ADRB2

Homo sapiens (Human)

Beta-2 adrenoreceptor; Beta-2 adrenoceptor; Beta-2 adrenergic receptor; B2AR; ADRB2R

G-protein coupled receptor 1 family, Adrenergic receptor subfamily, ADRB2 sub-subfamily

GPCR rhodopsin

The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine. Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins.

Cortical dysplasia, complex, with other brain malformations 6 (CDCBM6) [MIM:615771]: A disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have microcephaly, ataxia, and severe delayed psychomotor development. Brain imaging shows variable malformations of cortical development, including white matter streaks, dysmorphic basal ganglia, corpus callosum abnormalities, brainstem and cerebellar hypoplasia, cortical dysplasia, polymicrogyria. {ECO:0000269|PubMed:23246003}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Skin creases, congenital symmetric circumferential, 1 (CSCSC1) [MIM:156610]: An autosomal dominant disease characterized by multiple, symmetric, circumferential rings of folded skin, affecting primarily the limbs. Affected individuals also exhibit intellectual disability, cleft palate, and dysmorphic features. {ECO:0000269|PubMed:26637975}. The disease is caused by variants affecting the gene represented in this entry.

DB07543; DB01193; DB00866; DB01118; DB00182; DB01102; DB01274; DB01238; DB09204; DB06216; DB00335; DB01408; DB05590; DB09013; DB00195; DB00217; DB01295; DB00612; DB00901; DB08807; DB06726; DB08808; DB00248; DB00521; DB01136; DB04846; DB01407; DB00785; DB01151; DB11273; DB13345; DB00449; DB11278; DB00841; DB09273; DB06262; DB01363; DB01364; DB00668; DB01049; DB11587; DB01288; DB00983; DB05039; DB00221; DB01064; DB00598; DB01210; DB13139; DB01365; DB13624; DB01214; DB00264; DB01203; DB05849; DB04861; DB00368; DB00540; DB00334; DB09080; DB00816; DB01580; DB00715; DB01359; DB00925; DB00397; DB00960; DB01291; DB01366; DB01182; DB00571; DB06814; DB00852; DB01917; DB11124; DB00867; DB01001; DB00938; DB00489; DB03566; DB00127; DB00871; DB00373; DB00726; DB12248; DB09082; DB09185

P30542; P07550; P32121; Q96B67; Q9UII2; Q9ULD4-2; Q9NSI6-4; Q5M9N0-2; A0AVK6; Q658K8; O00472; Q15910-2; Q15486; P61978; Q5TCQ9; Q99685; O14745; Q9NR21-5; Q8WVD3; Q9H0X6; Q13573; P12931; Q5T0J7-2; Q8N0U2

NA

3D-structure; Cell membrane; Disulfide bond; Endosome; G-protein coupled receptor; Glycoprotein; Golgi apparatus; Hydroxylation; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix; Ubl conjugation

A

32266.1

282

0.15

36.1

8.02

2.1

-5.83

fccA

Shewanella frigidimarina

NA

fcc3

FAD-dependent oxidoreductase 2 family, FRD/SDH subfamily

Oxidoreductase

Electron carrier activity.Fumarate reductase (menaquinone).Metal ion binding.Nucleic acid binding.Succinate dehydrogenase activity.

Pigmentary disorder, reticulate, with systemic manifestations, X-linked (PDR) [MIM:301220]: An X-linked recessive disorder characterized by recurrent infections and sterile inflammation in various organs. Diffuse skin hyperpigmentation with a distinctive reticulate pattern is universally evident by early childhood. This is later followed in many patients by hypohidrosis, corneal inflammation and scarring, enterocolitis that resembles inflammatory bowel disease, and recurrent urethral strictures. Melanin and amyloid deposition is present in the dermis. Affected males also have a characteristic facies with frontally upswept hair and flared eyebrows. Female carriers have only restricted pigmentary changes along Blaschko's lines. {ECO:0000269|PubMed:27019227}. The disease is caused by variants affecting the gene represented in this entry. XLPDR is caused by a recurrent intronic mutation that results in missplicing and reduced POLA1 expression. This leads to a decrease in cytosolic RNA:DNA hybrids and constitutive activation of type I interferon responses, but has no effect on cell replication. {ECO:0000269|PubMed:27019227}.; DISEASE: Van Esch-O'Driscoll syndrome (VEODS) [MIM:301030]: An X-linked recessive syndrome characterized by different degrees of intellectual disability, moderate to severe short stature, microcephaly, hypogonadism, and variable congenital malformations. {ECO:0000269|PubMed:31006512}. The disease is caused by variants affecting the gene represented in this entry.

