TET5C_HUMAN
ID TET5C_HUMAN Reviewed; 391 AA.
AC Q5VWP2; A3KMG2; Q8NE25; Q9NXK0;
DT 14-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Terminal nucleotidyltransferase 5C {ECO:0000305};
DE EC=2.7.7.19 {ECO:0000269|PubMed:28931820, ECO:0000269|PubMed:32009146};
DE AltName: Full=Non-canonical poly(A) polymerase FAM46C {ECO:0000303|PubMed:28931820};
GN Name=TENT5C {ECO:0000312|HGNC:HGNC:24712};
GN Synonyms=FAM46C {ECO:0000312|HGNC:HGNC:24712};
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].
RC TISSUE=Colon mucosa;
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].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 FUNCTION (MICROBIAL INFECTION), AND INDUCTION.
RX PubMed=21478870; DOI=10.1038/nature09907;
RA Schoggins J.W., Wilson S.J., Panis M., Murphy M.Y., Jones C.T.,
RA Bieniasz P., Rice C.M.;
RT "A diverse range of gene products are effectors of the type I interferon
RT antiviral response.";
RL Nature 472:481-485(2011).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, RNA-BINDING, INTERACTION WITH BCCIP AND
RP PABPC1, MUTAGENESIS OF 90-ASP--ASP-92, AND CATALYTIC ACTIVITY.
RX PubMed=28931820; DOI=10.1038/s41467-017-00578-5;
RA Mroczek S., Chlebowska J., Kulinski T.M., Gewartowska O., Gruchota J.,
RA Cysewski D., Liudkovska V., Borsuk E., Nowis D., Dziembowski A.;
RT "The non-canonical poly(A) polymerase FAM46C acts as an onco-suppressor in
RT multiple myeloma.";
RL Nat. Commun. 8:619-619(2017).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=32009146; DOI=10.1093/nar/gkaa049;
RA Hu J.L., Liang H., Zhang H., Yang M.Z., Sun W., Zhang P., Luo L.,
RA Feng J.X., Bai H., Liu F., Zhang T., Yang J.Y., Gao Q., Long Y., Ma X.Y.,
RA Chen Y., Zhong Q., Yu B., Liao S., Wang Y., Zhao Y., Zeng M.S., Cao N.,
RA Wang J., Chen W., Yang H.T., Gao S.;
RT "FAM46B is a prokaryotic-like cytoplasmic poly(A) polymerase essential in
RT human embryonic stem cells.";
RL Nucleic Acids Res. 48:2733-2748(2020).
RN [7]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=34048638; DOI=10.1002/cac2.12163;
RA Zhang H., Zhang S.H., Hu J.L., Wu Y.T., Ma X.Y., Chen Y., Yu B., Liao S.,
RA Huang H., Gao S.;
RT "Structural and functional characterization of multiple myeloma associated
RT cytoplasmic poly(A) polymerase FAM46C.";
RL Cancer Commun. (Lond) 41:615-630(2021).
RN [8] {ECO:0007744|PDB:6W36, ECO:0007744|PDB:6W38, ECO:0007744|PDB:6W3I, ECO:0007744|PDB:6W3J}
RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 14-358 IN COMPLEXES WITH PLK4 AND
RP CEP192, INTERACTION WITH PLK4, MUTAGENESIS OF LYS-144; CYS-146; GLU-166;
RP CYS-320 AND LEU-321, AND SUBCELLULAR LOCATION.
RX PubMed=32433990; DOI=10.1016/j.str.2020.04.023;
RA Chen H., Lu D., Shang G., Gao G., Zhang X.;
RT "Structural and Functional Analyses of the FAM46C/Plk4 Complex.";
RL Structure 28:910-921.e4(2020).
CC -!- FUNCTION: Catalyzes the transfer of one adenosine molecule from an ATP
CC to an mRNA poly(A) tail bearing a 3'-OH terminal group and enhances
CC mRNA stability and gene expression (PubMed:32009146, PubMed:28931820,
CC PubMed:34048638). Can also elongate RNA oligos ending with uridine
CC molecule, provided that the sequence is adenosine-rich
CC (PubMed:34048638). Mainly targets mRNAs encoding endoplasmic reticulum-
CC targeted protein (PubMed:28931820). {ECO:0000269|PubMed:28931820,
CC ECO:0000269|PubMed:32009146, ECO:0000269|PubMed:34048638}.
