P35398

※ Protein Information

Tag	Content
UniProt Accession	RORA_HUMAN; P35398;
Entrez ID	6095
GenBank Protein ID	NM_002943.3; NM_134260.2; NM_134261.2; NM_134262.2;
GenBank Nucleotide ID	NP_002934.1; NP_599022.1; NP_599023.1; NP_599024.1;
Protein Name	Nuclear receptor ROR-alpha (Nuclear receptor RZR-alpha) (Nuclear receptor subfamily 1 group F member 1) (RAR-related orphan receptor A) (Retinoid-related orphan receptor-alpha)
Gene Name	RORA; NR1F1; RZRA
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcript(view all) Functional Description Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target genes regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates genes involved in photoreceptor development including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with MYOD1. Required for proper cerebellum development, regulates SHH gene expression, among others, to induce granule cells proliferation as well as expression of genes involved in calcium-mediated signal transduction. Regulates the circadian expression of several clock genes, including CLOCK, ARNTL/BMAL1, NPAS2 and CRY1. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORA-mediated activation of clock genes expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Regulates genes involved in lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant functions with RORC as positive or negative modulator of expression of genes encoding phase I and phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as CYP7B1 and SULT2A1. Induces a rhythmic expression of some of these genes. In addition, interplays functionally with NR1H2 and NR1H3 for the regulation of genes involved in cholesterol metabolism. Also involved in the regulation of hepatic glucose metabolism through the modulation of G6PC and PCK1. In adipose tissue, plays a role as negative regulator of adipocyte differentiation, probably acting through dual mechanisms. May suppress CEBPB-dependent adipogenesis through direct interaction and PPARG-dependent adipogenesis through competition for DNA-binding. Downstream of IL6 and TGFB and synergistically with RORC isoform 2, is implicated in the lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. Involved in hypoxia signaling by interacting with and activating the transcriptional activity of HIF1A. May inhibit cell growth in response to cellular stress. May exert an anti-inflammatory role by inducing CHUK expression and inhibiting NF-kappa-B signaling.
Sequence (Fasta)	MESAPAAPDP AASEPGSSGA DAAAGSRETP LNQESARKSE PPAPVRRQSY SSTSRGISVT 60 KKTHTSQIEI IPCKICGDKS SGIHYGVITC EGCKGFFRRS QQSNATYSCP RQKNCLIDRT 120 SRNRCQHCRL QKCLAVGMSR DAVKFGRMSK KQRDSLYAEV QKHRMQQQQR DHQQQPGEAE 180 PLTPTYNISA NGLTELHDDL SNYIDGHTPE GSKADSAVSS FYLDIQPSPD QSGLDINGIK 240 PEPICDYTPA SGFFPYCSFT NGETSPTVSM AELEHLAQNI SKSHLETCQY LREELQQITW 300 QTFLQEEIEN YQNKQREVMW QLCAIKITEA IQYVVEFAKR IDGFMELCQN DQIVLLKAGS 360 LEVVFIRMCR AFDSQNNTVY FDGKYASPDV FKSLGCEDFI SFVFEFGKSL CSMHLTEDEI 420 ALFSAFVLMS ADRSWLQEKV KIEKLQQKIQ LALQHVLQKN HREDGILTKL ICKVSTLRAL 480 CGRHTEKLMA FKAIYPDIVR LHFPPLYKEL FTSEFEPAMQ IDG 524 Fasta Sequence >P35398\|RORA; NR1F1; RZRA\|Homo sapiens (Human) MESAPAAPDPAASEPGSSGADAAAGSRETPLNQESARKSEPPAPVRRQSYSSTSRGISVTKKTHTSQIEIIPCKICGDKSSGIHYGVITCEGCKGFFRRSQQSNATYSCPRQKNCLIDRTSRNRCQHCRLQKCLAVGMSRDAVKFGRMSKKQRDSLYAEVQKHRMQQQQRDHQQQPGEAEPLTPTYNISANGLTELHDDLSNYIDGHTPEGSKADSAVSSFYLDIQPSPDQSGLDINGIKPEPICDYTPASGFFPYCSFTNGETSPTVSMAELEHLAQNISKSHLETCQYLREELQQITWQTFLQEEIENYQNKQREVMWQLCAIKITEAIQYVVEFAKRIDGFMELCQNDQIVLLKAGSLEVVFIRMCRAFDSQNNTVYFDGKYASPDVFKSLGCEDFISFVFEFGKSLCSMHLTEDEIALFSAFVLMSADRSWLQEKVKIEKLQQKIQLALQHVLQKNHREDGILTKLICKVSTLRALCGRHTEKLMAFKAIYPDIVRLHFPPLYKELFTSEFEPAMQIDG

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Serine Phosphorylation	Colon cancer/carcinoma	cell line	D	S35	20122401
1	[Reference]: RORalpha attenuates Wnt/beta-catenin signaling by PKCalpha-dependent phosphorylation in colon cancer.

