TOP2A

Homo sapiens (Human)

DNA topoisomerase II, alpha isozyme; DNA topoisomerase 2alpha; DNA topoisomerase 2-alpha

Type II topoisomerase family

Topoisomerase

Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation. Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands.

A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98. {ECO:0000269|PubMed:10556215}.

DB05706; DB06013; DB05022; DB06263; DB00276; DB06420; DB04975; DB06362; DB00537; DB00970; DB00694; DB06421; DB00380; DB00997; DB05129; DB00467; DB00445; DB00773; DB09047; DB04576; DB01645; DB01177; DB00978; DB04967; DB01204; DB00218; DB01059; DB01165; DB00487; DB01179; DB05920; DB04978; DB01208; DB00444; DB00685; DB00385; DB06042

O14497-1; P38398; P35222; Q05655

EC 5.6.2.3

3D-structure; Acetylation; Alternative splicing; ATP-binding; Biological rhythms; Cytoplasm; Direct protein sequencing; DNA-binding; Isomerase; Isopeptide bond; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Topoisomerase; Ubl conjugation

A,B

42640.6

373

0.1

33.34

8.64

5.05

-5.46

oxyR

Escherichia coli (strain K12)

NA

b3961;mor;momR;JW3933

LysR transcriptional regulatory family

Transcription

Bacterial-type RNA polymerase core promoter proximal region sequence-specific DNA binding.Transcription factor activity, bacterial-type RNA polymerase core promoter proximal region sequence-specific binding.

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.

NA

NA

NA

3D-structure; Activator; Direct protein sequencing; Disulfide bond; DNA-binding; Glutathionylation; Oxidation; Reference proteome; Repressor; S-nitrosylation; Stress response; Transcription; Transcription regulation

A,B

46013

412

0.07

44.76

5.57

-14.52

-5.45

xylA

Actinoplanes missouriensis (strain ATCC 14538 / DSM 43046 / CBS 188.64 / JCM 3121 / NBRC 102363 / NCIMB 12654 / NRRL B-3342 / UNCC 431)

NA

AMIS_10350;XI

Xylose isomerase family

Isomerase(intramolecular oxidoreductase)

Metal ion binding.Xylose isomerase activity.

Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. {ECO:0000269|PubMed:15534175}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Renal tubular dysgenesis (RTD) [MIM:267430]: Autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype). {ECO:0000269|PubMed:16116425}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Microvascular complications of diabetes 3 (MVCD3) [MIM:612624]: 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. {ECO:0000269|PubMed:10099885}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Intracerebral hemorrhage (ICH) [MIM:614519]: A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke. {ECO:0000269|PubMed:15277638}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB11195

NA

5.3.1.5

3D-structure; Carbohydrate metabolism; Cytoplasm; Isomerase; Magnesium; Metal-binding; Reference proteome; Xylose metabolism

A,B,C,D

35820.8

322

0.1

32.29

5.32

-11.33

-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

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

MT-CYB

Bos taurus (Bovine)

NA

CYTB;MTCYB;COB

Cytochrome b family

NA

Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c. Contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis. {ECO:0000269|PubMed:1327781, ECO:0000269|PubMed:20025846, ECO:0000269|PubMed:9485330, ECO:0000305|PubMed:189810}."

Combined oxidative phosphorylation deficiency 6 (COXPD6) [MIM:300816]: A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy. {ECO:0000269|PubMed:20362274, ECO:0000269|PubMed:22019070, ECO:0000269|PubMed:25583628, ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:26173962, ECO:0000269|PubMed:27178839}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, X-linked recessive, 4, with or without cerebellar ataxia (CMTX4) [MIM:310490]: A neuromuscular disorder characterized by progressive sensorimotor axonal neuropathy, distal sensory impairment, difficulty walking due to peripheral neuropathy and/or cerebellar ataxia, and deafness due to auditory neuropathy. Additional features include cognitive impairment, cerebellar atrophy, dysarthria, abnormal extraocular movements, tremor, dysmetria and spasticity. The age at onset ranges from infancy to young adulthood. {ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:26004228}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Deafness, X-linked, 5, with peripheral neuropathy (DFNX5) [MIM:300614]: A form of hearing loss characterized by absent or severely abnormal auditory brainstem response, abnormal middle ear reflexes, abnormal speech discrimination, loss of outer hair cell function, and cochlear nerve hypoplasia. DFNX5 patients manifest auditory neuropathy with childhood onset, associated with distal sensory impairment affecting the peripheral nervous system. {ECO:0000269|PubMed:25986071}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy (SEMDHL) [MIM:300232]: An X-linked recessive developmental disorder characterized by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy. {ECO:0000269|PubMed:28842795}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