DB04734; DB03147; DB01677; DB03343

NA

1.3.2.4

3D-structure; Electron transport; FAD; Flavoprotein; Heme; Iron; Metal-binding; Oxidoreductase; Periplasm; Transport

A

60177.2

568

0.06

27.7

6

-8.64

-5.82

ACADM

Homo sapiens (Human)

NA

NA

Acyl-CoA dehydrogenase family

Oxidoreductase

Acyl-CoA dehydrogenase activity.Flavin adenine dinucleotide binding.Identical protein binding.Medium-chain-acyl-CoA dehydrogenase activity.

Acyl-CoA dehydrogenase medium-chain deficiency (ACADMD) [MIM:201450]: An inborn error of mitochondrial fatty acid beta-oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy. {ECO:0000269|PubMed:10767181, ECO:0000269|PubMed:11349232, ECO:0000269|PubMed:11409868, ECO:0000269|PubMed:11486912, ECO:0000269|PubMed:1363805, ECO:0000269|PubMed:1671131, ECO:0000269|PubMed:1684086, ECO:0000269|PubMed:1902818, ECO:0000269|PubMed:2251268, ECO:0000269|PubMed:2393404, ECO:0000269|PubMed:2394825, ECO:0000269|PubMed:7603790, ECO:0000269|PubMed:7929823, ECO:0000269|PubMed:8198141, ECO:0000269|PubMed:9158144, ECO:0000269|PubMed:9882619}. The disease is caused by variants affecting the gene represented in this entry.

DB03415; DB03147; DB02910

PRO_0000000502 [P11310]

1.3.8.7

3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; Disease variant; FAD; Fatty acid metabolism; Flavoprotein; Lipid metabolism; Mitochondrion; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Transit peptide

A,B,C,D

85080.3

773

0.09

30.55

5.71

-7.7

-5.83

CA3

Homo sapiens (Human)

NA

NA

Alpha-carbonic anhydrase family

Lyase

Carbonate dehydratase activity.Nickel cation binding.Phosphatase activity.Zinc ion binding.

Cortical dysplasia, complex, with other brain malformations 6 (CDCBM6) [MIM:615771]: A disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have microcephaly, ataxia, and severe delayed psychomotor development. Brain imaging shows variable malformations of cortical development, including white matter streaks, dysmorphic basal ganglia, corpus callosum abnormalities, brainstem and cerebellar hypoplasia, cortical dysplasia, polymicrogyria. {ECO:0000269|PubMed:23246003}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Skin creases, congenital symmetric circumferential, 1 (CSCSC1) [MIM:156610]: An autosomal dominant disease characterized by multiple, symmetric, circumferential rings of folded skin, affecting primarily the limbs. Affected individuals also exhibit intellectual disability, cleft palate, and dysmorphic features. {ECO:0000269|PubMed:26637975}. The disease is caused by variants affecting the gene represented in this entry.

DB00819; DB00562; DB01194; DB00482; DB00606; DB01144; DB00869; DB08846; DB00311; DB00703; DB12418; DB00391; DB00273; DB00580; DB00909

P37235; Q9BS40

4.2.1.1

3D-structure; Acetylation; Cytoplasm; Glutathionylation; Lyase; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome; Zinc

A

29416.7

259

0.11

38.2

6.71

-1.07

-5.83

R

Escherichia phage lambda (Bacteriophage lambda)

NA

NA

Glycosyl hydrolase 24 family

Glycosidase

Lyase activity.Lysozyme activity.Lytic transglycosylase activity.

Estrogen resistance (ESTRR) [MIM:615363]: A disorder characterized by partial or complete resistance to estrogens, in the presence of elevated estrogen serum levels. Clinical features include absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, reduced bone mineral density, osteoporosis, continued growth into adulthood and very tall adult stature. Glucose intolerance, hyperinsulinemia and lipid abnormalities may also be present. {ECO:0000269|PubMed:23841731, ECO:0000269|PubMed:27754803}. The disease is caused by variants affecting the gene represented in this entry.

DB04206

NA

4.2.2.n2

3D-structure; Antimicrobial; Bacteriolytic enzyme; Cytolysis; Direct protein sequencing; Host cell lysis by virus; Host cytoplasm; Lyase; Reference proteome; Viral release from host cell

A,B,C

49834.9

462

0.07

18.78

9.6

18.29

-5.82

PAH

Homo sapiens (Human)

Phenylalanine4hydroxylase; Phenylalanine-4-hydroxylase; Phe4monooxygenase; Phe-4-monooxygenase

Biopterin-dependent aromatic amino acid hydroxylase family

Paired donor oxygen oxidoreductase

Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine.

Phenylalanine hydroxylase deficiency (PAH deficiency) [MIM:261600]: An autosomal recessive inborn error of phenylalanine metabolism characterized by intolerance to dietary intake of the essential amino acid phenylalanine. The disease spectrum depends on the degree of PAH deficiency and the phenylalanine levels in plasma. Severe deficiency causes classic phenylketonuria (PKU) that is characterized by plasma concentrations of phenylalanine persistently above 1200 umol/L. PKU patients develop profound and irreversible intellectual disability, unless low phenylalanine diet is introduced early in life. They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor. Less severe forms of PAH deficiency are characterized by phenylalanine levels above normal (120 umol/L) but below 1200 umol/L and include moderate PKU, mild PKU, non-PKU hyperphenylalaninemia (non-PKU HPA) and mild hyperphenylalaninemia. Individuals with PAH deficiency who have plasma phenylalanine concentrations consistently below 600 umol/L on an unrestricted diet are not at higher risk of developing intellectual, neurologic, and neuropsychological impairment than are individuals without PAH deficiency. {ECO:0000269|PubMed:10200057, ECO:0000269|PubMed:10679941, ECO:0000269|PubMed:11180595, ECO:0000269|PubMed:11326337, ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:11461196, ECO:0000269|PubMed:11935335, ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1301187, ECO:0000269|PubMed:1355066, ECO:0000269|PubMed:1358789, ECO:0000269|PubMed:1363837, ECO:0000269|PubMed:1363838, ECO:0000269|PubMed:1671810, ECO:0000269|PubMed:1672290, ECO:0000269|PubMed:1672294, ECO:0000269|PubMed:1679030, ECO:0000269|PubMed:1709636, ECO:0000269|PubMed:18538294, ECO:0000269|PubMed:1975559, ECO:0000269|PubMed:2014802, ECO:0000269|PubMed:22513348, ECO:0000269|PubMed:22526846, ECO:0000269|PubMed:23792259, ECO:0000269|PubMed:2564729, ECO:0000269|PubMed:2615649, ECO:0000269|PubMed:2840952, ECO:0000269|PubMed:32668217, ECO:0000269|PubMed:7833954, ECO:0000269|PubMed:8068076, ECO:0000269|PubMed:8088845, ECO:0000269|PubMed:8098245, ECO:0000269|PubMed:8406445, ECO:0000269|PubMed:8889583, ECO:0000269|PubMed:8889590, ECO:0000269|PubMed:9048935, ECO:0000269|PubMed:9101291, ECO:0000269|PubMed:9450897, ECO:0000269|PubMed:9452061, ECO:0000269|PubMed:9452062, ECO:0000269|PubMed:9521426, ECO:0000269|PubMed:9600453, ECO:0000269|PubMed:9634518, ECO:0000269|PubMed:9792407, ECO:0000269|PubMed:9792411, ECO:0000269|PubMed:9852673, ECO:0000269|PubMed:9950317}. The disease is caused by variants affecting the gene represented in this entry.

DB03673; DB04339; DB06778; DB04419; DB06262; DB04400; DB00368; DB00120; DB02562; DB00360

NA

EC 1.14.16.1

3D-structure; Allosteric enzyme; Direct protein sequencing; Disease variant; Iron; Metal-binding; Monooxygenase; Oxidoreductase; Phenylalanine catabolism; Phenylketonuria; Phosphoprotein; Proteomics identification; Reference proteome

A

35556.1

307

0.15

39.96

6.17

-3.5

-5.83

MGMT

Homo sapiens (Human)

NA

NA

MGMT family

Dna repair

Calcium ion binding.DNA binding.DNA-methyltransferase activity.Methylated-DNA-[protein]-cysteine S-methyltransferase activity.Methyltransferase activity.

Antley-Bixler syndrome, with genital anomalies and disordered steroidogenesis (ABS1) [MIM:201750]: A disease characterized by the association of Antley-Bixler syndrome with steroidogenesis defects and abnormal genitalia. Antley-Bixler syndrome is characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. {ECO:0000269|PubMed:14758361, ECO:0000269|PubMed:15264278, ECO:0000269|PubMed:15483095}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency (DISPORD) [MIM:613571]: A disorder resulting in a rare variant of congenital adrenal hyperplasia, with apparent combined P450C17 and P450C21 deficiency and accumulation of steroid metabolites. Affected girls are born with ambiguous genitalia, but their circulating androgens are low and virilization does not progress. Conversely, affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, in some cases resembling the pattern seen in patients with Antley-Bixler syndrome. {ECO:0000269|PubMed:14758361, ECO:0000269|PubMed:15220035}. The disease is caused by variants affecting the gene represented in this entry.

DB00151; DB11831; DB04531; DB02216; DB01593; DB14487; DB14533; DB14548

NA

2.1.1.63

3D-structure; Direct protein sequencing; DNA damage; DNA repair; DNA-binding; Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Transferase; Zinc

A

17946.7

166

0.07

43.65

7.27

0.43

-5.83

CES1

Homo sapiens (Human)

Serine esterase 1; Monocyte/macrophage serine esterase; Human carboxylesterase 1; HMSE; HCE1; CES1; Brain carboxylesterase hBr1; Acyl coenzyme A:cholesterol acyltransferase

Type-B carboxylesterase/lipase family

Carboxylic ester hydrolase

Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl coa ester.

Protoporphyria, erythropoietic, 1 (EPP1) [MIM:177000]: An autosomal recessive form of porphyria with onset usually before age 10 years. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Erythropoietic protoporphyria is marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals. {ECO:0000269|PubMed:10942404, ECO:0000269|PubMed:11375302, ECO:0000269|PubMed:12063482, ECO:0000269|PubMed:12601550, ECO:0000269|PubMed:1376018, ECO:0000269|PubMed:15286165, ECO:0000269|PubMed:17196862, ECO:0000269|PubMed:1755842, ECO:0000269|PubMed:7910885, ECO:0000269|PubMed:8757534, ECO:0000269|PubMed:9211198, ECO:0000269|PubMed:9585598, ECO:0000269|PubMed:9740232}. The disease is caused by variants affecting the gene represented in this entry.

DB07821; DB08224; DB03056; DB06442; DB01086; DB09061; DB14737; DB01101; DB02659; DB01410; DB00758; DB00907; DB04838; DB06695; DB00647; DB01452; DB00470; DB01039; DB14845; DB00875; DB11181; DB02161; DB00328; DB00762; DB00583; DB14009; DB00454; DB06693; DB00688; DB03721; DB01183; DB00198; DB09269; DB01599; DB09342; DB00881; DB14761; DB12404; DB06201; DB11362; DB00641; DB00382; DB00675; DB12095; DB09299; DB04795; DB00519; DB16349

Q8IVF2-3; A8MQ03; Q15125; Q5T7V8; Q5T749; Q13113; Q9NRQ2; Q9NR31; O95231

EC 3.1.1.1

3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; Glycoprotein; Hydrolase; Lipid droplet; Lipid metabolism; Phosphoprotein; Proteomics identification; Reference proteome; Serine esterase; Signal

A,B,C,D,E,F

58522.7

531

0.09

35.86

6.05

-5.56

-5.82

PON1

Homo sapiens (Human)

NA

PON

Paraoxonase family

Hydrolase

Acyl-L-homoserine-lactone lactonohydrolase activity.Aryldialkylphosphatase activity.Arylesterase activity.Calcium ion binding.Phospholipid binding.Protein homodimerization activity.

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.

DB01327; DB09130; DB01395; DB14598; DB14600; DB14596; DB00218; DB01085; DB01593; DB14487; DB14533; DB14548

NA

3.1.1.2; 3.1.1.81; 3.1.8.1

3D-structure; Calcium; Direct protein sequencing; Disulfide bond; Glycoprotein; HDL; Hydrolase; Metal-binding; Proteomics identification; Reference proteome; Secreted; Signal

A

37232.8

332

0.11

35.09

5.06

-17.08

-5.82

fpr

Escherichia coli (strain K12)

NA

mvrA;b3924;JW3895

Ferredoxin--NADP reductase type 1 family

Flavoprotein

FAD binding.Ferredoxin-NADP+ reductase activity.Oxidoreductase activity.

Noonan syndrome 13 (NS13) [MIM:619087]: 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. NS13 inheritance is autosomal dominant. There is considerable variability in severity. {ECO:0000269|PubMed:32721402}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

NA

1.18.1.2; 1.19.1.1

3D-structure; Cytoplasm; Direct protein sequencing; FAD; Flavoprotein; NADP; Nucleotide-binding; Oxidoreductase; Reference proteome

A

27346.2

244

0.08

30.68

7.25

0.42

-5.82

IMPA1

Homo sapiens (Human)

NA

IMPA

Inositol monophosphatase superfamily

Hydrolase

Identical protein binding.Inositol monophosphate 1-phosphatase activity.Inositol monophosphate 3-phosphatase activity.Inositol monophosphate 4-phosphatase activity.Inositol monophosphate phosphatase activity.Lithium ion binding.Magnesium ion binding.Manganese ion binding.Protein homodimerization activity.

Intellectual developmental disorder, autosomal recessive 59 (MRT59) [MIM:617323]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:26416544}. The disease is caused by variants affecting the gene represented in this entry.

DB03542; DB14509; DB01356; DB14507; DB14508

P29218; O14732; P54253; G5E9A7; P42858; P29218-3; O14732; Q7Z699

3.1.3.25; 3.1.3.94

3D-structure; Alternative splicing; Cytoplasm; Hydrolase; Intellectual disability; Lithium; Magnesium; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome

A,B

59299.9

544

0.07

37.53

5.38

-11.58

-5.82

PDE4B

Homo sapiens (Human)

cAMP-specific 3',5'-cyclic phosphodiesterase 4B; Type 4B cAMP phosphodiesterase; Type 4 cyclic adenosine monophosphate phosphodiesterase (type 4 PDE); PDE32; DPDE4

Cyclic nucleotide phosphodiesterase family, PDE4 subfamily

Phosphoric diester hydrolase

May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents. Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

Combined oxidative phosphorylation deficiency 33 (COXPD33) [MIM:617713]: An autosomal recessive disorder caused by multiple mitochondrial respiratory chain defects and impaired mitochondrial energy metabolism. Clinical manifestations are highly variable. Affected infants present with cardiomyopathy accompanied by multisystemic features involving liver, kidney, and brain. Death in infancy is observed in some patients. Children and adults present with myopathy and progressive external ophthalmoplegia. {ECO:0000269|PubMed:28942965}. The disease is caused by variants affecting the gene represented in this entry.

DB04149; DB03606; DB03807; DB06909; DB01959; DB08299; DB03349; DB00131; DB01427; DB00201; DB03849; DB05219; DB01647; DB00651; DB00824; DB02660; DB05266; DB01088; DB01113; DB01791; DB01656; DB01954; DB04530; DB01412; DB00277; DB09283

Q13936; Q08499

EC 3.1.4.53

3D-structure; Alternative splicing; cAMP; Cell membrane; Cytoplasm; Hydrolase; Membrane; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome; Zinc

A

37367.1

324

0.08

36.36

5

-20.82

-5.83

GFER

Homo sapiens (Human)

NA

HERV1;HPO;ALR

NA

Oxidoreductase

Flavin adenine dinucleotide binding.Flavin-linked sulfhydryl oxidase activity.Growth factor activity.Protein disulfide oxidoreductase activity.

Myopathy, mitochondrial progressive, with congenital cataract, hearing loss and developmental delay (MPMCD) [MIM:613076]: A disease characterized by progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay. {ECO:0000269|PubMed:19409522, ECO:0000269|PubMed:20593814}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

Q9H8W4; PRO_0000449628 [P0DTD1]

1.8.3.2

3D-structure; Alternative splicing; Cataract; Cytoplasm; Deafness; Disease variant; Disulfide bond; FAD; Flavoprotein; Growth factor; Mitochondrion; Oxidoreductase; Phosphoprotein; Primary mitochondrial disease; Proteomics identification; Reference proteome; Secreted

A

14170.4

126

0.11

48.59

6.58

-0.98

-5.82

xecC

Xanthobacter autotrophicus (strain ATCC BAA-1158 / Py2)

NA

Xaut_4867

Class-I pyridine nucleotide-disulfide oxidoreductase family

Oxidoreductase

2-oxopropyl-CoM reductase (carboxylating) activity.Flavin adenine dinucleotide binding.

LTC4 synthase deficiency is associated with a neurometabolic developmental disorder characterized by muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly. {ECO:0000269|PubMed:10896305, ECO:0000269|PubMed:9820300}.

DB03163; DB03147

NA

1.8.1.5

3D-structure; Disulfide bond; FAD; Flavoprotein; NADP; Oxidoreductase; Plasmid; Redox-active center; Reference proteome

A,B

114413

1044

0.08

25.66

5.68

-21.74

-5.83

NEIL1

Homo sapiens (Human)

NA

NA

FPG family

Dna binding protein / dna

Class I DNA-(apurinic or apyrimidinic site) lyase activity.Class III/IV DNA-(apurinic or apyrimidinic site) lyase activity.Damaged DNA binding.DNA-(apurinic or apyrimidinic site) lyase activity.DNA N-glycosylase activity.Hydrolase activity, acting on glycosyl bonds.Protein C-terminus binding.Zinc ion binding.

Glutaric aciduria 1 (GA1) [MIM:231670]: An autosomal recessive metabolic disorder characterized by progressive dystonia and athetosis due to gliosis and neuronal loss in the basal ganglia. {ECO:0000269|PubMed:14707522, ECO:0000269|PubMed:18775954, ECO:0000269|PubMed:24973495, ECO:0000269|PubMed:8541831, ECO:0000269|PubMed:8900227, ECO:0000269|PubMed:8900228, ECO:0000269|PubMed:9600243, ECO:0000269|PubMed:9711871}. The disease is caused by variants affecting the gene represented in this entry.

DB09130; DB14490; DB14491; DB14488; DB14501; DB14489; DB01592

NA

3.2.2.-; 4.2.99.18

3D-structure; Chromosome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair; DNA-binding; Glycosidase; Hydrolase; Lyase; Multifunctional enzyme; Nucleus; Proteomics identification; Reference proteome; RNA editing

A

32177.5

286

0.1

57.82

8.89

5.38

-5.83

metF

Thermus thermophilus

NA

NA

Methylenetetrahydrofolate reductase family

Oxidoreductase

Methylenetetrahydrofolate reductase (NAD(P)H) activity.Nucleotide binding.

