PRD16_HUMAN
ID PRD16_HUMAN Reviewed; 1276 AA.
AC Q9HAZ2; A6NHQ8; B1AJP7; B1AJP8; B1AJP9; B1WB48; Q8WYJ9; Q9C0I8;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 3.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Histone-lysine N-methyltransferase PRDM16 {ECO:0000305};
DE EC=2.1.1.367 {ECO:0000250|UniProtKB:A2A935};
DE AltName: Full=PR domain zinc finger protein 16 {ECO:0000305};
DE AltName: Full=PR domain-containing protein 16 {ECO:0000305};
DE AltName: Full=Transcription factor MEL1 {ECO:0000305};
DE Short=MDS1/EVI1-like gene 1 {ECO:0000303|PubMed:11050005};
GN Name=PRDM16 {ECO:0000312|HGNC:HGNC:14000};
GN Synonyms=KIAA1675 {ECO:0000312|EMBL:BAB21766.2},
GN MEL1 {ECO:0000303|PubMed:11050005}, PFM13;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT PRO-533, CHROMOSOMAL
RP TRANSLOCATION, DISEASE, AND TISSUE SPECIFICITY.
RX PubMed=11050005;
RA Mochizuki N., Shimizu S., Nagasawa T., Tanaka H., Taniwaki M., Yokota J.,
RA Morishita K.;
RT "A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1
RT gene and is transcriptionally activated in t(1;3)(p36;q21)-positive
RT leukemia cells.";
RL Blood 96:3209-3214(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Fang W., Yang X.-H., Huang S.;
RT "A family of novel PR-domain (PRDM) genes as candidate tumor suppressors.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-533.
RC TISSUE=Brain;
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-533.
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 [7]
RP FUNCTION, ALTERNATIVE SPLICING (ISOFORMS 2 AND 4), AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=12816872; DOI=10.1182/blood-2002-12-3944;
RA Nishikata I., Sasaki H., Iga M., Tateno Y., Imayoshi S., Asou N.,
RA Nakamura T., Morishita K.;
RT "A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed
RT mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid
RT differentiation.";
RL Blood 102:3323-3332(2003).
RN [8]
RP CHROMOSOMAL TRANSLOCATION, AND DISEASE.
RX PubMed=12557231; DOI=10.1002/gcc.10176;
RA Xinh P.T., Tri N.K., Nagao H., Nakazato H., Taketazu F., Fujisawa S.,
RA Yagasaki F., Chen Y.Z., Hayashi Y., Toyoda A., Hattori M., Sakaki Y.,
RA Tokunaga K., Sato Y.;
RT "Breakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21)
RT occur in the first intron and in the 5' region of MEL1.";
RL Genes Chromosomes Cancer 36:313-316(2003).
RN [9]
RP FUNCTION, ALTERNATIVE SPLICING (ISOFORM 4), AND DISEASE.
RX PubMed=14656887; DOI=10.1182/blood-2003-07-2482;
RA Yoshida M., Nosaka K., Yasunaga J., Nishikata I., Morishita K.,
RA Matsuoka M.;
RT "Aberrant expression of the MEL1S gene identified in association with
RT hypomethylation in adult T-cell leukemia cells.";
RL Blood 103:2753-2760(2004).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HDAC1; SKI; SMAD2 AND
RP SMAD3, AND REGION.
RX PubMed=19049980; DOI=10.1074/jbc.m808989200;
RA Takahata M., Inoue Y., Tsuda H., Imoto I., Koinuma D., Hayashi M.,
RA Ichikura T., Yamori T., Nagasaki K., Yoshida M., Matsuoka M., Morishita K.,
RA Yuki K., Hanyu A., Miyazawa K., Inazawa J., Miyazono K., Imamura T.;
RT "SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal
RT in gastric cancer cells.";
RL J. Biol. Chem. 284:3334-3344(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=22939622; DOI=10.1016/j.cell.2012.06.048;
RA Pinheiro I., Margueron R., Shukeir N., Eisold M., Fritzsch C.,
RA Richter F.M., Mittler G., Genoud C., Goyama S., Kurokawa M., Son J.,
RA Reinberg D., Lachner M., Jenuwein T.;
RT "Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian
RT heterochromatin integrity.";
RL Cell 150:948-960(2012).
