dmg

Arthrobacter globiformis

NA

NA

GcvT family

Oxidoreductase

Dimethylglycine oxidase activity.Nucleotide binding.

Curry-Jones syndrome (CRJS) [MIM:601707]: A multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. {ECO:0000269|PubMed:24859340, ECO:0000269|PubMed:27236920}. The disease is caused by variants affecting the gene represented in this entry. 8 individuals have been identified with the disease-causing mutation Phe-412 and all were mosaic. The mutation could not be reliably detected in blood, greatest success rates were obtained with affected tissues obtained by invasive procedures. It is thought that the mutation has arisen postzygotically early during embryonic development (PubMed:27236920). This mutation has also been identified in ameloblastoma, medulloblastoma, meningioma, and basal cell carcinoma, and has been reported as the oncogenic driver in some of these tumors (PubMed:24859340). {ECO:0000269|PubMed:24859340, ECO:0000269|PubMed:27236920}.

DB03256; DB03147

NA

1.5.3.10

3D-structure; Direct protein sequencing; FAD; Flavoprotein; Nucleotide-binding; Oxidoreductase

A

45912.2

427

0.07

43.46

4.83

-20.69

-9.1

HHAT

Homo sapiens (Human)

Skinny hedgehog protein 1; Melanoma antigen recognized by T-cells 2; MART-2; Hedgehog acyltransferase; HHAT

Membrane-bound acyltransferase family, HHAT subfamily

Acyltransferase

Catalyzes N-terminal palmitoylation of SHH; which is required for SHH signaling. May bind GTP. .

Nivelon-Nivelon-Mabille syndrome (NNMS) [MIM:600092]: An autosomal recessive syndrome characterized by progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Additional variable features include early infantile-onset seizures, intrauterine and postnatal growth retardation, generalized chondrodysplasia, and micromelia. 46,XY gonadal dysgenesis may be present. {ECO:0000269|PubMed:24784881, ECO:0000269|PubMed:30912300}. The disease is caused by variants affecting the gene represented in this entry.

NA

O00560

EC 2.3.1.-

3D-structure; Acyltransferase; Alternative splicing; Developmental protein; Disease variant; Dwarfism; Endoplasmic reticulum; Golgi apparatus; GTP-binding; Lipoprotein; Membrane; Nucleotide-binding; Palmitate; Proteomics identification; Reference proteome; Transferase; Transmembrane; Transmembrane helix

A

57096.2

491

0.17

42.88

7.18

0.62

-9.1

NR3C2

Homo sapiens (Human)

Nuclear receptor subfamily 3 group C member 2; Mineralocorticoid receptor; MLR; MCR; Inner ear mineralocorticoid receptor; Delta

Nuclear hormone receptor family, NR3 subfamily

Nuclear hormone receptor

Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels. Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol.

Pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:177735]: A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment. {ECO:0000269|PubMed:11134129, ECO:0000269|PubMed:12788847, ECO:0000269|PubMed:16954160, ECO:0000269|PubMed:16972228}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:605115]: Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion. {ECO:0000269|PubMed:10884226, ECO:0000269|PubMed:15908963, ECO:0000269|PubMed:15967794}. The disease is caused by variants affecting the gene represented in this entry.

DB04630; DB01013; DB04652; DB06780; DB01134; DB01395; DB00700; DB01023; DB16165; DB00687; DB13867; DB08906; DB00588; DB02998; DB00393; DB00396; DB00421; DB02901; DB13951; DB00624; DB13943; DB13944; DB15114

NA

NA

3D-structure; Alternative splicing; Cytoplasm; Disease variant; DNA-binding; Endoplasmic reticulum; Lipid-binding; Membrane; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Steroid-binding; Transcription; Transcription regulation; Zinc; Zinc-finger

A

29012.4

249

0.12

51.27

6.3

-2.08

-9.08

PYGL

Homo sapiens (Human)

NA

NA

Glycogen phosphorylase family

Transferase

AMP binding.ATP binding.Bile acid binding.Drug binding.Glucose binding.Glycogen phosphorylase activity.Linear malto-oligosaccharide phosphorylase activity.Protein homodimerization activity.Purine nucleobase binding.Pyridoxal phosphate binding.SHG alpha-glucan phosphorylase activity.Vitamin binding.

Glycogen storage disease 6 (GSD6) [MIM:232700]: A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected. {ECO:0000269|PubMed:9529348}. The disease is caused by variants affecting the gene represented in this entry.

