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A2A935

- PRD16_MOUSE

UniProt

A2A935 - PRD16_MOUSE

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Protein

PR domain zinc finger protein 16

Gene
Prdm16, Kiaa1675, Mel1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.4 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri230 – 25526C2H2-type 1; degenerateAdd
BLAST
Zinc fingeri282 – 30423C2H2-type 2Add
BLAST
Zinc fingeri310 – 33223C2H2-type 3Add
BLAST
Zinc fingeri338 – 36124C2H2-type 4Add
BLAST
Zinc fingeri367 – 38923C2H2-type 5Add
BLAST
Zinc fingeri395 – 41723C2H2-type 6Add
BLAST
Zinc fingeri424 – 44623C2H2-type 7; atypicalAdd
BLAST
Zinc fingeri951 – 97323C2H2-type 8Add
BLAST
Zinc fingeri979 – 100224C2H2-type 9Add
BLAST
Zinc fingeri1008 – 103023C2H2-type 10Add
BLAST

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. protein binding Source: UniProtKB
  3. sequence-specific DNA binding Source: UniProtKB
  4. SMAD binding Source: MGI
  5. transcription coactivator activity Source: UniProtKB

GO - Biological processi

  1. brown fat cell differentiation Source: UniProtKB
  2. negative regulation of granulocyte differentiation Source: UniProtKB
  3. negative regulation of transcription, DNA-templated Source: UniProtKB
  4. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  5. negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
  6. neurogenesis Source: MGI
  7. palate development Source: MGI
  8. positive regulation of transcription, DNA-templated Source: UniProtKB
  9. regulation of cellular respiration Source: UniProtKB
  10. somatic stem cell maintenance Source: MGI
  11. tongue development Source: MGI
  12. transcription, DNA-templated Source: UniProtKB-KW
  13. white fat cell differentiation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Differentiation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Prdm16
Synonyms:Kiaa1675, Mel1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 4

Organism-specific databases

MGIiMGI:1917923. Prdm16.

Subcellular locationi

Nucleus 1 Publication

GO - Cellular componenti

  1. nucleus Source: UniProtKB
  2. transcriptional repressor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice die at birth but embryos display altered brown adipose tissue differentiation.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi805 – 8062DL → AS: Loss of interaction with CTBP1 and CTBP2 and loss of repression of WAT-specific genes. 1 Publication
Mutagenesisi996 – 9961R → Q: Loss of DNA-binding activity but no effect on PRDM16-mediated BAT gene transcription activation. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12751275PR domain zinc finger protein 16PRO_0000384377Add
BLAST

Proteomic databases

PaxDbiA2A935.
PRIDEiA2A935.

PTM databases

PhosphoSiteiA2A935.

Expressioni

Tissue specificityi

Enriched in BAT compared to WAT. Detected in heart, lung, kidney and brain. Expressed in nuclei of cardiomyocytes.2 Publications

Developmental stagei

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.2 Publications

Gene expression databases

BgeeiA2A935.
GenevestigatoriA2A935.

Interactioni

Subunit structurei

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 SMAD3.5 Publications

Protein-protein interaction databases

BioGridi214194. 5 interactions.
DIPiDIP-60593N.
IntActiA2A935. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliA2A935.
SMRiA2A935. Positions 25-210, 229-496, 947-1057.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini82 – 211130SETAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni680 – 1038359Interaction with CTBP1 and CTBP2Add
BLAST
Regioni740 – 1275536Mediates interaction with SKI and regulation of TGF-beta signaling By similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi460 – 55899Pro-richAdd
BLAST

Sequence similaritiesi

Contains 10 C2H2-type zinc fingers.
Contains 1 SET domain.

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri230 – 25526C2H2-type 1; degenerateAdd
BLAST
Zinc fingeri282 – 30423C2H2-type 2Add
BLAST
Zinc fingeri310 – 33223C2H2-type 3Add
BLAST
Zinc fingeri338 – 36124C2H2-type 4Add
BLAST
Zinc fingeri367 – 38923C2H2-type 5Add
BLAST
Zinc fingeri395 – 41723C2H2-type 6Add
BLAST
Zinc fingeri424 – 44623C2H2-type 7; atypicalAdd
BLAST
Zinc fingeri951 – 97323C2H2-type 8Add
BLAST
Zinc fingeri979 – 100224C2H2-type 9Add
BLAST
Zinc fingeri1008 – 103023C2H2-type 10Add
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG5048.
GeneTreeiENSGT00530000063676.
HOGENOMiHOG000231144.
InParanoidiQ69ZD6.
OrthoDBiEOG72G16H.
TreeFamiTF315309.

