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Protein

Piwi-like protein 4

Gene

Piwil4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Associates with secondary piRNAs antisense and PIWIL2/MILI is required for such association. The piRNA process acts upstream of known mediators of DNA methylation. Participates in a piRNA amplification loop. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation.4 Publications

GO - Molecular functioni

  • piRNA binding Source: UniProtKB

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • DNA methylation involved in gamete generation Source: UniProtKB
  • gene silencing by RNA Source: UniProtKB
  • meiotic cell cycle Source: UniProtKB-KW
  • multicellular organism development Source: UniProtKB-KW
  • piRNA metabolic process Source: UniProtKB
  • regulation of translation Source: UniProtKB-KW
  • spermatogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Meiosis, RNA-mediated gene silencing, Spermatogenesis, Translation regulation

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-5601884. PIWI-interacting RNA (piRNA) biogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Piwi-like protein 4
Short name:
mAgo5
Gene namesi
Name:Piwil4
Synonyms:Miwi2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:3041167. Piwil4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • P granule Source: UniProtKB
  • piP-body Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Males show spermatogenesis defects due to demethylation and subsequent derepression of transposable elements. Meiotic-progression is impaired during early prophase of meiosis I, followed by a marked and progressive loss of germ cells with age.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 848848Piwi-like protein 4PRO_0000234573Add
BLAST

Post-translational modificationi

Arginine methylation by PRMT5 is required for the interaction with Tudor domain-containing protein (TDRD1, TDRKH/TDRD2 and TDRD9) and subsequent localization to the meiotic nuage, also named P granule.1 Publication

Keywords - PTMi

Methylation

Proteomic databases

PRIDEiQ8CGT6.

PTM databases

iPTMnetiQ8CGT6.
PhosphoSiteiQ8CGT6.

Expressioni

Tissue specificityi

Detected in male germ cells beginning around 14.5-15.5 dpc but is absent from female germ cells. From 15.5 dpc and until birth, it is present in male germ cells. Not detected in somatic cells of the embryonic gonad. Expression declines soon after birth, reaching undetectable levels in 4 day-old mice (at protein level).1 Publication

Gene expression databases

BgeeiQ8CGT6.
CleanExiMM_PIWIL4.
ExpressionAtlasiQ8CGT6. baseline and differential.
GenevisibleiQ8CGT6. MM.

Interactioni

Subunit structurei

Interacts with PRMT5 and WDR77 (PubMed:19584108). Interacts (when methylated on arginine residues) with TDRD1, TDRKH/TDRD2 and TDRD9 (PubMed:19584108, PubMed:23714778). Interacts with MOV10L1 (PubMed:20534472, PubMed:20547853).4 Publications

Structurei

3D structure databases

ProteinModelPortaliQ8CGT6.
SMRiQ8CGT6. Positions 95-835.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini263 – 379117PAZPROSITE-ProRule annotationAdd
BLAST
Domaini541 – 834294PiwiPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the argonaute family. Piwi subfamily.Curated
Contains 1 PAZ domain.PROSITE-ProRule annotation
Contains 1 Piwi domain.PROSITE-ProRule annotation

Phylogenomic databases

GeneTreeiENSGT00760000119148.
HOGENOMiHOG000254789.
HOVERGENiHBG049411.
InParanoidiQ8CGT6.
KOiK02156.
OMAiQATSDFQ.
OrthoDBiEOG712TVQ.
PhylomeDBiQ8CGT6.
TreeFamiTF354206.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR003100. PAZ_dom.
IPR003165. Piwi.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamiPF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
[Graphical view]
SMARTiSM00949. PAZ. 1 hit.
SM00950. Piwi. 1 hit.
[Graphical view]
SUPFAMiSSF101690. SSF101690. 1 hit.
SSF53098. SSF53098. 1 hit.
PROSITEiPS50821. PAZ. 1 hit.
PS50822. PIWI. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8CGT6-1) [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
MSGRARVRAR GITTGHSARE VGRSSRDLMV TSASPGDSEA GGGTSVISQP
60 70 80 90 100
YELGVSSGDG GRTFMERRGK GRQDFEELGV CTREKLTHVK DCKTGSSGIP
110 120 130 140 150
VRLVTNLFNL DLPQDWQLYQ YHVTYSPDLA SRRLRIALLY NHSILSDKAK
160 170 180 190 200
AFDGASLFLS EKLDQKVTEL TSETQRGETI KITLTLTSKL FPNSPVCIQF
210 220 230 240 250
FNVIFRKILK NLSMYQIGRN FYKPSEPVEI PQYKLSLWPG FAISVSHFES
260 270 280 290 300
KLLFNADVNY KVLRNETVLD FMTDLCLRTG MSCFTEMCHK QLVGLVVLTR
310 320 330 340 350
YNNKTYRIDD IDWSVKPTQA FQKRDGSEVT YVDYYKQQYD ITLSDLNQPV
360 370 380 390 400
LVSLLKRKRN DNSEPQMVHL MPELCFLTGL SSQATSDFRL MKAVAEETRL
410 420 430 440 450
SPVGRQQQLA RLVDDIQRNP VARFELETWG LHFGSQLSLT GRVVPSEKIL
460 470 480 490 500
LQDHTCQPAF AADWSKDMRS CKVLSSQPLN RWLIVCCNRA EHLIEAFLSC
510 520 530 540 550
LRRVGGSMGF NVGYPKIIKV DETPAAFLRA IQVHGDPDVQ LVMCILPSNQ
560 570 580 590 600
KNYYDSIKKY LSSDCPVPSQ CVLTRTLNKQ GTMLSVATKI AMQMTCKLGG
610 620 630 640 650
ELWSVEIPLK SLMVVGIDIC RDALNKNVVV VGFVASINSR ITRWFSRCVL
660 670 680 690 700
QRTAADIADC LKVCMTGALN RWYRHNHDLP ARIVVYRDGV GNGQLKAVLE
710 720 730 740 750
YEVPQLLKSV TECGSDARSC RLSVVVVRKR CLLRLFASTD HTVQNPPLGT
760 770 780 790 800
VVDSEATRPE WYDFYLISQT ANRGTVSPTH YNVIYDDNAL KPDHMQRLTF
810 820 830 840
KLCHLYYNWQ GLISVPAPCQ YAHKLTFLVA QSVHKEPSLE LANNLFYL
Note: No experimental confirmation available.
Length:848
Mass (Da):95,773
Last modified:March 24, 2009 - v3
Checksum:i907DB987D47947FD
GO
Isoform 2 (identifier: Q8CGT6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     811-848: GLISVPAPCQYAHKLTFLVAQSVHKEPSLELANNLFYL → SCHGIQAALKPVTVPLPQLLSTGTMQ

Note: No experimental confirmation available.
Show »
Length:836
Mass (Da):94,252
Checksum:i6E060595D0C1117F
GO
Isoform 3 (identifier: Q8CGT6-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     761-761: Missing.

Show »
Length:847
Mass (Da):95,587
Checksum:i08D0A952655C0974
GO

Sequence cautioni

The sequence AAN75583.1 differs from that shown. Reason: Erroneous gene model prediction. Curated
The sequence BAC28462.1 differs from that shown. Reason: Frameshift at position 745. Curated
The sequence CAO77951.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti644 – 6441W → R in BAF65667 (PubMed:18381894).Curated
Sequence conflicti808 – 8081N → D in BAF65667 (PubMed:18381894).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei761 – 7611Missing in isoform 3. 1 PublicationVSP_036666
Alternative sequencei811 – 84838GLISV…NLFYL → SCHGIQAALKPVTVPLPQLL STGTMQ in isoform 2. 1 PublicationVSP_018376Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY135692 Genomic DNA. Translation: AAN75583.1. Sequence problems.
AB258534 mRNA. Translation: BAF65667.1.
CT030247 Genomic DNA. Translation: CAO77949.1.
CT030247 Genomic DNA. Translation: CAO77951.1. Sequence problems.
AK033746 mRNA. Translation: BAC28462.1. Frameshift.
RefSeqiNP_808573.2. NM_177905.3.
UniGeneiMm.334969.

Genome annotation databases

EnsembliENSMUST00000115644; ENSMUSP00000111308; ENSMUSG00000036912. [Q8CGT6-1]
GeneIDi330890.
KEGGimmu:330890.
UCSCiuc009oet.1. mouse. [Q8CGT6-1]
uc009oev.1. mouse. [Q8CGT6-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY135692 Genomic DNA. Translation: AAN75583.1. Sequence problems.
AB258534 mRNA. Translation: BAF65667.1.
CT030247 Genomic DNA. Translation: CAO77949.1.
CT030247 Genomic DNA. Translation: CAO77951.1. Sequence problems.
AK033746 mRNA. Translation: BAC28462.1. Frameshift.
RefSeqiNP_808573.2. NM_177905.3.
UniGeneiMm.334969.

3D structure databases

ProteinModelPortaliQ8CGT6.
SMRiQ8CGT6. Positions 95-835.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

iPTMnetiQ8CGT6.
PhosphoSiteiQ8CGT6.

Proteomic databases

PRIDEiQ8CGT6.

Protocols and materials databases

DNASUi330890.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000115644; ENSMUSP00000111308; ENSMUSG00000036912. [Q8CGT6-1]
GeneIDi330890.
KEGGimmu:330890.
UCSCiuc009oet.1. mouse. [Q8CGT6-1]
uc009oev.1. mouse. [Q8CGT6-3]

Organism-specific databases

CTDi143689.
MGIiMGI:3041167. Piwil4.

Phylogenomic databases

GeneTreeiENSGT00760000119148.
HOGENOMiHOG000254789.
HOVERGENiHBG049411.
InParanoidiQ8CGT6.
KOiK02156.
OMAiQATSDFQ.
OrthoDBiEOG712TVQ.
PhylomeDBiQ8CGT6.
TreeFamiTF354206.

Enzyme and pathway databases

ReactomeiR-MMU-5601884. PIWI-interacting RNA (piRNA) biogenesis.

Miscellaneous databases

PROiQ8CGT6.
SOURCEiSearch...

Gene expression databases

BgeeiQ8CGT6.
CleanExiMM_PIWIL4.
ExpressionAtlasiQ8CGT6. baseline and differential.
GenevisibleiQ8CGT6. MM.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR003100. PAZ_dom.
IPR003165. Piwi.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamiPF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
[Graphical view]
SMARTiSM00949. PAZ. 1 hit.
SM00950. Piwi. 1 hit.
[Graphical view]
SUPFAMiSSF101690. SSF101690. 1 hit.
SSF53098. SSF53098. 1 hit.
PROSITEiPS50821. PAZ. 1 hit.
PS50822. PIWI. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis."
    Carmell M.A., Xuan Z., Zhang M.Q., Hannon G.J.
    Genes Dev. 16:2733-2742(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1).
  2. "DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes."
    Kuramochi-Miyagawa S., Watanabe T., Gotoh K., Totoki Y., Toyoda A., Ikawa M., Asada N., Kojima K., Yamaguchi Y., Ijiri T.W., Hata K., Li E., Matsuda Y., Kimura T., Okabe M., Sakaki Y., Sasaki H., Nakano T.
    Genes Dev. 22:908-917(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, DISRUPTION PHENOTYPE.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 667-848 (ISOFORM 2).
    Strain: C57BL/6J.
    Tissue: Epididymis.
  5. "MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline."
    Carmell M.A., Girard A., van de Kant H.J.G., Bourc'his D., Bestor T.H., de Rooij D.G., Hannon G.J.
    Dev. Cell 12:503-514(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  6. "A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice."
    Aravin A.A., Sachidanandam R., Bourc'his D., Schaefer C., Pezic D., Toth K.F., Bestor T., Hannon G.J.
    Mol. Cell 31:785-799(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  7. "Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members."
    Vagin V.V., Wohlschlegel J., Qu J., Jonsson Z., Huang X., Chuma S., Girard A., Sachidanandam R., Hannon G.J., Aravin A.A.
    Genes Dev. 23:1749-1762(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: METHYLATION, SUBCELLULAR LOCATION, INTERACTION WITH TDRD1; TDRKH AND TDRD9.
  8. "Loss of the Mili-interacting Tudor domain-containing protein-1 activates transposons and alters the Mili-associated small RNA profile."
    Reuter M., Chuma S., Tanaka T., Franz T., Stark A., Pillai R.S.
    Nat. Struct. Mol. Biol. 16:639-646(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  9. "Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway."
    Zheng K., Xiol J., Reuter M., Eckardt S., Leu N.A., McLaughlin K.J., Stark A., Sachidanandam R., Pillai R.S., Wang P.J.
    Proc. Natl. Acad. Sci. U.S.A. 107:11841-11846(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MOV10L1.
  10. "MOV10L1 is necessary for protection of spermatocytes against retrotransposons by Piwi-interacting RNAs."
    Frost R.J., Hamra F.K., Richardson J.A., Qi X., Bassel-Duby R., Olson E.N.
    Proc. Natl. Acad. Sci. U.S.A. 107:11847-11852(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MOV10L1.
  11. "Tdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline."
    Saxe J.P., Chen M., Zhao H., Lin H.
    EMBO J. 32:1869-1885(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TDRKH.
  12. "PIWI slicing and EXD1 drive biogenesis of nuclear piRNAs from cytosolic targets of the mouse piRNA pathway."
    Yang Z., Chen K.M., Pandey R.R., Homolka D., Reuter M., Janeiro B.K., Sachidanandam R., Fauvarque M.O., McCarthy A.A., Pillai R.S.
    Mol. Cell 61:138-152(2016) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiPIWL4_MOUSE
AccessioniPrimary (citable) accession number: Q8CGT6
Secondary accession number(s): A6P4B9
, A6X963, A6X964, Q8CC75
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: March 24, 2009
Last modified: June 8, 2016
This is version 97 of the entry and version 3 of the sequence. [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
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.