NA

P11216; P11217

2.4.1.1

3D-structure; Acetylation; Allosteric enzyme; Alternative splicing; Carbohydrate metabolism; Cytoplasm; Disease variant; Glycogen metabolism; Glycogen storage disease; Glycosyltransferase; Nucleotide-binding; Phosphoprotein; Proteomics identification; Pyridoxal phosphate; Reference proteome; Transferase

A,B

89481.9

778

0.11

34.96

6.49

-3.54

-9.08

CASR

Homo sapiens (Human)

hCasR; Parathyroid cell calciumreceptor; Parathyroid cell calcium-sensing receptor 1; Parathyroid calcium receptor; Parathyroid Cell calcium-sensing receptor; PCaR1; GPRC2A; CaSR

G-protein coupled receptor 3 family

GPCR glutamate

Senses fluctuations in the circulating calcium concentration and modulates the production of parathyroid hormone (PTH) in parathyroid glands. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. The G-protein-coupled receptor activity is activated by a co-agonist mechanism: aromatic amino acids, such as Trp or Phe, act concertedly with divalent cations, such as calcium or magnesium, to achieve full receptor activation. G-protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis.

Hypocalciuric hypercalcemia, familial 1 (HHC1) [MIM:145980]: A form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults. {ECO:0000269|PubMed:11762699, ECO:0000269|PubMed:15572418, ECO:0000269|PubMed:15579740, ECO:0000269|PubMed:15879434, ECO:0000269|PubMed:16598859, ECO:0000269|PubMed:16740594, ECO:0000269|PubMed:17473068, ECO:0000269|PubMed:17698911, ECO:0000269|PubMed:19179454, ECO:0000269|PubMed:19789209, ECO:0000269|PubMed:21566075, ECO:0000269|PubMed:21643651, ECO:0000269|PubMed:22114145, ECO:0000269|PubMed:23169696, ECO:0000269|PubMed:23966241, ECO:0000269|PubMed:25104082, ECO:0000269|PubMed:25292184, ECO:0000269|PubMed:26386835, ECO:0000269|PubMed:27434672, ECO:0000269|PubMed:7673400, ECO:0000269|PubMed:7726161, ECO:0000269|PubMed:7916660, ECO:0000269|PubMed:8636323, ECO:0000269|PubMed:8702647, ECO:0000269|PubMed:8878438, ECO:0000269|PubMed:9298824}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hyperparathyroidism, neonatal severe (NSHPT) [MIM:239200]: A disorder characterized by severe hypercalcemia, bone demineralization, and failure to thrive usually manifesting in the first 6 months of life. If untreated, NSHPT can be a devastating neurodevelopmental disorder, which in some cases is lethal without parathyroidectomy. {ECO:0000269|PubMed:14985373, ECO:0000269|PubMed:15572418, ECO:0000269|PubMed:17555508, ECO:0000269|PubMed:27434672, ECO:0000269|PubMed:8675635, ECO:0000269|PubMed:8878438, ECO:0000269|PubMed:9253359}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hypocalcemia, autosomal dominant 1 (HYPOC1) [MIM:601198]: A disorder of mineral homeostasis characterized by blood calcium levels below normal, and low or normal serum parathyroid hormone concentrations. Disease manifestations include mild or asymptomatic hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria with nephrocalcinosis or kidney stones, and ectopic and basal ganglia calcifications. Few patients manifest hypocalcemia and features of Bartter syndrome, including hypomagnesemia, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronemia. {ECO:0000269|PubMed:10487661, ECO:0000269|PubMed:12050233, ECO:0000269|PubMed:12107202, ECO:0000269|PubMed:12241879, ECO:0000269|PubMed:12574188, ECO:0000269|PubMed:12915654, ECO:0000269|PubMed:15551332, ECO:0000269|PubMed:16608894, ECO:0000269|PubMed:19179454, ECO:0000269|PubMed:22789683, ECO:0000269|PubMed:23169696, ECO:0000269|PubMed:23966241, ECO:0000269|PubMed:25766501, ECO:0000269|PubMed:7874174, ECO:0000269|PubMed:8702647, ECO:0000269|PubMed:8733126, ECO:0000269|PubMed:8813042, ECO:0000269|PubMed:8878438, ECO:0000269|PubMed:9253358, ECO:0000269|PubMed:9661634, ECO:0000269|PubMed:9920108}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Epilepsy, idiopathic generalized 8 (EIG8) [MIM:612899]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Seizure types are variable, but include myoclonic seizures, absence seizures, febrile seizures, complex partial seizures, and generalized tonic-clonic seizures. {ECO:0000269|PubMed:18756473}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB11093; DB11348; DB14481; DB01012; DB12865; DB00994; DB05695; DB05255; DB00127

Q15363; P41180-1

NA

3D-structure; Alternative splicing; Calcium; Cell membrane; Disease variant; Disulfide bond; Epilepsy; G-protein coupled receptor; Glycoprotein; Membrane; Metal-binding; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix; Ubl conjugation

A,B

52438.9

467

0.12

39.62

5.63

-10.18

-9.08

GRM5

Homo sapiens (Human)

MGLUR5; GPRC1E

G-protein coupled receptor 3 family

GPCR glutamate

G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity.

Charcot-Marie-Tooth disease, axonal, 2D (CMT2D) [MIM:601472]: A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:12690580, ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:17101916, ECO:0000269|PubMed:17663003, ECO:0000269|PubMed:20169446, ECO:0000269|PubMed:24604904, ECO:0000269|PubMed:25168514, ECO:0000269|PubMed:26244500, ECO:0000269|PubMed:26503042, ECO:0000269|PubMed:31173493}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neuronopathy, distal hereditary motor, autosomal dominant 5 (HMND5) [MIM:600794]: A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:12690580, ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:23279345, ECO:0000269|PubMed:24627108, ECO:0000269|PubMed:26503042}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spinal muscular atrophy, infantile, James type (SMAJI) [MIM:619042]: An autosomal dominant form of spinal muscular atrophy, a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAJI is a severe disease characterized by hypotonia manifesting in the first weeks or months of life, delayed motor development, motor regression, and muscle weakness and atrophy primarily affecting distal muscles. Additional variable features include feeding difficulties, poor overall growth, foot deformities, kyphosis, hyperlordosis, scoliosis, vocal cord dysfunction, and respiratory insufficiency. {ECO:0000269|PubMed:32181591}. The disease is caused by variants affecting the gene represented in this entry.

DB00659; DB05070; DB12733; DB06201

P41594; Q7Z6G3

NA

3D-structure; Alternative splicing; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; Methylation; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix

A

27065.4

247

0.13

42.92

9.24

11.34

-9.08

DHODH

Homo sapiens (Human)

Dihydroorotate oxidase; Dihydroorotate dehydrogenase (quinone), mitochondrial; DHOdehase; DHODH

Dihydroorotate dehydrogenase family, Type 2 subfamily

CH-CH donor oxidoreductase

Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.

Postaxial acrofacial dysostosis (POADS) [MIM:263750]: POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases. {ECO:0000269|PubMed:19915526}. The disease is caused by variants affecting the gene represented in this entry.

DB07559; DB07561; DB08172; DB08169; DB07443; DB07978; DB07975; DB04281; DB08249; DB07977; DB07976; DB04583; DB08008; DB01117; DB03523; DB03480; DB02613; DB04147; DB03247; DB01097; DB06481; DB08006; DB02262; DB05125; DB08880; DB07646

Q6ZMZ0; P49638

EC 1.3.5.2

3D-structure; Disease variant; Flavoprotein; FMN; Membrane; Mitochondrion; Mitochondrion inner membrane; Oxidoreductase; Proteomics identification; Pyrimidine biosynthesis; Reference proteome; Transit peptide; Transmembrane; Transmembrane helix

A

38341.4

353

0.05

39.27

9.28

5.52

-9.09

GRIN2A

Homo sapiens (Human)

NR2A; NMDA receptor NR2A; N-methyl D-aspartate receptor subtype 2A; HNR2A; Glutamate receptor ionotropic, NMDA 2A; Glutamate [NMDA] receptor subunit epsilon-1; GluN2A

Glutamate-gated ion channel (TC 1.A.10.1) family, NR1/GRIN1 subfamily

Glutamate-gated ion channel

Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have higher sensitivity to glutamate and faster kinetics than channels formed by GRIN1 and GRIN2B. Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning. Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium.

Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (NDHMSD) [MIM:614254]: An autosomal dominant neurodevelopmental disorder characterized by severe intellectual disability and developmental delay, absent speech, muscular hypotonia, dyskinesia, and hyperkinetic movements. Cortical blindness, cerebral atrophy, and seizures are present in some patients. {ECO:0000269|PubMed:21376300, ECO:0000269|PubMed:25167861, ECO:0000269|PubMed:25864721, ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28228639, ECO:0000269|PubMed:28389307, ECO:0000269|PubMed:38538865}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive (NDHMSR) [MIM:617820]: An autosomal recessive neurodevelopmental disorder characterized by severe intellectual disability and psychomotor developmental delay, involuntary and stereotypic movements, spasticity, and inability to walk without support. Intractable seizures manifest in some patients. {ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28051072}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 101 (DEE101) [MIM:619814]: A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE101 is an autosomal recessive, severe form characterized by onset of seizures in early infancy. Death in infancy may occur. {ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:34611970}. The disease is caused by variants affecting the gene represented in this entry.

