ID A0A3Q7SME9_VULVU Unreviewed; 1376 AA.
AC A0A3Q7SME9;
DT 10-APR-2019, integrated into UniProtKB/TrEMBL.
DT 10-APR-2019, sequence version 1.
DT 27-MAR-2024, entry version 22.
DE RecName: Full=PAN2-PAN3 deadenylation complex catalytic subunit PAN2 {ECO:0000256|HAMAP-Rule:MF_03182};
DE EC=3.1.13.4 {ECO:0000256|HAMAP-Rule:MF_03182};
DE AltName: Full=Inactive ubiquitin carboxyl-terminal hydrolase 52 {ECO:0000256|HAMAP-Rule:MF_03182};
DE AltName: Full=PAB1P-dependent poly(A)-specific ribonuclease {ECO:0000256|HAMAP-Rule:MF_03182};
DE AltName: Full=Poly(A)-nuclease deadenylation complex subunit 2 {ECO:0000256|HAMAP-Rule:MF_03182};
DE Short=PAN deadenylation complex subunit 2 {ECO:0000256|HAMAP-Rule:MF_03182};
GN Name=PAN2 {ECO:0000256|HAMAP-Rule:MF_03182,
GN ECO:0000313|RefSeq:XP_025857723.1};
OS Vulpes vulpes (Red fox).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Vulpes.
OX NCBI_TaxID=9627 {ECO:0000313|Proteomes:UP000286640, ECO:0000313|RefSeq:XP_025857723.1};
RN [1]
RP IDENTIFICATION.
RG RefSeq;
RL Submitted (JAN-2019) to UniProtKB.
RN [2] {ECO:0000313|RefSeq:XP_025857723.1}
RP IDENTIFICATION.
RC STRAIN=TameXAggressive cross {ECO:0000313|RefSeq:XP_025857723.1};
RC TISSUE=Blood {ECO:0000313|RefSeq:XP_025857723.1};
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
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 deadenlyation-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:0000256|HAMAP-Rule:MF_03182}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage of poly(A) to 5'-AMP.; EC=3.1.13.4;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_03182};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_03182};
CC Note=Binds 2 metal cations per subunit in the catalytic exonuclease
CC domain. {ECO:0000256|HAMAP-Rule:MF_03182};
CC -!- ACTIVITY REGULATION: Positively regulated by the regulatory subunit
CC PAN3. {ECO:0000256|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. Interacts with ZFP36. {ECO:0000256|HAMAP-
CC Rule:MF_03182}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000256|HAMAP-
CC Rule:MF_03182}. Nucleus {ECO:0000256|HAMAP-Rule:MF_03182}.
CC Note=Shuttles between nucleus and cytoplasm. {ECO:0000256|HAMAP-
CC Rule:MF_03182}.
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:0000256|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:0000256|HAMAP-Rule:MF_03182}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. PAN2 subfamily.
CC {ECO:0000256|HAMAP-Rule:MF_03182}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_03182}.
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DR RefSeq; XP_025857723.1; XM_026001938.1.
DR Proteomes; UP000286640; Unplaced.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell.
DR GO; GO:0031251; C:PAN complex; IEA:UniProtKB-UniRule.
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; IEA:UniProtKB-UniRule.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IEA:UniProtKB-UniRule.
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.
PE 3: Inferred from homology;
KW Cytoplasm {ECO:0000256|HAMAP-Rule:MF_03182};
KW Exonuclease {ECO:0000256|ARBA:ARBA00022839, ECO:0000256|HAMAP-
KW Rule:MF_03182}; Hydrolase {ECO:0000256|HAMAP-Rule:MF_03182};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, ECO:0000256|HAMAP-
KW Rule:MF_03182};
KW mRNA processing {ECO:0000256|ARBA:ARBA00022664, ECO:0000256|HAMAP-
KW Rule:MF_03182};
KW Nuclease {ECO:0000256|ARBA:ARBA00022722, ECO:0000256|HAMAP-Rule:MF_03182};
KW Nucleus {ECO:0000256|HAMAP-Rule:MF_03182};
KW Reference proteome {ECO:0000313|Proteomes:UP000286640}.
FT DOMAIN 695..1098
FT /note="USP"
FT /evidence="ECO:0000259|PROSITE:PS50235"
FT REGION 1..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..50
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1152
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03182"
FT BINDING 1154
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03182"
FT BINDING 1261
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03182"
FT BINDING 1313
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03182"
SQ SEQUENCE 1376 AA; 153042 MW; D23C083F4F715885 CRC64;
MRELCPCEGL PSGRTPTRPL EAELTGVEAA PNLPSRSSSS SESLTTADAQ CVSVGAGGRP
GLPCSSPRHN GRLRGRGTAR RGSRCPGRRG VCGGASRTGS FRRMRAGPRR ARPAGQGPGS
RFLFSPPCLE MIGNAGEFRV WLSIRRGGEL GKLEFPAELT ALALPLLVLI PRAPKYPPWR
NLGQDVHSRP TGAVLLKVGS GPLRACCKGG CATGLICRHH ELRGPGLWTG GVCPHHAFCP
GPCPGCPPEF KSATECGAGS GRGGLGGSSR PRGHATSFFG PALERYSSFQ VNGSDDIRQI
QSLENGILFL TKNNLKYMAR GGLIIFDYLL DESEDMHSVL LTDSSTLLVG GLQNHILEID
LNTVQETQKY AVETPGVTIM RQTNRFFFCG HTSGKVSLRD LRTFKVEHEF DAFSGSLSDF
DVHGNLLAAC GFSSRLTGLA CDRFLKVYDL RMMRAITPLQ VHVDPAFLRF IPTYTSRLAI
ISQSGQCQFC EPTGLANPAD IFHVNPVGPL LMTFDVSASK QALAFGDSEG CVHLWTDSPE
PSFNPYSRET EFALPCLVDS LPPLDWSQDL LPLSLIPVPL TTDALLSDWP AANSAPAPRR
APPVDAEILR TMKKVGFIGY APNPRTRLRN QIPYRLKESD SEFDSFSQVT ESPIGREEEP
HLHMVSKKYR KVTIKYSKLG LEDFDFKHYN KTLFAGLEPH IPNAYCNCMI QVLYFLEPVR
CLIQNHLCQK EFCLACELGF LFHMLDLSRG DPCQGSNFLR AFRTIPEASA LGLILADSDE
ASGKGSLARL IQRWNRFILT QLHQDMQELE VPQAYRGAGV SSFCSSGDSV IGQLFSCEME
NCSLCRCGSE TVRASSTLLF TLSYPEDKTG KSCDFAQVLK RSICLEQNTQ AWCDNCEKYQ
PTIQTRNIRH LPDILVINCE VNSLKEADFW RVQAEVAFKM AIKKHGGEIS KNKEFALADW
KELGSPEGML MCSSVEELKN VWLPFSIRMK MTKNKGLDVC NWTDGDEIQW GPARAEEEHG
VYVYDLMATV VHILDSRTGG SLVAHIKVGE TYHQRKEGVT HQQWYLFNDF LIEPIDKHEA
VQFDMSWKVP AILYYVKRNL NSKYNLNIKN PIEASVLLAE ASLARKQRKT HTTFIPLMLN
EMPQVGDLVG LDAEFVTLNE EEAELRSDGT KSTIKPSQMS VARITCVRGQ GPNEGIPFID
DYISTQEQVV DYLTQYSGIK PGDLDAKISS KHLTTLKSTY LKLRFLIDIG VKFVGHGLQK
DFRVINLMVP KDQVLDTVYL FHMPRKRMIS LRFLAWYFLD LKIQGETHDS IEDARTALQL
YRKYLELSKN GTEPESFHKV LKGLYEKGRK MDWKVPEPEG QTSPKNAAVF SSVLAL
//
