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A2A935 (PRD16_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 59. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
PR domain zinc finger protein 16
Alternative name(s):
PR domain-containing protein 16
Transcription factor MEL1
Short name=MDS1/EVI1-like gene 1
Gene names
Name:Prdm16
Synonyms:Kiaa1675, Mel1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1275 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds DNA and functions as a transcriptional regulator. 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. Together with CEBPB, regulates the differentiation of myoblastic precursors into brown adipose cells. Functions also as a repressor of TGF-beta signaling. May regulate granulocytes differentiation. Ref.6 Ref.7 Ref.8 Ref.9

Subunit structure

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 By similarity. Interacts 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 genes. Interacts with SMAD3. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9

Subcellular location

Nucleus Ref.7.

Tissue specificity

Enriched in BAT compared to WAT. Detected in heart, lung, kidney and brain. Expressed in nuclei of cardiomyocytes. Ref.6 Ref.10

Developmental stage

Expressed at E12.5, E13.5 and E14.5. Expressed in orofacial tissues, heart, liver, brain and limb bud. At E13.5, expressed throughout the ventricular myocardium, including endocardium and epicardium. Ref.5 Ref.10

Disruption phenotype

Mice die at birth but embryos display altered brown adipose tissue differentiation. Ref.8

Sequence similarities

Contains 10 C2H2-type zinc fingers.

Contains 1 SET domain.

Ontologies

Keywords
   Biological processDifferentiation
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Repressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbrown fat cell differentiation

Inferred from direct assay Ref.7Ref.8Ref.9. Source: UniProtKB

negative regulation of granulocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.7. Source: UniProtKB

negative regulation of transforming growth factor beta receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

neurogenesis

Inferred from direct assay PubMed 19050759. Source: MGI

palate development

Inferred from mutant phenotype PubMed 20007998. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.7Ref.9. Source: UniProtKB

regulation of cellular respiration

Inferred from direct assay Ref.6Ref.7. Source: UniProtKB

somatic stem cell maintenance

Inferred from direct assay PubMed 19379700. Source: MGI

tongue development

Inferred from mutant phenotype PubMed 20007998. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

white fat cell differentiation

Inferred from direct assay Ref.7. Source: UniProtKB

   Cellular_componentnucleus

Inferred from direct assay Ref.7. Source: UniProtKB

transcriptional repressor complex

Inferred from direct assay Ref.7. Source: UniProtKB

   Molecular_functionSMAD binding

Inferred from physical interaction Ref.5. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

sequence-specific DNA binding

Inferred from direct assay Ref.6. Source: UniProtKB

transcription coactivator activity

Inferred from direct assay Ref.6Ref.8. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: A2A935-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: A2A935-2)

The sequence of this isoform differs from the canonical sequence as follows:
     129-129: E → EQ
     868-868: Y → YS
     1174-1176: CVE → HMQ
     1177-1275: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: A2A935-3)

The sequence of this isoform differs from the canonical sequence as follows:
     868-868: Y → YS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12751275PR domain zinc finger protein 16
PRO_0000384377

Regions

Domain82 – 211130SET
Zinc finger230 – 25526C2H2-type 1; degenerate
Zinc finger282 – 30423C2H2-type 2
Zinc finger310 – 33223C2H2-type 3
Zinc finger338 – 36124C2H2-type 4
Zinc finger367 – 38923C2H2-type 5
Zinc finger395 – 41723C2H2-type 6
Zinc finger424 – 44623C2H2-type 7; atypical
Zinc finger951 – 97323C2H2-type 8
Zinc finger979 – 100224C2H2-type 9
Zinc finger1008 – 103023C2H2-type 10
Region680 – 1038359Interaction with CTBP1 and CTBP2
Region740 – 1275536Mediates interaction with SKI and regulation of TGF-beta signaling By similarity
Compositional bias460 – 55899Pro-rich

Natural variations

Alternative sequence1291E → EQ in isoform 2.
VSP_038066
Alternative sequence8681Y → YS in isoform 2 and isoform 3.
VSP_038067
Alternative sequence1174 – 11763CVE → HMQ in isoform 2.
VSP_038068
Alternative sequence1177 – 127599Missing in isoform 2.
VSP_038069

Experimental info

Mutagenesis805 – 8062DL → AS: Loss of interaction with CTBP1 and CTBP2 and loss of repression of WAT-specific genes. Ref.7
Mutagenesis9961R → Q: Loss of DNA-binding activity but no effect on PRDM16-mediated BAT gene transcription activation. Ref.6 Ref.7
Sequence conflict81R → K in BAC79382. Ref.1
Sequence conflict5101A → T in BAC79382. Ref.1
Sequence conflict7061G → D in BAC79382. Ref.1
Sequence conflict7321P → L in BAC79382. Ref.1
Sequence conflict7601R → Q in BAC79382. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 5, 2008. Version 1.
Checksum: 2F1F6B6C3EBFEC10

FASTA1,275140,858
        10         20         30         40         50         60 
MRSKARARKL AKSDGDVVNN MYEPDPDLLA GQSAEEETED GILSPIPMGP PSPFPTSEDF 

        70         80         90        100        110        120 
TPKEGSPYEA PVYIPEDIPI PPDFELRESS IPGAGLGIWA KRKMEIGERF GPYVVTPRAA 

       130        140        150        160        170        180 
LKEADFGWEM LTDTEVSSQE SCIKKQISED LGSEKFCVDA NQAGSGSWLK YIRVACSCDD 

       190        200        210        220        230        240 
QNLAMCQINE QIYYKVIKDI EPGEELLVHV KEGAYSLGVM APSLDEDPTF RCDECDELFQ 

       250        260        270        280        290        300 
CRLDLRRHKK YACSSAGAQL YEGLGEELKP EGLGVGSDGQ AHECKDCERM FPNKYSLEQH 

       310        320        330        340        350        360 
MIVHTEEREY KCDQCPKAFN WKSNLIRHQM SHDSGKRFEC ENCVKVFTDP SNLQRHIRSQ 

       370        380        390        400        410        420 
HVGARAHACP DCGKTFATSS GLKQHKHIHS TVKPFICEVC HKSYTQFSNL CRHKRMHADC 

       430        440        450        460        470        480 
RTQIKCKDCG QMFSTTSSLN KHRRFCEGKN HYTPGSIFTP GLPLTPSPMM DKTKPSPTLN 

       490        500        510        520        530        540 
HGGLGFSEYF PSRPHPGSLP FSAAPPAFPA LTPGFPGIFP PSLYPRPPLL PPTPLLKSPL 

       550        560        570        580        590        600 
NHAQDAKLPS PLGNPALPLV SAVSNSSQGA TAATGSEEKF DGRLEDAYAE KVKNRSPDMS 

       610        620        630        640        650        660 
DGSDFEDINT TTGTDLDTTT GTGSDLDSDL DSDRDKGKDK GKPVESKPEF GGASVPPGAM 

       670        680        690        700        710        720 
NSVAEVPAFY SQHSFFPPPE EQLLTASGAA GDSIKAIASI AEKYFGPGFM SMQEKKLGSL 

       730        740        750        760        770        780 
PYHSVFPFQF LPNFPHSLYP FTDRALAHNL LVKAEPKSPR DALKVGGPSA ECPFDLTTKP 

       790        800        810        820        830        840 
KEAKPALLAP KVPLIPSSGE EQPLDLSIGS RARASQNGGG REPRKNHVYG ERKPGVSEGL 

       850        860        870        880        890        900 
PKVCPAQLPQ QPSLHYAKPS PFFMDPIYRV EKRKVADPVG VLKEKYLRPS PLLFHPQMSA 

       910        920        930        940        950        960 
IETMTEKLES FAAMKADSGS SLQPLPHHPF NFRSPPPTLS DPILRKGKER YTCRYCGKIF 

       970        980        990       1000       1010       1020 
PRSANLTRHL RTHTGEQPYR CKYCDRSFSI SSNLQRHVRN IHNKEKPFKC HLCNRCFGQQ 

      1030       1040       1050       1060       1070       1080 
TNLDRHLKKH EHEGAPVSQH SGVLTNHLGT SASSPTSESD NHALLDEKED SYFSEIRNFI 

      1090       1100       1110       1120       1130       1140 
ANSEMNQAST RMDKRPEIQD LDSNPPCPGS ASAKPEDVEE EEEEELEEED DDSLAGKSQE 

      1150       1160       1170       1180       1190       1200 
DTVSPTPEPQ GVYEDEEDEE PPSLTMGFDH TRRCVEERGG GLLALEPTPT FGKGLDLRRA 

      1210       1220       1230       1240       1250       1260 
AEEAFEVKDV LNSTLDSEVL KQTLYRQAKN QAYAMMLSLS EDTPLHAPSQ SSLDAWLNIT 

      1270 
GPSSESGAFN PINHL 

« Hide

Isoform 2 [UniParc].

Checksum: 9B050B76A7B9E29F
Show »

FASTA1,178130,427
Isoform 3 [UniParc].

Checksum: 8A716E6E065ADEA4
Show »

FASTA1,276140,945

References

« Hide 'large scale' references
[1]"A 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."
Nishikata I., Sasaki H., Iga M., Tateno Y., Imayoshi S., Asou N., Nakamura T., Morishita K.
Blood 102:3323-3332(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: C57BL/6.
Tissue: Brain.
[4]"Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H.
DNA Res. 11:205-218(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 570-1275 (ISOFORM 3).
Tissue: Pancreatic islet.
[5]"PRDM16/MEL1: a novel Smad binding protein expressed in murine embryonic orofacial tissue."
Warner D.R., Horn K.H., Mudd L., Webb C.L., Greene R.M., Pisano M.M.
Biochim. Biophys. Acta 1773:814-820(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMAD3, DEVELOPMENTAL STAGE.
[6]"Transcriptional control of brown fat determination by PRDM16."
Seale P., Kajimura S., Yang W., Chin S., Rohas L.M., Uldry M., Tavernier G., Langin D., Spiegelman B.M.
Cell Metab. 6:38-54(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PPARGC1A AND PPARGC1B, MUTAGENESIS OF ARG-996, TISSUE SPECIFICITY.
[7]"Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex."
Kajimura S., Seale P., Tomaru T., Erdjument-Bromage H., Cooper M.P., Ruas J.L., Chin S., Tempst P., Lazar M.A., Spiegelman B.M.
Genes Dev. 22:1397-1409(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CTBP1; CTBP2; PPARGC1A AND PPARGC1B, SUBCELLULAR LOCATION, MUTAGENESIS OF 805-ASP-LEU-806.
[8]"PRDM16 controls a brown fat/skeletal muscle switch."
Seale P., Bjork B., Yang W., Kajimura S., Chin S., Kuang S., Scime A., Devarakonda S., Conroe H.M., Erdjument-Bromage H., Tempst P., Rudnicki M.A., Beier D.R., Spiegelman B.M.
Nature 454:961-967(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PPARA AND PPARG, DISRUPTION PHENOTYPE.
[9]"Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex."
Kajimura S., Seale P., Kubota K., Lunsford E., Frangioni J.V., Gygi S.P., Spiegelman B.M.
Nature 460:1154-1158(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CEBPA; CEBPB AND CEBPD.
[10]"Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy."
Arndt A.K., Schafer S., Drenckhahn J.D., Sabeh M.K., Plovie E.R., Caliebe A., Klopocki E., Musso G., Werdich A.A., Kalwa H., Heinig M., Padera R.F., Wassilew K., Bluhm J., Harnack C., Martitz J., Barton P.J., Greutmann M. expand/collapse author list , Berger F., Hubner N., Siebert R., Kramer H.H., Cook S.A., MacRae C.A., Klaassen S.
Am. J. Hum. Genet. 93:67-77(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB078338 mRNA. Translation: BAC79382.1.
AL627226 expand/collapse EMBL AC list , AL611950, AL627123, AL627127 Genomic DNA. Translation: CAM14956.1.
AL627226 expand/collapse EMBL AC list , AL611950, AL627123, AL627127 Genomic DNA. Translation: CAM14959.1.
AL627123 expand/collapse EMBL AC list , AL611950, AL627127, AL627226 Genomic DNA. Translation: CAM21844.1.
AL627123 expand/collapse EMBL AC list , AL611950, AL627127, AL627226 Genomic DNA. Translation: CAM21845.1.
AL627127 expand/collapse EMBL AC list , AL611950, AL627123, AL627226 Genomic DNA. Translation: CAM22275.1.
AL627127 expand/collapse EMBL AC list , AL611950, AL627123, AL627226 Genomic DNA. Translation: CAM22278.1.
AL611950 expand/collapse EMBL AC list , AL627123, AL627127, AL627226 Genomic DNA. Translation: CAM24998.1.
AL611950 expand/collapse EMBL AC list , AL627123, AL627127, AL627226 Genomic DNA. Translation: CAM25001.1.
BC059838 mRNA. Translation: AAH59838.1.
AK173230 mRNA. Translation: BAD32508.1.
RefSeqNP_081780.3. NM_027504.3.
XP_006539236.1. XM_006539173.1.
XP_006539240.1. XM_006539177.1.
UniGeneMm.257785.

3D structure databases

ProteinModelPortalA2A935.
SMRA2A935. Positions 22-223, 226-495, 876-1076.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid214194. 5 interactions.
DIPDIP-60593N.
IntActA2A935. 1 interaction.

PTM databases

PhosphoSiteA2A935.

Proteomic databases

PaxDbA2A935.
PRIDEA2A935.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000030902; ENSMUSP00000030902; ENSMUSG00000039410. [A2A935-1]
ENSMUST00000070313; ENSMUSP00000064546; ENSMUSG00000039410. [A2A935-2]
GeneID70673.
KEGGmmu:70673.
UCSCuc008wbu.1. mouse. [A2A935-1]
uc008wbx.1. mouse. [A2A935-2]

Organism-specific databases

CTD63976.
MGIMGI:1917923. Prdm16.
RougeSearch...

Phylogenomic databases

eggNOGCOG5048.
GeneTreeENSGT00530000063676.
HOGENOMHOG000231144.
InParanoidQ69ZD6.
OrthoDBEOG72G16H.
TreeFamTF315309.

Gene expression databases

BgeeA2A935.
GenevestigatorA2A935.

Family and domain databases

Gene3D3.30.160.60. 8 hits.
InterProIPR001214. SET_dom.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamPF00096. zf-C2H2. 4 hits.
[Graphical view]
SMARTSM00317. SET. 1 hit.
SM00355. ZnF_C2H2. 10 hits.
[Graphical view]
PROSITEPS50280. SET. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 8 hits.
PS50157. ZINC_FINGER_C2H2_2. 10 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPRDM16. mouse.
NextBio332055.
PROA2A935.
SOURCESearch...

Entry information

Entry namePRD16_MOUSE
AccessionPrimary (citable) accession number: A2A935
Secondary accession number(s): Q69ZD6, Q6PB79, Q7TPF4
Entry history
Integrated into UniProtKB/Swiss-Prot: September 22, 2009
Last sequence update: February 5, 2008
Last modified: April 16, 2014
This is version 59 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot