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

-5.45

RNGTT

Homo sapiens (Human)

NA

CAP1A

Non-receptor class of the protein-tyrosine phosphatase family; Eukaryotic GTase family

Transferase

GTP binding.MRNA guanylyltransferase activity.Polynucleotide 5'-phosphatase activity.Protein tyrosine/serine/threonine phosphatase activity.Protein tyrosine phosphatase activity.RNA guanylyltransferase activity.Triphosphatase activity.

Atrial fibrillation, familial, 14 (ATFB14) [MIM:615378]: 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:19808477}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Genetic variations in SCN2B may be involved in Brugada syndrome (PubMed:23559163). This tachyarrhythmia is 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:23559163}.

NA

Q92624; P16333-1

2.7.7.50; 3.6.1.74

3D-structure; Alternative splicing; GTP-binding; Host-virus interaction; Hydrolase; mRNA capping; mRNA processing; Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase; Nucleus; Protein phosphatase; Proteomics identification; Reference proteome; Transferase

A,B,C,D

21849.8

189

0.11

53.71

5.89

-2.91

-5.46

ODC1

Homo sapiens (Human)

ODC

Orn/Lys/Arg decarboxylase class-II family

Carbon-carbon lyase

Polyamines are essential for cell proliferation and are implicated in cellular processes, ranging from DNA replication to apoptosis. Catalyzes the first and rate-limiting step of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine.

Bachmann-Bupp syndrome (BABS) [MIM:619075]: An autosomal dominant disorder characterized by global developmental delay, alopecia, absolute or relative macrocephaly, and facial dysmorphism. Neuroimaging shows white matter abnormalities, prominent Virchow-Robin spaces, periventricular cysts, and abnormalities of the corpus callosum. {ECO:0000269|PubMed:30239107, ECO:0000269|PubMed:30475435}. The disease is caused by variants affecting the gene represented in this entry. BABS is due to truncating variants that lead to a gain of function. This phenomenon apparently results from truncation proximal to or involving the C-terminal region of ODC1 protein, distal enough to allow escape from nonsense-mediated decay. A gain of function is corroborated by elevated plasma levels of N-acetylputrescine, with otherwise normal polyamine levels, in affected individuals. {ECO:0000269|PubMed:30475435}.

DB06243; DB04263; DB03856; DB04083; DB02824; DB01917; DB00114; DB02209; DB00203; DB00127; DB00313

Q9H8Y8; Q92993; Q9UMX2; Q9UMX2-2

EC 4.1.1.17

3D-structure; Decarboxylase; Disease variant; Hypotrichosis; Lyase; Phosphoprotein; Polyamine biosynthesis; Proteomics identification; Pyridoxal phosphate; Reference proteome; S-nitrosylation

A,B

45682.9

410

0.11

40.93

5.61

-6.68

-5.46

metF

Escherichia coli (strain K12)

NA

b3941;JW3913

Methylenetetrahydrofolate reductase family

Oxidoreductase

FAD binding.Methylenetetrahydrofolate reductase (NAD(P)H) 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.

DB03147

NA

1.5.1.54

3D-structure; Amino-acid biosynthesis; FAD; Flavoprotein; Methionine biosynthesis; NAD; Oxidoreductase; Reference proteome

A,C,E

30855.9

274

0.09

27.54

5.84

-4.61

-5.45

GOT2

Homo sapiens (Human)

NA

KYAT4

Class-I pyridoxal-phosphate-dependent aminotransferase family

Transferase

4-hydroxyglutamate transaminase activity.Amino acid binding.Enzyme binding.Kynurenine-oxoglutarate transaminase activity.L-aspartate:2-oxoglutarate aminotransferase activity.L-phenylalanine:2-oxoglutarate aminotransferase activity.Phospholipid binding.Protein homodimerization activity.Pyridoxal phosphate binding.RNA binding.

Developmental and epileptic encephalopathy 82 (DEE82) [MIM:618721]: A form of epileptic encephalopathy, a heterogeneous group of severe 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. DEE82 is an autosomal recessive metabolic encephalopathy characterized by epilepsy from the first year of life, global developmental delay, hypotonia and feeding difficulties apparent soon after birth, and intellectual and motor disabilities. Other features include poor overall growth, progressive microcephaly and biochemical abnormalities, including increased serum lactate and ammonia. {ECO:0000269|PubMed:31422819}. The disease is caused by variants affecting the gene represented in this entry.

DB02783; DB00128; DB00151; DB00142; DB00114

NA

2.6.1.1; 2.6.1.7

3D-structure; Acetylation; Alternative splicing; Aminotransferase; Cell membrane; Direct protein sequencing; Disease variant; Epilepsy; Lipid transport; Membrane; Methylation; Mitochondrion; Nitration; Phosphoprotein; Proteomics identification; Pyridoxal phosphate; Reference proteome; Transferase; Transit peptide; Transport

A,B,C,D

44694.8

401

0.1

26.15

8.98

8.22

-5.46

PARP1

Homo sapiens (Human)

Protein poly-ADP-ribosyltransferase PARP1; Poly[ADP-ribose] synthetase-1; Poly[ADP-ribose] synthase 1; Poly(ADP-ribose)polymerase-1; PPOL; PARP-1; NAD(+)Poly [ADP-ribose] polymerase-1 ADP-ribosyltrans

ARTD/PARP family

Glycosyltransferases

Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of glutamate and aspartate residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF and CHFR. Also mediates serine ADP-ribosylation of target proteins following interaction with HPF1; HPF1 conferring serine specificity. Probably also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1. Catalyzes the poly-ADP-ribosylation of histones in a HPF1-dependent manner. Involved in the base excision repair (BER) pathway by catalyzing the poly-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation. In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. Acts as a regulator of transcription: positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming. Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.

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.

DB04010; DB03509; DB03072; DB03722; DB03073; DB07787; DB07096; DB07330; DB02498; DB13877; DB02701; DB11793; DB02690; DB09074; DB12332; DB11760; DB00277; DB07232; DB01593; DB14487; DB14533; DB14548

Q8IW19; Q7Z2E3; P42574; P49715; Q86WJ1-1; P26358; Q01094; Q96L91; P11308; O60741; P09429; Q13007; Q9BQ69; P08651; Q9Y530; P09874; Q8N2W9; P46063; Q9NTX7; Q14684-1; O95863; P63165; P04637; P0CG48; Q14191; P18887; P54577; Q2M1K9; Q02085

EC 2.4.2.30

3D-structure; Acetylation; ADP-ribosylation; Allosteric enzyme; Apoptosis; Chromosome; Cytoplasm; Direct protein sequencing; DNA damage; DNA repair; DNA-binding; Glycosyltransferase; Immunity; Innate immunity; Isopeptide bond; Metal-binding; NAD; Nucleotidyltransferase; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Transcription; Transcription regulation; Transferase; Ubl conjugation; Zinc; Zinc-finger

A,B

36904

329

0.08

35.9

6.83

-0.44

-5.45

DCK

Homo sapiens (Human)

dCK

DCK/DGK family

Kinase

Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.

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.

DB02594; DB00242; DB00631; DB00987; DB01262; DB05494; DB00879; DB01073; DB00441; DB00709; DB01280; DB00642; DB04961; DB00943

Q16854

EC 2.7.1.74

3D-structure; ATP-binding; Direct protein sequencing; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Transferase

B

27128.5

229

0.13

52.5

5.26

-7.8

-5.46

TARS

Homo sapiens (Human)

NA

TARS

Class-II aminoacyl-tRNA synthetase family

Ligase / ligase inhibitor

ATP binding.Protein homodimerization activity.Threonine-tRNA ligase activity.TRNA binding.

Trichothiodystrophy 7, non-photosensitive (TTD7) [MIM:618546]: A form of trichothiodystrophy, a disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD7 patients do not manifest cutaneous photosensitivity. They have cysteine- and threonine-deficient hair with alternating light and dark 'tiger-tail' banding pattern observed under polarization microscopy. Inheritance pattern is autosomal recessive. {ECO:0000269|PubMed:31374204}. The disease is caused by variants affecting the gene represented in this entry.

DB00156

Q9BPX7; Q96CV9; O43704; A2RTX5

6.1.1.3

3D-structure; Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; Disease variant; Ligase; Nucleotide-binding; Phosphoprotein; Protein biosynthesis; Proteomics identification; Reference proteome; RNA-binding; tRNA-binding; Ubl conjugation

A,B

33945.3

290

0.13

41.57

6.29

-3.28

-5.46

NOS1

Homo sapiens (Human)

Peptidyl-cysteine S-nitrosylase NOS1; Nitric oxide synthase, brain; Neuronal NOS; NOS, type I; NOS type I; NNOS; NC-NOS; N-NOS; BNOS

NOS family

Paired donor oxygen oxidoreductase

In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body.