NA

3D-structure; Electron transport; Heme; Iron; Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; Reference proteome; Respiratory chain; Transmembrane; Transmembrane helix; Transport; Ubiquinone

A,B

105644

944

0.1

37

9.24

19.42

-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

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

-5.46

soxA

Bacillus sp. (strain B-0618)

NA

sox

MSOX/MTOX family, MSOX subfamily

Oxidoreductase

Sarcosine oxidase activity.

Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer. {ECO:0000269|PubMed:10394368}.; DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:9753710}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Lipodystrophy, familial partial, 3 (FPLD3) [MIM:604367]: A form of lipodystrophy characterized by marked loss of subcutaneous fat from the extremities. Facial adipose tissue may be increased, decreased or normal. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia. {ECO:0000269|PubMed:11788685, ECO:0000269|PubMed:12453919}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Glioma 1 (GLM1) [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:10851250}. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.

DB03098; DB01918; DB03517; DB03147; DB03366; DB02083; DB02543

NA

1.5.3.1

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

A,B

42606.4

385

0.1

26.97

5.27

-17.18

-5.46

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

ALDH5A1

Homo sapiens (Human)

Succinic dehydrogenase; Succinate-semialdehyde dehydrogenase, mitochondrial; SSADH; NAD(+)-dependent succinic semialdehyde dehydrogenase; Aldehyde dehydrogenase family 5 member A1

Aldehyde dehydrogenase family

Aldehyde/oxo donor oxidoreductase

Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).

Succinic semialdehyde dehydrogenase deficiency (SSADHD) [MIM:271980]: A rare inborn error of 4-aminobutyric acid (GABA) metabolism, which leads to accumulation of 4-hydroxybutyric acid in physiologic fluids of patients. The disease is clinically characterized by developmental delay, hypotonia, intellectual disability, ataxia, seizures, hyperkinetic behavior, aggression, and sleep disturbances. {ECO:0000269|PubMed:11243727, ECO:0000269|PubMed:11901270, ECO:0000269|PubMed:14635103}. The disease is caused by variants affecting the gene represented in this entry.

DB00534; DB00157; DB09072; DB00139; DB00313

NA

EC 1.2.1.24

3D-structure; Acetylation; Alternative splicing; Disease variant; Disulfide bond; Mitochondrion; NAD; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Transit peptide

A

48555.9

455

0.08

33.52

6

-3.73

-5.46

CDK6

Homo sapiens (Human)

Serine/threonine-protein kinase PLSTIRE; Serine/threonine protein kinase PLSTIRE; Cell division protein kinase 6; CDKN6

Protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily

Kinase

Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e. g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases. Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition.

Microcephaly 12, primary, autosomal recessive (MCPH12) [MIM:616080]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. {ECO:0000269|PubMed:23918663}. The disease is caused by variants affecting the gene represented in this entry.

DB07379; DB12001; DB03496; DB07795; DB09073; DB11730; DB15442

P41238; Q8N5C1; P24385; P30281; P51946; Q14094; Q16543; P38936; P42771; P42772; P42773; P55273; Q08050-1; P08238; Q5XKR4; Q01196; Q9C019

EC 2.7.11.22

3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division; Cell projection; Cytoplasm; Cytoskeleton; Differentiation; Disease variant; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Primary microcephaly; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase

A

29850.2

263

0.1

34.55

7.23

0.46

-5.46

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

-5.46

WARS2

Homo sapiens (Human)

NA

NA

Class-I aminoacyl-tRNA synthetase family

Ligase / antibiotic

ATP binding.Tryptophan-tRNA ligase activity.

Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS) [MIM:617710]: An autosomal recessive, mitochondrial disorder with a broad phenotypic spectrum ranging from severe neonatal lactic acidosis, encephalomyopathy and early death to an attenuated course with milder manifestations. Clinical features include delayed psychomotor development, intellectual disability, hypotonia, dystonia, ataxia, and spasticity. Severe combined respiratory chain deficiency may be found in severely affected individuals. {ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:28650581, ECO:0000269|PubMed:28905505, ECO:0000269|PubMed:30920170, ECO:0000269|PubMed:35074316}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Parkinsonism-dystonia 3, childhood-onset (PKDYS3) [MIM:619738]: An autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances. {ECO:0000269|PubMed:29120065, ECO:0000269|PubMed:31970218, ECO:0000269|PubMed:34890876}. The disease is caused by variants affecting the gene represented in this entry.

DB00150

NA

6.1.1.2

3D-structure; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding; Disease variant; Dystonia; Ligase; Mitochondrion; Nucleotide-binding; Parkinsonism; Primary mitochondrial disease; Protein biosynthesis; Proteomics identification; Reference proteome; Transit peptide

A,B

36376.7

327

0.06

51.57

8.75

4.55

-5.46

MAPKAPK2

Homo sapiens (Human)

MK2; MK-2; MAPKactivated protein kinase 2; MAPKAPK-2; MAPKAP-K2; MAPKAP kinase 2; MAP kinaseactivated protein kinase 2; MAP kinase-activated protein kinase 2

Protein kinase superfamily, CAMK Ser/Thr protein kinase family

Kinase

Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation.

Erythrocytosis, familial, 4 (ECYT4) [MIM:611783]: An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal platelet and leukocyte counts. {ECO:0000269|PubMed:18184961, ECO:0000269|PubMed:18378852, ECO:0000269|PubMed:19208626, ECO:0000269|PubMed:22367913}. The disease is caused by variants affecting the gene represented in this entry.

DB07430; DB07431; DB07406; DB08358; DB07728; DB07234; DB02010

Q00613; P04792; Q16539; Q9QWH1; P47811

EC 2.7.11.1

3D-structure; Alternative splicing; ATP-binding; Cytoplasm; DNA damage; Isopeptide bond; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation

A

32100.5

290

0.1

43.53

8.76

5.44

-5.45

MAPK3

Homo sapiens (Human)

PRKM3; P44-MAPK; P44-ERK1; P44 Mitogen-activated protein kinase; Mitogen-activated protein kinase 3; Microtubule-associated protein-2 kinase; Microtubule-associated protein 2 kinase; MAPK 3; MAP kinas

Protein kinase superfamily, CMGC Ser/Thr protein kinase family, MAP kinase subfamily

Kinase

MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway.

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.

DB04604; DB00945; DB01169; DB08862; DB02587; DB01017; DB02733; DB06195; DB00605; DB13930

Q9HCU0; P53355; P49366; P28562; Q16828; P19419; Q49AJ0-4; Q96NJ5; Q02750; Q16539; P27361; Q96HT8; Q6GQQ9-2; Q9ULW8; Q15121; P14618-1; Q8N490; P23467; Q12913; Q14160; P13051-2; Q08509; Q60793; Q9EPI6; Q62132

EC 2.7.11.24

3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; Cell cycle; Cell junction; Cytoplasm; Direct protein sequencing; Host-virus interaction; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation

A

40525.2

352

0.09

41.34

6.45

-2.32

-5.46

CHRM2

Homo sapiens (Human)

M2 receptor; CHRM2

G-protein coupled receptor 1 family, Muscarinic acetylcholine receptor subfamily, CHRM2 sub-subfamily

GPCR rhodopsin

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.

Major depressive disorder (MDD) [MIM:608516]: A common psychiatric disorder. It is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning. {ECO:0000269|PubMed:15229186}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB03128; DB08897; DB05752; DB00321; DB00543; DB00517; DB01238; DB14185; DB00572; DB00767; DB01019; DB00835; DB09300; DB00411; DB01239; DB00568; DB00565; DB00363; DB00907; DB00785; DB00434; DB00496; DB01151; DB00804; DB08801; DB01075; DB01231; DB00280; DB09167; DB01135; DB01142; DB00366; DB09194; DB06702; DB01148; DB00483; DB00986; DB06787; DB11181; DB00725; DB00424; DB09262; DB00458; DB00332; DB01221; DB00408; DB00934; DB00454; DB06709; DB00940; DB01403; DB00462; DB00340; DB01336; DB01226; DB00622; DB00540; DB00334; DB01062; DB00383; DB01337; DB00715; DB01085; DB01338; DB06153; DB00387; DB00392; DB01069; DB00777; DB12278; DB01224; DB04834; DB11855; DB13581; DB00728; DB00747; DB01591; DB00202; DB00342; DB11235; DB01409; DB01036; DB00505; DB00508; DB00376; DB09089; DB00726; DB00809; DB09076; DB09185; DB00246

NA

NA

3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Synapse; Transducer; Transmembrane; Transmembrane helix

A

49469.8

438

0.13

34.71

9.4

15.67

-5.46

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

Stap-coc def

Staphylococcus aureus

def; Stap-coc Polypeptide deformylase

Polypeptide deformylase family

Carbon-nitrogen hydrolase

Removes the formyl group from the N-terminal Met of newly synthesized proteins. Requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions.

Immunodeficiency 43 (IMD43) [MIM:241600]: A disorder characterized by marked reduction in serum concentrations of immunoglobulins and albumin, and hypoproteinemia due to hypercatabolism. Patients may suffer from recurrent respiratory tract infections and severe skin disease. {ECO:0000269|PubMed:16549777}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Amyloidosis, hereditary systemic 6 (AMYLD6) [MIM:620659]: A form of hereditary systemic amyloidosis, a disorder characterized by amyloid deposition in multiple tissues resulting in a wide clinical spectrum. AMYLD6 is mainly characterized by gastrointestinal and cardiac symptoms. Neurologic involvement, sicca syndrome, and carpal tunnel syndrome may also be present. Inheritance is autosomal dominant. {ECO:0000269|PubMed:22693999}. The disease is caused by variants affecting the gene represented in this entry. Apart from the presence of causative mutations, beta-2-microglobulin may adopt the fibrillar configuration of amyloid, resulting in amyloidosis, when its serum levels are persistently high, as seen in patients on long-term hemodialysis (PubMed:7918443). In contrast to patients with dialysis-related amyloidosis, patients with hereditary amyloidosis have normal circulating concentrations of beta2-microglobulin (PubMed:22693999). {ECO:0000269|PubMed:22693999, ECO:0000269|PubMed:7918443}.

DB04310

NA

NA

3D-structure; Hydrolase; Iron; Metal-binding; Protein biosynthesis

A

20835.6

186

0.05

42.9

5.65

-7.59

-5.45

F3

Homo sapiens (Human)

Thromboplastin; TF; F3; Coagulation factor III; CD142 antigen

Tissue factor family

NA

Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited protolysis. TF plays a role in normal hemostasis by initiating the cell-surface assemblyand propagation of the coagulation protease cascade.

Intellectual developmental disorder, autosomal recessive 54 (MRT54) [MIM:617028]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT54 patients manifest intellectual disability, delayed speech and hyperactivity. {ECO:0000269|PubMed:27106596}. The disease may be caused by variants affecting the gene represented in this entry.

DB07207; DB07247; DB08232; DB06552; DB13150; DB00036; DB16732

P55085; P08709; Q9UM19; Q92544

NA

3D-structure; Alternative splicing; Blood coagulation; Disulfide bond; Glycoprotein; Hemostasis; Lipoprotein; Membrane; Palmitate; Proteomics identification; Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix

H

27479.3

249

0.09

32.92

7.22

0.48

-5.45