CC -!- FUNCTION: (Microbial infection) Seems to enhance replication of some
CC viruses, including yellow fever virus, in response to type I
CC interferon. {ECO:0000269|PubMed:21478870}.
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:28931820, ECO:0000269|PubMed:32009146,
CC ECO:0000269|PubMed:34048638};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11333;
CC Evidence={ECO:0000305|PubMed:34048638};
CC -!- SUBUNIT: Interacts with BCCIP and PABPC1; the interaction has no effect
CC on TENT5C poly(A) polymerase function (PubMed:28931820). Interacts with
CC PLK4; this interaction leads to the TENT5C recruitment into the
CC centrosome (PubMed:32433990). {ECO:0000269|PubMed:28931820,
CC ECO:0000269|PubMed:32433990}.
CC -!- INTERACTION:
CC Q5VWP2; Q9BQY4: RHOXF2; NbExp=3; IntAct=EBI-741787, EBI-372094;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28931820}. Cytoplasm
CC {ECO:0000269|PubMed:28931820}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:32433990}.
CC Note=Recruited into the centrosome through its interaction with PLK4.
CC {ECO:0000269|PubMed:32433990}.
CC -!- INDUCTION: By type I interferons. {ECO:0000269|PubMed:21478870}.
CC -!- SIMILARITY: Belongs to the TENT family. {ECO:0000305}.
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DR EMBL; AK000209; BAA91010.1; -; mRNA.
DR EMBL; AL365331; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036516; AAH36516.3; -; mRNA.
DR EMBL; BC131726; AAI31727.1; -; mRNA.
DR CCDS; CCDS896.1; -.
DR RefSeq; NP_060179.2; NM_017709.3.
DR PDB; 6W36; X-ray; 2.85 A; A=14-358.
DR PDB; 6W38; X-ray; 4.48 A; A=14-358.
DR PDB; 6W3I; X-ray; 3.80 A; A=14-358.
DR PDB; 6W3J; X-ray; 4.38 A; A=14-358.
DR PDBsum; 6W36; -.
DR PDBsum; 6W38; -.
DR PDBsum; 6W3I; -.
DR PDBsum; 6W3J; -.
DR AlphaFoldDB; Q5VWP2; -.
DR SMR; Q5VWP2; -.
DR BioGRID; 120205; 11.
DR IntAct; Q5VWP2; 9.
DR STRING; 9606.ENSP00000358458; -.
DR iPTMnet; Q5VWP2; -.
DR PhosphoSitePlus; Q5VWP2; -.
DR BioMuta; FAM46C; -.
DR DMDM; 117940143; -.
DR jPOST; Q5VWP2; -.
DR MassIVE; Q5VWP2; -.
DR PaxDb; Q5VWP2; -.
DR PeptideAtlas; Q5VWP2; -.
DR PRIDE; Q5VWP2; -.
DR ProteomicsDB; 65547; -.
DR Antibodypedia; 33893; 111 antibodies from 20 providers.
DR DNASU; 54855; -.
DR Ensembl; ENST00000369448.4; ENSP00000358458.3; ENSG00000183508.5.
DR GeneID; 54855; -.
DR KEGG; hsa:54855; -.
DR MANE-Select; ENST00000369448.4; ENSP00000358458.3; NM_017709.4; NP_060179.2.
DR UCSC; uc001ehe.4; human.
DR CTD; 54855; -.
DR DisGeNET; 54855; -.
DR GeneCards; TENT5C; -.
DR HGNC; HGNC:24712; TENT5C.
DR HPA; ENSG00000183508; Tissue enhanced (bone).
DR MIM; 613952; gene.
DR neXtProt; NX_Q5VWP2; -.
DR OpenTargets; ENSG00000183508; -.
DR PharmGKB; PA134955264; -.
DR VEuPathDB; HostDB:ENSG00000183508; -.
DR eggNOG; KOG3852; Eukaryota.
DR GeneTree; ENSGT00940000158856; -.
DR HOGENOM; CLU_008115_2_0_1; -.
DR InParanoid; Q5VWP2; -.
DR OMA; NTRDCMS; -.
DR OrthoDB; 612201at2759; -.
DR PhylomeDB; Q5VWP2; -.
DR TreeFam; TF315239; -.
DR BRENDA; 2.7.7.19; 2681.
DR PathwayCommons; Q5VWP2; -.
DR SignaLink; Q5VWP2; -.
DR BioGRID-ORCS; 54855; 10 hits in 1078 CRISPR screens.
