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 05-OCT-2010, entry version 90. DE RecName: Full=PR domain zinc finger protein 16; DE AltName: Full=PR domain-containing protein 16; DE AltName: Full=Transcription factor MEL1; DE Short=MDS1/EVI1-like gene 1; GN Name=PRDM16; Synonyms=KIAA1675, MEL1, PFM13; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT PRO-533, CHROMOSOMAL RP TRANSLOCATION, DISEASE, AND TISSUE SPECIFICITY. RX MEDLINE=20504068; PubMed=11050005; RA Mochizuki N., Shimizu S., Nagasawa T., Tanaka H., Taniwaki M., RA Yokota J., Morishita K.; RT "A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the RT MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)- RT positive 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 RT suppressors."; RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP PRO-533. RC TISSUE=Brain; RX MEDLINE=21082932; 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. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 7:347-355(2000). RN [4] RP SEQUENCE REVISION. RX MEDLINE=22158633; 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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 RP 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, ALTERNATIVE SPLICING (ISOFORMS 2 AND 4), AND TISSUE RP SPECIFICITY. RC TISSUE=Placenta; RX MEDLINE=22929811; 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 RT expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF- RT induced myeloid 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 RT t(1;3)(p36;q21) occur in the first intron and in the 5' region of RT 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, AND INTERACTION WITH HDAC1; SKI; SMAD2 RP AND SMAD3. 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., RA Morishita K., Yuki K., Hanyu A., Miyazawa K., Inazawa J., Miyazono K., RA Imamura T.; RT "SKI and MEL1 cooperate to inhibit transforming growth factor-beta RT signal in gastric cancer cells."; RL J. Biol. Chem. 284:3334-3344(2009). CC -!- FUNCTION: Binds DNA and functions as a transcriptional regulator. CC Functions in the differentiation of brown adipose tissue (BAT) CC which is specialized in dissipating chemical energy in the form of CC heat in response to cold or excess feeding while white adipose CC tissue (WAT) is specialized in the storage of excess energy and CC the control of systemic metabolism. Together with CEBPB, regulates CC the differentiation of myoblastic precursors into brown adipose CC cells. Functions also as a repressor of TGF-beta signaling. CC Isoform 4 may regulate granulocytes differentiation. 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 CC PPARGC1B; interaction with PPARGC1A or PPARGC1B activates the CC transcription of BAT-specific gene. Interacts with SMAD3 (By CC similarity). Interacts with HDAC1, SKI, SMAD2 and SMAD3; the CC interaction with SKI promotes the recruitment of SMAD3-HDAC1 CC complex on the promoter of TGF-beta target genes. CC -!- SUBCELLULAR LOCATION: Nucleus. 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 Note=No experimental confirmation available; CC Name=3; CC IsoId=Q9HAZ2-3; Sequence=VSP_038064, VSP_038065; CC Note=No experimental confirmation available; CC Name=4; Synonyms=MEL1S; CC IsoId=Q9HAZ2-4; Sequence=VSP_038063; CC Note=Produced by alternative promoter usage; CC -!- TISSUE SPECIFICITY: Expressed in uterus and kidney. CC -!- DISEASE: Note=A chromosomal aberration involving PRDM16 is found CC in myelodysplastic syndrome (MDS) and acute myeloid leukemia CC (AML). Reciprocal translocation t(1;3)(p36;q21). Isoform 4 is CC specifically expressed in adult T-cell leukemia. CC -!- SIMILARITY: Contains 10 C2H2-type zinc fingers. CC -!- SIMILARITY: Contains 1 SET domain. CC -!- SEQUENCE CAUTION: CC Sequence=BAB21766.2; Type=Erroneous initiation; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/PRDM16MEL1ID408.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AB078876; BAB84297.1; -; mRNA. DR EMBL; AF294278; AAG33382.1; -; mRNA. DR EMBL; AB051462; BAB21766.2; ALT_INIT; mRNA. DR EMBL; AL512383; CAH71132.1; -; Genomic_DNA. DR EMBL; AL008733; CAH71132.1; JOINED; Genomic_DNA. DR EMBL; AL354743; CAH71132.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAH71132.1; JOINED; Genomic_DNA. DR EMBL; AL512383; CAH71133.1; -; Genomic_DNA. DR EMBL; AL008733; CAH71133.1; JOINED; Genomic_DNA. DR EMBL; AL354743; CAH71133.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAH71133.1; JOINED; Genomic_DNA. DR EMBL; AL512383; CAH71134.1; -; Genomic_DNA. DR EMBL; AL008733; CAH71134.1; JOINED; Genomic_DNA. DR EMBL; AL354743; CAH71134.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAH71134.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAH71529.1; -; Genomic_DNA. DR EMBL; AL008733; CAH71529.1; JOINED; Genomic_DNA. DR EMBL; AL354743; CAH71529.1; JOINED; Genomic_DNA. DR EMBL; AL512383; CAH71529.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAH71530.1; -; Genomic_DNA. DR EMBL; AL008733; CAH71530.1; JOINED; Genomic_DNA. DR EMBL; AL354743; CAH71530.1; JOINED; Genomic_DNA. DR EMBL; AL512383; CAH71530.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAH71531.1; -; Genomic_DNA. DR EMBL; AL008733; CAH71531.1; JOINED; Genomic_DNA. DR EMBL; AL354743; CAH71531.1; JOINED; Genomic_DNA. DR EMBL; AL512383; CAH71531.1; JOINED; Genomic_DNA. DR EMBL; AL008733; CAI19629.1; -; Genomic_DNA. DR EMBL; AL354743; CAI19629.1; JOINED; Genomic_DNA. DR EMBL; AL512383; CAI19629.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAI19629.1; JOINED; Genomic_DNA. DR EMBL; AL008733; CAI19630.1; -; Genomic_DNA. DR EMBL; AL354743; CAI19630.1; JOINED; Genomic_DNA. DR EMBL; AL512383; CAI19630.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAI19630.1; JOINED; Genomic_DNA. DR EMBL; AL008733; CAI19631.1; -; Genomic_DNA. DR EMBL; AL354743; CAI19631.1; JOINED; Genomic_DNA. DR EMBL; AL512383; CAI19631.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAI19631.1; JOINED; Genomic_DNA. DR EMBL; AL354743; CAI22788.1; -; Genomic_DNA. DR EMBL; AL008733; CAI22788.1; JOINED; Genomic_DNA. DR EMBL; AL512383; CAI22788.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAI22788.1; JOINED; Genomic_DNA. DR EMBL; AL354743; CAI22789.1; -; Genomic_DNA. DR EMBL; AL008733; CAI22789.1; JOINED; Genomic_DNA. DR EMBL; AL512383; CAI22789.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAI22789.1; JOINED; Genomic_DNA. DR EMBL; AL354743; CAI22790.1; -; Genomic_DNA. DR EMBL; AL008733; CAI22790.1; JOINED; Genomic_DNA. DR EMBL; AL512383; CAI22790.1; JOINED; Genomic_DNA. DR EMBL; AL590438; CAI22790.1; JOINED; Genomic_DNA. DR EMBL; BC161614; AAI61614.1; -; mRNA. DR IPI; IPI00289654; -. DR IPI; IPI00642532; -. DR IPI; IPI00914925; -. DR IPI; IPI00963982; -. DR RefSeq; NP_071397.3; -. DR RefSeq; NP_955533.2; -. DR UniGene; Hs.99500; -. DR ProteinModelPortal; Q9HAZ2; -. DR SMR; Q9HAZ2; 56-211, 227-388, 281-416, 917-1011, 946-1030. DR STRING; Q9HAZ2; -. DR PRIDE; Q9HAZ2; -. DR Ensembl; ENST00000270722; ENSP00000270722; ENSG00000142611. DR GeneID; 63976; -. DR KEGG; hsa:63976; -. DR UCSC; uc001akd.1; human. DR UCSC; uc001ake.1; human. DR CTD; 63976; -. DR GeneCards; GC01P003008; -. DR HGNC; HGNC:14000; PRDM16. DR MIM; 605557; gene. DR PharmGKB; PA33714; -. DR eggNOG; prNOG19352; -. DR HOVERGEN; HBG005619; -. DR OMA; FNEYFPS; -. DR PhylomeDB; Q9HAZ2; -. DR NextBio; 65776; -. DR ArrayExpress; Q9HAZ2; -. DR Bgee; Q9HAZ2; -. DR CleanEx; HS_PRDM16; -. DR Genevestigator; Q9HAZ2; -. DR GermOnline; ENSG00000142611; Homo sapiens. DR GO; GO:0017053; C:transcriptional repressor complex; ISS:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB. DR GO; GO:0016564; F:transcription repressor activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0050873; P:brown fat cell differentiation; ISS:UniProtKB. DR GO; GO:0030853; P:negative regulation of granulocyte differen...; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from R...; IDA:UniProtKB. DR GO; GO:0030512; P:negative regulation of transforming growth ...; IDA:UniProtKB. DR GO; GO:0030512; P:negative regulation of transforming growth ...; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-d...; IDA:UniProtKB. DR GO; GO:0043457; P:regulation of cellular respiration; ISS:UniProtKB. DR GO; GO:0006350; P:transcription; IEA:UniProtKB-KW. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Gene3D; G3DSA:3.30.160.60; Znf_C2H2/integrase_DNA-bd; 3. DR Pfam; PF00096; zf-C2H2; 4. DR SMART; SM00317; SET; 1. DR SMART; SM00355; ZnF_C2H2; 10. 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 Activator; Alternative promoter usage; Alternative splicing; KW Chromosomal rearrangement; Complete proteome; Differentiation; KW DNA-binding; Metal-binding; Nucleus; Polymorphism; Repeat; Repressor; KW Transcription; Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 1276 PR domain zinc finger protein 16. FT /FTId=PRO_0000047773. FT DOMAIN 83 215 SET. FT ZN_FING 230 253 C2H2-type 1; atypical. FT ZN_FING 281 303 C2H2-type 2. FT ZN_FING 309 331 C2H2-type 3. FT ZN_FING 337 360 C2H2-type 4. FT ZN_FING 366 388 C2H2-type 5. FT ZN_FING 394 416 C2H2-type 6. FT ZN_FING 423 445 C2H2-type 7; atypical. FT ZN_FING 951 973 C2H2-type 8. FT ZN_FING 979 1002 C2H2-type 9. FT ZN_FING 1008 1032 C2H2-type 10. FT REGION 679 1038 Interaction with CTBP1 and CTBP2 (By FT similarity). FT REGION 739 1276 Mediates interaction with SKI and FT regulation of TGF-beta signaling. FT COMPBIAS 459 557 Pro-rich. FT VAR_SEQ 1 184 Missing (in isoform 4). FT /FTId=VSP_038063. FT VAR_SEQ 191 191 Q -> QV (in isoform 3). FT /FTId=VSP_038064. FT VAR_SEQ 868 868 Missing (in isoform 3). FT /FTId=VSP_038065. FT VAR_SEQ 1233 1251 Missing (in isoform 2). FT /FTId=VSP_006932. FT VARIANT 533 533 S -> P (in dbSNP:rs870124). FT /FTId=VAR_031433. FT VARIANT 633 633 P -> L (in dbSNP:rs2493292). FT /FTId=VAR_031434. FT CONFLICT 50 52 PPS -> SPP (in Ref. 2; AAG33382). FT CONFLICT 324 324 L -> F (in Ref. 2; AAG33382). FT CONFLICT 491 491 S -> Y (in Ref. 2; AAG33382). FT CONFLICT 1022 1022 N -> K (in Ref. 1; BAB84297). 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 //