dbPTM

NR1D2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	NR1D2_HUMAN
UniProt AC	Q14995
Protein Name	Nuclear receptor subfamily 1 group D member 2
Gene Name	NR1D2
Organism	Homo sapiens (Human).
Sequence Length	579
Subcellular Localization	Nucleus .
Protein Description	Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components ARNTL/BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle..
Protein Sequence	MEVNAGGVIAYISSSSSASSPASCHSEGSENSFQSSSSSVPSSPNSSNSDTNGNPKNGDLANIEGILKNDRIDCSMKTSKSSAPGMTKSHSGVTKFSGMVLLCKVCGDVASGFHYGVHACEGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKKCLSVGMSRDAVRFGRIPKREKQRMLIEMQSAMKTMMNSQFSGHLQNDTLVEHHEQTALPAQEQLRPKPQLEQENIKSSSPPSSDFAKEEVIGMVTRAHKDTFMYNQEQQENSAESMQPQRGERIPKNMEQYNLNHDHCGNGLSSHFPCSESQQHLNGQFKGRNIMHYPNGHAICIANGHCMNFSNAYTQRVCDRVPIDGFSQNENKNSYLCNTGGRMHLVCPLSKSPYVDPHKSGHEIWEEFSMSFTPAVKEVVEFAKRIPGFRDLSQHDQVNLLKAGTFEVLMVRFASLFDAKERTVTFLSGKKYSVDDLHSMGAGDLLNSMFEFSEKLNALQLSDEEMSLFTAVVLVSADRSGIENVNSVEALQETLIRALRTLIMKNHPNEASIFTKLLLKLPDLRSLNNMHSEELLAFKVHP

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
46	Phosphorylation	SVPSSPNSSNSDTNG CCCCCCCCCCCCCCC	33.99	-
68	Ubiquitination	ANIEGILKNDRIDCS CCHHHHHHCCEEEEC	55.68	-
78	Phosphorylation	RIDCSMKTSKSSAPG EEEECEECCCCCCCC	32.52	22964224
79	Phosphorylation	IDCSMKTSKSSAPGM EEECEECCCCCCCCC	25.64	22964224
81	Phosphorylation	CSMKTSKSSAPGMTK ECEECCCCCCCCCCC	31.34	22964224
82	Phosphorylation	SMKTSKSSAPGMTKS CEECCCCCCCCCCCC	42.07	22964224
87	Phosphorylation	KSSAPGMTKSHSGVT CCCCCCCCCCCCCCC	35.00	22964224
138	Ubiquitination	IQQNIQYKKCLKNEN HHHHHCHHHHHCCCC	22.19	-
162	Acetylation	RCQQCRFKKCLSVGM HHHHCCHHHHHHCCC	24.19	17996965
163	Acetylation	CQQCRFKKCLSVGMS HHHCCHHHHHHCCCC	37.38	17996965
193	Phosphorylation	RMLIEMQSAMKTMMN HHHHHHHHHHHHHHH	29.08	-
241	Phosphorylation	EQENIKSSSPPSSDF HHHHHHCCCCCCHHH	41.69	24114839
242	Phosphorylation	QENIKSSSPPSSDFA HHHHHCCCCCCHHHH	48.17	25159151
330	Phosphorylation	KGRNIMHYPNGHAIC CCCCCCCCCCCCEEE	4.88	-
421	Ubiquitination	KEVVEFAKRIPGFRD HHHHHHHHHCCCCCC	57.06	-
460	Phosphorylation	LFDAKERTVTFLSGK HHCCCCCEEEEECCC	25.62	19413330
462	Phosphorylation	DAKERTVTFLSGKKY CCCCCEEEEECCCCC	20.46	19413330
467	Ubiquitination	TVTFLSGKKYSVDDL EEEEECCCCCCHHHH	45.20	-
470	Phosphorylation	FLSGKKYSVDDLHSM EECCCCCCHHHHHHC	28.13	24247654
553	Ubiquitination	NEASIFTKLLLKLPD CHHHHHHHHHHHCCC	26.79	-
557	Ubiquitination	IFTKLLLKLPDLRSL HHHHHHHHCCCHHHH	58.92	21906983

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
46	S	Phosphorylation	Kinase	GSK3-BETA	P49841	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
374	C	Oxidation	21123168
When subjected to oxidative stress conditions, Cys-384 undergoes oxidation to form a disulfide bridge with Cys-374, also triggering a ligand switch that results in release of bound heme and derepression of target genes.
384	C	Oxidation	21123168
When subjected to oxidative stress conditions, Cys-384 undergoes oxidation to form a disulfide bridge with Cys-374, also triggering a ligand switch that results in release of bound heme and derepression of target genes.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of NR1D2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
TAF9_HUMAN	TAF9	physical	9611234
NCOR1_HUMAN	NCOR1	physical	9611234
TF2B_HUMAN	GTF2B	physical	9611234
TAF6_HUMAN	TAF6	physical	9611234
SIN3B_HUMAN	SIN3B	physical	9611234
HDAC1_HUMAN	HDAC1	physical	9611234
ANM6_HUMAN	PRMT6	physical	23455924
RBPMS_HUMAN	RBPMS	physical	25416956
TRIM1_HUMAN	MID2	physical	25416956
KRA42_HUMAN	KRTAP4-2	physical	25416956
K1C40_HUMAN	KRT40	physical	25416956
KR109_HUMAN	KRTAP10-9	physical	25416956
NT2NL_HUMAN	NOTCH2NL	physical	25416956
RORG_HUMAN	RORC	physical	23555304
CLOCK_HUMAN	CLOCK	physical	23555304
UBP48_HUMAN	USP48	physical	28514442
NR1D1_HUMAN	NR1D1	physical	28514442
SATB2_HUMAN	SATB2	physical	28514442
ZN703_HUMAN	ZNF703	physical	28514442

Drug and Disease Associations

Kegg Disease
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of NR1D2_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-460 AND THR-462, ANDMASS SPECTROMETRY.	19413330 [Abstract]

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