDB; HostDB:ENSG00000164329; -. DR eggNOG; KOG2277; Eukaryota. DR GeneTree; ENSGT00940000156640; -. DR HOGENOM; CLU_046147_0_0_1; -. DR InParanoid; Q6PIY7; -. DR OMA; RTYAYAD; -. DR OrthoDB; 1080369at2759; -. DR PhylomeDB; Q6PIY7; -. DR TreeFam; TF315661; -. DR BRENDA; 2.7.7.19; 2681. DR PathwayCommons; Q6PIY7; -. DR SignaLink; Q6PIY7; -. DR SIGNOR; Q6PIY7; -. DR BioGRID-ORCS; 167153; 13 hits in 1153 CRISPR screens. DR ChiTaRS; TENT2; human. DR GenomeRNAi; 167153; -. DR Pharos; Q6PIY7; Tbio. DR PRO; PR:Q6PIY7; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q6PIY7; Protein. DR Bgee; ENSG00000164329; Expressed in calcaneal tendon and 183 other cell types or tissues. DR ExpressionAtlas; Q6PIY7; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0031380; C:nuclear RNA-directed RNA polymerase complex; IC:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:1990817; F:poly(A) RNA polymerase activity; IDA:UniProtKB. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl. DR GO; GO:0071044; P:histone mRNA catabolic process; IMP:UniProtKB. DR GO; GO:0031124; P:mRNA 3'-end processing; IDA:UniProtKB. DR GO; GO:0006378; P:mRNA polyadenylation; IBA:GO_Central. DR GO; GO:2000626; P:negative regulation of miRNA catabolic process; IDA:UniProtKB. DR CDD; cd05402; NT_PAP_TUTase; 1. DR Gene3D; 1.10.1410.10; -; 1. DR Gene3D; 3.30.460.10; Beta Polymerase, domain 2; 1. DR InterPro; IPR043519; NT_sf. DR InterPro; IPR002058; PAP_assoc. DR PANTHER; PTHR12271; POLY A POLYMERASE CID PAP -RELATED; 1. DR PANTHER; PTHR12271:SF40; POLY(A) RNA POLYMERASE GLD2; 1. DR Pfam; PF03828; PAP_assoc; 1. DR SUPFAM; SSF81301; Nucleotidyltransferase; 1. DR SUPFAM; SSF81631; PAP/OAS1 substrate-binding domain; 1. DR Genevisible; Q6PIY7; HS. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Cytoplasm; Magnesium; Manganese; KW Metal-binding; mRNA processing; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Transferase. FT CHAIN 1..484 FT /note="Poly(A) RNA polymerase GLD2" FT /id="PRO_0000341549" FT DOMAIN 386..440 FT /note="PAP-associated" FT REGION 72..97 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 76..92 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 74..96 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 213 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:O13833" FT BINDING 215 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:O13833" FT MOD_RES 62 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 69 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 95 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 225..228 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_034324" FT MUTAGEN 215 FT /note="D->A: Catalytically inactive." FT /evidence="ECO:0000269|PubMed:23200856" FT CONFLICT 9 FT /note="R -> H (in Ref. 1; BAC04629)" FT /evidence="ECO:0000305" SQ SEQUENCE 484 AA; 56028 MW; 26167D53ABDA979D CRC64; MFPNSILGRP PFTPNHQQHN NFFTLSPTVY SHQQLIDAQF NFQNADLSRA VSLQQLTYGN VSPIQTSASP LFRGRKRLSD EKNLPLDGKR QRFHSPHQEP TVVNQIVPLS GERRYSMPPL FHTHYVPDIV RCVPPFREIA FLEPREITLP EAKDKLSQQI LELFETCQQQ ISDLKKKELC RTQLQREIQL LFPQSRLFLV GSSLNGFGTR SSDGDLCLVV KEEPCFFQVN QKTEARHILT LVHKHFCTRL SGYIERPQLI RAKVPIVKFR DKVSCVEFDL NVNNIVGIRN TFLLRTYAYL ENRVRPLVLV IKKWASHHQI NDASRGTLSS YSLVLMVLHY LQTLPEPILP SLQKIYPESF SPAIQLHLVH QAPCNVPPYL SKNESNLGDL LLGFLKYYAT EFDWNSQMIS VREAKAIPRP DGIEWRNKYI CVEEPFDGTN TARAVHEKQK FDMIKDQFLK SWHRLKNKRD LNSILPVRAA VLKR //