PUM1_PONAB
ID PUM1_PONAB Reviewed; 1186 AA.
AC Q5R5X3;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Pumilio homolog 1 {ECO:0000305};
GN Name=PUM1;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Sequence-specific RNA-binding protein that acts as a post-
CC transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds
CC to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-
CC UGUANAUA-3', that is related to the Nanos Response Element (NRE).
CC Mediates post-transcriptional repression of transcripts via different
CC mechanisms: acts via direct recruitment of the CCR4-POP2-NOT
CC deadenylase leading to translational inhibition and mRNA degradation.
CC Also mediates deadenylation-independent repression by promoting
CC accessibility of miRNAs. Following growth factor stimulation,
CC phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a
CC local conformational change that exposes miRNA-binding sites, promoting
CC association of miR-221 and miR-222, efficient suppression of CDKN1B/p27
CC expression, and rapid entry to the cell cycle. Acts as a post-
CC transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and
CC facilitating miRNA regulation. Represses a program of genes necessary
CC to maintain genomic stability such as key mitotic, DNA repair and DNA
CC replication factors. Its ability to repress those target mRNAs is
CC regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage)
CC which, due to its high abundance and multitude of PUMILIO binding
CC sites, is able to sequester a significant fraction of PUM1 and PUM2 in
CC the cytoplasm. Involved in neuronal functions by regulating ATXN1 mRNA
CC levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to
CC their down-regulation independently of the miRNA machinery. Plays a
CC role in cytoplasmic sensing of viral infection (By similarity). In
CC testis, acts as a post-transcriptional regulator of spermatogenesis by
CC binding to the 3'-UTR of mRNAs coding for regulators of p53/TP53.
CC Involved in embryonic stem cell renewal by facilitating the exit from
CC the ground state: acts by targeting mRNAs coding for naive pluripotency
CC transcription factors and accelerates their down-regulation at the
CC onset of differentiation (By similarity). Binds specifically to miRNA
CC MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a
CC postranscriptional level (By similarity).
CC {ECO:0000250|UniProtKB:Q14671, ECO:0000250|UniProtKB:Q80U78}.
CC -!- SUBUNIT: Recruits the CCR4-POP2-NOT deadenylase leading to
CC translational inhibition and mRNA degradation (By similarity).
CC Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (By
CC similarity). {ECO:0000250|UniProtKB:Q14671}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14671}.
CC Cytoplasm, P-body {ECO:0000250|UniProtKB:Q14671}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:Q14671}.
CC -!- DOMAIN: The pumilio repeats mediate the association with RNA by packing
CC together to form a right-handed superhelix that approximates a half
CC donut. RNA-binding occurs on the concave side of the surface. PUM1 is
CC composed of 8 pumilio repeats of 36 residues; each repeat binds a
CC single nucleotide in its RNA target. Residues at positions 12 and 16 of
CC the pumilio repeat bind each RNA base via hydrogen bonding or van der
CC Waals contacts with the Watson-Crick edge, while the amino acid at
CC position 13 makes a stacking interaction. The recognition of RNA by
CC pumilio repeats is base specific: cysteine and glutamine at position 12
CC and 16, respectively, bind adenine; asparagine and glutamine bind
CC uracil; and serine and glutamate bind guanine.
CC {ECO:0000250|UniProtKB:Q14671}.
CC -!- PTM: Phosphorylation at Ser-714 promotes RNA-binding activity.
CC Following growth factor stimulation phosphorylated at Ser-714,
CC promoting binding to the 3'-UTR of CDKN1B/p27 mRNA.
CC {ECO:0000250|UniProtKB:Q14671}.
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DR EMBL; CR860728; CAH92843.1; -; mRNA.
DR RefSeq; NP_001127595.1; NM_001134123.1.
DR AlphaFoldDB; Q5R5X3; -.
DR SMR; Q5R5X3; -.
DR STRING; 9601.ENSPPYP00000001871; -.
DR GeneID; 100174674; -.
DR KEGG; pon:100174674; -.
DR CTD; 9698; -.
DR eggNOG; KOG1488; Eukaryota.
DR InParanoid; Q5R5X3; -.
DR OrthoDB; 207351at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISS:UniProtKB.
DR GO; GO:0008344; P:adult locomotory behavior; ISS:UniProtKB.
DR GO; GO:0035196; P:miRNA processing; ISS:UniProtKB.
DR GO; GO:0061157; P:mRNA destabilization; ISS:UniProtKB.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; ISS:UniProtKB.
DR GO; GO:0016441; P:post-transcriptional gene silencing; ISS:UniProtKB.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0051983; P:regulation of chromosome segregation; ISS:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0048863; P:stem cell differentiation; ISS:UniProtKB.
DR CDD; cd07920; Pumilio; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR033133; PUM-HD.
DR InterPro; IPR033712; Pumilio_RNA-bd.
DR InterPro; IPR001313; Pumilio_RNA-bd_rpt.
DR Pfam; PF00806; PUF; 8.
DR SMART; SM00025; Pumilio; 8.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50302; PUM; 8.