RN [12]
RP INTERACTION WITH ZNF516.
RX PubMed=25578880; DOI=10.1016/j.molcel.2014.12.005;
RA Dempersmier J., Sambeat A., Gulyaeva O., Paul S.M., Hudak C.S.,
RA Raposo H.F., Kwan H.Y., Kang C., Wong R.H., Sul H.S.;
RT "Cold-inducible Zfp516 activates UCP1 transcription to promote browning of
RT white fat and development of brown fat.";
RL Mol. Cell 57:235-246(2015).
RN [13]
RP VARIANT LVNC8 SER-816, VARIANTS CMD1LL LYS-271; LEU-291 AND PRO-887,
RP VARIANT MET-1101, AND TISSUE SPECIFICITY.
RX PubMed=23768516; DOI=10.1016/j.ajhg.2013.05.015;
RA Arndt A.K., Schafer S., Drenckhahn J.D., Sabeh M.K., Plovie E.R.,
RA Caliebe A., Klopocki E., Musso G., Werdich A.A., Kalwa H., Heinig M.,
RA Padera R.F., Wassilew K., Bluhm J., Harnack C., Martitz J., Barton P.J.,
RA Greutmann M., Berger F., Hubner N., Siebert R., Kramer H.H., Cook S.A.,
RA MacRae C.A., Klaassen S.;
RT "Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16
RT as a cause of cardiomyopathy.";
RL Am. J. Hum. Genet. 93:67-77(2013).
RN [14]
RP VARIANT MET-1101.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
CC -!- FUNCTION: Binds DNA and functions as a transcriptional regulator
CC (PubMed:12816872). Displays histone methyltransferase activity and
CC monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (By
CC similarity). Probably catalyzes the monomethylation of free histone H3
CC in the cytoplasm which is then transported to the nucleus and
CC incorporated into nucleosomes where SUV39H methyltransferases use it as
CC a substrate to catalyze histone H3 'Lys-9' trimethylation (By
CC similarity). Likely to be one of the primary histone methyltransferases
CC along with MECOM/PRDM3 that direct cytoplasmic H3K9me1 methylation (By
CC similarity). Functions in the differentiation of brown adipose tissue
CC (BAT) which is specialized in dissipating chemical energy in the form
CC of heat in response to cold or excess feeding while white adipose
CC tissue (WAT) is specialized in the storage of excess energy and the
CC control of systemic metabolism (By similarity). Together with CEBPB,
CC regulates the differentiation of myoblastic precursors into brown
CC adipose cells (By similarity). Functions as a repressor of TGF-beta
CC signaling (PubMed:19049980). {ECO:0000250|UniProtKB:A2A935,
CC ECO:0000269|PubMed:12816872, ECO:0000269|PubMed:19049980}.
CC -!- FUNCTION: [Isoform 4]: Binds DNA and functions as a transcriptional
CC regulator (PubMed:12816872). Functions as a repressor of TGF-beta
CC signaling (PubMed:14656887). May regulate granulocyte differentiation
CC (PubMed:12816872). {ECO:0000269|PubMed:12816872,
CC ECO:0000269|PubMed:14656887}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60280, Rhea:RHEA-COMP:15542, Rhea:RHEA-COMP:15546,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.367;
CC Evidence={ECO:0000250|UniProtKB:A2A935};
CC -!- SUBUNIT: Interacts with CEBPA, CEBPB and CEBPD; the interaction is
CC direct. Interacts with PPARG and PPARA; controls brown adipocytes
CC differentiation. Interacts with CTBP1 and CTBP2; represses the
CC expression of WAT-specific genes. Interacts with PPARGC1A and PPARGC1B;
CC interaction with PPARGC1A or PPARGC1B activates the transcription of
CC BAT-specific gene (By similarity). Interacts with HDAC1, SKI, SMAD2 and
CC SMAD3; the interaction with SKI promotes the recruitment of SMAD3-HDAC1
CC complex on the promoter of TGF-beta target genes (PubMed:19049980).
