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Protein

2',5'-phosphodiesterase 12

Gene

PDE12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Enzyme that cleaves 2',5'-phosphodiester bond linking adenosines of the 5'-triphosphorylated oligoadenylates, triphosphorylated oligoadenylates referred as 2-5A modulates the 2-5A system. This enzyme degraded triphosphorylated 2-5A to produce AMP and ATP. Also cleaves 3',5'-phosphodiester bond of oligoadenylates. Plays a role as a negative regulator of the The 2-5A system that is one of the major pathways for antiviral and antitumor functions induced by interferons (IFNs). Suppression of this enzyme induces reduction of viral replication in Hela cells, thus counteracting the antiviral pathway probably by inhibiting the 2-5A system.4 Publications

Catalytic activityi

Exonucleolytic cleavage of poly(A) to 5'-AMP.3 Publications

Cofactori

Mg2+1 Publication

pH dependencei

Optimum pH is 8.0 for 2'-5' oligoadenylate exonuclease activity.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei351 – 3511By similarity
Metal bindingi351 – 3511Magnesium 1By similarity
Metal bindingi496 – 4961Magnesium 2By similarity
Metal bindingi498 – 4981Magnesium 2By similarity
Active sitei561 – 5611By similarity
Active sitei599 – 5991By similarity
Metal bindingi599 – 5991Magnesium 2By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Exonuclease, Hydrolase, Nuclease

Keywords - Biological processi

mRNA processing

Keywords - Ligandi

Magnesium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
2',5'-phosphodiesterase 12 (EC:3.1.4.-)
Short name:
2'-PDE
Short name:
2-PDE
Alternative name(s):
Mitochondrial deadenylase (EC:3.1.13.4)
Gene namesi
Name:PDE12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:25386. PDE12.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA162399016.

Polymorphism and mutation databases

BioMutaiPDE12.
DMDMi172046137.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 1616Mitochondrion1 PublicationAdd
BLAST
Chaini17 – 6095932',5'-phosphodiesterase 12PRO_0000324312Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei217 – 2171PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6L8Q7.
MaxQBiQ6L8Q7.
PaxDbiQ6L8Q7.
PeptideAtlasiQ6L8Q7.
PRIDEiQ6L8Q7.

PTM databases

iPTMnetiQ6L8Q7.
PhosphoSiteiQ6L8Q7.

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

BgeeiENSG00000174840.
CleanExiHS_PDE12.
ExpressionAtlasiQ6L8Q7. baseline and differential.
GenevisibleiQ6L8Q7. HS.

Organism-specific databases

HPAiHPA043171.

Interactioni

Protein-protein interaction databases

BioGridi128397. 28 interactions.
IntActiQ6L8Q7. 7 interactions.
STRINGi9606.ENSP00000309142.

Structurei

Secondary structure

1
609
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi163 – 1686Combined sources
Beta strandi182 – 1876Combined sources
Helixi190 – 1923Combined sources
Beta strandi193 – 20210Combined sources
Helixi214 – 2163Combined sources
Beta strandi223 – 2275Combined sources
Beta strandi232 – 2354Combined sources
Helixi239 – 2413Combined sources
Beta strandi246 – 2516Combined sources
Beta strandi262 – 2654Combined sources
Helixi279 – 2824Combined sources
Helixi283 – 2853Combined sources
Beta strandi294 – 3018Combined sources
Helixi305 – 3084Combined sources
Helixi311 – 3155Combined sources
Helixi323 – 3253Combined sources
Helixi328 – 34114Combined sources
Beta strandi345 – 3539Combined sources
Helixi354 – 3596Combined sources
Helixi361 – 3677Combined sources
Beta strandi370 – 38718Combined sources
Turni388 – 3903Combined sources
Beta strandi391 – 3966Combined sources
Helixi401 – 4077Combined sources
Helixi409 – 4113Combined sources
Helixi412 – 4176Combined sources
Turni418 – 4203Combined sources
Helixi422 – 4309Combined sources
Beta strandi434 – 44411Combined sources
Beta strandi449 – 4568Combined sources
Helixi464 – 48320Combined sources
Beta strandi486 – 4883Combined sources
Beta strandi491 – 4966Combined sources
Helixi504 – 5118Combined sources
Beta strandi512 – 5143Combined sources
Helixi519 – 5224Combined sources
Beta strandi540 – 5423Combined sources
Beta strandi550 – 5534Combined sources
Beta strandi556 – 5583Combined sources
Beta strandi561 – 5666Combined sources
Turni567 – 5693Combined sources
Beta strandi570 – 5756Combined sources
Helixi581 – 5855Combined sources
Beta strandi588 – 5925Combined sources
Beta strandi595 – 5995Combined sources
Beta strandi602 – 6087Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4Z0VX-ray1.78A155-609[»]
4Z2BX-ray1.80A155-609[»]
4ZKFX-ray1.82A154-609[»]
ProteinModelPortaliQ6L8Q7.
SMRiQ6L8Q7. Positions 161-609.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the CCR4/nocturin family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0620. Eukaryota.
COG5239. LUCA.
GeneTreeiENSGT00550000074364.
HOGENOMiHOG000006935.
HOVERGENiHBG061027.
KOiK19612.
OMAiYPSAQEK.
OrthoDBiEOG091G097K.
PhylomeDBiQ6L8Q7.
TreeFamiTF323175.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
SUPFAMiSSF56219. SSF56219. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6L8Q7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MWRLPGARAA LRVIRTAVEK LSRAEAGSQT AAGAMERAVV RCVPSEPKLS
60 70 80 90 100
LSFALADGSH KNMQRDQSEP LGRVLSRIAT NALKGHAKAA AAKKSRKSRP
110 120 130 140 150
NASGGAACSG PGPEPAVFCE PVVKLYYREE AVAEDVLNVD AWQDGAVLQI
160 170 180 190 200
GDVKYKVERN PPAFTELQLP RYIMAGFPVC PKLSLEFGDP ASSLFRWYKE
210 220 230 240 250
AKPGAAEPEV GVPSSLSPSS PSSSWTETDV EERVYTPSNA DIGLRLKLHC
260 270 280 290 300
TPGDGQRFGH SRELESVCVV EAGPGTCTFD HRHLYTKKVT EDALIRTVSY
310 320 330 340 350
NILADTYAQT EFSRTVLYPY CAPYALELDY RQNLIQKELT GYNADVICLQ
360 370 380 390 400
EVDRAVFSDS LVPALEAFGL EGVFRIKQHE GLATFYRKSK FSLLSQHDIS
410 420 430 440 450
FYEALESDPL HKELLEKLVL YPSAQEKVLQ RSSVLQVSVL QSTKDSSKRI
460 470 480 490 500
CVANTHLYWH PKGGYIRLIQ MAVALAHIRH VSCDLYPGIP VIFCGDFNST
510 520 530 540 550
PSTGMYHFVI NGSIPEDHED WASNGEEERC NMSLTHFFKL KSACGEPAYT
560 570 580 590 600
NYVGGFHGCL DYIFIDLNAL EVEQVIPLPS HEEVTTHQAL PSVSHPSDHI