Variation Asp-298 in NOS3 may be associated with susceptibility to coronary spasm. {ECO:0000269|PubMed:11740345, ECO:0000269|PubMed:9737779}.

DB02143; DB02727; DB01997; DB03892; DB02207; DB03710; DB00155; DB00843; DB00997; DB03147; DB03247; DB01942; DB01221; DB02077; DB01821; DB09241; DB03144; DB03449; DB02044; DB02644; DB08019; DB08018; DB02027; DB03461; DB04223; DB06096; DB02991; DB03707

Q08AM6

EC 1.14.13.39

3D-structure; Alternative splicing; Calmodulin-binding; Cell membrane; Cell projection; FAD; Flavoprotein; FMN; Heme; Iron; Membrane; Metal-binding; NADP; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Synapse; Ubl conjugation

A,B

34875.7

299

0.1

42.94

5.96

-6.25

-5.45

CTH

Homo sapiens (Human)

Gamma-cystathionase; Cysteine-protein sulfhydrase

Trans-sulfuration enzymes family

NA

Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.

Cystathioninuria (CSTNU) [MIM:219500]: Autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion. {ECO:0000269|PubMed:12574942, ECO:0000269|PubMed:18476726}. The disease is caused by variants affecting the gene represented in this entry.

DB02328; DB03928; DB00151; DB04217; DB00114

P32929; Q96NT3; Q96NT3-2; Q96HA8; Q6P9E2

EC 4.4.1.1

3D-structure; Alternative splicing; Amino-acid biosynthesis; Calmodulin-binding; Cysteine biosynthesis; Cytoplasm; Disease variant; Lipid metabolism; Lyase; Proteomics identification; Pyridoxal phosphate; Reference proteome

A,B,C,D

86026

782

0.08

32.4

6.27

-9.46

-5.45

RRM2

Homo sapiens (Human)

NA

RR2

Ribonucleoside diphosphate reductase small chain family

Oxidoreductase

Metal ion binding.Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor.

Pyruvate kinase hyperactivity (PKHYP) [MIM:102900]: Autosomal dominant phenotype characterized by increase of red blood cell ATP. {ECO:0000269|PubMed:9090535}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Pyruvate kinase deficiency of red cells (PKRD) [MIM:266200]: A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia. {ECO:0000269|PubMed:10087985, ECO:0000269|PubMed:10772876, ECO:0000269|PubMed:11328279, ECO:0000269|PubMed:11960989, ECO:0000269|PubMed:1536957, ECO:0000269|PubMed:1896471, ECO:0000269|PubMed:19085939, ECO:0000269|PubMed:2018831, ECO:0000269|PubMed:21794208, ECO:0000269|PubMed:7706479, ECO:0000269|PubMed:8161798, ECO:0000269|PubMed:8180378, ECO:0000269|PubMed:8476433, ECO:0000269|PubMed:8481523, ECO:0000269|PubMed:8483951, ECO:0000269|PubMed:8664896, ECO:0000269|PubMed:8807089, ECO:0000269|PubMed:9075576, ECO:0000269|PubMed:9482576, ECO:0000269|PubMed:9827908, ECO:0000269|PubMed:9886305, ECO:0000269|Ref.24}. The disease is caused by variants affecting the gene represented in this entry.

DB00242; DB05260; DB05801; DB05003; DB05428

P41002; Q9UM11; P23921; O00560

1.17.4.1

3D-structure; Alternative splicing; Cytoplasm; Deoxyribonucleotide synthesis; Iron; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation

A,B,C,D

33579.4

286

0.14

43.7

5.12

-12.86

-5.45

NT5C2

Homo sapiens (Human)

NA

PNT5;NT5B;NT5CP

5'(3')-deoxyribonucleotidase family

Hydrolase

5'-nucleotidase activity.Metal ion binding.Nucleoside phosphotransferase activity.Nucleotide binding.

Spastic paraplegia 45, autosomal recessive (SPG45) [MIM:613162]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Some SPG45 patients manifest intellectual disability, contractures and learning disability. {ECO:0000269|PubMed:24482476, ECO:0000269|PubMed:28884889}. The disease is caused by variants affecting the gene represented in this entry.

DB00171; DB00811; DB06408

P48047; P51116; Q8IVS8; Q7L9L4; Q86TA1; Q70IA8; Q9Y5B8; Q6ZVK8; O00560; Q9NRS6

2.7.1.77; 3.1.3.5; 3.1.3.99

3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding; Cytoplasm; Disease variant; Hereditary spastic paraplegia; Hydrolase; Magnesium; Metal-binding; Neurodegeneration; Nucleotide metabolism; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Transferase

A

53978.4

467

0.14

30.87

8.25

3.41

-5.46

COMT

Homo sapiens (Human)

S-COMT; MB-COMT; Catechol-O-methyltransferase; COMT

Class I-like SAM-binding methyltransferase superfamily, Cation-dependent O-methyltransferase family

Methyltransferase

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.

Schizophrenia (SCZD) [MIM:181500]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:15645182}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

DB07462; DB02342; DB02105; DB08049; DB00118; DB00714; DB03336; DB00286; DB00255; DB00841; DB00988; DB15488; DB00494; DB00668; DB00783; DB00977; DB01064; DB00968; DB01141; DB03907; DB04820; DB06152; DB11632; DB00252; DB01420; DB00323

Q6P5T0; P30518; Q8NFU1; Q8NHW4; P34972; Q96BA8; P50402; Q5JX71; O14843; O00258; P08034; O75712; Q9NTQ9; O95377; Q8TDT2; Q8N6U8; O15529; P31937; Q9H2F3; O95279; Q5SR56; A6NDP7; Q0D2K0; Q7RTS5; Q9UHJ9-5; Q8IY26; Q9H6H4; Q6NTF9-3; O75783; Q99500; Q9Y6D0; Q3KNW5; O60669; P22732; Q96G79; Q5T1Q4; Q9NY26; Q9NP94; Q6P1K1; P30825; Q9UHI5; B2RUZ4; Q9UPZ6; Q96MV1; Q9NV29; A0PK00; Q9NUH8; Q9P0S9; Q14656; Q6UW68; Q9H0R3; O95807; P34981; Q15645; Q15836; O95183; O76024; P30260; Q9H816; Q92997; P29323-3; P22607; P06396; Q15323; Q6A162; P26371; O15116; P20645; O14744; Q5T160; Q9UJD0; Q2MKA7; Q8N488; O75880; Q14141; Q9UNE7; Q15645; Q9NYH9; Q8NA23-2

EC 2.1.1.6

3D-structure; Alternative initiation; Catecholamine metabolism; Cell membrane; Cytoplasm; Direct protein sequencing; Lipid metabolism; Magnesium; Membrane; Metal-binding; Methyltransferase; Neurotransmitter degradation; Phosphoprotein; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Schizophrenia; Signal-anchor; Transferase; Transmembrane; Transmembrane helix

A

23851.2

214

0.07

25.99

5.25

-7.75

-5.45

PFF0160c

Plasmodium falciparum (isolate 3D7)

NA

NA

Dihydroorotate dehydrogenase family, Type 2 subfamily

Oxidoreductase

Dihydroorotate dehydrogenase activity.

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.

DB01117

NA

1.3.5.2

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

A,B

42573.5

378

0.1

36.63

8.21

3.17

-5.45

nfsB

Enterobacter cloacae

NA

nfsI;nfnB

Nitroreductase family

Oxidoreductase

Oxidoreductase activity.

A chromosomal aberration involving NFKB2 is found in a case of B-cell non Hodgkin lymphoma (B-NHL). Translocation t(10;14)(q24;q32) with IGHA1. The resulting oncogene is also called Lyt-10C alpha variant.; DISEASE: A chromosomal aberration involving NFKB2 is found in a cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement produces the p80HT gene which codes for a truncated 80 kDa protein (p80HT).; DISEASE: In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions.; DISEASE: Immunodeficiency, common variable, 10 (CVID10) [MIM:615577]: A primary immunodeficiency characterized by childhood-onset of recurrent infections, hypogammaglobulinemia, and decreased numbers of memory and marginal zone B-cells. Some patients may develop autoimmune features and have circulating autoantibodies. An unusual feature is central adrenal insufficiency. {ECO:0000269|PubMed:24140114, ECO:0000269|PubMed:25524009}. The disease is caused by variants affecting the gene represented in this entry.

DB03793; DB03247

NA

1.-.-.-

3D-structure; Flavoprotein; FMN; NAD; NADP; Oxidoreductase

A,B,C,D

47619.4

432

0.08

38.43

5.52

-12.98

-5.46

alr1529

Nostoc sp. (strain PCC 7120 / SAG 25.82 / UTEX 2576)

NA

NA

NA

Hydrolase

NA

Desbuquois dysplasia 1 (DBQD1) [MIM:251450]: A chondrodysplasia characterized by severe prenatal and postnatal growth retardation (less than -5 SD), joint laxity, short extremities, progressive scoliosis, round face, midface hypoplasia, prominent bulging eyes. The main radiologic features are short long bones with metaphyseal splay, a 'Swedish key' appearance of the proximal femur (exaggerated trochanter), and advance carpal and tarsal bone age. Two forms of Desbuquois dysplasia are distinguished on the basis of the presence or absence of characteristic hand anomalies: an extra ossification center distal to the second metacarpal, delta phalanx, bifid distal thumb phalanx, and phalangeal dislocations. {ECO:0000269|PubMed:19853239, ECO:0000269|PubMed:20425819, ECO:0000269|PubMed:21037275, ECO:0000269|PubMed:21412251, ECO:0000269|PubMed:21654728, ECO:0000269|PubMed:22539336}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Epiphyseal dysplasia, multiple, 7 (EDM7) [MIM:617719]: A form of multiple epiphyseal dysplasia, a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. EDM7 inheritance is autosomal recessive. {ECO:0000269|PubMed:28742282}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

NA

3D-structure; Reference proteome

A,B,C,D

45603.2

401

0.11

49.26

7.67

1.26

-5.46

GPT2

Homo sapiens (Human)

NA

AAT2;ALT2

Class-I pyridoxal-phosphate-dependent aminotransferase family, Alanine aminotransferase subfamily

Transferase

L-alanine:2-oxoglutarate aminotransferase activity.Pyridoxal phosphate binding.

Neurodevelopmental disorder with spastic paraplegia and microcephaly (NEDSPM) [MIM:616281]: An autosomal recessive syndrome characterized by severe psychomotor developmental delay, dysarthria, walking difficulties, moderately to severely impaired intellectual development, poor or absent speech, and progressive microcephaly. {ECO:0000269|PubMed:25758935}. The disease is caused by variants affecting the gene represented in this entry.

DB00160; DB00142; DB00780; DB00114

NA

2.6.1.2

3D-structure; Acetylation; Alternative splicing; Aminotransferase; Disease variant; Intellectual disability; Proteomics identification; Pyridoxal phosphate; Reference proteome; Transferase

A

48717.7

436

0.09

47.17

6.07

-4.32

-5.45

PLD2

Homo sapiens (Human)

hPLD2; Phosphatidylcholine-hydrolyzing phospholipase D2; PLD1C; PLD 2; Choline phosphatase 2

Phospholipase D family

Phosphoric diester hydrolase

May have a role in signal-induced cytoskeletal regulation and/or endocytosis.

Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly (MRT80) [MIM:620653]: An autosomal recessive disorder characterized by global developmental delay, mildly to moderately impaired intellectual development, attention deficit-hyperactivity disorder, hypotonia, seizure, poor social skills, and autistic traits. Brain imaging shows fronto-temporal lissencephaly and pachygyria. {ECO:0000269|PubMed:37880421}. The disease is caused by variants affecting the gene represented in this entry.

DB00122; DB14006

P05067; P23528; P62993; P15153; P13051-2

EC 3.1.4.4

3D-structure; Alternative splicing; Cell membrane; Hydrolase; Lipid degradation; Lipid metabolism; Lipoprotein; Membrane; Phosphoprotein; Proteomics identification; Reference proteome; Repeat

A

66788.7

586

0.1

41.26

6.54

-3.31

-5.45

GNE

Homo sapiens (Human)

UDPGlcNAc2epimerase/ManAc kinase; GNE; Bifunctional UDPNacetylglucosamine 2epimerase/Nacetylmannosamine kinase

UDP-N-acetylglucosamine 2-epimerase family; ROK (NagC/XylR) family

Kinase

Regulates and initiates biosynthesis of N- acetylneuraminic acid (NeuAc), a precursor of sialic acids. Plays an essential role in early development. Required for normal sialylation in hematopoietic cells. Sialylation is implicated in cell adhesion, signal transduction, tumorigenicity and metastatic behavior of malignant cells. {ECO:0000250, ECO:0000269|PubMed:10334995}.

Sialuria (SIALURIA) [MIM:269921]: In sialuria, free sialic acid accumulates in the cytoplasm and gram quantities of neuraminic acid are secreted in the urine. The metabolic defect involves lack of feedback inhibition of UDP-GlcNAc 2-epimerase by CMP-Neu5Ac, resulting in constitutive overproduction of free Neu5Ac. Clinical features include variable degrees of developmental delay, coarse facial features and hepatomegaly. Sialuria inheritance is autosomal dominant. {ECO:0000269|PubMed:10330343, ECO:0000269|PubMed:10356312, ECO:0000269|PubMed:11326336, ECO:0000269|PubMed:2808337}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Nonaka myopathy (NM) [MIM:605820]: An autosomal recessive myopathy characterized by early adult onset and progressive distal muscle weakness that preferentially affects the anterior tibial muscles, usually sparing the quadriceps femoris. Some individuals may have involvement of the upper limbs or proximal muscles. Muscle biopsy reveals presence of rimmed vacuoles. {ECO:0000269|PubMed:11528398, ECO:0000269|PubMed:11916006, ECO:0000269|PubMed:12177386, ECO:0000269|PubMed:12325084, ECO:0000269|PubMed:12409274, ECO:0000269|PubMed:12473753, ECO:0000269|PubMed:12473769, ECO:0000269|PubMed:12473780, ECO:0000269|PubMed:12497639, ECO:0000269|PubMed:12811782, ECO:0000269|PubMed:12913203, ECO:0000269|PubMed:14707127, ECO:0000269|PubMed:15146476, ECO:0000269|PubMed:16503651}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thrombocytopenia 12 with or without myopathy (THC12) [MIM:620757]: A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC12 is an autosomal recessive form manifesting from infancy or early childhood with bleeding episodes. Clinical features include petechiae, easy bruising, epistaxis, hematomas, menorrhagia, and increased bleeding after trauma or surgery. Rare patients may have thrombocytopenia without bleeding. Some affected individuals have myopathic features, usually apparent in the second or third decades of life. {ECO:0000269|PubMed:25257349, ECO:0000269|PubMed:30171045, ECO:0000269|PubMed:33198675, ECO:0000269|PubMed:34788986, ECO:0000269|PubMed:34858435, ECO:0000269|PubMed:35052006, ECO:0000269|PubMed:38237079}. The disease is caused by variants affecting the gene represented in this entry.

NA

P12814; Q6UY14-3; Q969Y2; Q15323; P60370; P60409; P60410; P60411; Q9BQ66; P26371; Q9BYQ4; Q7Z3S9; O43597; Q6UY14-3; Q6P5X5; P27918; A8MQ03; Q16610; Q9UHF1; P28799; P49639; Q5T749; Q15323; O76011; Q6A162; P78385; P78386; O43790; Q07627; Q8IUG1; P60409; P60410; Q8IUC1; P60328; Q52LG2; Q3SY46; Q9BYP8; Q3LHN2; Q3SYF9; Q9BYR8; Q9BYR6; Q9BYQ7; Q9BYQ6; Q9BYR3; P26371; Q3LI64; Q3LI66; Q3LI67; Q9BYQ4; Q9BYQ3; Q9BYQ0; Q99750; Q8IV28; P0DPK4; O15496; O43609; O43610; P14373; Q8IWZ5; Q15654; O14817; Q2TAL6; Q9BRX9; O76024; Q9NZC7-5

NA

3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding; Cytoplasm; Disease variant; Hydrolase; Kinase; Metal-binding; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Transferase; Zinc

A

41589.2

384

0.07

35.07

7.05

0.19

-5.46

CTSL

Homo sapiens (Human)

Major excreted protein; MEP; Cathepsin L1; CTSL1

Peptidase C1 family

Peptidase

Important for the overall degradation of proteins in lysosomes.

Charcot-Marie-Tooth disease, axonal, 2DD (CMT2DD) [MIM:618036]: 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:29499166}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hypomagnesemia, seizures, and impaired intellectual development 2 (HOMGSMR2) [MIM:618314]: An autosomal dominant disease characterized by generalized seizures in infancy, severe hypomagnesemia, and renal magnesium wasting. Seizures persist despite magnesium supplementation and are associated with significant intellectual disability. {ECO:0000269|PubMed:30388404}. The disease is caused by variants affecting the gene represented in this entry.

DB07477; DB12010; DB03661; DB14962

O60911; O43765; P0DTC2; P59594; G5EFH4

EC 3.4.22.15

3D-structure; Alternative initiation; Cell membrane; Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond; Glycoprotein; Host-virus interaction; Hydrolase; Lysosome; Membrane; Nucleus; Protease; Proteomics identification; Reference proteome; Secreted; Signal; Thiol protease; Zymogen

A

23519.9

214

0.12

30.95

4.79

-9.97

-5.45