CC Interacts with ZNF516; the interaction is direct and may play a role in
CC the transcription of brown adipose tissue-specific gene
CC (PubMed:25578880). {ECO:0000250|UniProtKB:A2A935,
CC ECO:0000269|PubMed:19049980, ECO:0000269|PubMed:25578880}.
CC -!- INTERACTION:
CC Q9HAZ2; Q09028: RBBP4; NbExp=3; IntAct=EBI-2795620, EBI-620823;
CC Q9HAZ2-2; P56546: Ctbp2; Xeno; NbExp=2; IntAct=EBI-5282871, EBI-1384883;
CC Q9HAZ2-4; P56546: Ctbp2; Xeno; NbExp=2; IntAct=EBI-4566658, EBI-1384883;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19049980}. Cytoplasm
CC {ECO:0000269|PubMed:22939622}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9HAZ2-1; Sequence=Displayed;
CC Name=2; Synonyms=MEL1L;
CC IsoId=Q9HAZ2-2; Sequence=VSP_006932;
CC Name=3;
CC IsoId=Q9HAZ2-3; Sequence=VSP_038064, VSP_038065;
CC Name=4; Synonyms=MEL1S;
CC IsoId=Q9HAZ2-4; Sequence=VSP_038063;
CC -!- TISSUE SPECIFICITY: Expressed in uterus and kidney. Expressed in both
CC cardiomyocytes and interstitial cells. {ECO:0000269|PubMed:11050005,
CC ECO:0000269|PubMed:12816872, ECO:0000269|PubMed:23768516}.
CC -!- DISEASE: Left ventricular non-compaction 8 (LVNC8) [MIM:615373]: A form
CC of left ventricular non-compaction, a cardiomyopathy due to myocardial
CC morphogenesis arrest and characterized by a hypertrophic left
CC ventricle, a severely thickened 2-layered myocardium, numerous
CC prominent trabeculations, deep intertrabecular recesses, and poor
CC systolic function. Clinical manifestations are variable. Some affected
CC individuals experience no symptoms at all, others develop heart
CC failure. In some cases, left ventricular non-compaction is associated
CC with other congenital heart anomalies. LVNC8 is an autosomal dominant
CC condition. {ECO:0000269|PubMed:23768516}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Cardiomyopathy, dilated 1LL (CMD1LL) [MIM:615373]: A disorder
CC characterized by ventricular dilation and impaired systolic function,
CC resulting in congestive heart failure and arrhythmia. Patients are at
CC risk of premature death. {ECO:0000269|PubMed:23768516}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=A chromosomal aberration involving PRDM16 is found in
CC myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
CC Reciprocal translocation t(1;3)(p36;q21). Isoform 4 is specifically
CC expressed in adult T-cell leukemia. {ECO:0000269|PubMed:11050005,
CC ECO:0000269|PubMed:12557231}.
CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the PRDM16 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB21766.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PRDM16MEL1ID408.html";
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DR EMBL; AB078876; BAB84297.1; -; mRNA.
DR EMBL; AF294278; AAG33382.1; -; mRNA.
DR EMBL; AB051462; BAB21766.2; ALT_INIT; mRNA.
DR EMBL; AL008733; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354743; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL512383; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590438; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC161614; AAI61614.1; -; mRNA.
DR CCDS; CCDS41236.2; -. [Q9HAZ2-1]
DR CCDS; CCDS44048.2; -. [Q9HAZ2-2]
DR RefSeq; NP_071397.3; NM_022114.3. [Q9HAZ2-1]
DR RefSeq; NP_955533.2; NM_199454.2. [Q9HAZ2-2]
DR RefSeq; XP_011540247.1; XM_011541945.2.
DR PDB; 2N1I; NMR; -; A=54-226.
DR PDB; 6BW4; X-ray; 2.00 A; B/D=1-12.
DR PDBsum; 2N1I; -.
DR PDBsum; 6BW4; -.
DR AlphaFoldDB; Q9HAZ2; -.
DR SMR; Q9HAZ2; -.
DR BioGRID; 122023; 181.
DR IntAct; Q9HAZ2; 19.
DR MINT; Q9HAZ2; -.
DR STRING; 9606.ENSP00000270722; -.
DR iPTMnet; Q9HAZ2; -.
DR PhosphoSitePlus; Q9HAZ2; -.
DR BioMuta; PRDM16; -.
DR DMDM; 259016328; -.
DR jPOST; Q9HAZ2; -.
DR MassIVE; Q9HAZ2; -.
DR MaxQB; Q9HAZ2; -.
DR PaxDb; Q9HAZ2; -.
DR PeptideAtlas; Q9HAZ2; -.
DR PRIDE; Q9HAZ2; -.
DR ProteomicsDB; 81460; -. [Q9HAZ2-1]
DR ProteomicsDB; 81461; -. [Q9HAZ2-2]
DR ProteomicsDB; 81462; -. [Q9HAZ2-3]
DR ProteomicsDB; 81463; -. [Q9HAZ2-4]
DR Antibodypedia; 26849; 234 antibodies from 30 providers.
DR DNASU; 63976; -.
DR Ensembl; ENST00000270722.10; ENSP00000270722.5; ENSG00000142611.17. [Q9HAZ2-1]
DR Ensembl; ENST00000378391.6; ENSP00000367643.2; ENSG00000142611.17. [Q9HAZ2-2]
DR GeneID; 63976; -.
DR KEGG; hsa:63976; -.
DR MANE-Select; ENST00000270722.10; ENSP00000270722.5; NM_022114.4; NP_071397.3.
DR UCSC; uc001ake.4; human. [Q9HAZ2-1]
DR CTD; 63976; -.
DR DisGeNET; 63976; -.
DR GeneCards; PRDM16; -.
DR HGNC; HGNC:14000; PRDM16.
DR HPA; ENSG00000142611; Tissue enhanced (choroid plexus, stomach).
DR MalaCards; PRDM16; -.
DR MIM; 605557; gene.
DR MIM; 615373; phenotype.
DR neXtProt; NX_Q9HAZ2; -.
DR OpenTargets; ENSG00000142611; -.
DR Orphanet; 1606; 1p36 deletion syndrome.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR Orphanet; 54260; Left ventricular noncompaction.
DR PharmGKB; PA33714; -.
DR VEuPathDB; HostDB:ENSG00000142611; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000160951; -.
DR InParanoid; Q9HAZ2; -.
DR OMA; EGCIKKQ; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q9HAZ2; -.
DR TreeFam; TF315309; -.
DR BRENDA; 2.1.1.367; 2681.
DR BRENDA; 2.1.1.370; 2681.
DR PathwayCommons; Q9HAZ2; -.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR SignaLink; Q9HAZ2; -.
DR SIGNOR; Q9HAZ2; -.
DR BioGRID-ORCS; 63976; 11 hits in 1086 CRISPR screens.
DR ChiTaRS; PRDM16; human.
DR GeneWiki; PRDM16; -.
DR GenomeRNAi; 63976; -.
DR Pharos; Q9HAZ2; Tbio.
DR PRO; PR:Q9HAZ2; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9HAZ2; protein.
DR Bgee; ENSG00000142611; Expressed in sural nerve and 139 other tissues.
DR ExpressionAtlas; Q9HAZ2; baseline and differential.
DR Genevisible; Q9HAZ2; HS.
DR GO; GO:0016235; C:aggresome; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:ARUK-UCL.
DR GO; GO:0046974; F:histone methyltransferase activity (H3-K9 specific); ISS:UniProtKB.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:ARUK-UCL.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0050873; P:brown fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0070828; P:heterochromatin organization; ISS:UniProtKB.
DR GO; GO:0030853; P:negative regulation of granulocyte differentiation; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0043457; P:regulation of cellular respiration; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd19213; PR-SET_PRDM16; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR044410; PRDM16_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; PF00096; zf-C2H2; 9.
DR SMART; SM00317; SET; 1.
DR SMART; SM00355; ZnF_C2H2; 10.
DR SUPFAM; SSF57667; SSF57667; 5.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50280; SET; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 8.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 10.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative promoter usage; Alternative splicing;
KW Cardiomyopathy; Chromosomal rearrangement; Cytoplasm; Differentiation;
KW Disease variant; DNA-binding; Metal-binding; Methyltransferase; Nucleus;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1276
FT /note="Histone-lysine N-methyltransferase PRDM16"
FT /id="PRO_0000047773"
FT DOMAIN 82..211
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT ZN_FING 230..253
FT /note="C2H2-type 1; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 281..303
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 309..331
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 337..360
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 366..388
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 394..416
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 423..445
FT /note="C2H2-type 7; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 951..973
FT /note="C2H2-type 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 979..1002
FT /note="C2H2-type 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 1008..1032
FT /note="C2H2-type 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 533..657
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 679..1038
FT /note="Interaction with CTBP1, CTBP2 and ZNF516"
FT /evidence="ECO:0000250|UniProtKB:A2A935"
FT REGION 739..1276
FT /note="Mediates interaction with SKI and regulation of TGF-
FT beta signaling"
FT /evidence="ECO:0000269|PubMed:19049980"
FT REGION 772..804
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1033..1065
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1105..1163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 558..572
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 577..601
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 602..626
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 628..643
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1039..1060
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1115..1135
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..184
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_038063"
FT VAR_SEQ 191
FT /note="Q -> QV (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_038064"
FT VAR_SEQ 868
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_038065"
FT VAR_SEQ 1233..1251
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11050005"
FT /id="VSP_006932"
FT VARIANT 271
FT /note="E -> K (in CMD1LL; unknown pathological
FT significance; dbSNP:rs200052869)"
FT /evidence="ECO:0000269|PubMed:23768516"
FT /id="VAR_070212"
FT VARIANT 291
FT /note="P -> L (in CMD1LL; unknown pathological
FT significance; dbSNP:rs397514744)"
FT /evidence="ECO:0000269|PubMed:23768516"
FT /id="VAR_070213"
FT VARIANT 533
FT /note="S -> P (in dbSNP:rs870124)"
FT /evidence="ECO:0000269|PubMed:11050005,
FT ECO:0000269|PubMed:11214970, ECO:0000269|PubMed:15489334"
FT /id="VAR_031433"
FT VARIANT 633
FT /note="P -> L (in dbSNP:rs2493292)"
FT /id="VAR_031434"
FT VARIANT 816
FT /note="N -> S (in LVNC8; dbSNP:rs397514743)"
FT /evidence="ECO:0000269|PubMed:23768516"
FT /id="VAR_070214"
FT VARIANT 887
FT /note="L -> P (in CMD1LL; unknown pathological
FT significance; dbSNP:rs202115331)"
FT /evidence="ECO:0000269|PubMed:23768516"
FT /id="VAR_070215"
FT VARIANT 1101
FT /note="V -> M (in dbSNP:rs201654872)"
FT /evidence="ECO:0000269|PubMed:23768516"
FT /id="VAR_070216"
FT CONFLICT 50..52
FT /note="PPS -> SPP (in Ref. 2; AAG33382)"
FT /evidence="ECO:0000305"
FT CONFLICT 324
FT /note="L -> F (in Ref. 2; AAG33382)"
FT /evidence="ECO:0000305"
FT CONFLICT 491
FT /note="S -> Y (in Ref. 2; AAG33382)"
FT /evidence="ECO:0000305"
FT CONFLICT 1022
FT /note="N -> K (in Ref. 1; BAB84297)"
FT /evidence="ECO:0000305"
FT STRAND 84..91
FT /evidence="ECO:0007829|PDB:2N1I"
FT TURN 92..94
FT /evidence="ECO:0007829|PDB:2N1I"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:2N1I"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:2N1I"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:2N1I"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:2N1I"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:2N1I"
FT HELIX 167..170
FT /evidence="ECO:0007829|PDB:2N1I"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:2N1I"
FT STRAND 183..188
FT /evidence="ECO:0007829|PDB:2N1I"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:2N1I"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:2N1I"
FT HELIX 216..219
FT /evidence="ECO:0007829|PDB:2N1I"
FT TURN 222..225
FT /evidence="ECO:0007829|PDB:2N1I"
SQ SEQUENCE 1276 AA; 140251 MW; AD16C5C0EE89A528 CRC64;
MRSKARARKL AKSDGDVVNN MYEPNRDLLA SHSAEDEAED SAMSPIPVGP PSPFPTSEDF
TPKEGSPYEA PVYIPEDIPI PADFELRESS IPGAGLGVWA KRKMEAGERL GPCVVVPRAA
AKETDFGWEQ ILTDVEVSPQ EGCITKISED LGSEKFCVDA NQAGAGSWLK YIRVACSCDD
QNLTMCQISE QIYYKVIKDI EPGEELLVHV KEGVYPLGTV PPGLDEEPTF RCDECDELFQ
SKLDLRRHKK YTCGSVGAAL YEGLAEELKP EGLGGGSGQA HECKDCERMF PNKYSLEQHM
VIHTEEREYK CDQCPKAFNW KSNLIRHQMS HDSGKRFECE NCVKVFTDPS NLQRHIRSQH
VGARAHACPD CGKTFATSSG LKQHKHIHST VKPFICEVCH KSYTQFSNLC RHKRMHADCR
TQIKCKDCGQ MFSTTSSLNK HRRFCEGKNH YTPGGIFAPG LPLTPSPMMD KAKPSPSLNH
ASLGFNEYFP SRPHPGSLPF STAPPTFPAL TPGFPGIFPP SLYPRPPLLP PTSLLKSPLN
HTQDAKLPSP LGNPALPLVS AVSNSSQGTT AAAGPEEKFE SRLEDSCVEK LKTRSSDMSD
GSDFEDVNTT TGTDLDTTTG TGSDLDSDVD SDPDKDKGKG KSAEGQPKFG GGLAPPGAPN
SVAEVPVFYS QHSFFPPPDE QLLTATGAAG DSIKAIASIA EKYFGPGFMG MQEKKLGSLP
YHSAFPFQFL PNFPHSLYPF TDRALAHNLL VKAEPKSPRD ALKVGGPSAE CPFDLTTKPK
DVKPILPMPK GPSAPASGEE QPLDLSIGSR ARASQNGGGR EPRKNHVYGE RKLGAGEGLP
QVCPARMPQQ PPLHYAKPSP FFMDPIYSRV EKRKVTDPVG ALKEKYLRPS PLLFHPQMSA
IETMTEKLES FAAMKADSGS SLQPLPHHPF NFRSPPPTLS DPILRKGKER YTCRYCGKIF
PRSANLTRHL RTHTGEQPYR CKYCDRSFSI SSNLQRHVRN IHNKEKPFKC HLCNRCFGQQ
TNLDRHLKKH EHENAPVSQH PGVLTNHLGT SASSPTSESD NHALLDEKED SYFSEIRNFI
ANSEMNQAST RTEKRADMQI VDGSAQCPGL ASEKQEDVEE EDDDDLEEDD EDSLAGKSQD
DTVSPAPEPQ AAYEDEEDEE PAASLAVGFD HTRRCAEDHE GGLLALEPMP TFGKGLDLRR
AAEEAFEVKD VLNSTLDSEA LKHTLCRQAK NQAYAMMLSL SEDTPLHTPS QGSLDAWLKV
TGATSESGAF HPINHL
