ID   PAN2_HUMAN              Reviewed;        1202 AA.
AC   Q504Q3; O75189; Q76E12; Q8IVE1;
DT   20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 3.
DT   27-MAR-2024, entry version 170.
DE   RecName: Full=PAN2-PAN3 deadenylation complex catalytic subunit PAN2 {ECO:0000255|HAMAP-Rule:MF_03182};
DE            EC=3.1.13.4 {ECO:0000255|HAMAP-Rule:MF_03182};
DE   AltName: Full=Inactive ubiquitin carboxyl-terminal hydrolase 52 {ECO:0000255|HAMAP-Rule:MF_03182};
DE   AltName: Full=PAB1P-dependent poly(A)-specific ribonuclease {ECO:0000255|HAMAP-Rule:MF_03182};
DE   AltName: Full=Poly(A)-nuclease deadenylation complex subunit 2 {ECO:0000255|HAMAP-Rule:MF_03182};
DE            Short=PAN deadenylation complex subunit 2 {ECO:0000255|HAMAP-Rule:MF_03182};
GN   Name=PAN2 {ECO:0000255|HAMAP-Rule:MF_03182}; Synonyms=KIAA0710, USP52;
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 [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY,
RP   SUBCELLULAR LOCATION, INTERACTION WITH PAN3 AND POLYADENYLATE-BINDING
RP   PROTEIN, MUTAGENESIS OF ASP-1087, AND VARIANT LEU-179.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=14583602; DOI=10.1074/jbc.m309125200;
RA   Uchida N., Hoshino S., Katada T.;
RT   "Identification of a human cytoplasmic poly(A) nuclease complex stimulated
RT   by poly(A)-binding protein.";
RL   J. Biol. Chem. 279:1383-1391(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT LEU-179.
RC   TISSUE=Brain;
RX   PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA   Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA   Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. X. The
RT   complete sequences of 100 new cDNA clones from brain which can code for
RT   large proteins in vitro.";
RL   DNA Res. 5:169-176(1998).
RN   [3]
RP   SEQUENCE REVISION.
RA   Ohara O., Suyama M., Nagase T., Ishikawa K.;
RL   Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP   ASN-32 AND LEU-179.
RC   TISSUE=Eye, and 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   [5]
RP   LACK OF UBIQUITIN CARBOXYL TERMINAL HYDROLASE ACTIVITY.
RX   PubMed=14715245; DOI=10.1016/j.bbrc.2003.12.050;
RA   Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S.,
RA   Lopez-Otin C.;
RT   "Cloning and enzymatic analysis of 22 novel human ubiquitin-specific
RT   proteases.";
RL   Biochem. Biophys. Res. Commun. 314:54-62(2004).
RN   [6]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=16284618; DOI=10.1038/nsmb1016;
RA   Yamashita A., Chang T.-C., Yamashita Y., Zhu W., Zhong Z., Chen C.-Y.A.,
RA   Shyu A.-B.;
RT   "Concerted action of poly(A) nucleases and decapping enzyme in mammalian
RT   mRNA turnover.";
RL   Nat. Struct. Mol. Biol. 12:1054-1063(2005).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1189, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=16964243; DOI=10.1038/nbt1240;
RA   Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT   "A probability-based approach for high-throughput protein phosphorylation
RT   analysis and site localization.";
RL   Nat. Biotechnol. 24:1285-1292(2006).
RN   [8]
RP   SUBCELLULAR LOCATION.
RX   PubMed=18625844; DOI=10.1083/jcb.200801196;
RA   Zheng D., Ezzeddine N., Chen C.Y., Zhu W., He X., Shyu A.B.;
RT   "Deadenylation is prerequisite for P-body formation and mRNA decay in
RT   mammalian cells.";
RL   J. Cell Biol. 182:89-101(2008).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, AND IDENTIFICATION BY
RP   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   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [11]
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., Buerckstuemmer T.,
RA   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   [12]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=23398456; DOI=10.1042/bj20130026;
RA   Bett J.S., Ibrahim A.F., Garg A.K., Kelly V., Pedrioli P., Rocha S.,
RA   Hay R.T.;
RT   "The P-body component USP52/PAN2 is a novel regulator of HIF1A mRNA
RT   stability.";
RL   Biochem. J. 451:185-194(2013).
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1189, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=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   [14]
RP   INTERACTION WITH PAN3.
RX   PubMed=23932717; DOI=10.1016/j.molcel.2013.07.011;
RA   Christie M., Boland A., Huntzinger E., Weichenrieder O., Izaurralde E.;
RT   "Structure of the PAN3 pseudokinase reveals the basis for interactions with
RT   the PAN2 deadenylase and the GW182 proteins.";
RL   Mol. Cell 51:360-373(2013).
RN   [15]
RP   INTERACTION WITH PAN3.
RX   PubMed=28559491; DOI=10.1261/rna.061556.117;
RA   Chen C.A., Zhang Y., Xiang Y., Han L., Chang J.T., Shyu A.B.;
RT   "Antagonistic actions of two human Pan3 isoforms on global mRNA turnover.";
RL   RNA 23:1404-1418(2017).
RN   [16]
RP   VARIANT [LARGE SCALE ANALYSIS] VAL-1201.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation
CC       complex, one of two cytoplasmic mRNA deadenylases involved in general
CC       and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A)
CC       tails of RNA and the activity is stimulated by poly(A)-binding protein
CC       (PABP). PAN deadenylation is followed by rapid degradation of the
CC       shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are
CC       then degraded by two alternative mechanisms, namely exosome-mediated
CC       3'-5' exonucleolytic degradation, or deadenylation-dependent mRNA
CC       decaping and subsequent 5'-3' exonucleolytic degradation by XRN1. Also
CC       acts as an important regulator of the HIF1A-mediated hypoxic response.
CC       Required for HIF1A mRNA stability independent of poly(A) tail length
CC       regulation. {ECO:0000255|HAMAP-Rule:MF_03182,
CC       ECO:0000269|PubMed:14583602, ECO:0000269|PubMed:16284618,
CC       ECO:0000269|PubMed:23398456}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Exonucleolytic cleavage of poly(A) to 5'-AMP.; EC=3.1.13.4;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_03182,
CC         ECO:0000269|PubMed:14583602};
CC   -!- COFACTOR:
CC       Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_03182};
CC       Note=Binds 2 metal cations per subunit in the catalytic exonuclease
CC       domain. {ECO:0000255|HAMAP-Rule:MF_03182};
CC   -!- ACTIVITY REGULATION: Positively regulated by the regulatory subunit
CC       PAN3. {ECO:0000255|HAMAP-Rule:MF_03182}.
CC   -!- SUBUNIT: Forms a heterotrimer with an asymmetric homodimer of the
CC       regulatory subunit PAN3 to form the poly(A)-nuclease (PAN)
CC       deadenylation complex (PubMed:14583602, PubMed:23932717). Interacts
CC       with PAN3 isoform 1/Pan3L and isoform 3/Pan3S (PubMed:28559491).
CC       Interacts with ZFP36 (By similarity). {ECO:0000255|HAMAP-Rule:MF_03182,
CC       ECO:0000269|PubMed:14583602, ECO:0000269|PubMed:23932717,
CC       ECO:0000269|PubMed:28559491}.
CC   -!- INTERACTION:
CC       Q504Q3; Q58A45: PAN3; NbExp=6; IntAct=EBI-1058976, EBI-2513054;
CC       Q504Q3; Q9HCJ0: TNRC6C; NbExp=7; IntAct=EBI-1058976, EBI-6507625;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14583602,
CC       ECO:0000269|PubMed:16284618}. Cytoplasm, P-body {ECO:0000255|HAMAP-
CC       Rule:MF_03182, ECO:0000269|PubMed:18625844,
CC       ECO:0000269|PubMed:23398456}. Nucleus {ECO:0000255|HAMAP-Rule:MF_03182,
CC       ECO:0000269|PubMed:16284618}. Note=Shuttles between nucleus and
CC       cytoplasm. {ECO:0000255|HAMAP-Rule:MF_03182,
CC       ECO:0000269|PubMed:16284618}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q504Q3-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q504Q3-2; Sequence=VSP_023749;
CC       Name=3;
CC         IsoId=Q504Q3-3; Sequence=VSP_023748;
CC   -!- DOMAIN: Contains a pseudo-UCH domain. This ubiquitin C-terminal
CC       hydrolase (UCH)-like or ubiquitin specific protease (USP)-like domain
CC       is predicted to be catalytically inactive because it lacks the active
CC       site catalytic triad characteristic of thiol proteases, with residues
CC       at the equivalent structural positions that are incompatible with
CC       catalysis, and it cannot bind ubiquitin. It functions as a structural
CC       scaffold for intra- and intermolecular interactions in the complex.
