ID PDE12_HUMAN Reviewed; 609 AA. AC Q6L8Q7; B4DTU8; Q8IYU3; Q8NDU2; Q8TE78; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 18-MAR-2008, sequence version 2. DT 09-DEC-2015, entry version 92. DE RecName: Full=2',5'-phosphodiesterase 12; DE Short=2'-PDE; DE Short=2-PDE; DE EC=3.1.4.-; DE AltName: Full=Mitochondrial deadenylase; DE EC=3.1.13.4; DE Flags: Precursor; GN Name=PDE12; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE RP SPECIFICITY. RX PubMed=15231837; DOI=10.1074/jbc.M400089200; RA Kubota K., Nakahara K., Ohtsuka T., Yoshida S., Kawaguchi J., RA Fujita Y., Ozeki Y., Hara A., Yoshimura C., Furukawa H., Haruyama H., RA Ichikawa K., Yamashita M., Matsuoka T., Iijima Y.; RT "Identification of 2'-phosphodiesterase, which plays a role in the 2- RT 5A system regulated by interferon."; RL J. Biol. Chem. 279:37832-37841(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP TRP-23. RC TISSUE=Placenta; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT TRP-23. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 122-609 (ISOFORM 1). RC TISSUE=Lymph node; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [6] RP IDENTIFICATION BY 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-217, AND IDENTIFICATION RP BY 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=21245038; DOI=10.1093/nar/gkq1282; RA Poulsen J.B., Andersen K.R., Kjaer K.H., Durand F., Faou P., RA Vestergaard A.L., Talbo G.H., Hoogenraad N., Brodersen D.E., RA Justesen J., Martensen P.M.; RT "Human 2'-phosphodiesterase localizes to the mitochondrial matrix with RT a putative function in mitochondrial RNA turnover."; RL Nucleic Acids Res. 39:3754-3770(2011). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=21666256; DOI=10.1093/nar/gkr470; RA Rorbach J., Nicholls T.J., Minczuk M.; RT "PDE12 removes mitochondrial RNA poly(A) tails and controls RT translation in human mitochondria."; RL Nucleic Acids Res. 39:7750-7763(2011). RN [11] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, CATALYTIC ACTIVITY, RP TRANSIT PEPTIDE CLEAVAGE SITE, AND SUBCELLULAR LOCATION. RX PubMed=22285541; DOI=10.1016/j.biochi.2012.01.012; RA Poulsen J.B., Andersen K.R., Kjaer K.H., Vestergaard A.L., RA Justesen J., Martensen P.M.; RT "Characterization of human phosphodiesterase 12 and identification of RT a novel 2'-5' oligoadenylate nuclease - The ectonucleotide RT pyrophosphatase/phosphodiesterase 1."; RL Biochimie 94:1098-1107(2012). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). CC -!- FUNCTION: Enzyme that cleaves 2',5'-phosphodiester bond linking CC adenosines of the 5'-triphosphorylated oligoadenylates, CC triphosphorylated oligoadenylates referred as 2-5A modulates the CC 2-5A system. This enzyme degraded triphosphorylated 2-5A to CC produce AMP and ATP. Also cleaves 3',5'-phosphodiester bond of CC oligoadenylates. Plays a role as a negative regulator of the The CC 2-5A system that is one of the major pathways for antiviral and CC antitumor functions induced by interferons (IFNs). Suppression of CC this enzyme induces reduction of viral replication in Hela cells, CC thus counteracting the antiviral pathway probably by inhibiting CC the 2-5A system. {ECO:0000269|PubMed:15231837, CC ECO:0000269|PubMed:21245038, ECO:0000269|PubMed:21666256, CC ECO:0000269|PubMed:22285541}. CC -!