DR PROSITE; PS50303; PUM_HD; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Differentiation; Methylation; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding; Spermatogenesis;
KW Translation regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT CHAIN 2..1186
FT /note="Pumilio homolog 1"
FT /id="PRO_0000312355"
FT DOMAIN 828..1168
FT /note="PUM-HD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00318"
FT REPEAT 848..883
FT /note="Pumilio 1"
FT REPEAT 884..919
FT /note="Pumilio 2"
FT REPEAT 920..955
FT /note="Pumilio 3"
FT REPEAT 956..991
FT /note="Pumilio 4"
FT REPEAT 992..1027
FT /note="Pumilio 5"
FT REPEAT 1028..1063
FT /note="Pumilio 6"
FT REPEAT 1064..1099
FT /note="Pumilio 7"
FT REPEAT 1103..1142
FT /note="Pumilio 8"
FT REGION 22..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 233..272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 485..524
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 613..648
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 742..775
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 863..867
FT /note="Adenine-nucleotide binding in RNA target"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT REGION 899..903
FT /note="Uracil-nucleotide binding in RNA target"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT REGION 935..939
FT /note="Adenine-nucleotide binding in RNA target"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT REGION 971..975
FT /note="Non-specific-nucleotide binding in RNA target"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT REGION 1007..1011
FT /note="Adenine-nucleotide binding in RNA target"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT REGION 1043..1047
FT /note="Uracil-nucleotide binding in RNA target"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT REGION 1079..1083
FT /note="Guanine-nucleotide binding in RNA target"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT REGION 1080..1083
FT /note="Guanine-nucleotide binding in RNA target"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT REGION 1122..1126
FT /note="Uracil-nucleotide binding in RNA target"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT COMPBIAS 33..61
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..272
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 619..648
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 757..775
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 75
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 112
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 305
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TB72"
FT MOD_RES 514
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8TB72"
FT MOD_RES 709
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 714
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 796
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 806
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
FT MOD_RES 822
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14671"
SQ SEQUENCE 1186 AA; 126443 MW; 9FB008AEF89F0017 CRC64;
MSVACVLKRK AVLWQDSFSP HLKHHPQEPA NPNMPVVLTS GTGSQAQPQP AANQALAAGT
HSSPVPGSIG VAGRSQDDAM VDYFFQRQHG EQLGGGGSGG GGYNNSKHRW PTGDNIHAEH
QVRSMDELNH DFQALALEGR AMGEQLLPGK KFWETDESSK DGPKGIFLGD QWRDSAWGTS
DHSVSQPIMV QRRPGQSFHV NSEVNSVLSP RSESGGLGVS MVEYVLSSSP GDSCLRKGGF
GPRDADSDEN DKGEKKNKGT FDGDKLGDLK EEGDVMDKTN GLPVQNGIDA DVKDFSRTPG
NCQNSANEVD LLGPNQNGSE GLAQLTSTNG AKPVEDFSNM ESQSVPLDPM EHVGMEPLQF
DYSGTQVPVD SAAATVGLFD YNSQQQLFQR PNALAVQQLT AAQQQQYALA AAHQPHIGLA
PAAFVPNPYI ISAAPPGTDP YTAGLAAAAT LGPAVVPHQY YGVTPWGVYP ASLFQQQAAA
AAAATNSANQ QTTPQAQQGQ QQVLRGGASQ RPLTPNQNQQ GQQTDPLVAA AAVNSALAFG
QGLAAGMPGY PVLAPAAYYD QTGALVVNAG ARNGLGAPVR LVAPAPVIIS SSAAQAAVAA
AAASANGAAG GLAGTTNGPF RPLGTQQPQP QPQQQPNNNL ASSSFYGNNS LNSNSQSSSL
FSQGSAQPAN TSLGFGSSSS LGATLGSALG GFGTAVANSN TGSGSRRDSL TGSSDLYKRT
SSSLTPIGHS FYNGLSFSSS PGPVGMPLPS QGPGHSQTPP PSLSSHGSSS SLNLGGLTNG
GGRYISAAPG AEAKYRSASS ASSLFSPSST LFSSSRLRYG MSDVMPSGRS RLLEDFRNNR
YPNLQLREIA GHIMEFSQDQ HGSRFIQLKL ERATPAERQL VFNEILQAAY QLMVDVFGNY
VIQKFFEFGS LEQKLALAER IRGHVLSLAL QMYGCRVIQK ALEFIPSDQQ NEMVRELDGH
VLKCVKDQNG NHVVQKCIEC VQPQSLQFII DAFKGQVFAL STHPYGCRVI QRILEHCLPD
QTLPILEELH QHTEQLVQDQ YGNYVIQHVL EHGRPEDKSK IVAEIRGNVL VLSQHKFASN
VVEKCVTHAS RTERAVLIDE VCTMNDGPHS ALYTMMKDQY ANYVVQKMID VAEPGQRKIV
MHKIRPHIAT LRKYTYGKHI LAKLEKYYMK NGVDLGPICG PPNGII