ALVCDLKWK
Length:609
Mass (Da):67,352
Last modified:March 18, 2008 - v2
Checksum:i1D1F3AB4795B52A4
GO
Isoform 2 (identifier: Q6L8Q7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     527-535: EERCNMSLT → GGFGGNFLL
     536-609: Missing.

Show »
Length:535
Mass (Da):58,890
Checksum:i900326406AB885B2
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti23 – 231R → W.2 Publications
Corresponds to variant rs2241988 [ dbSNP | Ensembl ].
VAR_039698

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei527 – 5359EERCNMSLT → GGFGGNFLL in isoform 2. 1 PublicationVSP_032202
Alternative sequencei536 – 60974Missing in isoform 2. 1 PublicationVSP_032203Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB115695 mRNA. Translation: BAD20938.1.
AK074423 mRNA. Translation: BAB85079.1.
AK300374 mRNA. Translation: BAG62110.1.
CH471055 Genomic DNA. Translation: EAW65342.1.
AL831824 mRNA. Translation: CAD38538.1.
CCDSiCCDS33772.1. [Q6L8Q7-1]
RefSeqiNP_808881.3. NM_177966.6. [Q6L8Q7-1]
UniGeneiHs.572993.

Genome annotation databases

EnsembliENST00000311180; ENSP00000309142; ENSG00000174840. [Q6L8Q7-1]
GeneIDi201626.
KEGGihsa:201626.
UCSCiuc003diw.5. human. [Q6L8Q7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB115695 mRNA. Translation: BAD20938.1.
AK074423 mRNA. Translation: BAB85079.1.
AK300374 mRNA. Translation: BAG62110.1.
CH471055 Genomic DNA. Translation: EAW65342.1.
AL831824 mRNA. Translation: CAD38538.1.
CCDSiCCDS33772.1. [Q6L8Q7-1]
RefSeqiNP_808881.3. NM_177966.6. [Q6L8Q7-1]
UniGeneiHs.572993.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4Z0VX-ray1.78A155-609[»]
4Z2BX-ray1.80A155-609[»]
4ZKFX-ray1.82A154-609[»]
ProteinModelPortaliQ6L8Q7.
SMRiQ6L8Q7. Positions 161-609.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128397. 28 interactions.
IntActiQ6L8Q7. 7 interactions.
STRINGi9606.ENSP00000309142.

PTM databases

iPTMnetiQ6L8Q7.
PhosphoSiteiQ6L8Q7.

Polymorphism and mutation databases

BioMutaiPDE12.
DMDMi172046137.

Proteomic databases

EPDiQ6L8Q7.
MaxQBiQ6L8Q7.
PaxDbiQ6L8Q7.
PeptideAtlasiQ6L8Q7.
PRIDEiQ6L8Q7.

Protocols and materials databases

DNASUi201626.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000311180; ENSP00000309142; ENSG00000174840. [Q6L8Q7-1]
GeneIDi201626.
KEGGihsa:201626.
UCSCiuc003diw.5. human. [Q6L8Q7-1]

Organism-specific databases

CTDi201626.
GeneCardsiPDE12.
H-InvDBHIX0003393.
HGNCiHGNC:25386. PDE12.
HPAiHPA043171.
MIMi616519. gene.
neXtProtiNX_Q6L8Q7.
PharmGKBiPA162399016.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0620. Eukaryota.
COG5239. LUCA.
GeneTreeiENSGT00550000074364.
HOGENOMiHOG000006935.
HOVERGENiHBG061027.
KOiK19612.
OMAiYPSAQEK.
OrthoDBiEOG091G097K.
PhylomeDBiQ6L8Q7.
TreeFamiTF323175.

Miscellaneous databases

ChiTaRSiPDE12. human.
GenomeRNAii201626.
PROiQ6L8Q7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000174840.
CleanExiHS_PDE12.
ExpressionAtlasiQ6L8Q7. baseline and differential.
GenevisibleiQ6L8Q7. HS.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
SUPFAMiSSF56219. SSF56219. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiPDE12_HUMAN
AccessioniPrimary (citable) accession number: Q6L8Q7
Secondary accession number(s): B4DTU8
, Q8IYU3, Q8NDU2, Q8TE78
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 18, 2008
Last modified: September 7, 2016
This is version 99 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.