Family and domain databases

Gene3Di3.30.160.60. 8 hits.
InterProiIPR001214. SET_dom.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF00096. zf-C2H2. 4 hits.
[Graphical view]
SMARTiSM00317. SET. 1 hit.
SM00355. ZnF_C2H2. 10 hits.
[Graphical view]
PROSITEiPS50280. SET. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 8 hits.
PS50157. ZINC_FINGER_C2H2_2. 10 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: A2A935-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MRSKARARKL AKSDGDVVNN MYEPDPDLLA GQSAEEETED GILSPIPMGP     50
PSPFPTSEDF TPKEGSPYEA PVYIPEDIPI PPDFELRESS IPGAGLGIWA 100
KRKMEIGERF GPYVVTPRAA LKEADFGWEM LTDTEVSSQE SCIKKQISED 150
LGSEKFCVDA NQAGSGSWLK YIRVACSCDD QNLAMCQINE QIYYKVIKDI 200
EPGEELLVHV KEGAYSLGVM APSLDEDPTF RCDECDELFQ CRLDLRRHKK 250
YACSSAGAQL YEGLGEELKP EGLGVGSDGQ AHECKDCERM FPNKYSLEQH 300
MIVHTEEREY KCDQCPKAFN WKSNLIRHQM SHDSGKRFEC ENCVKVFTDP 350
SNLQRHIRSQ HVGARAHACP DCGKTFATSS GLKQHKHIHS TVKPFICEVC 400
HKSYTQFSNL CRHKRMHADC RTQIKCKDCG QMFSTTSSLN KHRRFCEGKN 450
HYTPGSIFTP GLPLTPSPMM DKTKPSPTLN HGGLGFSEYF PSRPHPGSLP 500
FSAAPPAFPA LTPGFPGIFP PSLYPRPPLL PPTPLLKSPL NHAQDAKLPS 550
PLGNPALPLV SAVSNSSQGA TAATGSEEKF DGRLEDAYAE KVKNRSPDMS 600
DGSDFEDINT TTGTDLDTTT GTGSDLDSDL DSDRDKGKDK GKPVESKPEF 650
GGASVPPGAM NSVAEVPAFY SQHSFFPPPE EQLLTASGAA GDSIKAIASI 700
AEKYFGPGFM SMQEKKLGSL PYHSVFPFQF LPNFPHSLYP FTDRALAHNL 750
LVKAEPKSPR DALKVGGPSA ECPFDLTTKP KEAKPALLAP KVPLIPSSGE 800
EQPLDLSIGS RARASQNGGG REPRKNHVYG ERKPGVSEGL PKVCPAQLPQ 850
QPSLHYAKPS PFFMDPIYRV EKRKVADPVG VLKEKYLRPS PLLFHPQMSA 900
IETMTEKLES FAAMKADSGS SLQPLPHHPF NFRSPPPTLS DPILRKGKER 950
YTCRYCGKIF PRSANLTRHL RTHTGEQPYR CKYCDRSFSI SSNLQRHVRN 1000
IHNKEKPFKC HLCNRCFGQQ TNLDRHLKKH EHEGAPVSQH SGVLTNHLGT 1050
SASSPTSESD NHALLDEKED SYFSEIRNFI ANSEMNQAST RMDKRPEIQD 1100
LDSNPPCPGS ASAKPEDVEE EEEEELEEED DDSLAGKSQE DTVSPTPEPQ 1150
GVYEDEEDEE PPSLTMGFDH TRRCVEERGG GLLALEPTPT FGKGLDLRRA 1200
AEEAFEVKDV LNSTLDSEVL KQTLYRQAKN QAYAMMLSLS EDTPLHAPSQ 1250
SSLDAWLNIT GPSSESGAFN PINHL 1275
Length:1,275
Mass (Da):140,858
Last modified:February 5, 2008 - v1
Checksum:i2F1F6B6C3EBFEC10
GO
Isoform 2 (identifier: A2A935-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:1,178
Mass (Da):130,427
Checksum:i9B050B76A7B9E29F
GO
Isoform 3 (identifier: A2A935-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     868-868: Y → YS

Note: No experimental confirmation available.

Show »
Length:1,276
Mass (Da):140,945
Checksum:i8A716E6E065ADEA4
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei129 – 1291E → EQ in isoform 2. VSP_038066
Alternative sequencei868 – 8681Y → YS in isoform 2 and isoform 3. VSP_038067
Alternative sequencei1174 – 11763CVE → HMQ in isoform 2. VSP_038068
Alternative sequencei1177 – 127599Missing in isoform 2. VSP_038069Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti8 – 81R → K in BAC79382. 1 Publication
Sequence conflicti510 – 5101A → T in BAC79382. 1 Publication
Sequence conflicti706 – 7061G → D in BAC79382. 1 Publication
Sequence conflicti732 – 7321P → L in BAC79382. 1 Publication
Sequence conflicti760 – 7601R → Q in BAC79382. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB078338 mRNA. Translation: BAC79382.1.
AL627226
, AL611950, AL627123, AL627127 Genomic DNA. Translation: CAM14956.1.
AL627226
, AL611950, AL627123, AL627127 Genomic DNA. Translation: CAM14959.1.
AL627123
, AL611950, AL627127, AL627226 Genomic DNA. Translation: CAM21844.1.
AL627123
, AL611950, AL627127, AL627226 Genomic DNA. Translation: CAM21845.1.
AL627127
, AL611950, AL627123, AL627226 Genomic DNA. Translation: CAM22275.1.
AL627127
, AL611950, AL627123, AL627226 Genomic DNA. Translation: CAM22278.1.
AL611950
, AL627123, AL627127, AL627226 Genomic DNA. Translation: CAM24998.1.
AL611950
, AL627123, AL627127, AL627226 Genomic DNA. Translation: CAM25001.1.
BC059838 mRNA. Translation: AAH59838.1.
AK173230 mRNA. Translation: BAD32508.1.
CCDSiCCDS38989.1. [A2A935-1]
CCDS71532.1. [A2A935-2]
RefSeqiNP_001277955.1. NM_001291026.1.
NP_001277958.1. NM_001291029.1. [A2A935-2]
NP_081780.3. NM_027504.3. [A2A935-1]
XP_006539236.1. XM_006539173.1. [A2A935-3]
UniGeneiMm.257785.