※ Disease Cross-ref Annotation

Database	Annotation
CTD (Curated) (count: 2)	MESH:D001321 ; Autistic Disorder MESH:D013274 ; Stomach Neoplasms
GWASdb (count: 174) (view all)	rs3743266; Bone mineral density; bone resorption disease rs3743266; Menarche (age at onset); obesity\|type 2 diabetes mellitus\|cardiovascular system disease\|osteoporosis\|breast cancer\|Alzheimer's disease rs2290430; Myasthenia gravis; myasthenia gravis rs17270188; Smoking initiation; nicotine dependence rs16942660; post-traumatic stress disorder; post-traumatic stress disorder rs8036966; Smoking initiation; nicotine dependence rs2162069; Smoking initiation; nicotine dependence rs17237290; Rosuvastatin induced change in C-reactive protein (CRP); metabolic syndrome X\|type 2 diabetes mellitus\|hypertension\|myocardial infarction rs340005; Gamma gluatamyl transferase levels; liver disease\|alcohol abuse rs339969; Liver enzyme levels (gamma-glutamyl transferase); liver disease rs339969; Gamma gluatamyl transferase levels (interaction with age); alcohol abuse\|liver disease rs340029; C-reactive protein; metabolic syndrome X\|type 2 diabetes mellitus\|hypertension\|myocardial infarction rs340029; Gamma gluatamyl transferase levels (interaction with age); alcohol abuse\|liver disease rs7172348; Socioeconomic Factors; Null rs980000; Menarche (age at onset); obesity\|type 2 diabetes mellitus\|cardiovascular system disease\|osteoporosis\|breast cancer\|Alzheimer's disease rs3784609; Total ventricular volume; Alzheimer's disease rs339978; Menarche (age at onset); obesity\|type 2 diabetes mellitus\|cardiovascular system disease\|osteoporosis\|breast cancer\|Alzheimer's disease rs17237318; Total ventricular volume; Alzheimer's disease rs1657800; Type 2 diabetes and 6 quantitative traits; type 2 diabetes mellitus rs10519058; Type 2 diabetes and 6 quantitative traits; type 2 diabetes mellitus rs880626; Epilepsy; epilepsy syndrome rs16942951; Multiple complex diseases; Null rs7180547; Sasang constitution (Soeum); Null rs8027032; Suicide attempts in bipolar disorder; bipolar disorder rs8038077; Alzheimer's disease; Alzheimer's disease rs17303111; Suicide attempts in bipolar disorder; bipolar disorder rs2414680; Suicide attempts in bipolar disorder; bipolar disorder rs6494221; HIV-1 viral setpoint; Human immunodeficiency virus infectious disease rs12909890; Multiple complex diseases; Null rs16943012; Type 2 diabetes; type 2 diabetes mellitus rs11635314; Hypertension (early onset hypertension); hypertension rs341415; Self-reported allergy; hypersensitivity reaction disease rs12594992; Type 2 diabetes; type 2 diabetes mellitus rs7178643; Multiple complex diseases; Null rs9920962; IgE levels; selective IgE deficiency disease rs9920962; Self-reported allergy; hypersensitivity reaction disease rs7172011; IgE levels; selective IgE deficiency disease rs7172011; Self-reported allergy; hypersensitivity reaction disease rs11632684; IgE levels; selective IgE deficiency disease rs11632684; Self-reported allergy; hypersensitivity reaction disease rs1351544; Self-reported allergy; hypersensitivity reaction disease rs1817479; Self-reported allergy; hypersensitivity reaction disease rs8025324; Self-reported allergy; hypersensitivity reaction disease rs1318929; Taste perception; sensory system disease rs16943064; Self-reported allergy; hypersensitivity reaction disease rs11637301; Self-reported allergy; hypersensitivity reaction disease rs9920592; Self-reported allergy; hypersensitivity reaction disease rs9920593; Self-reported allergy; hypersensitivity reaction disease rs1020730; Self-reported allergy; hypersensitivity reaction disease rs922783; Self-reported allergy; hypersensitivity reaction disease rs12900122; Self-reported allergy; hypersensitivity reaction disease rs16943087; Self-reported allergy; hypersensitivity reaction disease rs2279292; Self-reported allergy; hypersensitivity reaction disease rs529034832; Self-reported allergy; hypersensitivity reaction disease rs8025689; Self-reported allergy; hypersensitivity reaction disease rs9302215; Taste perception; sensory system disease rs12591650; Subcutaneous adipose tissue; obesity