DB01931; DB00659; DB06151; DB08838; DB01238; DB00289; DB05824; DB04620; DB03929; DB00647; DB00843; DB00228; DB11823; DB13146; DB06741; DB00142; DB00874; DB08954; DB06738; DB09409; DB09481; DB01043; DB00454; DB00333; DB04896; DB01173; DB00312; DB01174; DB01708; DB00418; DB00193

P05067; P35637; Q12879-1; Q13224; Q62936

NA

3D-structure; Alternative splicing; Calcium; Cell membrane; Disease variant; Disulfide bond; Epilepsy; Glycoprotein; Intellectual disability; Ion channel; Ion transport; Ligand-gated ion channel; Magnesium; Membrane; Metal-binding; Phosphoprotein; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix; Transport; Zinc

B

53395.6

469

0.11

29.84

8.72

5.65

-9.09

CPS1

Homo sapiens (Human)

Carbamoyl-phosphate synthase [ammonia], mitochondrial; CPSase I; CPS1

NA

Carbon-nitrogen ligase

Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.

Carbamoyl phosphate synthetase 1 deficiency (CPS1D) [MIM:237300]: An autosomal recessive disorder of the urea cycle causing hyperammonemia. It can present as a devastating metabolic disease dominated by severe hyperammonemia in neonates or as a more insidious late-onset condition, generally manifesting as life-threatening hyperammonemic crises under catabolic situations. Clinical features include protein intolerance, intermittent ataxia, seizures, lethargy, developmental delay and intellectual disability. {ECO:0000269|PubMed:11388595, ECO:0000269|PubMed:11474210, ECO:0000269|PubMed:12655559, ECO:0000269|PubMed:12955727, ECO:0000269|PubMed:15164414, ECO:0000269|PubMed:15617192, ECO:0000269|PubMed:16737834, ECO:0000269|PubMed:17310273, ECO:0000269|PubMed:20578160, ECO:0000269|PubMed:21120950, ECO:0000269|PubMed:22173106, ECO:0000269|PubMed:23649895, ECO:0000269|PubMed:24813853, ECO:0000269|PubMed:26440671, ECO:0000269|PubMed:9711878}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Pulmonary hypertension, neonatal (PHN) [MIM:615371]: A disease characterized by elevated pulmonary artery pressure. Pulmonary hypertension in the neonate is associated with multiple underlying problems such as respiratory distress syndrome, meconium aspiration syndrome, congenital diaphragmatic hernia, bronchopulmonary dysplasia, sepsis, or congenital heart disease. {ECO:0000269|PubMed:11407344}. Disease susceptibility is associated with variants affecting the gene represented in this entry. CPS1 variants influence the availability of precursors for nitric oxide (NO) synthesis and play a role in clinical situations where endogenous NO production is critically important, such as neonatal pulmonary hypertension, increased pulmonary artery pressure following surgical repair of congenital heart defects or hepatovenocclusive disease following bone marrow transplantation. Infants with neonatal pulmonary hypertension homozygous for Thr-1406 have lower L-arginine concentrations than neonates homozygous for Asn-1406 (PubMed:11407344). {ECO:0000269|PubMed:11407344}.

DB11118; DB06775

P10398; P04049; P63104

EC 6.3.4.16

3D-structure; Acetylation; Allosteric enzyme; Alternative splicing; ATP-binding; Cell membrane; Disease variant; Glycoprotein; Ligase; Membrane; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Transit peptide; Urea cycle

A

156194

1422

0.08

33.61

5.78

-19.83

-9.09

SIRT2

Homo sapiens (Human)

SIR2like protein 2; SIR2L2; SIR2L; SIR2-like protein 2; Regulatory protein SIR2 homolog 2; NADdependent protein deacetylase sirtuin2; NAD-dependent protein deacetylase sirtuin-2

Sirtuin family, Class I subfamily

Carbon-nitrogen hydrolase

Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression. Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response. Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition. Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection. During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis. Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy. Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation. Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia. Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300. Deacetylates also EIF5A. Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor. NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors.

Deafness, autosomal recessive, 39 (DFNB39) [MIM:608265]: A form of profound prelingual sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:19576567}. The disease is caused by variants affecting the gene represented in this entry.

DB15493

O60566; O60729; P11413; Q92831; Q04206; Q9BYB0; Q12834; Q9UM11

EC 3.5.1.-

3D-structure; Acetylation; Alternative splicing; Autophagy; Cell cycle; Cell division; Cell membrane; Cell projection; Chromosome; Cytoplasm; Cytoskeleton; Differentiation; Immunity; Innate immunity; Meiosis; Membrane; Metal-binding; Microtubule; Mitosis; NAD; Neurodegeneration; Neurogenesis; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Transcription; Transcription regulation; Transferase; Ubl conjugation; Zinc

A

34093.1

301

0.1

45.2

5.59

-6.94

-9.09

H3F3A

Homo sapiens (Human)

PP781; Histone H3.3; H3F3; H3.3B; H3.3A

Histone H3 family

NA

Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.

Glioma (GLM) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:22286061, ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23539269}. The gene represented in this entry is involved in disease pathogenesis. H3F3A mutations affecting residues involved in post-translational modifications of histone H3.3 are recurrent in malignant, aggressive gliomas including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG) (PubMed:22286061, PubMed:22286216). The mechanism through which mutations lead to tumorigenesis involves altered histones methylation, impaired regulation of Polycomb repressive complex 2 (PRC2) activity, and aberrant epigenetic regulation of gene expression (PubMed:23539183, PubMed:23539269, PubMed:23603901). {ECO:0000269|PubMed:22286061, ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23539183, ECO:0000269|PubMed:23539269, ECO:0000269|PubMed:23603901}.; DISEASE: Bryant-Li-Bhoj neurodevelopmental syndrome 1 (BRYLIB1) [MIM:619720]: An autosomal dominant disorder predominantly characterized by global developmental delay, impaired intellectual development, poor or absent speech, and delayed motor milestones. Clinical manifestations are highly variable, including abnormal head shape, dysmorphic facial features, oculomotor abnormalities, feeding problems, and non-specific brain imaging abnormalities. Additional features may include hearing loss, seizures, short stature, and mild skeletal defects. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}. The disease is caused by variants affecting the gene represented in this entry. BRYLIB1 is caused by variants in H3-3A. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}.; DISEASE: Bryant-Li-Bhoj neurodevelopmental syndrome 2 (BRYLIB2) [MIM:619721]: An autosomal dominant disorder predominantly characterized by global developmental delay, impaired intellectual development, poor or absent speech, and delayed motor milestones. Clinical manifestations are highly variable, including abnormal head shape, dysmorphic facial features, oculomotor abnormalities, feeding problems, and non-specific brain imaging abnormalities. Additional features may include hearing loss, seizures, short stature, and mild skeletal defects. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}. The disease is caused by variants affecting the gene represented in this entry. BRYLIB2 is caused by variants in H3-3B. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}.; DISEASE: H3F3A and H3F3B mutations affecting residues involved in post-translational modifications of histone H3.3 are implicated in the pathogenesis of some bone and cartilage neoplasms. Mutations have been found with high prevalence in chondroblastoma and giant cell tumors of bone, and with low frequency in osteosarcoma, conventional chondrosarcoma and clear cell chondrosarcoma. Chondroblastoma samples frequently carry a H3F3B mutation affecting residue Lys-37 (H3K36), although H3F3A is mutated in some cases. Most giant cell tumors of bone harbor H3F3A mutations affecting residue Gly-35 (H3G34). {ECO:0000269|PubMed:24162739}.

NA

Q9NVP2; P45973; Q13111; Q9UER7; Q9UER7-1; Q9Y6K1; P62805; P49321-2; Q8IZL8; Q5VWG9; Q9VK33; Q8R5C8

NA

3D-structure; Acetylation; ADP-ribosylation; Chromosome; Citrullination; Direct protein sequencing; Disease variant; DNA-binding; Hydroxylation; Intellectual disability; Lipoprotein; Methylation; Nucleosome core; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation

A,C

86148.9

766

0.1

37.57

8.25

7.16

-9.09

thiO

Bacillus subtilis (strain 168)

NA

goxB;yjbR;BSU11670

DAO family, ThiO subfamily

Oxidoreductase

FAD binding.Glycine oxidase activity.Oxidoreductase activity.

Hypervalinemia and hyperleucine-isoleucinemia (HVLI) [MIM:618850]: An autosomal recessive metabolic disorder characterized by highly elevated plasma concentrations of valine and leucine/isoleucine. Affected individuals suffer from headache and mild memory impairment. {ECO:0000269|PubMed:25653144}. The disease is caused by variants affecting the gene represented in this entry. A patient with hypervalinemia and hyperleucine-isoleucinemia was identified as compound heterozygote for Gln-170 (inherited from his father) and Lys-264 (inherited from his mother), both variants reduced the catalytic activity of the enzyme. After treatment with vitamin B6, a precursor of pyridoxal 5'-phosphate, a BCAT2 cofactor, the blood levels of branched chain amino acids, especially valine, were decreased and brain lesions were improved. {ECO:0000269|PubMed:25653144}.

DB02713; DB03147

NA

1.4.3.19

3D-structure; Cytoplasm; FAD; Flavoprotein; Herbicide resistance; Oxidoreductase; Reference proteome; Thiamine biosynthesis

A,B,C,D

40395.8

364

0.1

36.07

6.02

-6.35

-9.07

RARB

Homo sapiens (Human)

RAR-epsilon; RAR-beta; Nuclear receptor subfamily 1 group B member 2; NR1B2; HBV-activated protein; HAP

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function. Receptor for retinoic acid.

Microphthalmia, syndromic, 12 (MCOPS12) [MIM:615524]: A form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS12 patients manifest variable features, including diaphragmatic hernia, pulmonary hypoplasia, and cardiac abnormalities. {ECO:0000269|PubMed:24075189, ECO:0000269|PubMed:27120018}. The disease is caused by variants affecting the gene represented in this entry.

DB00459; DB00210; DB00523; DB02877; DB00926; DB05785; DB04942; DB00799; DB00755; DB12808

O95273; P50222; Q9UBK2; P62195; P28702; P28702-3; P48443; P03255

NA

3D-structure; Alternative splicing; Cytoplasm; Disease variant; DNA-binding; Metal-binding; Microphthalmia; Nucleus; Phosphoprotein; Proto-oncogene; Receptor; Reference proteome; Transcription; Transcription regulation; Zinc; Zinc-finger

A,B

25904.1

229

0.06

44.34

7.55

0.73

-9.07

SEC14L3

Homo sapiens (Human)

NA

TAP2

NA

Transport protein

Lipid binding.Transporter activity.

Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia (CDP-PBHM) [MIM:300863]: A disease characterized by chondrodysplasia, severe platyspondyly, hydrocephaly, and facial features with microphthalmia. Bone abnormalities include a distinctive metaphyseal cupping of the metacarpals, metatarsals, and phalanges. Affected females show a milder phenotype with small stature, sometimes associated with body asymmetry and mild intellectual disability. {ECO:0000269|PubMed:20181727}. The disease is caused by variants affecting the gene represented in this entry.

DB14003; DB14001; DB14002; DB11635; DB11251; DB00163

NA

NA

3D-structure; Alternative splicing; Lipid-binding; Proteomics identification; Reference proteome; Transport

A

46148.7

401

0.1

45.19

5.79

-5.94

-9.07

HRAS

Homo sapiens (Human)

p21ras; cHras; c-H-ras; Transforming protein p21; HaRas; Ha-Ras; H-Ras-1; GTPase HRas, Nterminally processed

Small GTPase superfamily, Ras family

Small GTPase

Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Involved in the activation of Ras protein signal transduction.

Costello syndrome (CSTLO) [MIM:218040]: A rare condition characterized by prenatally increased growth, postnatal growth deficiency, intellectual disability, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities. {ECO:0000269|PubMed:16170316, ECO:0000269|PubMed:16329078, ECO:0000269|PubMed:16443854, ECO:0000269|PubMed:17054105, ECO:0000269|PubMed:18039947, ECO:0000269|PubMed:18247425, ECO:0000269|PubMed:19995790}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040]: Variant of Costello syndrome. {ECO:0000269|PubMed:17412879}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470]: A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. {ECO:0000269|PubMed:12727991}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors. {ECO:0000269|PubMed:3670300}.; DISEASE: Bladder cancer (BLC) [MIM:109800]: A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. {ECO:0000269|PubMed:6298635, ECO:0000269|PubMed:6844927}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:163200]: A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis. {ECO:0000269|PubMed:22683711}. The disease is caused by variants affecting the gene represented in this entry.

DB04315; DB04137; DB02210; DB08751; DB03226; DB15588

Q99996-3; P53677-2; P10398; Q9NXL2-1; Q9UII2; Q9H7T9; Q00994; Q9H2G9; P15056; Q7Z569; Q5PSV4; Q9ULD4-2; Q96LL4; Q96HB5; Q49A88-3; Q96GN5-2; P24941; O95674; Q9H3R5; Q9Y4F5-3; Q86XR8; Q494V2-2; Q8WUX9; Q14117; Q9Y6W6; O14641; A0AVK6; Q8NB25; Q8IZU1; O94868-3; P15407; P15408; P52655; Q96CS2; Q9BT25; Q8IV36; O43248; Q53GQ0; P10809; Q8NDH6-2; Q8IY31-2; Q8NA54; Q13352; P28290-2; Q9BVG8-5; Q2M2Z5; Q6P597; P57682; Q9UH77; P08727; Q14525; Q14847-2; Q96LR2; P27338; Q99558; Q96EZ8; Q8TAC0; Q5JXC2; Q8NEH6; Q9Y605; Q96HT8; Q9GZM8; P21359; Q8N5V2; Q6PHZ7; Q9BZ95-3; A5D8V7; O43482; Q9BR81; O15534; Q9BUL5; O00329; O00329-2; Q9UPR0; Q96I34; Q15435-3; P04049; P11233; Q15311; Q12967; Q9NS23-2; Q9NS23-4; Q8WWW0; Q8TBY0; Q9P2K3-2; Q9NZL6; O15211; Q8IXN7; Q13671; Q13671-1; Q8WVD3; Q9BY12-3; Q13435; Q12824; Q13573; Q07889; Q86W54-2; Q92783-2; O75886; Q13586; Q8N4C7; O75528; P54274-2; Q9BXU0; Q5T0J7-2; Q5T1C6; Q8IUR5-4; P36406; Q86WT6-2; Q99598; Q6PF05; Q9UGJ1-2; Q9Y5Z9; P22415; Q495M9; Q9H270; Q8NEZ2; P19544-6; O43829; Q9C0F3; Q7Z637; Q86V28; P42337; Q9Z0S9; Q9EQZ6; P27671; Q5EBH1; Q5EBH1-1; P52306-5

NA

3D-structure; Acetylation; Alternative splicing; Cell membrane; Cytoplasm; Direct protein sequencing; Disease variant; Glycoprotein; Golgi apparatus; GTP-binding; Hydrolase; Isopeptide bond; Lipoprotein; Membrane; Methylation; Nucleotide-binding; Nucleus; Palmitate; Prenylation; Proteomics identification; Proto-oncogene; Reference proteome; S-nitrosylation; Ubl conjugation

E,F

28737.2

259

0.1

30.69

5.64

-4.15

-9.08

pchF

Pseudomonas putida (Arthrobacter siderocapsulatus)

NA

NA

NA

Oxidoreductase

4-cresol dehydrogenase (hydroxylating) activity.Flavin adenine dinucleotide binding.Oxidoreductase activity, acting on CH-OH group of donors.

Dihydrolipoamide dehydrogenase deficiency (DLDD) [MIM:246900]: An autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. {ECO:0000269|PubMed:10448086, ECO:0000269|PubMed:11687750, ECO:0000269|PubMed:12925875, ECO:0000269|PubMed:15712224, ECO:0000269|PubMed:16442803, ECO:0000269|PubMed:16770810, ECO:0000269|PubMed:17404228, ECO:0000269|PubMed:20160912, ECO:0000269|PubMed:8506365, ECO:0000269|PubMed:8968745, ECO:0000269|PubMed:9540846, ECO:0000269|PubMed:9934985}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

NA

1.17.9.1

3D-structure; Direct protein sequencing; FAD; Flavoprotein; Oxidoreductase; Plasmid

A

57240.8

515

0.1

30.94

6.06

-4.42

-9.06

DLD

Homo sapiens (Human)

NA

PHE3;LAD;GCSL

Class-I pyridine nucleotide-disulfide oxidoreductase family

Oxidoreductase

Dihydrolipoyl dehydrogenase activity.Electron carrier activity.Flavin adenine dinucleotide binding.Lipoamide binding.NAD binding.

Dihydrolipoamide dehydrogenase deficiency (DLDD) [MIM:246900]: An autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. {ECO:0000269|PubMed:10448086, ECO:0000269|PubMed:11687750, ECO:0000269|PubMed:12925875, ECO:0000269|PubMed:15712224, ECO:0000269|PubMed:16442803, ECO:0000269|PubMed:16770810, ECO:0000269|PubMed:17404228, ECO:0000269|PubMed:20160912, ECO:0000269|PubMed:8506365, ECO:0000269|PubMed:8968745, ECO:0000269|PubMed:9540846, ECO:0000269|PubMed:9934985}. The disease is caused by variants affecting the gene represented in this entry.

DB03147; DB00145; DB00157

P42858; O14713; O00330; P30041; P62258

1.8.1.4

3D-structure; Acetylation; Alternative splicing; Cell projection; Cilium; Cytoplasmic vesicle; Disease variant; Disulfide bond; FAD; Flagellum; Flavoprotein; Mitochondrion; NAD; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Redox-active center; Reference proteome; Transit peptide

A,B,C,D,E,F,G,H

49832.7

471

0.06

26.19

6.51

-2.02

-9.06

MAOB

Homo sapiens (Human)

MAO-B; Amine oxidase [flavin-containing] B

Flavin monoamine oxidase family

CH-NH(2) donor oxidoreductase

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.

Microvascular complications of diabetes 5 (MVCD5) [MIM:612633]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Disease susceptibility is associated with variants affecting the gene represented in this entry. Homozygosity for the Leu-55 allele is strongly associated with the development of retinal disease in diabetic patients.

DB08176; DB02211; DB08516; DB08480; DB01472; DB04307; DB07512; DB07513; DB00915; DB00182; DB06698; DB04889; DB00215; DB09130; DB04147; DB00988; DB01363; DB00668; DB01175; DB02509; DB03147; DB14914; DB00614; DB04818; DB02095; DB01247; DB00601; DB01577; DB01442; DB01171; DB08082; DB02643; DB04677; DB03894; DB08804; DB04820; DB00184; DB04821; DB12612; DB01626; DB00780; DB00191; DB00388; DB01132; DB00721; DB01168; DB01367; DB09363; DB06654; DB01037; DB01104; DB14569; DB09042; DB00752; DB16446; DB09185; DB04832; DB00909

P55212; P28329-3; Q8NI60; Q5RI15; Q92915-2; P22607; Q53GS7; P06396; P01112; O14901; P13473-2; P21397; Q9BVL2; O75400-2; P62826; Q6NTF9-3; Q9Y371; Q7Z699; Q9UMX0; Q9Y649

EC 1.4.3.4

3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; FAD; Flavoprotein; Membrane; Mitochondrion; Mitochondrion outer membrane; Oxidoreductase; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix

A,B

56019.9

494

0.09

34.81

6.51

-2.2

-9.05

GRIN2A

Homo sapiens (Human)

NR2A; NMDA receptor NR2A; N-methyl D-aspartate receptor subtype 2A; HNR2A; Glutamate receptor ionotropic, NMDA 2A; Glutamate [NMDA] receptor subunit epsilon-1; GluN2A

Glutamate-gated ion channel (TC 1.A.10.1) family, NR1/GRIN1 subfamily

Glutamate-gated ion channel

Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have higher sensitivity to glutamate and faster kinetics than channels formed by GRIN1 and GRIN2B. Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning. Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium.

Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (NDHMSD) [MIM:614254]: An autosomal dominant neurodevelopmental disorder characterized by severe intellectual disability and developmental delay, absent speech, muscular hypotonia, dyskinesia, and hyperkinetic movements. Cortical blindness, cerebral atrophy, and seizures are present in some patients. {ECO:0000269|PubMed:21376300, ECO:0000269|PubMed:25167861, ECO:0000269|PubMed:25864721, ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:28228639, ECO:0000269|PubMed:28389307, ECO:0000269|PubMed:38538865}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive (NDHMSR) [MIM:617820]: An autosomal recessive neurodevelopmental disorder characterized by severe intellectual disability and psychomotor developmental delay, involuntary and stereotypic movements, spasticity, and inability to walk without support. Intractable seizures manifest in some patients. {ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:28051072}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 101 (DEE101) [MIM:619814]: A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE101 is an autosomal recessive, severe form characterized by onset of seizures in early infancy. Death in infancy may occur. {ECO:0000269|PubMed:27164704, ECO:0000269|PubMed:34611970}. The disease is caused by variants affecting the gene represented in this entry.

DB01931; DB00659; DB06151; DB08838; DB01238; DB00289; DB05824; DB04620; DB03929; DB00647; DB00843; DB00228; DB11823; DB13146; DB06741; DB00142; DB00874; DB08954; DB06738; DB09409; DB09481; DB01043; DB00454; DB00333; DB04896; DB01173; DB00312; DB01174; DB01708; DB00418; DB00193

P05067; P35637; Q12879-1; Q13224; Q62936

NA

3D-structure; Alternative splicing; Calcium; Cell membrane; Disease variant; Disulfide bond; Epilepsy; Glycoprotein; Intellectual disability; Ion channel; Ion transport; Ligand-gated ion channel; Magnesium; Membrane; Metal-binding; Phosphoprotein; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix; Transport; Zinc

B

63014.6

557

0.1

28.81

8.59

7.66

-9.05

HMGCS2

Homo sapiens (Human)

HMGCS2; HMG-CoAsynthase; 3-hydroxy-3-methylglutaryl coenzyme A synthase 2

Thiolase-like superfamily, HMG-CoA synthase family

Acyltransferase

This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.

3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911]: A metabolic disorder characterized by severe hypoketotic hypoglycemia, encephalopathy, and hepatomegaly. {ECO:0000269|PubMed:11228257, ECO:0000269|PubMed:11479731, ECO:0000269|PubMed:12647205, ECO:0000269|PubMed:16601895, ECO:0000269|PubMed:23751782, ECO:0000269|PubMed:25511235, ECO:0000269|PubMed:29597274}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 2.3.3.10

3D-structure; Acetylation; Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism; Disease variant; Lipid biosynthesis; Lipid metabolism; Mitochondrion; Phosphoprotein; Proteomics identification; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase; Transit peptide

A,D

102499

920

0.1

33.48

6.72

-1.41

-9.06