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

-11.12

TRBC1

Homo sapiens (Human)

TCRBC1; BV05S1J2.2

NA

NA

Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens. Binding of alpha-beta TR to pMH complex initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell growth and differentiation. The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity. Constant region of T cell receptor (TR) alpha chain.

Immunodeficiency 57 with autoinflammation (IMD57) [MIM:618108]: An autosomal recessive primary immunodeficiency characterized by lymphopenia and recurrent viral, bacterial, and fungal infections. Patients exhibit early-onset inflammatory bowel disease involving the upper and lower gastrointestinal tract, and develop progressive polyarthritis. {ECO:0000269|PubMed:30026316}. The disease is caused by variants affecting the gene represented in this entry. RIPK1-deficient immune cells from IMD57 patients have impaired proinflammatory signaling leading to dysregulated cytokine secretion and are prone to necroptosis. {ECO:0000269|PubMed:30026316}.; DISEASE: Autoinflammation with episodic fever and lymphadenopathy (AIEFL) [MIM:618852]: An autosomal dominant immunologic disorder characterized by early onset of recurrent episodes of unexplained fever, lymphadenopathy, hepatosplenomegaly, and increased levels of inflammatory cytokines and chemokines in patient serum. {ECO:0000269|PubMed:31827280, ECO:0000269|PubMed:31827281}. The disease is caused by variants affecting the gene represented in this entry.

DB02740

NA

NA

3D-structure; Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Membrane; Proteomics identification; Receptor; Reference proteome; T cell receptor; Transmembrane; Transmembrane helix

C,B,A

84668.2

736

0.13

39.96

5.8

-14.36

-11.12

ADRA2A

Homo sapiens (Human)

Alpha-2AAR; Alpha-2A adrenoreceptor; Alpha-2A adrenoceptor; Alpha-2A adrenergic receptor; Alpha-2 adrenergic receptor subtype C10; ADRAR; ADRA2R

G-protein coupled receptor 1 family, Adrenergic receptor subfamily, ADRA2A sub-subfamily

GPCR rhodopsin

The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol. Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.

Lipodystrophy, familial partial, 8 (FPLD8) [MIM:620679]: An autosomal dominant form of partial lipodystrophy, a disorder characterized by abnormal subcutaneous fat distribution. FPLD8 patients show selective loss of subcutaneous adipose tissue from the limbs, beginning around 13 to 15 years of age, and abnormal accumulation of subcutaneous adipose tissue in the dorsal neck and face, as well as in the posterior thoracic and abdominal regions. The disorder is associated with metabolic abnormalities, including diabetes mellitus and hyperlipidemia. {ECO:0000269|PubMed:27376152}. The disease may be caused by variants affecting the gene represented in this entry.

DB01472; DB00321; DB00543; DB00182; DB00714; DB00964; DB09229; DB01238; DB14185; DB06216; DB00865; DB00217; DB00484; DB01200; DB00248; DB01136; DB04846; DB00477; DB09202; DB00575; DB00363; DB01151; DB00633; DB01576; DB11273; DB13345; DB00320; DB00449; DB11278; DB09167; DB04855; DB06262; DB01363; DB05492; DB00751; DB00668; DB01049; DB00696; DB01175; DB06678; DB09194; DB00800; DB06623; DB00629; DB01018; DB00502; DB11577; DB00555; DB06707; DB00589; DB04948; DB09195; DB00408; DB08815; DB00934; DB01365; DB01577; DB01403; DB00968; DB06148; DB00370; DB09205; DB09242; DB06711; DB01149; DB00368; DB00540; DB06229; DB00935; DB01267; DB00715; DB01186; DB01608; DB00925; DB00692; DB00397; DB09286; DB09244; DB06153; DB00413; DB00457; DB00433; DB01069; DB00852; DB01224; DB11124; DB11738; DB00268; DB09304; DB06764; DB13025; DB00697; DB00797; DB00193; DB00656; DB00726; DB11477; DB06694; DB01392; DB00246; DB01624

NA

NA

3D-structure; Cell membrane; Direct protein sequencing; Disulfide bond; G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Methylation; Palmitate; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

R

30303.9

263

0.16

35.08

9.66

16.82

-11.07

NAAA

Homo sapiens (Human)

Nacylsphingosine amidohydrolaselike; Nacylethanolaminehydrolyzing acid amidase subunit beta; NAAA; Acid ceramidaselike protein; ASAHlike protein

Acid ceramidase family

Carbon-nitrogen hydrolase

Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N- palmitoylethanolamine > N-myristoylethanolamine > N- lauroylethanolamine = N-stearoylethanolamine > N- arachidonoylethanolamine > N-oleoylethanolamine. Also exhibits weak hydrolytic activity against the ceramides N- lauroylsphingosine and N-palmitoylsphingosine.

Hypertriglyceridemia, transient infantile (HTGTI) [MIM:614480]: An autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis. {ECO:0000269|PubMed:22226083, ECO:0000269|PubMed:24549054}. The disease is caused by variants affecting the gene represented in this entry.

DB09061; DB14009; DB14011

NA

EC 3.5.1.-

3D-structure; Alternative splicing; Autocatalytic cleavage; Direct protein sequencing; Disulfide bond; Fatty acid metabolism; Glycoprotein; Hydrolase; Lipid degradation; Lipid metabolism; Lysosome; Membrane; Proteomics identification; Reference proteome; Signal; Zymogen

A,B

36877.8

328

0.11

44.37

7.72

1.08

-11.06

AKR1C3

Homo sapiens (Human)

NA

PGFS;DDH1;HSD17B5;KIAA0119

Aldo/keto reductase family

Oxidoreductase

15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity.Alditol:NADP+ 1-oxidoreductase activity.Aldo-keto reductase (NADP) activity.Androsterone dehydrogenase activity.Delta4-3-oxosteroid 5beta-reductase activity.Dihydrotestosterone 17-beta-dehydrogenase activity.Geranylgeranyl reductase activity.Indanol dehydrogenase activity.Ketoreductase activity.Ketosteroid monooxygenase activity.NADP-retinol dehydrogenase activity.Oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor.Phenanthrene 9,10-monooxygenase activity.Prostaglandin D2 11-ketoreductase activity.Prostaglandin-F synthase activity.Prostaglandin H2 endoperoxidase reductase activity.Retinal dehydrogenase activity.Retinol dehydrogenase activity.Testosterone 17-beta-dehydrogenase (NADP+) activity.Testosterone dehydrogenase (NAD+) activity.Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity.

Neurodevelopmental disorder with language impairment and behavioral abnormalities (NEDLIB) [MIM:618917]: A neurodevelopmental disorder characterized by global developmental delay, impaired intellectual development, poor or absent speech, and behavioral abnormalities, such as autism spectrum disorder, repetitive behaviors, and hyperactivity. Some patients develop seizures and manifest developmental regression. {ECO:0000269|PubMed:31300657}. The disease is caused by variants affecting the gene represented in this entry. The genetic variation producing the missense variant p.Q607E, associated with NEDLIB, is predicted to deeply affect RNA editing. In a physiological context, the adenosine (A) residue of the original glutamine (Q) codon CAG is post-transcriptionaly edited to inosine (I) by ADAR2, leading to a codon recognized by the ribosome as arginine (R). The glutamate (E) codon GAG, resulting from the genetic variation, is predicted to be edited 90% less than the normal CAG codon. If edited, the codon GIG would be translated as p.Q607G. {ECO:0000305|PubMed:31300657}.