CC       {ECO:0000255|HAMAP-Rule:MF_03182}.
CC   -!- DOMAIN: The linker, or PAN3 interaction domain (PID), between the WD40
CC       repeats and the pseudo-UCH domain mediates interaction with PAN3.
CC       {ECO:0000255|HAMAP-Rule:MF_03182}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. PAN2 subfamily.
CC       {ECO:0000255|HAMAP-Rule:MF_03182}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA31685.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AB107585; BAD02263.1; -; mRNA.
DR   EMBL; AB014610; BAA31685.2; ALT_INIT; mRNA.
DR   EMBL; BC024043; AAH24043.1; -; mRNA.
DR   EMBL; BC094885; AAH94885.1; -; mRNA.
DR   CCDS; CCDS44922.1; -. [Q504Q3-1]
DR   CCDS; CCDS53802.1; -. [Q504Q3-3]
DR   CCDS; CCDS8915.1; -. [Q504Q3-2]
DR   RefSeq; NP_001120932.1; NM_001127460.2. [Q504Q3-1]
DR   RefSeq; NP_001159751.1; NM_001166279.1. [Q504Q3-3]
DR   RefSeq; NP_055686.3; NM_014871.4. [Q504Q3-2]
DR   AlphaFoldDB; Q504Q3; -.
DR   SMR; Q504Q3; -.
DR   BioGRID; 115252; 399.
DR   ComplexPortal; CPX-2259; PAN2-PAN3 mRNA deadenylation complex.
DR   DIP; DIP-50708N; -.
DR   IntAct; Q504Q3; 23.
DR   STRING; 9606.ENSP00000481859; -.
DR   MEROPS; C19.978; -.
DR   GlyGen; Q504Q3; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q504Q3; -.
DR   PhosphoSitePlus; Q504Q3; -.
DR   BioMuta; PAN2; -.
DR   DMDM; 296439280; -.
DR   EPD; Q504Q3; -.
DR   jPOST; Q504Q3; -.
DR   MassIVE; Q504Q3; -.
DR   MaxQB; Q504Q3; -.
DR   PaxDb; 9606-ENSP00000401721; -.
DR   PeptideAtlas; Q504Q3; -.
DR   ProteomicsDB; 62400; -. [Q504Q3-1]
DR   ProteomicsDB; 62401; -. [Q504Q3-2]
DR   ProteomicsDB; 62402; -. [Q504Q3-3]
DR   Pumba; Q504Q3; -.
DR   Antibodypedia; 28142; 158 antibodies from 24 providers.
DR   DNASU; 9924; -.
DR   Ensembl; ENST00000257931.9; ENSP00000257931.5; ENSG00000135473.16. [Q504Q3-3]
DR   Ensembl; ENST00000425394.7; ENSP00000401721.2; ENSG00000135473.16. [Q504Q3-1]
DR   Ensembl; ENST00000440411.8; ENSP00000388231.3; ENSG00000135473.16. [Q504Q3-2]
DR   Ensembl; ENST00000548043.5; ENSP00000449861.1; ENSG00000135473.16. [Q504Q3-1]
DR   Ensembl; ENST00000610546.4; ENSP00000481859.1; ENSG00000135473.16. [Q504Q3-1]
DR   GeneID; 9924; -.
DR   KEGG; hsa:9924; -.
DR   MANE-Select; ENST00000440411.8; ENSP00000388231.3; NM_014871.6; NP_055686.4. [Q504Q3-2]
DR   UCSC; uc001skx.3; human. [Q504Q3-1]
DR   AGR; HGNC:20074; -.
DR   CTD; 9924; -.
DR   DisGeNET; 9924; -.
DR   GeneCards; PAN2; -.
DR   HGNC; HGNC:20074; PAN2.
DR   HPA; ENSG00000135473; Low tissue specificity.
DR   MIM; 617447; gene.
DR   neXtProt; NX_Q504Q3; -.
DR   OpenTargets; ENSG00000135473; -.
DR   PharmGKB; PA162398664; -.
DR   VEuPathDB; HostDB:ENSG00000135473; -.
DR   eggNOG; KOG1275; Eukaryota.
