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Protein

Pumilio homolog 1

Gene

Pum1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation. Also mediates deadenylation-independent repression by promoting accessibility of miRNAs. Following growth factor stimulation, phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA-binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle (By similarity). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (By similarity). Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm (By similarity). Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery (PubMed:25768905). In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3'-UTR of mRNAs coding for regulators of p53/TP53 (PubMed:22342750). Involved in embryonic stem cell renewal by facilitating the exit from the ground state: acts by targeting mRNAs coding for naive pluripotency transcription factors and accelerates their down-regulation at the onset of differentiation (PubMed:24412312). Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level (By similarity).By similarity3 Publications

GO - Molecular functioni

  • miRNA binding Source: MGI
  • mRNA 3'-UTR binding Source: UniProtKB
  • RNA binding Source: MGI

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processDifferentiation, Spermatogenesis, Translation regulation

Enzyme and pathway databases

ReactomeiR-MMU-432722 Golgi Associated Vesicle Biogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Pumilio homolog 1Curated
Gene namesi
Name:Pum1Imported
Synonyms:Kiaa00991 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1931749 Pum1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mice are viable and grow to adulthood without apparent defects except that they are smaller than wild-type mice at 8 weeks of age (PubMed:22342750, PubMed:25768905). Males mice however show significantly reduced sperm counts and fertility: testicular hypoplasia is observed (PubMed:22342750). Heterozygous knockout mice manifest neurological dysfunction, hyperactivity, and progressive cerebellar signs including gross and fine motor incoordination (PubMed:25768905, PubMed:29474920). They show spontaneous seizures, abnormal EEG activity with generalized epileptiform spikes by the age of 16 weeks, and have smaller than normal cerebella (PubMed:29474920).3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000759182 – 1189Pumilio homolog 1Add BLAST1188

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei19PhosphoserineBy similarity1
Modified residuei75PhosphoserineCombined sources1
Modified residuei98PhosphoserineBy similarity1
Modified residuei106PhosphoserineBy similarity1
Modified residuei112PhosphothreonineBy similarity1
Modified residuei124PhosphoserineCombined sources1
Modified residuei159PhosphoserineBy similarity1
Modified residuei197PhosphoserineBy similarity1
Modified residuei209PhosphoserineBy similarity1
Modified residuei229PhosphoserineCombined sources1
Modified residuei305PhosphoserineBy similarity1
Modified residuei515PhosphothreonineBy similarity1
Modified residuei710PhosphoserineCombined sources1
Modified residuei715PhosphoserineBy similarity1
Modified residuei797Omega-N-methylarginineBy similarity1
Modified residuei807PhosphoserineBy similarity1
Modified residuei823PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-715 promotes RNA-binding activity. Following growth factor stimulation phosphorylated at Ser-715, promoting binding to the 3'-UTR of CDKN1B/p27 mRNA.By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

PaxDbiQ80U78
PeptideAtlasiQ80U78
PRIDEiQ80U78

PTM databases

iPTMnetiQ80U78
PhosphoSitePlusiQ80U78

Expressioni

Tissue specificityi

Widely expressed. Expressed in brain, heart, kidney, liver, lung, skin, intestine, spleen, testis and thymus. Weakly or not expressed in muscles and stomach. Expressed at various stages of myeloid and lymphoid cell development (PubMed:12667987). Highly expressed in testis (PubMed:22342750). Expressed in all major brain regions (at protein level) (PubMed:25768905).3 Publications

Developmental stagei

During the development of the testis, expressed 2 days postpartum (dpp) and then starts to increase at 14 dpp when pachytene spermatocytes first appear.1 Publication

Gene expression databases

BgeeiENSMUSG00000028580 Expressed in 279 organ(s), highest expression level in embryo
CleanExiMM_PUM1
ExpressionAtlasiQ80U78 baseline and differential
GenevisibleiQ80U78 MM

Interactioni

Subunit structurei

Recruits the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (By similarity). Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (By similarity).By similarity

Protein-protein interaction databases

BioGridi219849, 2 interactors
IntActiQ80U78, 3 interactors
MINTiQ80U78
STRINGi10090.ENSMUSP00000030315

Structurei

3D structure databases

ProteinModelPortaliQ80U78
SMRiQ80U78
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini829 – 1171PUM-HDPROSITE-ProRule annotationAdd BLAST343
Repeati849 – 884Pumilio 1Add BLAST36
Repeati885 – 920Pumilio 2Add BLAST36
Repeati921 – 958Pumilio 3Add BLAST38
Repeati959 – 994Pumilio 4Add BLAST36
Repeati995 – 1030Pumilio 5Add BLAST36
Repeati1031 – 1066Pumilio 6Add BLAST36
Repeati1067 – 1102Pumilio 7Add BLAST36
Repeati1106 – 1145Pumilio 8Add BLAST40

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni864 – 868Adenine-nucleotide binding in RNA targetBy similarity5
Regioni900 – 904Uracil-nucleotide binding in RNA targetBy similarity5
Regioni936 – 940Adenine-nucleotide binding in RNA targetBy similarity5
Regioni974 – 978Non-specific-nucleotide binding in RNA targetBy similarity5
Regioni1010 – 1014Adenine-nucleotide binding in RNA targetBy similarity5
Regioni1046 – 1050Uracil-nucleotide binding in RNA targetBy similarity5
Regioni1082 – 1086Guanine-nucleotide binding in RNA targetBy similarity5
Regioni1083 – 1086Guanine-nucleotide binding in RNA targetBy similarity4
Regioni1125 – 1129Uracil-nucleotide binding in RNA targetBy similarity5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi393 – 614Ala-richAdd BLAST222
Compositional biasi476 – 524Gln-richAdd BLAST49
Compositional biasi643 – 816Ser-richAdd BLAST174

Domaini

The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface. PUM1 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1488 Eukaryota
COG5099 LUCA
GeneTreeiENSGT00390000017241
HOGENOMiHOG000238461
HOVERGENiHBG049462
InParanoidiQ80U78
KOiK17943
OMAiFIPPDQQ
OrthoDBiEOG091G04QO
PhylomeDBiQ80U78
TreeFamiTF318160

Family and domain databases

CDDicd07920 Pumilio, 1 hit
Gene3Di1.25.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR033133 PUM-HD
IPR033712 Pumilio_RNA-bd
IPR001313 Pumilio_RNA-bd_rpt
PfamiView protein in Pfam
PF00806 PUF, 8 hits
SMARTiView protein in SMART
SM00025 Pumilio, 8 hits
SUPFAMiSSF48371 SSF48371, 1 hit
PROSITEiView protein in PROSITE
PS50302 PUM, 8 hits
PS50303 PUM_HD, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q80U78-1) [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
MSVACVLKRK AVLWQDSFSP HLKHHPQEPA NPNMPVVLTS GTGSQAQPQP
60 70 80 90 100
AANQALAAGT HSSPVPGSIG VAGRSQDDAM VDYFFQRQHG EQLGGGGSGG
110 120 130 140 150
GGYNTSKHRW PTGDNIHAEH QVRSMDELNH DFQALALEGR AMGEQLLPGK
160 170 180 190 200
KFWETDESSK DGPKGIFLGD QWRDSAWGTS DHSVSQPIMV QRRPGQSFHV
210 220 230 240 250
NSEVNSVLSP RSESGGLGVS MVEYVLSSSP GDSCLRKGGF GPRDADSDEN
260 270 280 290 300
DKGEKKNKGT FDGDKLGDLK EEGDVMDKTN GLPVQNGIDA DVKDFSRTPG
310 320 330 340 350
NCQNSANEVD LLGPNQNGSE GLAQLTSTNG AKPVEDFSNM ESQSVPLDPM
360 370 380 390 400
EHVGMEPLQF DYSGTQVPVD SAAATVGLFD YNSQQQLFQR PNALAVQQLT
410 420 430 440 450
AAQQQQYALA AAHQPHIAGL APAAFVPNPY IISAAPPGTD PYTAGLAAAA
460 470 480 490 500
TLGPAVVPHQ YYGVTPWGVY PASLFQQQAA AAAAATNSAT QQSAPQAQQG
510 520 530 540 550
QQQVLRGGAS QRPLTPNQNQ QGQQTDPLVA AAAVNSALAF GQGLAAGMPG
560 570 580 590 600
YPVLAPAAYY DQTGALVVNA GARNGLGAPV RLVAPAPVII SSSAAQAAVA
610 620 630 640 650
AAAASANGAA GGLAGTTNGP FRPLGTQQPQ PQPQQQPSNN LASSSFYGNN
660 670 680 690 700
SLSSNSQSSS LFSQGSAQPA NTSLGFGSSS SLGATLGSAL GGFGTAVANS
710 720 730 740 750
NTGSGSRRDS LTGSSDLYKR TSSSLAPIGH SFYSSLSYSS SPGPVGMPLP
760 770 780 790 800
SQGPGHSQTP PPSLSSHGSS SSLNLGGLTN GSGRYISAAP GAEAKYRSAS
810 820 830 840 850
SASSLFSPSS TLFSSSRLRY GMSDVMPSGR SRLLEDFRNN RYPNLQLREI
860 870 880 890 900
AGHIMEFSQD QHGSRFIQLK LERATAAERQ LVFNEILQAA YQLMVDVFGN
910 920 930 940 950
YVIQKFFEFG SHEQKLALAE RIRGHVLSLA LQMYGCRVIQ KALEFIPSDQ
960 970 980 990 1000
QVINEMVREL DGHVLKCVKD QNGNHVVQKC IECVQPQSLQ FIIDAFKGQV
1010 1020 1030 1040 1050
FALSTHPYGC RVIQRILEHC LPDQTLPILE ELHQHTEQLV QDQYGNYVIQ
1060 1070 1080 1090 1100
HVLEHGRPED KSKIVAEIRG NVLVLSQHKF ASNVVEKCVT HASRTERAVL
1110 1120 1130 1140 1150
IDEVCTMNDG PHSALYTMMK DQYANYVVQK MIDVAEPGQR KIVMHKIRPH
1160 1170 1180
IATLRKYTYG KHILAKLEKY YMKNGVDLGP ICGPPNGII
Length:1,189
Mass (Da):126,619
Last modified:February 2, 2004 - v2
Checksum:iCCB18634FBE3468A
GO
Isoform 2 (identifier: Q80U78-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     418-418: Missing.
     952-953: Missing.