DB07700; DB01561; DB01536; DB00997; DB01039; DB02266; DB13751; DB00328; DB06077; DB00959; DB00157; DB03461; DB09074; DB00776; DB02056; DB01698; DB02901

P17516

1.1.1.-; 1.1.1.188; 1.1.1.210; 1.1.1.239; 1.1.1.357; 1.1.1.53; 1.1.1.62; 1.1.1.64

3D-structure; Alternative splicing; Cytoplasm; Lipid metabolism; NAD; NADP; Oxidoreductase; Proteomics identification; Reference proteome

A

35846.8

315

0.09

47.59

8.54

4.51

-11.04

KDM1B

Homo sapiens (Human)

Lysine-specific histone demethylase 2; LSD2; Flavin-containing amine oxidase domain-containing protein 1; C6orf193; AOF1

Flavin monoamine oxidase family

CH-NH(2) donor oxidoreductase

Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated 'Lys-4' of histone H3. Has no effect on tri-methylated 'Lys-4', mono-, di- or tri-methylated 'Lys-9', mono-, di- or tri-methylated 'Lys-27', mono-, di- or tri-methylated 'Lys-36' of histone H3, or on mono-, di- or tri-methylated 'Lys-20' of histone H4. Histone demethylase that demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor.

Angioedema, hereditary, 1 (HAE1) [MIM:106100]: An autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema due to C1 esterase inhibitor deficiency is comprised of two clinically indistinguishable forms. In hereditary angioedema type 1, serum levels of C1 esterase inhibitor are decreased, while in type 2, the levels are normal or elevated, but the protein is non-functional. {ECO:0000269|PubMed:12773530, ECO:0000269|PubMed:1363816, ECO:0000269|PubMed:1451784, ECO:0000269|PubMed:14635117, ECO:0000269|PubMed:16409206, ECO:0000269|PubMed:2118657, ECO:0000269|PubMed:2296585, ECO:0000269|PubMed:22994404, ECO:0000269|PubMed:2365061, ECO:0000269|PubMed:24456027, ECO:0000269|PubMed:3178731, ECO:0000269|PubMed:7814636, ECO:0000269|PubMed:7883978, ECO:0000269|PubMed:8172583, ECO:0000269|PubMed:8529136, ECO:0000269|PubMed:8755917, ECO:0000269|Ref.41}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q96L03

EC 1.-.-.-

3D-structure; Alternative splicing; Chromatin regulator; Chromosome; Developmental protein; FAD; Flavoprotein; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Repressor; Transcription; Transcription regulation; Zinc; Zinc-finger

A,C

85795.5

763

0.1

37.87

8.41

9.16

-11.05

MAOA

Homo sapiens (Human)

Monoamine oxidase A; Amine oxidase [flavin-containing] A

Flavin monoamine oxidase family

CH-NH(2) donor oxidoreductase

MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine. 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.

Brunner syndrome (BRNRS) [MIM:300615]: A form of X-linked non-dysmorphic mild intellectual disability. Male patients are affected by borderline intellectual deficit and exhibit abnormal behavior, including disturbed regulation of impulsive aggression. Obligate female carriers have normal intelligence and behavior. {ECO:0000269|PubMed:8211186}. The disease is caused by variants affecting the gene represented in this entry.

DB01472; DB00918; DB00182; DB06698; DB04889; DB13876; DB01445; DB06774; DB00215; DB04017; DB09130; DB05205; DB07641; DB00988; DB01363; DB00668; DB12329; DB01175; DB03147; DB14914; DB00614; DB01381; DB07919; DB04818; DB01247; DB00601; DB01577; DB00805; DB01442; DB01171; DB08804; DB00952; DB04820; DB00184; DB04821; DB06412; DB01626; DB00780; DB00191; DB00388; DB00397; DB09244; DB04850; DB00721; DB01168; DB00571; DB00852; DB09363; DB00140; DB00953; DB06654; DB01037; DB01104; DB00669; DB14569; DB09042; DB00624; DB13943; DB13944; DB13946; DB09245; DB00752; DB15328; DB09185; DB04832; DB00315; DB00909

P27338

EC 1.4.3.4

3D-structure; Acetylation; Alternative splicing; Catecholamine metabolism; Direct protein sequencing; Disease variant; FAD; Flavoprotein; Intellectual disability; Membrane; Mitochondrion; Mitochondrion outer membrane; Neurotransmitter degradation; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix

A

58195.3

513

0.11

34.97

7.98

2.87

-10.98

MTNR1A

Homo sapiens (Human)

Mel1a receptor; Mel1AR; Mel-1A-R

G-protein coupled receptor 1 family

GPCR rhodopsin

Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity. High affinity receptor for melatonin.