DR GenomeRNAi; 54855; -.
DR Pharos; Q5VWP2; Tbio.
DR PRO; PR:Q5VWP2; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5VWP2; protein.
DR Bgee; ENSG00000183508; Expressed in secondary oocyte and 176 other tissues.
DR Genevisible; Q5VWP2; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004652; F:polynucleotide adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:1990817; F:RNA adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0048255; P:mRNA stabilization; IDA:UniProtKB.
DR GO; GO:0045596; P:negative regulation of cell differentiation; IMP:UniProtKB.
DR InterPro; IPR012937; TET5.
DR PANTHER; PTHR12974; PTHR12974; 1.
DR Pfam; PF07984; NTP_transf_7; 1.
DR SMART; SM01153; DUF1693; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Cytoskeleton; Host-virus interaction;
KW Nucleotidyltransferase; Nucleus; Reference proteome; RNA-binding;
KW Transferase.
FT CHAIN 1..391
FT /note="Terminal nucleotidyltransferase 5C"
FT /id="PRO_0000259933"
FT VARIANT 67
FT /note="H -> Q (in dbSNP:rs1630312)"
FT /id="VAR_060132"
FT MUTAGEN 90..92
FT /note="DLD->ALA: Loss of poly(a) polymerase activity."
FT /evidence="ECO:0000269|PubMed:28931820"
FT MUTAGEN 144
FT /note="K->P: Decreases substantially the interaction with
FT PLK4. Weakens binding to PLK4; when associated with E-230
FT and E-321. Abolishes the inhibitory effect of TENT5C on the
FT cell viability; when associated with E-320 and E-321."
FT /evidence="ECO:0000269|PubMed:32433990"
FT MUTAGEN 146
FT /note="C->P: Decreases substantially the interaction with
FT PLK4. Weakens binding to PLK4; when associated with E-230
FT and E-321."
FT /evidence="ECO:0000269|PubMed:32433990"
FT MUTAGEN 166
FT /note="E->Q: Does not affect colocalization with PLK4 in
FT centrosome. Increases cell viability."
FT /evidence="ECO:0000269|PubMed:32433990"
FT MUTAGEN 320
FT /note="C->E: Slightly decreases the binding to PLK4; when
FT associated with E-321. Abolishes the inhibitory effect of
FT TENT5C on the cell viability; when associated with P-144
FT and E-321."
FT /evidence="ECO:0000269|PubMed:32433990"
FT MUTAGEN 321
FT /note="L->E: Slightly decreases the binding to PLK4; when
FT associated with E-320. Abolishes the inhibitory effect of
FT TENT5C on the cell viability; when associated with P-144
FT and E-320."
FT /evidence="ECO:0000269|PubMed:32433990"
FT CONFLICT 150
FT /note="D -> V (in Ref. 1; BAA91010)"
FT /evidence="ECO:0000305"
FT HELIX 19..29
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 48..62
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 73..80
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 102..116
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 131..138
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 139..149
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 151..157
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 164..172
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 189..196
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 211..217
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 219..227
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 243..252
FT /evidence="ECO:0007829|PDB:6W36"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 260..277
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 281..295
FT /evidence="ECO:0007829|PDB:6W36"
FT TURN 296..298
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 300..317
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:6W36"
FT HELIX 323..340
FT /evidence="ECO:0007829|PDB:6W36"
SQ SEQUENCE 391 AA; 44944 MW; 1B73C6688284F8AC CRC64;
MAEESSCTRD CMSFSVLNWD QVSRLHEVLT EVVPIHGRGN FPTLEITLKD IVQTVRSRLE
EAGIKVHDVR LNGSAAGHVL VKDNGLGCKD LDLIFHVALP TEAEFQLVRD VVLCSLLNFL
PEGVNKLKIS PVTLKEAYVQ KLVKVCTDTD RWSLISLSNK NGKNVELKFV DSIRRQFEFS
VDSFQIILDS LLFFYDCSNN PISEHFHPTV IGESMYGDFE EAFDHLQNRL IATKNPEEIR
GGGLLKYSNL LVRDFRPTDQ EEIKTLERYM CSRFFIDFPD ILEQQRKLET YLQNHFAEEE
RSKYDYLMIL RRVVNESTVC LMGHERRQTL NLISLLALRV LAEQNIIPSA TNVTCYYQPA
PYVSDGNFSN YYVAHPPVTY SQPYPTWLPC N