Genome annotation databases

EnsembliENSMUST00000030902; ENSMUSP00000030902; ENSMUSG00000039410. [A2A935-1]
ENSMUST00000070313; ENSMUSP00000064546; ENSMUSG00000039410. [A2A935-2]
GeneIDi70673.
KEGGimmu:70673.
UCSCiuc008wbu.1. mouse. [A2A935-1]
uc008wbx.1. mouse. [A2A935-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB078338 mRNA. Translation: BAC79382.1 .
AL627226
, AL611950 , AL627123 , AL627127 Genomic DNA. Translation: CAM14956.1 .
AL627226
, AL611950 , AL627123 , AL627127 Genomic DNA. Translation: CAM14959.1 .
AL627123
, AL611950 , AL627127 , AL627226 Genomic DNA. Translation: CAM21844.1 .
AL627123
, AL611950 , AL627127 , AL627226 Genomic DNA. Translation: CAM21845.1 .
AL627127
, AL611950 , AL627123 , AL627226 Genomic DNA. Translation: CAM22275.1 .
AL627127
, AL611950 , AL627123 , AL627226 Genomic DNA. Translation: CAM22278.1 .
AL611950
, AL627123 , AL627127 , AL627226 Genomic DNA. Translation: CAM24998.1 .
AL611950
, AL627123 , AL627127 , AL627226 Genomic DNA. Translation: CAM25001.1 .
BC059838 mRNA. Translation: AAH59838.1 .
AK173230 mRNA. Translation: BAD32508.1 .
CCDSi CCDS38989.1. [A2A935-1 ]
CCDS71532.1. [A2A935-2 ]
RefSeqi NP_001277955.1. NM_001291026.1.
NP_001277958.1. NM_001291029.1. [A2A935-2 ]
NP_081780.3. NM_027504.3. [A2A935-1 ]
XP_006539236.1. XM_006539173.1. [A2A935-3 ]
UniGenei Mm.257785.

3D structure databases

ProteinModelPortali A2A935.
SMRi A2A935. Positions 25-210, 229-496, 947-1057.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 214194. 5 interactions.
DIPi DIP-60593N.
IntActi A2A935. 1 interaction.

PTM databases

PhosphoSitei A2A935.

Proteomic databases

PaxDbi A2A935.
PRIDEi A2A935.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000030902 ; ENSMUSP00000030902 ; ENSMUSG00000039410 . [A2A935-1 ]
ENSMUST00000070313 ; ENSMUSP00000064546 ; ENSMUSG00000039410 . [A2A935-2 ]
GeneIDi 70673.
KEGGi mmu:70673.
UCSCi uc008wbu.1. mouse. [A2A935-1 ]
uc008wbx.1. mouse. [A2A935-2 ]

Organism-specific databases

CTDi 63976.
MGIi MGI:1917923. Prdm16.
Rougei Search...

Phylogenomic databases

eggNOGi COG5048.
GeneTreei ENSGT00530000063676.
HOGENOMi HOG000231144.
InParanoidi Q69ZD6.
OrthoDBi EOG72G16H.
TreeFami TF315309.

Miscellaneous databases

ChiTaRSi PRDM16. mouse.
NextBioi 332055.
PROi A2A935.
SOURCEi Search...

Gene expression databases

Bgeei A2A935.
Genevestigatori A2A935.

Family and domain databases

Gene3Di 3.30.160.60. 8 hits.
InterProi IPR001214. SET_dom.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view ]
Pfami PF00096. zf-C2H2. 4 hits.
[Graphical view ]
SMARTi SM00317. SET. 1 hit.
SM00355. ZnF_C2H2. 10 hits.
[Graphical view ]
PROSITEi PS50280. SET. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 8 hits.
PS50157. ZINC_FINGER_C2H2_2. 10 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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. 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. Cited for: DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.

Entry informationi

Entry nameiPRD16_MOUSE
AccessioniPrimary (citable) accession number: A2A935
Secondary accession number(s): Q69ZD6, Q6PB79, Q7TPF4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 22, 2009
Last sequence update: February 5, 2008
Last modified: September 3, 2014
This is version 63 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi