PRDM6_MOUSE
ID PRDM6_MOUSE Reviewed; 596 AA.
AC Q3UZD5; B9EIB0; Q2I2X0; Q2I2X1; Q3UX75;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Putative histone-lysine N-methyltransferase PRDM6;
DE EC=2.1.1.361 {ECO:0000305|PubMed:17662997};
DE AltName: Full=PR domain zinc finger protein 6;
DE AltName: Full=PR domain-containing protein 6;
DE AltName: Full=PR domain-containing protein in smooth muscle;
GN Name=Prdm6; Synonyms=Gm92, Prism;
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 [MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 162-596 (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND INTERACTION WITH HDAC1; HDAC2; HDAC3; CBX1 AND EP300.
RX PubMed=16537907; DOI=10.1128/mcb.26.7.2626-2636.2006;
RA Davis C.A., Haberland M., Arnold M.A., Sutherland L.B., McDonald O.G.,
RA Richardson J.A., Childs G., Harris S., Owens G.K., Olson E.N.;
RT "PRISM/PRDM6, a transcriptional repressor that promotes the proliferative
RT gene program in smooth muscle cells.";
RL Mol. Cell. Biol. 26:2626-2636(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Egg;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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, ALTERNATIVE SPLICING (ISOFORM 4), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=17662997; DOI=10.1016/j.yjmcc.2007.06.008;
RA Wu Y., Ferguson J.E. III, Wang H., Kelley R., Ren R., McDonough H.,
RA Meeker J., Charles P.C., Wang H., Patterson C.;
RT "PRDM6 is enriched in vascular precursors during development and inhibits
RT endothelial cell proliferation, survival, and differentiation.";
RL J. Mol. Cell. Cardiol. 44:47-58(2008).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND MUTAGENESIS OF CYS-264 AND ARG-550.
RX PubMed=27181681; DOI=10.1016/j.ajhg.2016.03.022;
RA Li N., Subrahmanyan L., Smith E., Yu X., Zaidi S., Choi M., Mane S.,
RA Nelson-Williams C., Bahjati M., Kazemi M., Hashemi M., Fathzadeh M.,
RA Narayanan A., Tian L., Montazeri F., Mani M., Begleiter M.L., Coon B.G.,
RA Lynch H.T., Olson E.N., Zhao H., Ruland J., Lifton R.P., Mani A.;
RT "Mutations in the histone modifier PRDM6 are associated with isolated
RT nonsyndromic patent ductus arteriosus.";
RL Am. J. Hum. Genet. 98:1082-1091(2016).
CC -!- FUNCTION: Putative histone methyltransferase that acts as a
CC transcriptional repressor of smooth muscle gene expression
CC (PubMed:16537907, PubMed:17662997). Promotes the transition from
CC differentiated to proliferative smooth muscle by suppressing
CC differentiation and maintaining the proliferative potential of vascular
CC smooth muscle cells (PubMed:27181681, PubMed:16537907,
CC PubMed:17662997). Also plays a role in endothelial cells by inhibiting
CC endothelial cell proliferation, survival and differentiation. It is
CC unclear whether it has histone methyltransferase activity in vivo.
CC According to some authors, it does not act as a histone
CC methyltransferase by itself and represses transcription by recruiting
CC EHMT2/G9a (PubMed:16537907). According to others, it possesses histone
CC methyltransferase activity when associated with other proteins and
CC specifically methylates 'Lys-20' of histone H4 in vitro. 'Lys-20'
CC methylation represents a specific tag for epigenetic transcriptional
CC repression (PubMed:17662997). {ECO:0000269|PubMed:16537907,
CC ECO:0000269|PubMed:17662997, ECO:0000269|PubMed:27181681}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60344, Rhea:RHEA-COMP:15554, Rhea:RHEA-COMP:15555,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.361;
CC Evidence={ECO:0000305|PubMed:17662997};
CC -!- SUBUNIT: Interacts with HDAC1, HDAC2, HDAC3, CBX1 and EP300.
CC {ECO:0000269|PubMed:16537907}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16537907,
CC ECO:0000269|PubMed:17662997, ECO:0000269|PubMed:27181681}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q3UZD5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UZD5-2; Sequence=VSP_036371;
CC Name=3;
CC IsoId=Q3UZD5-3; Sequence=VSP_036372;
CC Name=4;
CC IsoId=Q3UZD5-4; Sequence=VSP_036373;
CC -!- TISSUE SPECIFICITY: Expressed in a variety of smooth muscle-containing
CC tissues and displays especially robust expression in the cardiac
CC outflow tract and descending aorta during embryogenesis. Also enriched
CC in vascular precursors during development.
CC {ECO:0000269|PubMed:16537907, ECO:0000269|PubMed:17662997,
CC ECO:0000269|PubMed:27181681}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in ductus arteriosus prenatally,
CC expression declines rapildy after birth. {ECO:0000269|PubMed:27181681}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; DQ340564; ABC69307.1; -; mRNA.
DR EMBL; DQ340565; ABC69308.1; -; mRNA.
DR EMBL; AK133910; BAE21922.1; -; mRNA.
DR EMBL; AK135836; BAE22684.1; -; mRNA.
DR EMBL; AK135840; BAE22688.1; -; mRNA.
DR EMBL; BC139295; AAI39296.1; -; mRNA.
DR CCDS; CCDS29253.1; -. [Q3UZD5-1]
DR RefSeq; NP_001028453.1; NM_001033281.3. [Q3UZD5-1]
DR RefSeq; XP_017173378.1; XM_017317889.1. [Q3UZD5-1]
DR AlphaFoldDB; Q3UZD5; -.
DR SMR; Q3UZD5; -.
DR BioGRID; 230402; 1.
DR STRING; 10090.ENSMUSP00000089513; -.
DR PhosphoSitePlus; Q3UZD5; -.
DR jPOST; Q3UZD5; -.
DR PaxDb; Q3UZD5; -.
DR PRIDE; Q3UZD5; -.
DR ProteomicsDB; 289884; -. [Q3UZD5-1]
DR ProteomicsDB; 289885; -. [Q3UZD5-2]
DR ProteomicsDB; 289886; -. [Q3UZD5-3]
DR ProteomicsDB; 289887; -. [Q3UZD5-4]
DR Antibodypedia; 25663; 110 antibodies from 17 providers.
DR Ensembl; ENSMUST00000091900; ENSMUSP00000089513; ENSMUSG00000069378. [Q3UZD5-1]
DR GeneID; 225518; -.
DR KEGG; mmu:225518; -.
DR UCSC; uc008exv.1; mouse. [Q3UZD5-1]
DR UCSC; uc008exw.1; mouse. [Q3UZD5-3]
DR CTD; 93166; -.
DR MGI; MGI:2684938; Prdm6.
DR VEuPathDB; HostDB:ENSMUSG00000069378; -.
DR eggNOG; KOG1721; Eukaryota.
DR eggNOG; KOG2461; Eukaryota.
DR GeneTree; ENSGT00940000155852; -.
DR HOGENOM; CLU_032452_0_0_1; -.
DR InParanoid; Q3UZD5; -.
DR OMA; IGPFQGI; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q3UZD5; -.
DR TreeFam; TF106403; -.
DR BioGRID-ORCS; 225518; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Prdm6; mouse.
DR PRO; PR:Q3UZD5; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q3UZD5; protein.
DR Bgee; ENSMUSG00000069378; Expressed in external carotid artery and 107 other tissues.
DR ExpressionAtlas; Q3UZD5; baseline and differential.
DR Genevisible; Q3UZD5; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0042054; F:histone methyltransferase activity; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0051151; P:negative regulation of smooth muscle cell differentiation; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0022008; P:neurogenesis; IDA:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR CDD; cd19191; PR-SET_PRDM6; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR044416; PRDM6_PR-SET.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00856; SET; 1.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00317; SET; 1.
DR SMART; SM00355; ZnF_C2H2; 4.
DR SUPFAM; SSF57667; SSF57667; 2.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50280; SET; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 2.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromatin regulator; Metal-binding;
KW Methyltransferase; Nucleus; Reference proteome; Repeat; Repressor;
KW S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase; Zinc; Zinc-finger.
FT CHAIN 1..596
FT /note="Putative histone-lysine N-methyltransferase PRDM6"
FT /id="PRO_0000363959"
FT DOMAIN 247..366
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT ZN_FING 474..496
FT /note="C2H2-type 1; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 502..524
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 530..552
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 558..580
FT /note="C2H2-type 4; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 25..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..75
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..392
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_036372"
FT VAR_SEQ 1..201
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16537907"
FT /id="VSP_036371"
FT VAR_SEQ 28..58
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_036373"
FT MUTAGEN 264
FT /note="C->S: Loss of function in histone modification."
FT /evidence="ECO:0000269|PubMed:27181681"
FT MUTAGEN 550
FT /note="R->Q: Loss of function in histone modification. Loss
FT of nuclear localization."
FT /evidence="ECO:0000269|PubMed:27181681"
SQ SEQUENCE 596 AA; 64503 MW; 1DEDC155893CC809 CRC64;
MLKPGDPGGS AFLKVDPAYL QHWQQLFPHG GGGGGPLKAS GAALALGAPQ PLQPPPPPPP
PPPERAEPPP DGLRPRPASL SSTPAPSSTS ASSASSCAAA AAAAALAGLS ALPVAQMPVF
APLAAAAVAA EPLPPKDLCL GASAGPGPAK CGGGGGSVGD GRGVPRFRCS AEELDYYLYG
QQRMEIIPLN QHTSDPNNRC DMCADNRNGE CPMHGPLHSL RRLVGTSSAA AAAPPPELPE
WLRDLPREVC LCTSTVPGLA YGICAAQRIQ QGTWIGPFQG VLLSPEKVQT GVVRNTQHLW
EIYDQDGTLQ HFIDGGEPSK SSWMRYIRCA RHCGEQNLTV VQYRSNIFYR ACIDIPRGTE
LLVWYNDSYT SFFGIPLQCI AQDENLNVPS TVMEAMCRQD ALQPFNKSSK LSPSGQQRSV
VFPQTPCSRN FSLLDKSGPM EAGFNQINVK NQRVLASPTS TSQLHSEFSD WHLWKCGQCF
KTFTQRILLQ MHVCTQNPDR PYQCGHCSQS FSQPSELRNH VVTHSSDRPF KCGYCGRAFA
GATTLNNHIR THTGEKPFKC ERCERSFTQA TQLSRHQRMP NECKPITESP ESIEVD
