Q7Z3Z4 (PIWL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Piwi-like protein 4

Gene names

Name:	PIWIL4
Synonyms:	HIWI2, PIWI

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	852 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Plays a central role during spermatogenesis by repressing transposable elements and prevent 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 govern 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 By similarity. May be involved in the chromatin-modifying pathway by inducing 'Lys-9' methylation of histone H3 at some loci. Ref.1 Ref.5
Subunit structure	Interacts with PRMT5 and WDR77. Interacts (when methylated on arginine residues) with TDRD1, TDRKH/TDRD2 and TDRD9 By similarity.
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. Note: Probable component of the meiotic nuage, also named P granule, a germ-cell-specific organelle required to repress transposon during meiosis. PIWIL2/MILI is required for nuclear localization By similarity.
Tissue specificity	Expressed in testis. According to Ref.5, it is ubiquitously expressed. Ref.5
Post-translational modification	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 By similarity.
Sequence similarities	Belongs to the argonaute family. Piwi subfamily. Contains 1 PAZ domain. Contains 1 Piwi domain.
Sequence caution	The sequence BAC04873.1 differs from that shown. Reason: Erroneous initiation. The sequence CAH18436.1 differs from that shown. Reason: Frameshift at position 454.

Ontologies

Keywords
Biological process	Differentiation Meiosis RNA-mediated gene silencing Spermatogenesis Translation regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	RNA-binding
Molecular function	Developmental protein
PTM	Methylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA methylation involved in gamete generation Inferred from sequence or structural similarity. Source: UniProtKB cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW gene silencing by RNA Inferred from sequence or structural similarity. Source: UniProtKB meiosis Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW piRNA metabolic process Inferred from sequence or structural similarity. Source: UniProtKB regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW spermatogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	nucleus Inferred from sequence or structural similarity. Source: UniProtKB piP-body Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	piRNA binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7Z3Z4-1)

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.

Isoform 2 (identifier: Q7Z3Z4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-29: MSGRARVKARGIARSPSATEVGRIQASPL → MG
     522-522: I → M
     523-852: Missing.