rs11633029; Self-reported allergy; hypersensitivity reaction disease rs11637671; Self-reported allergy; hypersensitivity reaction disease rs11639084; Self-reported allergy; hypersensitivity reaction disease rs7164773; Type 2 diabetes; type 2 diabetes mellitus rs10519067; Self-reported allergy; hypersensitivity reaction disease rs10519068; IgE levels; selective IgE deficiency disease rs10519068; Self-reported allergy; hypersensitivity reaction disease rs11071557; Self-reported allergy; hypersensitivity reaction disease rs11071558; Self-reported allergy; hypersensitivity reaction disease rs11071559; Asthma; asthma rs11071559; Self-reported allergy; hypersensitivity reaction disease rs922781; Attention deficit hyperactivity disorder; attention deficit hyperactivity disorder rs12441037; Abdominal aortic aneurysm; abdominal aortic aneurysm rs341366; post-traumatic stress disorder; post-traumatic stress disorder rs341366; Schizophrenia; schizophrenia rs341366; ldl cholesterol; atherosclerosis\|coronary artery disease rs6494226; Abdominal aortic aneurysm; abdominal aortic aneurysm rs2414681; post-traumatic stress disorder; post-traumatic stress disorder rs2414681; Schizophrenia; schizophrenia rs10519074; post-traumatic stress disorder; post-traumatic stress disorder rs10519074; Schizophrenia; schizophrenia rs10519074; Cholesterol; arteriosclerosis\|coronary artery disease\|lipid metabolism disorder rs7169281; post-traumatic stress disorder; post-traumatic stress disorder rs7169281; Schizophrenia; schizophrenia rs12440095; White matter integrity; bipolar disorder\|brain disease rs8041061; Amyotrophic Lateral Sclerosis; amyotrophic lateral sclerosis rs8041061; post-traumatic stress disorder; post-traumatic stress disorder rs8041061; Schizophrenia; schizophrenia rs8042149; post-traumatic stress disorder; post-traumatic stress disorder rs8042149; Schizophrenia; schizophrenia rs4775301; Amyotrophic Lateral Sclerosis; amyotrophic lateral sclerosis rs4775301; post-traumatic stress disorder; post-traumatic stress disorder rs4775301; Schizophrenia; schizophrenia rs8023252; Amyotrophic Lateral Sclerosis; amyotrophic lateral sclerosis rs8024133; post-traumatic stress disorder; post-traumatic stress disorder rs8024133; Schizophrenia; schizophrenia rs11071561; post-traumatic stress disorder; post-traumatic stress disorder rs11071561; Schizophrenia; schizophrenia rs341401; Amyotrophic Lateral Sclerosis; amyotrophic lateral sclerosis rs341401; post-traumatic stress disorder; post-traumatic stress disorder rs341401; Schizophrenia; schizophrenia rs10519080; Hypertension (essential hypertension); hypertension rs341408; Major depressive disorder; major depressive disorder rs341408; Hypertension (essential hypertension); hypertension rs1902618; Pulmonary function decline; chronic obstructive pulmonary disease\|asthma rs729978; Suicide attempts in bipolar disorder; bipolar disorder rs729977; Suicide attempts in bipolar disorder; bipolar disorder rs12592999; Suicide attempts in bipolar disorder; bipolar disorder rs4775313; Type 2 diabetes; type 2 diabetes mellitus rs4774376; Lymphocyte counts; asthma\|leukemia\|lymphoma\|lymphopenia\|cardiovascular system disease rs3803487; Suicide attempts in bipolar disorder; bipolar disorder rs17237465; Suicide attempts in bipolar disorder; bipolar disorder rs2899663; Type 2 diabetes; type 2 diabetes mellitus rs2414686; Type 2 diabetes; type 2 diabetes mellitus rs41346644; Multiple complex diseases; Null rs8023563; Depression (quantitative trait); mental depression rs8028646; Depression (quantitative trait); mental depression rs8033151; Depression (quantitative trait); mental depression rs11071568; Depression (quantitative trait); mental depression rs2128166; Depression (quantitative trait); mental depression rs4264335; Depression (quantitative trait); mental depression rs2062095; Alzheimer's disease; Alzheimer's disease rs2062095; Smoking quantity; nicotine dependence rs2062092; Alzheimer's disease; Alzheimer's disease rs4775319; Depression (quantitative trait); mental depression rs4638513; Depression (quantitative trait); mental depression rs4547277; Depression (quantitative