Q9HAZ2A6NHQ8B1AJP7B1AJP8B1AJP9B1WB48Q8WYJ9Q9C0I8PRD16_HUMANHistone-lysine N-methyltransferase PRDM162.1.1.367PR domain zinc finger protein 16PR domain-containing protein 16Transcription factor MEL1MDS1/EVI1-like gene 1PRDM16KIAA1675MEL1PFM13Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoA novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)VARIANT PRO-533CHROMOSOMAL TRANSLOCATIONDISEASETISSUE SPECIFICITYA family of novel PR-domain (PRDM) genes as candidate tumor suppressors.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)VARIANT PRO-533Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.SEQUENCE REVISIONThe DNA sequence and biological annotation of human chromosome 1.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)VARIANT PRO-533A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation.FUNCTIONALTERNATIVE SPLICING (ISOFORMS 2 AND 4)TISSUE SPECIFICITYBreakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21) occur in the first intron and in the 5' region of MEL1.CHROMOSOMAL TRANSLOCATIONDISEASEAberrant expression of the MEL1S gene identified in association with hypomethylation in adult T-cell leukemia cells.FUNCTIONALTERNATIVE SPLICING (ISOFORM 4)DISEASESKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells.FUNCTIONSUBCELLULAR LOCATIONINTERACTION WITH HDAC1; SKI; SMAD2 AND SMAD3REGIONPrdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity.IDENTIFICATION BY MASS SPECTROMETRYSUBCELLULAR LOCATIONCold-inducible Zfp516 activates UCP1 transcription to promote browning of white fat and development of brown fat.INTERACTION WITH ZNF516Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy.VARIANT LVNC8 SER-816VARIANTS CMD1LL LYS-271; LEU-291 AND PRO-887VARIANT MET-1101TISSUE SPECIFICITYAnalysis of protein-coding genetic variation in 60,706 humans.VARIANT MET-1101Binds DNA and functions as a transcriptional regulator (PubMed:12816872). Displays histone methyltransferase activity and monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (By similarity). Probably catalyzes the monomethylation of free histone H3 in the cytoplasm which is then transported to the nucleus and incorporated into nucleosomes where SUV39H methyltransferases use it as a substrate to catalyze histone H3 'Lys-9' trimethylation (By similarity). Likely to be one of the primary histone methyltransferases along with MECOM/PRDM3 that direct cytoplasmic H3K9me1 methylation (By similarity). Functions in the differentiation of brown adipose tissue (BAT) which is specialized in dissipating chemical energy in the form of heat in response to cold or excess feeding while white adipose tissue (WAT) is specialized in the storage of excess energy and the control of systemic metabolism (By similarity). Together with CEBPB, regulates the differentiation of myoblastic precursors into brown adipose cells (By similarity). Functions as a repressor of TGF-beta signaling (PubMed:19049980).Isoform 4Binds DNA and functions as a transcriptional regulator (PubMed:12816872). Functions as a repressor of TGF-beta signaling (PubMed:14656887). May regulate granulocyte differentiation (PubMed:12816872).L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) + N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteineInteracts with CEBPA, CEBPB and CEBPD; the interaction is direct. Interacts with PPARG and PPARA; controls brown adipocytes differentiation. Interacts with CTBP1 and CTBP2; represses the expression of WAT-specific genes. Interacts with PPARGC1A and PPARGC1B; interaction with PPARGC1A or PPARGC1B activates the transcription of BAT-specific gene (By similarity). Interacts with HDAC1, SKI, SMAD2 and SMAD3; the interaction with SKI promotes the recruitment of SMAD3-HDAC1 complex on the promoter of TGF-beta target genes (PubMed:19049980). Interacts with ZNF516; the interaction is direct and may play a role in the transcription of brown adipose tissue-specific gene (PubMed:25578880).Q9HAZ2Q09028false3Q9HAZ2-2P56546true2Q9HAZ2-4P56546true2NucleusCytoplasmQ9HAZ2-11Q9HAZ2-22MEL1LQ9HAZ2-33Q9HAZ2-44MEL1SExpressed in uterus and kidney. Expressed in both cardiomyocytes and interstitial cells.Left ventricular non-compaction 8
LVNC8
A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC8 is an autosomal dominant condition.The disease is caused by variants affecting the gene represented in this entry.Cardiomyopathy, dilated, 1LL
CMD1LL
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.The disease is caused by variants affecting the gene represented in this entry.A chromosomal aberration involving PRDM16 is found in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Reciprocal translocation t(1;3)(p36;q21). Isoform 4 is specifically expressed in adult T-cell leukemia.Isoform 4Produced by alternative promoter usage.Belongs to the PRDM16 family.Extended N-terminus.3D-structureActivatorAlternative promoter usageAlternative splicingCardiomyopathyChromosomal rearrangementCytoplasmDifferentiationDisease variantDNA-bindingMetal-bindingMethyltransferaseNucleusReference proteomeRepeatRepressorTranscriptionTranscription regulationTransferaseZincZinc-fingerQQVEKPLSPPLNSLPVMPPSSPPLFSYNKMRSKARARKLAKSDGDVVNNMYEPNRDLLASHSAEDEAEDSAMSPIPVGPPSPFPTSEDFTPKEGSPYEAPVYIPEDIPIPADFELRESSIPGAGLGVWAKRKMEAGERLGPCVVVPRAAAKETDFGWEQILTDVEVSPQEGCITKISEDLGSEKFCVDANQAGAGSWLKYIRVACSCDDQNLTMCQISEQIYYKVIKDIEPGEELLVHVKEGVYPLGTVPPGLDEEPTFRCDECDELFQSKLDLRRHKKYTCGSVGAALYEGLAEELKPEGLGGGSGQAHECKDCERMFPNKYSLEQHMVIHTEEREYKCDQCPKAFNWKSNLIRHQMSHDSGKRFECENCVKVFTDPSNLQRHIRSQHVGARAHACPDCGKTFATSSGLKQHKHIHSTVKPFICEVCHKSYTQFSNLCRHKRMHADCRTQIKCKDCGQMFSTTSSLNKHRRFCEGKNHYTPGGIFAPGLPLTPSPMMDKAKPSPSLNHASLGFNEYFPSRPHPGSLPFSTAPPTFPALTPGFPGIFPPSLYPRPPLLPPTSLLKSPLNHTQDAKLPSPLGNPALPLVSAVSNSSQGTTAAAGPEEKFESRLEDSCVEKLKTRSSDMSDGSDFEDVNTTTGTDLDTTTGTGSDLDSDVDSDPDKDKGKGKSAEGQPKFGGGLAPPGAPNSVAEVPVFYSQHSFFPPPDEQLLTATGAAGDSIKAIASIAEKYFGPGFMGMQEKKLGSLPYHSAFPFQFLPNFPHSLYPFTDRALAHNLLVKAEPKSPRDALKVGGPSAECPFDLTTKPKDVKPILPMPKGPSAPASGEEQPLDLSIGSRARASQNGGGREPRKNHVYGERKLGAGEGLPQVCPARMPQQPPLHYAKPSPFFMDPIYSRVEKRKVTDPVGALKEKYLRPSPLLFHPQMSAIETMTEKLESFAAMKADSGSSLQPLPHHPFNFRSPPPTLSDPILRKGKERYTCRYCGKIFPRSANLTRHLRTHTGEQPYRCKYCDRSFSISSNLQRHVRNIHNKEKPFKCHLCNRCFGQQTNLDRHLKKHEHENAPVSQHPGVLTNHLGTSASSPTSESDNHALLDEKEDSYFSEIRNFIANSEMNQASTRTEKRADMQIVDGSAQCPGLASEKQEDVEEEDDDDLEEDDEDSLAGKSQDDTVSPAPEPQAAYEDEEDEEPAASLAVGFDHTRRCAEDHEGGLLALEPMPTFGKGLDLRRAAEEAFEVKDVLNSTLDSEALKHTLCRQAKNQAYAMMLSLSEDTPLHTPSQGSLDAWLKVTGATSESGAFHPINHL
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