DR   GeneTree; ENSGT00390000013978; -.
DR   HOGENOM; CLU_002369_0_0_1; -.
DR   InParanoid; Q504Q3; -.
DR   OMA; TQELLWT; -.
DR   OrthoDB; 9810at2759; -.
DR   PhylomeDB; Q504Q3; -.
DR   TreeFam; TF105657; -.
DR   BRENDA; 3.1.13.4; 2681.
DR   PathwayCommons; Q504Q3; -.
DR   Reactome; R-HSA-429947; Deadenylation of mRNA.
DR   SignaLink; Q504Q3; -.
DR   SIGNOR; Q504Q3; -.
DR   BioGRID-ORCS; 9924; 30 hits in 1174 CRISPR screens.
DR   ChiTaRS; PAN2; human.
DR   GeneWiki; USP52; -.
DR   GenomeRNAi; 9924; -.
DR   Pharos; Q504Q3; Tbio.
DR   PRO; PR:Q504Q3; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q504Q3; Protein.
DR   Bgee; ENSG00000135473; Expressed in right lobe of thyroid gland and 197 other cell types or tissues.
DR   ExpressionAtlas; Q504Q3; baseline and differential.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0000932; C:P-body; IBA:GO_Central.
DR   GO; GO:0031251; C:PAN complex; IDA:UniProtKB.
DR   GO; GO:0000175; F:3'-5'-RNA exonuclease activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR   GO; GO:0004535; F:poly(A)-specific ribonuclease activity; IDA:UniProtKB.
DR   GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR   GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IBA:GO_Central.
DR   GO; GO:0010606; P:positive regulation of cytoplasmic mRNA processing body assembly; IEA:UniProtKB-UniRule.
DR   CDD; cd06143; PAN2_exo; 1.
DR   CDD; cd02672; Peptidase_C19P; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 1.
DR   Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
DR   HAMAP; MF_03182; PAN2; 1.
DR   InterPro; IPR013520; Exonuclease_RNaseT/DNA_pol3.
DR   InterPro; IPR030843; PAN2.
DR   InterPro; IPR048841; PAN2_N.
DR   InterPro; IPR028881; PAN2_UCH_dom.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR012337; RNaseH-like_sf.
DR   InterPro; IPR036397; RNaseH_sf.
DR   InterPro; IPR028889; USP_dom.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   InterPro; IPR036322; WD40_repeat_dom_sf.
DR   PANTHER; PTHR15728; DEADENYLATION COMPLEX CATALYTIC SUBUNIT PAN2; 1.
DR   PANTHER; PTHR15728:SF0; PAN2-PAN3 DEADENYLATION COMPLEX CATALYTIC SUBUNIT PAN2; 1.
DR   Pfam; PF20770; PAN2_N; 1.
DR   Pfam; PF00929; RNase_T; 1.
DR   Pfam; PF13423; UCH_1; 1.
DR   SMART; SM00479; EXOIII; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF53098; Ribonuclease H-like; 1.
DR   SUPFAM; SSF50978; WD40 repeat-like; 1.
DR   PROSITE; PS50235; USP_3; 1.
DR   Genevisible; Q504Q3; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Exonuclease; Hydrolase; Metal-binding;
KW   mRNA processing; Nuclease; Nucleus; Phosphoprotein; Reference proteome;
KW   Repeat; WD repeat.
FT   CHAIN           1..1202
FT                   /note="PAN2-PAN3 deadenylation complex catalytic subunit
FT                   PAN2"
FT                   /id="PRO_0000280521"
FT   REPEAT          153..193
FT                   /note="WD 1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT   REPEAT          195..231
FT                   /note="WD 2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT   REPEAT          244..280
FT                   /note="WD 3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT   REPEAT          328..367
FT                   /note="WD 4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT   DOMAIN          486..924
FT                   /note="USP"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT   DOMAIN          975..1147
FT                   /note="Exonuclease"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT   REGION          368..485
FT                   /note="Linker"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT   BINDING         978
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O95453, ECO:0000255|HAMAP-
FT                   Rule:MF_03182"
FT   BINDING         980
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O95453, ECO:0000255|HAMAP-
FT                   Rule:MF_03182"
FT   BINDING         1087
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O95453, ECO:0000255|HAMAP-
FT                   Rule:MF_03182"
FT   BINDING         1139
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:O95453, ECO:0000255|HAMAP-
FT                   Rule:MF_03182"
FT   MOD_RES         791
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648"
FT   MOD_RES         1189
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:16964243,
FT                   ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         643
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:9734811"
FT                   /id="VSP_023748"
FT   VAR_SEQ         689..692
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14583602,
FT                   ECO:0000303|PubMed:15489334"
FT                   /id="VSP_023749"
FT   VARIANT         32
FT                   /note="S -> N (in dbSNP:rs11558139)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_031162"
FT   VARIANT         179
FT                   /note="I -> L (in dbSNP:rs1918496)"
FT                   /evidence="ECO:0000269|PubMed:14583602,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9734811"
FT                   /id="VAR_031163"
FT   VARIANT         1201
FT                   /note="A -> V (in a colorectal cancer sample; somatic
FT                   mutation; dbSNP:rs1330054285)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036359"
FT   MUTAGEN         1087
FT                   /note="D->A: Loss of exonuclease activity."
FT                   /evidence="ECO:0000269|PubMed:14583602"
FT   CONFLICT        9
FT                   /note="G -> E (in Ref. 4; AAH94885)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1091
FT                   /note="I -> V (in Ref. 4; AAH94885)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1202 AA;  135368 MW;  579194C102FCA019 CRC64;
     MNFEGLDPGL AEYAPAMHSA LDPVLDAHLN PSLLQNVELD PEGVALEALP VQESVHIMEG
     VYSELHSVVA EVGVPVSVSH FDLHEEMLWV GSHGGHATSF FGPALERYSS FQVNGSDDIR
     QIQSLENGIL FLTKNNLKYM ARGGLIIFDY LLDENEDMHS LLLTDSSTLL VGGLQNHIIE
     IDLNTVQETQ KYAVETPGVT IMRQTNRFFF CGHTSGKVSL RDLRTFKVEH EFDAFSGSLS
     DFDVHGNLLA ACGFSSRLTG LACDRFLKVY DLRMMRAITP LQVHVDPAFL RFIPTYTSRL
     AIISQSGQCQ FCEPTGLANP ADIFHVNPVG PLLMTFDVSA SKQALAFGDS EGCVHLWTDS
     PEPSFNPYSR ETEFALPCLV DSLPPLDWSQ DLLPLSLIPV PLTTDTLLSD WPAANSAPAP
     RRAPPVDAEI LRTMKKVGFI GYAPNPRTRL RNQIPYRLKE SDSEFDSFSQ VTESPVGREE
     EPHLHMVSKK YRKVTIKYSK LGLEDFDFKH YNKTLFAGLE PHIPNAYCNC MIQVLYFLEP
     VRCLIQNHLC QKEFCLACEL GFLFHMLDLS RGDPCQGNNF LRAFRTIPEA SALGLILADS
     DEASGKGNLA RLIQRWNRFI LTQLHQDMQE LEIPQAYRGA GGSSFCSSGD SVIGQLFSCE
     MENCSLCRCG SETVRASSTL LFTLSYPDGS KSDKTGKNYD FAQVLKRSIC LDQNTQAWCD
     TCEKYQPTIQ TRNIRHLPDI LVINCEVNSS KEADFWRMQA EVAFKMAVKK HGGEISKNKE
     FALADWKELG SPEGVLVCPS IEELKNVWLP FSIRMKMTKN KGLDVCNWTD GDEMQWGPAR
     AEEEHGVYVY DLMATVVHIL DSRTGGSLVA HIKVGETYHQ RKEGVTHQQW YLFNDFLIEP
     IDKHEAVQFD MNWKVPAILY YVKRNLNSRY NLNIKNPIEA SVLLAEASLA RKQRKTHTTF
     IPLMLNEMPQ IGDLVGLDAE FVTLNEEEAE LRSDGTKSTI KPSQMSVARI TCVRGQGPNE
     GIPFIDDYIS TQEQVVDYLT QYSGIKPGDL DAKISSKHLT TLKSTYLKLR FLIDIGVKFV
     GHGLQKDFRV INLMVPKDQV LDTVYLFHMP RKRMISLRFL AWYFLDLKIQ GETHDSIEDA
     RTALQLYRKY LELSKNGTEP ESFHKVLKGL YEKGRKMDWK VPEPEGQTSP KNAAVFSSVL
     AL
//