Spermatogenic failure 5 (SPGF5) [MIM:243060]: An infertility disorder caused by spermatogenesis defects. Semen from affected men show close to 100% morphologically abnormal multiflagellar spermatozoa with low motility, oversized irregular heads, and abnormal midpiece and acrosome. {ECO:0000269|PubMed:17435757, ECO:0000269|PubMed:21733974}. The disease is caused by variants affecting the gene represented in this entry.

DB06594; DB01065; DB00980; DB02709; DB09071

P27797; A8MQ03; Q8IUG1; P49286; O76081; P57088

NA

3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

D

31301

276

0.15

37.33

9.22

9.92

-10.97

CASP7

Homo sapiens (Human)

MCH3; ICE-like apoptotic protease 3; ICE-LAP3; CMH-1; CASP-7; Apoptotic protease Mch-3

Peptidase C14A family

Peptidase

Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death. Involved in the activation cascade of caspases responsible for apoptosis execution.

Pregnancy loss, recurrent, 3 (RPRGL3) [MIM:614391]: A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. {ECO:0000269|PubMed:17339269}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB05408; DB03384; DB06255

Q13490; P83105; P42858; Q8N4N3-2; P43364; Q16236; Q9GZT8; Q13177; P27986-2; P21673; Q86WV1-2; P17405; P98170

EC 3.4.22.60

3D-structure; Acetylation; Allosteric enzyme; Alternative splicing; Apoptosis; Cytoplasm; Hydrolase; Nucleus; Phosphoprotein; Protease; Proteomics identification; Reference proteome; RNA-binding; Secreted; Thiol protease; Ubl conjugation; Zymogen

A,B

47441.5

417

0.11

20.98

8.38

6.12

-10.95

poxB

Escherichia coli (strain K12)

NA

b0871;JW0855

TPP enzyme family

Oxidoreductase

Flavin adenine dinucleotide binding.Identical protein binding.Lipid binding.Magnesium ion binding.Pyruvate dehydrogenase (quinone) activity.Thiamine pyrophosphate 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

P07003

1.2.5.1

3D-structure; Cell inner membrane; Cell membrane; Direct protein sequencing; FAD; Flavoprotein; Lipid-binding; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Oxidoreductase; Pyruvate; Reference proteome; Thiamine pyrophosphate; Ubiquinone

A,B,C,D,E,F,G,H,I,J,K,L

113027

1046

0.07

35.99

5.75

-24.38

-10.94

ache

Tetronarce californica (Pacific electric ray) (Torpedo californica)

NA

NA

Type-B carboxylesterase/lipase family

NA

Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions.

Noonan syndrome 5 (NS5) [MIM:611553]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. {ECO:0000269|PubMed:17603482, ECO:0000269|PubMed:17603483, ECO:0000269|PubMed:20683980}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: LEOPARD syndrome 2 (LPRD2) [MIM:611554]: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness. {ECO:0000269|PubMed:17603483}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated, 1NN (CMD1NN) [MIM:615916]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:24777450}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

3.1.1.7

3D-structure; Alternative splicing; Cell membrane; Direct protein sequencing; Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; Membrane; Neurotransmitter degradation; Serine esterase; Signal; Synapse

A

59779.2

529

0.12

48.49

5.8

-8.48

-10.94

Pseudo LasR

Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)

NA

Autoinducer-regulated transcriptional regulatory protein family

NA

Transcriptional activator of elastase structural gene (LasB). Binds to the PAI autoinducer.

Growth hormone deficiency, isolated, 1A (IGHD1A) [MIM:262400]: An autosomal recessive, severe deficiency of growth hormone leading to dwarfism. Patients often develop antibodies to administered growth hormone. {ECO:0000269|PubMed:8364549}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 1B (IGHD1B) [MIM:612781]: An autosomal recessive deficiency of growth hormone leading to short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:12655557}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Kowarski syndrome (KWKS) [MIM:262650]: A syndrome clinically characterized by short stature associated with bioinactive growth hormone, normal or slightly increased growth hormone secretion, pathologically low insulin-like growth factor 1 levels, and normal catch-up growth on growth hormone replacement therapy. {ECO:0000269|PubMed:17519310, ECO:0000269|PubMed:8552145, ECO:0000269|PubMed:9276733}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 2 (IGHD2) [MIM:173100]: An autosomal dominant deficiency of growth hormone leading to short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:11502836, ECO:0000269|PubMed:9152628}. The disease is caused by variants affecting the gene represented in this entry.

DB08324

NA

NA

3D-structure; Activator; DNA-binding; Quorum sensing; Reference proteome; Transcription; Transcription regulation

A

18305.5

163

0.12

46.52

5.19

-6.78

-10.93

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

-10.88

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

63184.8

559

0.1

29.67

8.51

6.66

-10.88

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

-10.87

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

-10.88

MT-CO2

Homo sapiens (Human)

NA

MTCO2;COXII;COII;COX2

Cytochrome c oxidase subunit 2 family

Immune system

Copper ion binding.Cytochrome-c oxidase activity.

Mitochondrial complex IV deficiency (MT-C4D) [MIM:220110]: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and intellectual disability. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh syndrome. {ECO:0000269|PubMed:10486321}. The disease is caused by variants affecting the gene represented in this entry.

DB02659; DB04464; DB05412

Q9NZ94-2; P49281-3

7.1.1.9

3D-structure; Copper; Disease variant; Electron transport; Magnesium; Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; Primary mitochondrial disease; Proteomics identification; Reference proteome; Respiratory chain; Translocase; Transmembrane; Transmembrane helix; Transport

C

21687.9

189

0.11

38

5.68

-3.26

-10.85

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

-10.84

N/A

Lysinibacillus sphaericus (Bacillus sphaericus)

NA

NA

Peptidase C59 family

Hydrolase

Penicillin amidase activity.

Usher syndrome 3B (USH3B) [MIM:614504]: A syndrome characterized by progressive vision and hearing loss during early childhood. Some patients have the so-called 'Charles Bonnet syndrome,' involving decreased visual acuity and vivid visual hallucinations. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life. {ECO:0000269|PubMed:22279524}. The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, axonal, 2W (CMT2W) [MIM:616625]: An autosomal 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. CMT2W patients manifest a peripheral neuropathy mainly affecting the lower limbs and resulting in gait difficulties and distal sensory impairment. Most patients also have upper limb involvement. {ECO:0000269|PubMed:22930593, ECO:0000269|PubMed:26072516, ECO:0000269|PubMed:29235198}. The disease is caused by variants affecting the gene represented in this entry.

DB01822; DB03661; DB00417

NA

3.5.1.11

3D-structure; Antibiotic resistance; Direct protein sequencing; Hydrolase; Zymogen

A,B,C,D

32972.1

295

0.11

30.94

5.65

-4.18

-10.82

NR1H3

Homo sapiens (Human)

Nuclear receptor subfamily 1 group H member 3; Nuclear receptor LXRalpha; Nuclear orphan receptor LXR-alpha; Liver X receptor alpha; LXRalpha; LXRA

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

Interaction with retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism. Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity.

Okur-Chung neurodevelopmental syndrome (OCNDS) [MIM:617062]: An autosomal dominant neurodevelopmental disorder characterized by developmental delay, intellectual disability, behavioral problems, hypotonia, speech problems, microcephaly, pachygyria and variable dysmorphic features. {ECO:0000269|PubMed:27048600}. The disease is caused by variants affecting the gene represented in this entry.

DB08175; DB08063; DB11994; DB07929; DB13174; DB07080

O60869; O60341; Q99750; Q15788; O75376; Q07869; Q07869-1; Q03181; P37231; P19793; P28702; P48443; O43463; P42858; Q99750; O95817; G5E9A7; O95872; P02545; Q99750; P28702; P28702-3; P48443; Q7Z699

NA

3D-structure; Activator; Alternative splicing; Cytoplasm; DNA-binding; Metal-binding; Nucleus; Proteomics identification; Receptor; Reference proteome; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A

25389.9

220

0.09

46.42

5.51

-6.58

-10.81