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FLASH GENE

Symbol

UCP1

contributors: mct - updated : 28-03-2018

HGNC name	uncoupling protein 1 (mitochondrial, proton carrier)
HGNC id	12517

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	8.91 kb     6 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	cytosine-phosphate-guanine/HTF
	Binding site   enhancer
text structure	a new regulatory motif in the promoter that binds NR4As to stimulate UCP1 gene transcription
	binding sites for KLF11 and KLF15 in the UCP1 promoter, and cooperative action of KLF11 and KLF15 on the UCP1 promoter was essential for induction of UCP1 in the process of brown adipocyte differentiation of mesenchymal stem cells
	regulatory CREs in the UCP1 enhancer

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_021833 6 - 1000 NP_068605 - 307 - 2008 11317671

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose brown   highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol not specific adipocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	three tandemly repeated mitochondrial protein domains
	an ATP binding site
	three matrix loops involved in the control of transport

conjugated

PhosphoP

mono polymer

dimer

HOMOLOGY

Homologene

FAMILY

mitochondrial carrier family

CATEGORY

transport carrier

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,organelle,membrane
text	localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT)
	integral membrane protein found in the mitochondrial inner membrane of brown adipose tissue

basic FUNCTION	dissipating the proton electrochemical gradient and uncoupling fuel oxidation from ADP-ATP conversion
	H+ transporter, fatty acid dependent
	BAT-specific protein present only in the inner mitochondorial membrane of brown adipocytes
	phosphoprotein, and cold-acclimation increases the proportion of UCP1 that is serine phosphorylated
	identified as a second protein propagating basal proton leak, lending support to the hypothesis that basal leak pathways are perpetrated by members of the mitochondrial anion carrier family but not by other mitochondrial inner membrane proteins
	adipose tissue-specific UCP1 expression potentially involves demethylation of CpG dinucleotides found in regulatory CREs in the UCP1 enhancer, as well as modification of histone tails
	catalyzes the dissipation of mitochondrial proton motive force as heat
	potently reduces mitochondrial superoxide production after cold acclimation and during fatty acid oxidation
	can affect reactive oxygen containing species production by isolated mitochondria from brown adipose tissue
	catalyzes proton leak across the mitochondrial inner membrane to disengage substrate oxidation from ATP production
	UCP1 is a hallmark of BAT, being the pivotal player for cold-induced thermogenesis
	contributes to thermogenesis, and its expression is regulated at the transcriptional level, and is also regulated post-transcriptionally
	is the established mediator of brown adipose tissue-dependent thermogenesis
	is certainly a unique mitochondrial transporter able to uncouple respiration from ADP phosphorylation in mitochondria
	UCP1 has retained all of the key features of mitochondrial carriers, indicating that it operates by a conventional carrier-like mechanism
	generates heat by causing proton leak across the mitochondrial inner membrane that requires fatty acid (FA)
	differences in molecular mechanisms of the inhibition between the highly homologous transporters UCP1 and UCP3 indicate that UCP3 has adapted to fulfill a different role and possibly another transport function in brown adipose tissue (BAT)
	expression of UCP1 in brown adipose tissue (BAT) is essential for mammalian thermogenesis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

mitochondrial transport

text	energy transfer

PATHWAY

metabolism

energetic

signaling

a component

uncoupling protein constituent of inner mitochondrial membrane

INTERACTION

DNA

RNA

small molecule

protein	concomitant MYOD1 and IGF2 inactivation accelerates differentiation of a brown preadipocyte cell line and induces lipid accumulation and increased UCP1 and PRDM16 expression
	fatty acids induce a conformational change in UCP1
	UCP1 expression is differently affected by RARA in mouse and human adipocytes (PMUID: 24059847)
	PRDM16 is recruited to the UCP1 enhancer
	cardiolipin stabilizes UCP1, as demonstrated by reconstitution experiments and thermostability assays, indicating that the lipid has an integral role in the functioning of the protein, similar to other mitochondrial carriers
	KDM1A interacts with ZNF516 to Promote UCP1 transcription and brown fat program
	TENM2 deficiency induces UCP1 expression in differentiating human fat cells
	CLK2 is likely a regulatory component of diet-induced thermogenesis in brown adipose tissue (BAT) through increased CREB-dependent expression of UCP1
	reduced UCP1 expression under inflammation is mediated by the increased expression of CCAR2, which inhibits SIRT1 activity
	stress activated kinase MAP2K6 acts as a repressor of UCP1 expression, suggesting that its inhibition promotes adipose tissue browning and increases organismal energy expenditure

cell & other

REGULATION

activated by	coenzyme Q (ubiquinone)
	by fatty acids

induced by

BMP7

inhibited by	low concentration of nucleeotides
	purine nucleotides

repressed by

SESN2 and antioxidants that inhibit UCP1 expression through suppressing ROS-mediated MAPK14 activation, implying a critical role of ROS in proper BAT metabolism

Other

regulated by PPARA and PPARG in mice

ASSOCIATED DISORDERS

corresponding disease(s)

related resource

MITOP database

Susceptibility

obesity, diabetes

Variant & Polymorphism SNP	a minor role of the 5'utr polymorphism in obesity and diabetes
	SNP in type 2 diabetes mellitus (allele GG)

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

transgenic mice with muscular overexpression of uncoupling protein 1 (Ucp1), a potent mitochondrial uncoupler, displayed age-dependent deterioration of the NMJ that correlated with progressive signs of denervation and a mild late-onset motor neuron pathology