GLD2_HUMAN
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 03-AUG-2022, entry version 130.
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};
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},
GN PAPD4 {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).
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. In
CC contrast to the canonical nuclear poly(A) RNA polymerase, it only adds
CC poly(A) to selected cytoplasmic mRNAs (PubMed:15070731). Does not play
CC a role in replication-dependent histone mRNA degradation
CC (PubMed:18172165). Adds a single nucleotide to the 3' end of specific
CC miRNAs, monoadenylation stabilizes and prolongs the activity of some
CC but not all miRNAs (PubMed:23200856). {ECO:0000269|PubMed:15070731,
CC ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:23200856}.
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 -!- 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: Interacts with CPEB1, CPEB2, CPSF1 and PABPC1.
CC {ECO:0000250|UniProtKB:Q91YI6}.
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}.
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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. [Q6PIY7-1]
DR RefSeq; XP_016864645.1; XM_017009156.1. [Q6PIY7-1]
DR RefSeq; XP_016864646.1; XM_017009157.1. [Q6PIY7-2]
DR RefSeq; XP_016864647.1; XM_017009158.1.
DR RefSeq; XP_016864648.1; XM_017009159.1. [Q6PIY7-2]
DR RefSeq; XP_016864649.1; XM_017009160.1. [Q6PIY7-2]
DR AlphaFoldDB; Q6PIY7; -.
DR SMR; Q6PIY7; -.
DR BioGRID; 127943; 41.
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; Q6PIY7; -.
DR PeptideAtlas; Q6PIY7; -.
DR PRIDE; Q6PIY7; -.
DR ProteomicsDB; 67187; -. [Q6PIY7-1]
DR ProteomicsDB; 67188; -. [Q6PIY7-2]
DR Antibodypedia; 24569; 108 antibodies from 20 providers.
DR DNASU; 167153; -.
DR Ensembl; ENST00000296783.7; ENSP00000296783.3; ENSG00000164329.14. [Q6PIY7-1]
DR Ensembl; ENST00000423041.6; ENSP00000393412.2; ENSG00000164329.14. [Q6PIY7-2]
DR Ensembl; ENST00000428308.6; ENSP00000396861.2; ENSG00000164329.14. [Q6PIY7-1]
DR Ensembl; ENST00000453514.6; ENSP00000397563.1; ENSG00000164329.14. [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 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; LNRKELC; -.
DR OrthoDB; 803033at2759; -.
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; 10 hits in 1079 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 181 other tissues.
DR ExpressionAtlas; Q6PIY7; baseline and differential.
DR Genevisible; Q6PIY7; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0031380; C:nuclear RNA-directed RNA polymerase complex; IC:UniProtKB.
DR GO; GO:0034062; F:5'-3' RNA polymerase activity; IDA:UniProtKB.
DR GO; GO:0070566; F:adenylyltransferase activity; IDA: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:0016779; F:nucleotidyltransferase activity; IBA:GO_Central.
DR GO; GO:0004652; F:polynucleotide adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:1990603; P:dark adaptation; IEA:Ensembl.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0071044; P:histone mRNA catabolic process; IMP: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 GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR GO; GO:0031123; P:RNA 3'-end processing; IBA:GO_Central.
DR GO; GO:0043631; P:RNA polyadenylation; IDA:UniProtKB.
DR GO; GO:0043489; P:RNA stabilization; IDA:UniProtKB.
DR Gene3D; 3.30.460.10; -; 1.
DR InterPro; IPR043519; NT_sf.
DR InterPro; IPR002058; PAP_assoc.
DR InterPro; IPR045100; TUTase_dom.
DR Pfam; PF03828; PAP_assoc; 1.
DR Pfam; PF19088; TUTase; 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; 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"
FT BINDING 215
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
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