Show »
Length:1,186
Mass (Da):126,336
Checksum:iE3988AF20E34091A
GO
Isoform 3 (identifier: Q80U78-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     418-418: Missing.

Show »
Length:1,188
Mass (Da):126,548
Checksum:i3959D5DC5825A160
GO
Isoform 4 (identifier: Q80U78-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     181-189: DHSVSQPIM → GNLALASLL
     190-1189: Missing.

Note: No experimental confirmation available.
Show »
Length:189
Mass (Da):20,206
Checksum:i41749718B6FF8B1B
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9Q6M7E9Q6M7_MOUSE
Pumilio homolog 1
Pum1
944Annotation score:
Q3TTW5Q3TTW5_MOUSE
Pumilio homolog 1
Pum1
1,092Annotation score:
A8WHM8A8WHM8_MOUSE
Pumilio homolog 1
Pum1
218Annotation score:

Sequence cautioni

The sequence BAC65487 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti186Q → H in AAG42319 (PubMed:12667987).Curated1
Sequence conflicti545A → D in AAG42319 (PubMed:12667987).Curated1
Sequence conflicti552P → T in AAG42319 (PubMed:12667987).Curated1
Sequence conflicti555A → G in AAG42319 (PubMed:12667987).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_009315181 – 189DHSVSQPIM → GNLALASLL in isoform 4. 1 Publication9
Alternative sequenceiVSP_009316190 – 1189Missing in isoform 4. 1 PublicationAdd BLAST1000
Alternative sequenceiVSP_009317418Missing in isoform 2 and isoform 3. 1 Publication1
Alternative sequenceiVSP_009318952 – 953Missing in isoform 2. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF321909 mRNA Translation: AAG42319.1
AK122205 mRNA Translation: BAC65487.1 Different initiation.
AK052145 mRNA Translation: BAC34857.1
BC048174 mRNA Translation: AAH48174.1
BC050747 mRNA Translation: AAH50747.1
CCDSiCCDS18710.1 [Q80U78-1]
CCDS51311.1 [Q80U78-2]
CCDS51312.1 [Q80U78-3]
RefSeqiNP_001153075.1, NM_001159603.1 [Q80U78-2]
NP_001153076.1, NM_001159604.1 [Q80U78-3]
NP_109647.2, NM_030722.2 [Q80U78-1]
UniGeneiMm.440206

Genome annotation databases

EnsembliENSMUST00000030315; ENSMUSP00000030315; ENSMUSG00000028580 [Q80U78-1]
ENSMUST00000097862; ENSMUSP00000095474; ENSMUSG00000028580 [Q80U78-3]
ENSMUST00000097864; ENSMUSP00000095476; ENSMUSG00000028580 [Q80U78-2]
ENSMUST00000200938; ENSMUSP00000144158; ENSMUSG00000106966 [Q80U78-3]
ENSMUST00000202398; ENSMUSP00000144210; ENSMUSG00000106966 [Q80U78-2]
ENSMUST00000202551; ENSMUSP00000143996; ENSMUSG00000106966 [Q80U78-1]
GeneIDi80912
KEGGimmu:80912
UCSCiuc008uzl.2 mouse [Q80U78-4]
uc008uzm.3 mouse [Q80U78-1]
uc008uzn.3 mouse [Q80U78-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF321909 mRNA Translation: AAG42319.1
AK122205 mRNA Translation: BAC65487.1 Different initiation.
AK052145 mRNA Translation: BAC34857.1
BC048174 mRNA Translation: AAH48174.1
BC050747 mRNA Translation: AAH50747.1
CCDSiCCDS18710.1 [Q80U78-1]
CCDS51311.1 [Q80U78-2]
CCDS51312.1 [Q80U78-3]
RefSeqiNP_001153075.1, NM_001159603.1 [Q80U78-2]
NP_001153076.1, NM_001159604.1 [Q80U78-3]
NP_109647.2, NM_030722.2 [Q80U78-1]
UniGeneiMm.440206

3D structure databases

ProteinModelPortaliQ80U78
SMRiQ80U78
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi219849, 2 interactors
IntActiQ80U78, 3 interactors
MINTiQ80U78
STRINGi10090.ENSMUSP00000030315

PTM databases

iPTMnetiQ80U78
PhosphoSitePlusiQ80U78

Proteomic databases

PaxDbiQ80U78
PeptideAtlasiQ80U78
PRIDEiQ80U78

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030315; ENSMUSP00000030315; ENSMUSG00000028580 [Q80U78-1]
ENSMUST00000097862; ENSMUSP00000095474; ENSMUSG00000028580 [Q80U78-3]
ENSMUST00000097864; ENSMUSP00000095476; ENSMUSG00000028580 [Q80U78-2]
ENSMUST00000200938; ENSMUSP00000144158; ENSMUSG00000106966 [Q80U78-3]
ENSMUST00000202398; ENSMUSP00000144210; ENSMUSG00000106966 [Q80U78-2]
ENSMUST00000202551; ENSMUSP00000143996; ENSMUSG00000106966 [Q80U78-1]
GeneIDi80912
KEGGimmu:80912
UCSCiuc008uzl.2 mouse [Q80U78-4]
uc008uzm.3 mouse [Q80U78-1]
uc008uzn.3 mouse [Q80U78-2]

Organism-specific databases

CTDi9698
MGIiMGI:1931749 Pum1
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1488 Eukaryota
COG5099 LUCA
GeneTreeiENSGT00390000017241
HOGENOMiHOG000238461
HOVERGENiHBG049462
InParanoidiQ80U78
KOiK17943
OMAiFIPPDQQ
OrthoDBiEOG091G04QO
PhylomeDBiQ80U78
TreeFamiTF318160

Enzyme and pathway databases

ReactomeiR-MMU-432722 Golgi Associated Vesicle Biogenesis

Miscellaneous databases

ChiTaRSiPum1 mouse
PROiPR:Q80U78
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028580 Expressed in 279 organ(s), highest expression level in embryo
CleanExiMM_PUM1
ExpressionAtlasiQ80U78 baseline and differential
GenevisibleiQ80U78 MM

Family and domain databases

CDDicd07920 Pumilio, 1 hit
Gene3Di1.25.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR033133 PUM-HD
IPR033712 Pumilio_RNA-bd
IPR001313 Pumilio_RNA-bd_rpt
PfamiView protein in Pfam
PF00806 PUF, 8 hits
SMARTiView protein in SMART
SM00025 Pumilio, 8 hits
SUPFAMiSSF48371 SSF48371, 1 hit
PROSITEiView protein in PROSITE
PS50302 PUM, 8 hits
PS50303 PUM_HD, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPUM1_MOUSE
AccessioniPrimary (citable) accession number: Q80U78
Secondary accession number(s): Q80X96
, Q80YU8, Q8BPV7, Q9EPU6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: February 2, 2004
Last modified: October 10, 2018
This is version 131 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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