- CATALYTIC ACTIVITY: Exonucleolytic cleavage of poly(A) to 5'-AMP. CC {ECO:0000269|PubMed:21245038, ECO:0000269|PubMed:21666256, CC ECO:0000269|PubMed:22285541}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:22285541}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 8.0 for 2'-5' oligoadenylate exonuclease activity. CC {ECO:0000269|PubMed:22285541}; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000269|PubMed:21245038, ECO:0000269|PubMed:21666256, CC ECO:0000269|PubMed:22285541}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q6L8Q7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6L8Q7-2; Sequence=VSP_032202, VSP_032203; CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:15231837}. CC -!- SIMILARITY: Belongs to the CCR4/nocturin family. {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; AB115695; BAD20938.1; -; mRNA. DR EMBL; AK074423; BAB85079.1; -; mRNA. DR EMBL; AK300374; BAG62110.1; -; mRNA. DR EMBL; CH471055; EAW65342.1; -; Genomic_DNA. DR EMBL; AL831824; CAD38538.1; -; mRNA. DR CCDS; CCDS33772.1; -. [Q6L8Q7-1] DR RefSeq; NP_808881.3; NM_177966.5. [Q6L8Q7-1] DR UniGene; Hs.572993; -. DR PDB; 4Z0V; X-ray; 1.78 A; A=155-609. DR PDB; 4Z2B; X-ray; 1.80 A; A=155-609. DR PDB; 4ZKF; X-ray; 1.82 A; A=154-609. DR PDBsum; 4Z0V; -. DR PDBsum; 4Z2B; -. DR PDBsum; 4ZKF; -. DR ProteinModelPortal; Q6L8Q7; -. DR SMR; Q6L8Q7; 161-609. DR BioGrid; 128397; 23. DR IntAct; Q6L8Q7; 7. DR STRING; 9606.ENSP00000309142; -. DR PhosphoSite; Q6L8Q7; -. DR BioMuta; PDE12; -. DR DMDM; 172046137; -. DR MaxQB; Q6L8Q7; -. DR PaxDb; Q6L8Q7; -. DR PRIDE; Q6L8Q7; -. DR DNASU; 201626; -. DR Ensembl; ENST00000311180; ENSP00000309142; ENSG00000174840. [Q6L8Q7-1] DR GeneID; 201626; -. DR KEGG; hsa:201626; -. DR UCSC; uc003diw.4; human. [Q6L8Q7-1] DR CTD; 201626; -. DR GeneCards; PDE12; -. DR H-InvDB; HIX0003393; -. DR HGNC; HGNC:25386; PDE12. DR HPA; HPA043171; -. DR neXtProt; NX_Q6L8Q7; -. DR PharmGKB; PA162399016; -. DR eggNOG; KOG0620; Eukaryota. DR eggNOG; COG5239; LUCA. DR GeneTree; ENSGT00550000074364; -. DR HOGENOM; HOG000006935; -. DR HOVERGEN; HBG061027; -. DR KO; K19612; -. DR OMA; DSSKRIC; -. DR OrthoDB; EOG7T4MJP; -. DR PhylomeDB; Q6L8Q7; -. DR TreeFam; TF323175; -. DR ChiTaRS; PDE12; human. DR GenomeRNAi; 201626; -. DR NextBio; 90179; -. DR PRO; PR:Q6L8Q7; -. DR Proteomes; UP000005640; Chromosome 3. DR Bgee; Q6L8Q7; -. DR CleanEx; HS_PDE12; -. DR ExpressionAtlas; Q6L8Q7; baseline and differential. DR Genevisible; Q6L8Q7; HS. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; IEA:UniProtKB-EC. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR Gene3D; 3.60.10.10; -; 1. DR InterPro; IPR005135; Endo/exonuclease/phosphatase. DR Pfam; PF03372; Exo_endo_phos; 1. DR SUPFAM; SSF56219; SSF56219; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; Exonuclease; KW Hydrolase; Magnesium; Metal-binding; Mitochondrion; mRNA processing; KW Nuclease; Phosphoprotein; Polymorphism; Reference proteome; KW Transit peptide. FT TRANSIT 1 16 Mitochondrion. FT {ECO:0000305|PubMed:22285541}. FT CHAIN 17 609 2',5'-phosphodiesterase 12. FT /FTId=PRO_0000324312. FT ACT_SITE 351 351 {ECO:0000250}. FT ACT_SITE 561 561 {ECO:0000250}. FT ACT_SITE 599 599 {ECO:0000250}. FT METAL 351 351 Magnesium 1. {ECO:0000250}. FT METAL 496 496 Magnesium 2. {ECO:0000250}. FT METAL 498 498 Magnesium 2. {ECO:0000250}. FT METAL 599 599 Magnesium 2. {ECO:0000250}. FT MOD_RES 217 217 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT VAR_SEQ 527 535 EERCNMSLT -> GGFGGNFLL (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_032202. FT VAR_SEQ 536 609 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_032203. FT VARIANT 23 23 R -> W (in dbSNP:rs2241988). FT {ECO:0000269|PubMed:14702039, FT ECO:0000269|Ref.3}. FT /FTId=VAR_039698. FT STRAND 163 168 {ECO:0000244|PDB:4Z0V}. FT STRAND 182 187 {ECO:0000244|PDB:4Z0V}. FT HELIX 190 192 {ECO:0000244|PDB:4Z0V}. FT STRAND 193 202 {ECO:0000244|PDB:4Z0V}. FT HELIX 214 216 {ECO:0000244|PDB:4Z2B}. FT STRAND 223 227 {ECO:0000244|PDB:4Z0V}. FT STRAND 232 235 {ECO:0000244|PDB:4Z2B}. FT HELIX 239 241 {ECO:0000244|PDB:4Z0V}. FT STRAND 246 251 {ECO:0000244|PDB:4Z0V}. FT STRAND 262 265 {ECO:0000244|PDB:4Z0V}. FT HELIX 279 282 {ECO:0000244|PDB:4Z0V}. FT HELIX 283 285 {ECO:0000244|PDB:4Z0V}. FT STRAND 294 301 {ECO:0000244|PDB:4Z0V}. FT HELIX 305 308 {ECO:0000244|PDB:4Z0V}. FT HELIX 311 315 {ECO:0000244|PDB:4Z0V}. FT HELIX 323 325 {ECO:0000244|PDB:4Z0V}. FT HELIX 328 341 {ECO:0000244|PDB:4Z0V}. FT STRAND 345 353 {ECO:0000244|PDB:4Z0V}. FT HELIX 354 359 {ECO:0000244|PDB:4Z0V}. FT HELIX 361 367 {ECO:0000244|PDB:4Z0V}. FT STRAND 370 387 {ECO:0000244|PDB:4Z0V}. FT TURN 388 390 {ECO:0000244|PDB:4Z0V}. FT STRAND 391 396 {ECO:0000244|PDB:4Z0V}. FT HELIX 401 407 {ECO:0000244|PDB:4Z0V}. FT HELIX 409 411 {ECO:0000244|PDB:4Z0V}. FT HELIX 412 417 {ECO:0000244|PDB:4Z0V}. FT TURN 418 420 {ECO:0000244|PDB:4Z0V}. FT HELIX 422 430 {ECO:0000244|PDB:4Z0V}. FT STRAND 434 444 {ECO:0000244|PDB:4Z0V}. FT STRAND 449 456 {ECO:0000244|PDB:4Z0V}. FT HELIX 464 483 {ECO:0000244|PDB:4Z0V}. FT STRAND 486 488 {ECO:0000244|PDB:4Z0V}. FT STRAND 491 496 {ECO:0000244|PDB:4Z0V}. FT HELIX 504 511 {ECO:0000244|PDB:4Z0V}. FT STRAND 512 514 {ECO:0000244|PDB:4Z0V}. FT HELIX 519 522 {ECO:0000244|PDB:4Z0V}. FT STRAND 540 542 {ECO:0000244|PDB:4Z0V}. FT STRAND 550 553 {ECO:0000244|PDB:4Z0V}. FT STRAND 556 558 {ECO:0000244|PDB:4Z0V}. FT STRAND 561 566 {ECO:0000244|PDB:4Z0V}. FT TURN 567 569 {ECO:0000244|PDB:4Z0V}. FT STRAND 570 575 {ECO:0000244|PDB:4Z0V}. FT HELIX 581 585 {ECO:0000244|PDB:4Z0V}. FT STRAND 588 592 {ECO:0000244|PDB:4Z0V}. FT STRAND 595 599 {ECO:0000244|PDB:4Z0V}. FT STRAND 602 608 {ECO:0000244|PDB:4Z0V}. SQ SEQUENCE 609 AA; 67352 MW; 1D1F3AB4795B52A4 CRC64; MWRLPGARAA LRVIRTAVEK LSRAEAGSQT AAGAMERAVV RCVPSEPKLS LSFALADGSH KNMQRDQSEP LGRVLSRIAT NALKGHAKAA AAKKSRKSRP NASGGAACSG PGPEPAVFCE PVVKLYYREE AVAEDVLNVD AWQDGAVLQI GDVKYKVERN PPAFTELQLP RYIMAGFPVC PKLSLEFGDP ASSLFRWYKE AKPGAAEPEV GVPSSLSPSS PSSSWTETDV EERVYTPSNA DIGLRLKLHC TPGDGQRFGH SRELESVCVV EAGPGTCTFD HRHLYTKKVT EDALIRTVSY NILADTYAQT EFSRTVLYPY CAPYALELDY RQNLIQKELT GYNADVICLQ EVDRAVFSDS LVPALEAFGL EGVFRIKQHE GLATFYRKSK FSLLSQHDIS FYEALESDPL HKELLEKLVL YPSAQEKVLQ RSSVLQVSVL QSTKDSSKRI CVANTHLYWH PKGGYIRLIQ MAVALAHIRH VSCDLYPGIP VIFCGDFNST PSTGMYHFVI NGSIPEDHED WASNGEEERC NMSLTHFFKL KSACGEPAYT NYVGGFHGCL DYIFIDLNAL EVEQVIPLPS HEEVTTHQAL PSVSHPSDHI ALVCDLKWK //