PHF19_MOUSE
ID PHF19_MOUSE Reviewed; 578 AA.
AC Q9CXG9;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=PHD finger protein 19;
DE AltName: Full=Polycomb-like protein 3;
GN Name=Phf19; Synonyms=Pcl3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, H3K36ME3-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=23104054; DOI=10.1038/nsmb.2434;
RA Ballare C., Lange M., Lapinaite A., Martin G.M., Morey L., Pascual G.,
RA Liefke R., Simon B., Shi Y., Gozani O., Carlomagno T., Benitah S.A.,
RA Di Croce L.;
RT "Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb
RT activity.";
RL Nat. Struct. Mol. Biol. 19:1257-1265(2012).
RN [5]
RP FUNCTION, ASSOCIATION WITH THE PRC2 COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=23160351; DOI=10.1038/nsmb.2449;
RA Brien G.L., Gambero G., O'Connell D.J., Jerman E., Turner S.A., Egan C.M.,
RA Dunne E.J., Jurgens M.C., Wynne K., Piao L., Lohan A.J., Ferguson N.,
RA Shi X., Sinha K.M., Loftus B.J., Cagney G., Bracken A.P.;
RT "Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to
RT embryonic stem cell genes during differentiation.";
RL Nat. Struct. Mol. Biol. 19:1273-1281(2012).
RN [6]
RP FUNCTION, ASSOCIATION WITH THE PRC2 COMPLEX, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF TRP-48; TYR-54; PHE-72; ASP-74; ASN-75 AND TYR-78.
RX PubMed=22438827; DOI=10.1371/journal.pgen.1002576;
RA Hunkapiller J., Shen Y., Diaz A., Cagney G., McCleary D.,
RA Ramalho-Santos M., Krogan N., Ren B., Song J.S., Reiter J.F.;
RT "Polycomb-like 3 promotes polycomb repressive complex 2 binding to CpG
RT islands and embryonic stem cell self-renewal.";
RL PLoS Genet. 8:E1002576-E1002576(2012).
RN [7]
RP FUNCTION.
RX PubMed=23273982; DOI=10.1016/j.molcel.2012.11.026;
RA Cai L., Rothbart S.B., Lu R., Xu B., Chen W.Y., Tripathy A., Rockowitz S.,
RA Zheng D., Patel D.J., Allis C.D., Strahl B.D., Song J., Wang G.G.;
RT "An H3K36 methylation-engaging Tudor motif of Polycomb-like proteins
RT mediates PRC2 complex targeting.";
RL Mol. Cell 49:571-582(2013).
CC -!- FUNCTION: Polycomb group (PcG) protein that specifically binds histone
CC H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex,
CC thus enhancing PRC2 H3K27me3 methylation activity (PubMed:23104054,
CC PubMed:23160351, PubMed:22438827, PubMed:23273982). Probably involved
CC in the transition from an active state to a repressed state in
CC embryonic stem cells: acts by binding to H3K36me3, a mark for
CC transcriptional activation, and recruiting H3K36me3 histone
CC demethylases RIOX1 or KDM2B, leading to demethylation of H3K36 and
CC recruitment of the PRC2 complex that mediates H3K27me3 methylation,
CC followed by de novo silencing (PubMed:23160351). Recruits the PRC2
CC complex to CpG islands and contributes to embryonic stem cell self-
CC renewal (PubMed:22438827). Also binds histone H3 dimethylated at 'Lys-
CC 36' (H3K36me2) (By similarity). {ECO:0000250|UniProtKB:Q5T6S3,
CC ECO:0000269|PubMed:22438827, ECO:0000269|PubMed:23104054,
CC ECO:0000269|PubMed:23160351, ECO:0000269|PubMed:23273982}.
CC -!- SUBUNIT: Associates with the PRC2 complex, which consists of the core
CC components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various
CC combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2
CC and EPOP (PubMed:23160351, PubMed:22438827). Forms a dimeric PRC2.1
CC (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and
CC PHF19 or MTF2; PHF19 and MTF2 stabilize the dimeric structure which
CC enhances PRC2 interaction with chromatin. Interacts with SUZ12;
CC competes with AEBP2 for SUZ12 binding. Interacts with EZH2 (via its
CC Tudor domain). Interacts with RIOX1 (By similarity).
CC {ECO:0000250|UniProtKB:Q5T6S3, ECO:0000269|PubMed:22438827,
CC ECO:0000269|PubMed:23160351}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22438827,
CC ECO:0000269|PubMed:23104054, ECO:0000269|PubMed:23160351}.
CC Note=Localizes to chromatin as part of the PRC2 complex.
CC {ECO:0000269|PubMed:22438827, ECO:0000269|PubMed:23104054,
CC ECO:0000269|PubMed:23160351}.
CC -!- DOMAIN: The Tudor domain recognizes and binds H3K36me3.
CC {ECO:0000269|PubMed:23104054}.
CC -!- SIMILARITY: Belongs to the Polycomblike family. {ECO:0000305}.
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DR EMBL; AK014380; BAB29309.1; -; mRNA.
DR EMBL; AL929068; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027776; AAH27776.1; -; mRNA.
DR CCDS; CCDS15955.1; -.
DR RefSeq; NP_082992.1; NM_028716.4.
DR RefSeq; XP_006498442.1; XM_006498379.2.
DR AlphaFoldDB; Q9CXG9; -.
DR SMR; Q9CXG9; -.
DR BioGRID; 216426; 3.
DR STRING; 10090.ENSMUSP00000028232; -.
DR PhosphoSitePlus; Q9CXG9; -.
DR EPD; Q9CXG9; -.
DR MaxQB; Q9CXG9; -.
DR PaxDb; Q9CXG9; -.
DR PeptideAtlas; Q9CXG9; -.
DR PRIDE; Q9CXG9; -.
DR ProteomicsDB; 288195; -.
DR Antibodypedia; 30114; 158 antibodies from 26 providers.
DR DNASU; 74016; -.
DR Ensembl; ENSMUST00000028232; ENSMUSP00000028232; ENSMUSG00000026873.
DR GeneID; 74016; -.
DR KEGG; mmu:74016; -.
DR UCSC; uc008jjh.1; mouse.
DR CTD; 26147; -.
DR MGI; MGI:1921266; Phf19.
DR VEuPathDB; HostDB:ENSMUSG00000026873; -.
DR eggNOG; KOG4323; Eukaryota.
DR GeneTree; ENSGT00950000183180; -.
DR HOGENOM; CLU_032773_1_0_1; -.
DR InParanoid; Q9CXG9; -.
DR OMA; VTERGPH; -.
DR OrthoDB; 281828at2759; -.
DR PhylomeDB; Q9CXG9; -.
DR TreeFam; TF106420; -.
DR Reactome; R-MMU-212300; PRC2 methylates histones and DNA.
DR BioGRID-ORCS; 74016; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Phf19; mouse.
DR PRO; PR:Q9CXG9; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9CXG9; protein.
DR Bgee; ENSMUSG00000026873; Expressed in prostate gland ventral lobe and 79 other tissues.
DR ExpressionAtlas; Q9CXG9; baseline and differential.
DR Genevisible; Q9CXG9; MM.
DR GO; GO:0035098; C:ESC/E(Z) complex; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0061087; P:positive regulation of histone H3-K27 methylation; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0048863; P:stem cell differentiation; IMP:UniProtKB.
DR GO; GO:0019827; P:stem cell population maintenance; IMP:UniProtKB.
DR CDD; cd15581; PHD2_PHF19; 1.
DR CDD; cd04508; TUDOR; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR040477; KDM4_Tudor_2.
DR InterPro; IPR025894; Mtf2_C_dom.
DR InterPro; IPR042017; PHF19_PHD2.
DR InterPro; IPR002999; Tudor.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF14061; Mtf2_C; 1.
DR Pfam; PF00628; PHD; 1.
DR Pfam; PF18104; Tudor_2; 1.
DR SMART; SM00249; PHD; 2.
DR SMART; SM00333; TUDOR; 1.
DR SUPFAM; SSF57903; SSF57903; 2.
DR PROSITE; PS01359; ZF_PHD_1; 2.
DR PROSITE; PS50016; ZF_PHD_2; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..578
FT /note="PHD finger protein 19"
FT /id="PRO_0000318571"
FT DOMAIN 40..93
FT /note="Tudor"
FT ZN_FING 94..149
FT /note="PHD-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 193..247
FT /note="PHD-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 72..78
FT /note="Histone H3K36me3 binding"
FT /evidence="ECO:0000250"
FT REGION 348..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 486..528
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 529..578
FT /note="Interaction with SUZ12"
FT /evidence="ECO:0000250|UniProtKB:Q5T6S3"
FT REGION 529..542
FT /note="Important for PRC2 dimer stability"
FT /evidence="ECO:0000250|UniProtKB:Q5T6S3"
FT SITE 45
FT /note="Histone H3K36me3 binding"
FT /evidence="ECO:0000250"
FT SITE 53
FT /note="Histone H3K36me3 binding"
FT /evidence="ECO:0000250"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T6S3"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T6S3"
FT MUTAGEN 48
FT /note="W->A: Impairs ability to promote H3K27me3
FT methylation without affecting ability to associate with the
FT PRC2 complex; when associated with A-54."
FT /evidence="ECO:0000269|PubMed:22438827"
FT MUTAGEN 54
FT /note="Y->A: Impairs ability to promote H3K27me3
FT methylation without affecting ability to associate with the
FT PRC2 complex; when associated with A-48."
FT /evidence="ECO:0000269|PubMed:22438827"
FT MUTAGEN 72
FT /note="F->A: Impairs ability to promote H3K27me3
FT methylation without affecting ability to associate with the
FT PRC2 complex; when associated with A-74."
FT /evidence="ECO:0000269|PubMed:22438827"
FT MUTAGEN 74
FT /note="D->A: Impairs ability to promote H3K27me3
FT methylation without affecting ability to associate with the
FT PRC2 complex; when associated with A-72."
FT /evidence="ECO:0000269|PubMed:22438827"
FT MUTAGEN 75
FT /note="N->S: Does not affect ability to promote H3K27me3
FT methylation; when associated with S-78."
FT /evidence="ECO:0000269|PubMed:22438827"
FT MUTAGEN 78
FT /note="Y->S: Does not affect ability to promote H3K27me3
FT methylation; when associated with S-75."
FT /evidence="ECO:0000269|PubMed:22438827"
SQ SEQUENCE 578 AA; 65236 MW; 4772F62BB03C0411 CRC64;
METQALEPGT LEAFGATSPN KGGLSKTKKN FKDLMSKVTE GQFVLCRWTD GLYYLGKIKR
VSSPKQSCLV TFEDNSKYWV LWKDIQHAGV PGEEPKCDVC MGKTSGPMNE ILICGKCGLG
YHQQCHIPIA VDANWPLLTH WFCRRCIFAL AVRKGGALKK GAIAKTLQAV KMVLSYQPEE
LDWDSPHRTN QQQCYCYCGG PGEWYLRMLQ CYRCRQWFHE ACTQCLSEPM VFGDRFYLFF
CSVCNQGPEY IERLPLRWVD IVHLALYNLG VQSKKRYFDF EEILAFVNHH WELLQLGKLT
STPMTERGPH LLNALNSYKS RFLCGKEIKK KKCIFRLRIR VPPAPPGKLL PDRALMPSDK
GTSELLRKKG KSKPGLLPQE PQQQKRRVYR RKRSKFLLED AIPSSDFTSA WSTDHHLASI
FDFTLDEIQS LKSGSSGQTF FSDVDSTDAA STSGSASTSL SYDSRWTVGS RKRKLTAKVH
RPLRAKQRAA ELEGRCASDS NAEGAVGPEQ PDEGIDSHTL ESISGDDSSL SHLKSSITNY
FGAAGRLACG EKYRVLARRV TPEGKVQYLL EWEGTTPY