Isoform 3 (identifier: Q7Z3Z4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: Missing.
     522-522: I → M
     523-852: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 852	852	Piwi-like protein 4		PRO_0000234572
Regions
	Domain	268 – 384	117	PAZ
	Domain	546 – 838	293	Piwi
Natural variations
	Alternative sequence	1 – 69	69	Missing in isoform 3.		VSP_036665
	Alternative sequence	1 – 29	29	MSGRA…QASPL → MG in isoform 2.		VSP_021031
	Alternative sequence	522	1	I → M in isoform 2 and isoform 3.		VSP_021032
	Alternative sequence	523 – 852	330	Missing in isoform 2 and isoform 3.		VSP_021033
	Natural variant	78	1	Q → R. Corresponds to variant rs12276921 [ dbSNP | Ensembl ].		VAR_028367
	Natural variant	167	1	K → R. Corresponds to variant rs12272255 [ dbSNP | Ensembl ].		VAR_055533
	Natural variant	327	1	Q → L. Ref.2 Corresponds to variant rs11020845 [ dbSNP | Ensembl ].		VAR_026291
	Natural variant	370	1	A → P. Ref.2 Corresponds to variant rs57607909 [ dbSNP | Ensembl ].		VAR_061025
Experimental info
	Sequence conflict	99	1	T → A in BAC81341. Ref.1
	Sequence conflict	153	1	K → E in BAC04179. Ref.2
	Sequence conflict	510	1	A → T in BAC04873. Ref.2
	Sequence conflict	701	1	K → E in BAC04179. Ref.2
	Sequence conflict	719	1	S → G in BAC04179. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 37769EE078B96D13	FASTA	852	96,589
	10 20 30 40 50 60 MSGRARVKAR GIARSPSATE VGRIQASPLP RSVDLSNNEA SSSNGFLGTS RISTNDKYGI 70 80 90 100 110 120 SSGDAGSTFM ERGVKNKQDF MDLSICTREK LAHVRNCKTG SSGIPVKLVT NLFNLDFPQD 130 140 150 160 170 180 WQLYQYHVTY IPDLASRRLR IALLYSHSEL SNKAKAFDGA ILFLSQKLEE KVTELSSETQ 190 200 210 220 230 240 RGETIKMTIT LKRELPSSSP VCIQVFNIIF RKILKKLSMY QIGRNFYNPS EPMEIPQHKL 250 260 270 280 290 300 SLWPGFAISV SYFERKLLFS ADVSYKVLRN ETVLEFMTAL CQRTGLSCFT QTCEKQLIGL 310 320 330 340 350 360 IVLTRYNNRT YSIDDIDWSV KPTHTFQKRD GTEITYVDYY KQQYDITVSD LNQPMLVSLL 370 380 390 400 410 420 KKKRNDNSEA QLAHLIPELC FLTGLTDQAT SDFQLMKAVA EKTRLSPSGR QQRLARLVDN 430 440 450 460 470 480 IQRNTNARFE LETWGLHFGS QISLTGRIVP SEKILMQDHI CQPVSAADWS KDIRTCKILN 490 500 510 520 530 540 AQSLNTWLIL CSDRTEYVAE SFLNCLRRVA GSMGFNVDYP KIIKVQENPA AFVRAIQQYV 550 560 570 580 590 600 DPDVQLVMCI LPSNQKTYYD SIKKYLSSDC PVPSQCVLAR TLNKQGMMMS IATKIAMQMT 610 620 630 640 650 660 CKLGGELWAV EIPLKSLMVV GIDVCKDALS KDVMVVGCVA SVNPRITRWF SRCILQRTMT 670 680 690 700 710 720 DVADCLKVFM TGALNKWYKY NHDLPARIIV YRAGVGDGQL KTLIEYEVPQ LLSSVAESSS 730 740 750 760 770 780 NTSSRLSVIV VRKKCMPRFF TEMNRTVQNP PLGTVVDSEA TRNEWYDFYL ISQVACRGTV 790 800 810 820 830 840 SPTYYNVIYD DNGLKPDHMQ RLTFKLCHLY YNWPGIVSVP APCQYAHKLT FLVAQSIHKE 850 PSLELANHLF YL
	Isoform 2 [UniParc]. Checksum: 41496B6996BF9BA3	FASTA	495	56,442
	10 20 30 40 50 60 MGPRSVDLSN NEASSSNGFL GTSRISTNDK YGISSGDAGS TFMERGVKNK QDFMDLSICT 70 80 90 100 110 120 REKLAHVRNC KTGSSGIPVK LVTNLFNLDF PQDWQLYQYH VTYIPDLASR RLRIALLYSH 130 140 150 160 170 180 SELSNKAKAF DGAILFLSQK LEEKVTELSS ETQRGETIKM TITLKRELPS SSPVCIQVFN 190 200 210 220 230 240 IIFRKILKKL SMYQIGRNFY NPSEPMEIPQ HKLSLWPGFA ISVSYFERKL LFSADVSYKV 250 260 270 280 290 300 LRNETVLEFM TALCQRTGLS CFTQTCEKQL IGLIVLTRYN NRTYSIDDID WSVKPTHTFQ 310 320 330 340 350 360 KRDGTEITYV DYYKQQYDIT VSDLNQPMLV SLLKKKRNDN SEAQLAHLIP ELCFLTGLTD 370 380 390 400 410 420 QATSDFQLMK AVAEKTRLSP SGRQQRLARL VDNIQRNTNA RFELETWGLH FGSQISLTGR 430 440 450 460 470 480 IVPSEKILMQ DHICQPVSAA DWSKDIRTCK ILNAQSLNTW LILCSDRTEY VAESFLNCLR 490 RVAGSMGFNV DYPKM
	Isoform 3 [UniParc]. Checksum: 24A10ED388F6BD36	FASTA	453	52,174
	10 20 30 40 50 60 MERGVKNKQD FMDLSICTRE KLAHVRNCKT GSSGIPVKLV TNLFNLDFPQ DWQLYQYHVT 70 80 90 100 110 120 YIPDLASRRL RIALLYSHSE LSNKAKAFDG AILFLSQKLE EKVTELSSET QRGETIKMTI 130 140 150 160 170 180 TLKRELPSSS PVCIQVFNII FRKILKKLSM YQIGRNFYNP SEPMEIPQHK LSLWPGFAIS 190 200 210 220 230 240 VSYFERKLLF SADVSYKVLR NETVLEFMTA LCQRTGLSCF TQTCEKQLIG LIVLTRYNNR 250 260 270 280 290 300 TYSIDDIDWS VKPTHTFQKR DGTEITYVDY YKQQYDITVS DLNQPMLVSL LKKKRNDNSE 310 320 330 340 350 360 AQLAHLIPEL CFLTGLTDQA TSDFQLMKAV AEKTRLSPSG RQQRLARLVD NIQRNTNARF 370 380 390 400 410 420 ELETWGLHFG SQISLTGRIV PSEKILMQDH ICQPVSAADW SKDIRTCKIL NAQSLNTWLI 430 440 450 LCSDRTEYVA ESFLNCLRRV AGSMGFNVDY PKM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of eight members of the Argonaute family in the human genome." Sasaki T., Shiohama A., Minoshima S., Shimizu N. Genomics 82:323-330(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANTS LEU-327 AND PRO-370. Tissue: Cerebellum and Testis.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Salivary gland.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[5]	"The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus." Sugimoto K., Kage H., Aki N., Sano A., Kitagawa H., Nagase T., Yatomi Y., Ohishi N., Takai D. Biochem. Biophys. Res. Commun. 359:497-502(2007) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE FUNCTION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB079366 mRNA. Translation: BAC81341.1. AK093475 mRNA. Translation: BAC04179.1. AK096837 mRNA. Translation: BAC04873.1. Different initiation. AK293616 mRNA. Translation: BAG57076.1. CR749642 mRNA. Translation: CAH18436.1. Frameshift. BC031060 mRNA. Translation: AAH31060.1.
IPI	IPI00747170. IPI00783354. IPI00923483.
RefSeq	NP_689644.2. NM_152431.2.
UniGene	Hs.660188.
3D structure databases
ProteinModelPortal	Q7Z3Z4.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q7Z3Z4. 2 interactions.
STRING	9606.ENSP00000299001.
PTM databases
PhosphoSite	Q7Z3Z4.
Polymorphism databases
DMDM	116242716.
Proteomic databases
PaxDb	Q7Z3Z4.
PRIDE	Q7Z3Z4.
Protocols and materials databases
DNASU	143689.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299001; ENSP00000299001; ENSG00000134627. ENST00000446230; ENSP00000413838; ENSG00000134627. ENST00000543336; ENSP00000444575; ENSG00000134627.
GeneID	143689.
KEGG	hsa:143689.
UCSC	uc001pfa.3. human.
Organism-specific databases
CTD	143689.
GeneCards	GC11P094278.
H-InvDB	HIX0079403.
HGNC	HGNC:18444. PIWIL4.
HPA	HPA036588.
MIM	610315. gene.
neXtProt	NX_Q7Z3Z4.
PharmGKB	PA38333.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG286051.
HOGENOM	HOG000254789.
HOVERGEN	HBG049411.
InParanoid	Q7Z3Z4.
KO	K02156.
OMA	FLNCLRR.
OrthoDB	EOG4QJRMH.
Gene expression databases
ArrayExpress	Q7Z3Z4.
Bgee	Q7Z3Z4.
CleanEx	HS_PIWIL4.
Genevestigator	Q7Z3Z4.
GermOnline	ENSG00000134627. Homo sapiens.
Family and domain databases
InterPro	IPR003100. PAZ. IPR003165. Piwi. IPR012337. RNaseH-like_dom. [Graphical view]
Pfam	PF02170. PAZ. 1 hit. PF02171. Piwi. 1 hit. [Graphical view]
SMART	SM00949. PAZ. 1 hit. SM00950. Piwi. 1 hit. [Graphical view]
SUPFAM	SSF101690. PAZ. 1 hit. SSF53098. RNaseH_fold. 1 hit.
PROSITE	PS50821. PAZ. 1 hit. PS50822. PIWI. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PIWIL4. human.
GenomeRNAi	143689.
NextBio	84780.
SOURCE	Search...

Entry information

Entry name

PIWL4_HUMAN

Accession

Primary (citable) accession number: Q7Z3Z4
Secondary accession number(s): B4DEG5 , Q68CZ4, Q8N8G9, Q8N9V8, Q8NEH2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 16, 2006
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 86 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.