Brugada syndrome 7 (BRGDA7) [MIM:613120]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:20031595}. The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Atrial fibrillation, familial, 16 (ATFB16) [MIM:613120]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:20558140, ECO:0000269|PubMed:21051419}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

NA

NA

3D-structure; FAD; Flavoprotein; Nucleotide-binding; Oxidoreductase

A

32632.1

292

0.09

39.75

8.99

3.35

-5.82

pelA

Niveispirillum irakense (Azospirillum irakense)

NA

NA

NA

Lyase

Lyase activity.

A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas. {ECO:0000269|PubMed:15938644}.; DISEASE: A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A. {ECO:0000269|PubMed:12112524, ECO:0000269|PubMed:16161041}.; DISEASE: A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17. {ECO:0000269|PubMed:12112524}.; DISEASE: Neuroblastoma 3 (NBLST3) [MIM:613014]: A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system. {ECO:0000269|PubMed:18724359, ECO:0000269|PubMed:18923523, ECO:0000269|PubMed:18923525, ECO:0000269|PubMed:21242967, ECO:0000269|PubMed:22932897}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: The ALK signaling pathway plays an important role in glioblastoma, the most common malignant brain tumor of adults and one of the most lethal cancers. It regulates both glioblastoma migration and growth. {ECO:0000269|PubMed:15908427}.; DISEASE: A chromosomal aberration involving ALK is found in one subject with colorectal cancer. Translocation t(2;2)(p23.1;p23.3). A 5 million base pair tandem duplication generates an in-frame WDCP-ALK gene fusion. {ECO:0000269|PubMed:22327622}.; DISEASE: A chromosomal aberration involving ALK has been identified in a subset of patients with non-small-cell lung carcinoma. This aberration leads to the production of a fusion protein between the N-terminus of EML4 et the C-terminus of ALK. It is unclear whether the fusion protein is caused by a simple inversion within 2p (inv(2)(p21p23)) or whether the chromosome translocation involving 2p is more complex. When tested in a heterologous system, the fusion protein EML4-ALK possesses transforming activity that is dependent on ALK catalytic activity, possibly due to spontaneous dimerization mediated by the EML4 moiety, leading to ALK kinase activation. {ECO:0000269|PubMed:17625570}.

NA

NA

NA

3D-structure; Lyase; Signal

A

41907.5

384

0.08

43.72

6.11

-3.46

-5.83

Pseudo mdeA

Pseudomonas putida (Arthrobacter siderocapsulatus)

Pseudo MGL; L-methionine gamma-lyase; L-methioninase; Homocysteine desulfhydrase

Trans-sulfuration enzymes family, L-methionine gamma-lyase subfamily

Carbon-sulfur lyases

Catalyzes the alpha,gamma-elimination of L-methionine to produce methanethiol, 2-oxobutanoate and ammonia. Is involved in L-methionine catabolism. In fact, shows a multicatalytic function since it also catalyzes gamma-replacement of L-methionine with thiol compounds, alpha,gamma-elimination and gamma-replacement reactions of L-homocysteine and its S-substituted derivatives, O-substituted-L-homoserines and DL-selenomethionine, and, to a lesser extent, alpha,beta-elimination and beta-replacement reactions of L-cysteine, S-methyl-L-cysteine, and O-acetyl-L-serine. Also catalyzes deamination and gamma-addition reactions of L-vinylglycine. Thus, the enzyme is able to cleave C-S, C-Se, and C-O bonds of sulfur, selenium, and oxygen amino acids, respectively.

Lecithin-cholesterol acyltransferase deficiency (LCATD) [MIM:245900]: A disorder of lipoprotein metabolism characterized by inadequate esterification of plasmatic cholesterol. Two clinical forms are recognized: complete LCAT deficiency and fish-eye disease. LCATD is generally referred to the complete form which is associated with absence of both alpha and beta LCAT activities resulting in esterification anomalies involving both HDL (alpha-LCAT activity) and LDL (beta-LCAT activity). It causes a typical triad of diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure. {ECO:0000269|PubMed:11423760, ECO:0000269|PubMed:12957688, ECO:0000269|PubMed:15994445, ECO:0000269|PubMed:16051254, ECO:0000269|PubMed:16216249, ECO:0000269|PubMed:1681161, ECO:0000269|PubMed:1859405, ECO:0000269|PubMed:2370048, ECO:0000269|PubMed:7607641, ECO:0000269|PubMed:7711728, ECO:0000269|PubMed:8318557, ECO:0000269|PubMed:8432868, ECO:0000269|PubMed:8807342, ECO:0000269|PubMed:9007616, ECO:0000269|PubMed:9741700}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Fish-eye disease (FED) [MIM:136120]: A disorder of lipoprotein metabolism due to partial lecithin-cholesterol acyltransferase deficiency that affects only alpha-LCAT activity. FED is characterized by low plasma HDL and corneal opacities due to accumulation of cholesterol deposits in the cornea ('fish-eye'). {ECO:0000269|PubMed:1516702, ECO:0000269|PubMed:1571050, ECO:0000269|PubMed:15994445, ECO:0000269|PubMed:1737840, ECO:0000269|PubMed:21901787, ECO:0000269|PubMed:8620346, ECO:0000269|PubMed:9261271}. The disease is caused by variants affecting the gene represented in this entry.

DB04083

NA

EC 4.4.1.11

3D-structure; Direct protein sequencing; Lyase; Pyridoxal phosphate

A,C

85234.4

796

0.07

37.1

6.21

-11.34

-5.82

CUL4A/CUL4B-DDB1-CRBN

Homo sapiens (Human)

NA

Cullin family

NA

NA

Orotic aciduria 1 (ORAC1) [MIM:258900]: A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and intellectual disability. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. {ECO:0000269|PubMed:9042911}. The disease is caused by variants affecting the gene represented in this entry.

NA

P54253; Q86VP6; Q16531; Q92466; P08238; O94888; P55072

NA

3D-structure; Alternative splicing; Biological rhythms; DNA damage; DNA repair; Host-virus interaction; Isopeptide bond; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation; Ubl conjugation pathway

B

42669.7

368

0.1

44.94

8.72

6.58

-5.82

CD38

Homo sapiens (Human)

cADPr hydrolase 1; T10; Cyclic ADPribose hydrolase 1; ADPribosyl cyclase 1; ADPRC 1; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1; ADP-ribosyl cyclase 1; 2'-phospho-cyclic-ADP-ribose transferase;

ADP-ribosyl cyclase family

Glycosylase

Has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system. Synthesizes the second messagers cyclic ADP-ribose and nicotinate-adenine dinucleotide phosphate, the former a second messenger for glucose-induced insulin secretion.

Intellectual developmental disorder with hypotonia and behavioral abnormalities (IDDHBA) [MIM:618748]: An autosomal dominant neurodevelopmental disorder with onset in infancy. IDDHBA is characterized by hypotonia, global developmental delay, learning disability, and behavioral abnormalities, such as autistic features and attention deficit-hyperactivity disorder. Additional variable features may include non-specific facial dysmorphism, congenital heart defects, ocular anomalies, and poor feeding. {ECO:0000269|PubMed:30905399}. The disease is caused by variants affecting the gene represented in this entry.

DB09331; DB14811; DB16370

NA

EC 3.2.2.6

3D-structure; Alternative splicing; Diabetes mellitus; Disulfide bond; Glycoprotein; Hydrolase; Membrane; NAD; NADP; Proteomics identification; Receptor; Reference proteome; Signal-anchor; Transferase; Transmembrane; Transmembrane helix

A

29222.8

252

0.1

50.29

6.19

-2.71

-5.82