trait); mental depression rs1482051; Depression (quantitative trait); mental depression rs8029250; Alzheimer's disease; Alzheimer's disease rs12906588; Depression (quantitative trait); mental depression rs1482050; Adverse response to chemotherapy (neutropenia/leucopenia) (5-fluorouracil); neutropenia rs1351545; Cognitive impairment induced by topiramate; cognitive disorder rs8034886; Urinary metabolites; kidney disease rs12594733; HDL cholesterol; cholesterol ester storage disease\|cholesterol embolism\|coronary artery disease rs12912233; Depression (quantitative trait); mental depression rs4775340; Depression (quantitative trait); mental depression rs17237521; Anti-TNF treatment response in rheumatoid arthritis (by DAS-28 score change at 3 months); rheumatoid arthritis rs17237521; Methotrexate clearance (acute lymphoblastic leukemia); acute lymphocytic leukemia\|acute leukemia rs6494238; Response to cytadine analogues (cytosine arabinoside); cancer rs8031801; Response to cytadine analogues (cytosine arabinoside); cancer rs1589702; Coronary heart disease; coronary artery disease rs7168987; Drug response to Etoposide; Null rs7175830; Depression (quantitative trait); mental depression rs1949752; Depression (quantitative trait); mental depression rs11631179; Drug response to Etoposide; Null rs16943453; Smoking initiation; nicotine dependence rs10519096; Myasthenia gravis; myasthenia gravis rs10519097; Myasthenia gravis; myasthenia gravis rs11071581; Multiple complex diseases; Null rs10162779; Blood pressure, CVD RF and other traits (body mass index (BMI), waist:hip ratio, renin activity in plasma, aldosterone concentration in plasma, BNP levels in plasma, alcohol consumption); hypertension rs809736; Response to citalopram treatment; major depressive disorder rs809736; Alzheimer's disease; Alzheimer's disease rs809736; Vaspin levels; obesity\|type 2 diabetes mellitus rs7172342; Schizophrenia; schizophrenia rs4774384; Schizophrenia; schizophrenia rs782947; Alzheimer's disease; Alzheimer's disease rs782905; Biliary atresia; biliary atresia rs11071586; Alzheimer's disease; Alzheimer's disease rs11071586; Serum metabolites; Null rs782909; Diabetes Mellitus; diabetes mellitus rs1437537; Salmonella-induced pyroptosis; Null rs13329643; Diabetes Mellitus; diabetes mellitus rs11071587; Alcohol dependence; alcohol dependence rs11071587; post-traumatic stress disorder; post-traumatic stress disorder rs11071588; post-traumatic stress disorder; post-traumatic stress disorder rs1437547; Normoxic and mild-hypoxic adaptation in populations residing at low and moderate altitudes; asthma\|chronic obstructive pulmonary disease rs1816625; Smoking initiation; nicotine dependence rs12593790; Smoking initiation; nicotine dependence rs16943698; Smoking initiation; nicotine dependence rs1465811; Smoking initiation; nicotine dependence rs11071590; Multiple complex diseases; Null rs11071591; Multiple complex diseases; Null rs4774388; Smoking initiation; nicotine dependence rs1816624; Smoking initiation; nicotine dependence rs17204938; Lung function (forced expiratory volume in 1 second); lung disease rs1550226; Smoking initiation; nicotine dependence rs930358; Salmonella-induced pyroptosis; Null

Database

Annotation

CTD (Curated)
(count: 2)

MESH:D001321 ; Autistic Disorder
MESH:D013274 ; Stomach Neoplasms

GWASdb
(count: 174)
(view all)

rs3743266; Bone mineral density; bone resorption disease
rs3743266; Menarche (age at onset); obesity|type 2 diabetes mellitus|cardiovascular system disease|osteoporosis|breast cancer|Alzheimer's disease
rs2290430; Myasthenia gravis; myasthenia gravis
rs17270188; Smoking initiation; nicotine dependence
rs16942660; post-traumatic stress disorder; post-traumatic stress disorder
rs8036966; Smoking initiation; nicotine dependence

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 2)	183 PGEAEPLTPTYNISA dbPAF 35 ETPLNQESARKSEPP dbPAF
Ubiquitination (count: 1)	144 GMSRDAVKFGRMSKK PLMD
Sumoylation (count: 1)	240 GLDINGIKPEPICDY PLMD

※ Protein-Protein Interaction

Network

Interaction

Source

P35398

Q92905

HPRD

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction