ID A0A2K6TPM6_SAIBB Unreviewed; 1220 AA.
AC A0A2K6TPM6;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 27-MAR-2024, entry version 28.
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|Ensembl:ENSSBOP00000021595.1};
OS Saimiri boliviensis boliviensis (Bolivian squirrel monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Saimiriinae; Saimiri.
OX NCBI_TaxID=39432 {ECO:0000313|Ensembl:ENSSBOP00000021595.1, ECO:0000313|Proteomes:UP000233220};
RN [1] {ECO:0000313|Ensembl:ENSSBOP00000021595.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-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 AlphaFoldDB; A0A2K6TPM6; -.
DR STRING; 39432.ENSSBOP00000021595; -.
DR Ensembl; ENSSBOT00000038433.1; ENSSBOP00000021595.1; ENSSBOG00000027343.1.
DR GeneTree; ENSGT00390000013978; -.
DR OMA; TQELLWT; -.
DR Proteomes; UP000233220; 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:UP000233220};
KW Transferase {ECO:0000256|ARBA:ARBA00022679}.
FT DOMAIN 517..927
FT /note="USP"
FT /evidence="ECO:0000259|PROSITE:PS50235"
FT BINDING 981
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 983
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 1090
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 1142
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 1220 AA; 137584 MW; 8CE4D35C35B9BE22 CRC64;
MNFEGLDPGL AEYAPAMHSA LDPVLDAHLN PSLLQNVELD PEGVALEALP VQESVHIMEG
VYSELHSVVA EVGVPVSVSH FDLHEEMLWV GSHGGHATSF FGPALERYSS FQVNGSDDIR
QIQSLENGIL FLTKNNLKYM ARGGLIIFDY LLDENEDMHS LLLTDSSTLL VGGLQNHILE
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 LELPQAYRGA GGSFCSSGDS VIGQLFSCEM
ENCSLCRCGS ETVRASSTLL FTLSYPDDKT GKNYDFAQVL KRSICLDQNT QAWCDNCEKY
QPTIQTRNIR HLPDILVINC EVNSSKEADF WRMQAEFAFK MAVKKHSGEI SKNKEFALAD
WKELGSPEGV LVCPSIEELK NVWLPFSIRM KMTKNKGLDV CNWTDGDEIL AAWVPPSQWG
PARAEEEHGV YVYDLMATVV HILDSRTGGS LVAHIKVGET YHQRKEGVTH QQWYLFNDFL
IEPIDKHEAV QFDMNWKVPA ILYYVKRNLN SRYNLNIKNP IEASVLLAEA SLARKQRKTH
TTFIPLMLNE MPQIGDLVGL DAEFVTLNEE EAELRSDGTK STIKPSQMSV ARITCVRGQG
PNEGIPFIDD YISTQEQVVD YLTQYSGIKP GDLDAKISSK HLTTLKSTYL KLRFLIDIGV
KFVGHGLQKD FRVINLMVPK DQVLDTVYLF HMPRKRMISL RFLAWYFLDL KIQGETHDSI
EDARTALQLY RKYLELSKNG TEPESFHKVL KGLYEKGRKM DWKVPEPEGQ TSPKSKTWDG
TRETELGGFC ILFWVGLGEG
//
