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

AMD1

Homo sapiens (Human)

SamDC; S-adenosylmethioninedecarboxylase; AdoMetDC; AMD

Eukaryotic AdoMetDC family

Carbon-carbon lyase

Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels. Essential for biosynthesis of the polyamines spermidine and spermine.

Niemann-Pick disease A (NPDA) [MIM:257200]: An early-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Niemann-Pick disease type A is a primarily neurodegenerative disorder characterized by onset within the first year of life, intellectual disability, digestive disorders, failure to thrive, major hepatosplenomegaly, and severe neurologic symptoms. The severe neurological disorders and pulmonary infections lead to an early death, often around the age of four. Clinical features are variable. A phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. {ECO:0000269|PubMed:12556236, ECO:0000269|PubMed:1391960, ECO:0000269|PubMed:15221801, ECO:0000269|PubMed:15877209, ECO:0000269|PubMed:1618760, ECO:0000269|PubMed:1718266, ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:19405096, ECO:0000269|PubMed:2023926, ECO:0000269|PubMed:20386867, ECO:0000269|PubMed:22818240, ECO:0000269|PubMed:23252888, ECO:0000269|PubMed:23430884, ECO:0000269|PubMed:26499107, ECO:0000269|PubMed:27338287, ECO:0000269|PubMed:8680412, ECO:0000269|PubMed:8693491, ECO:0000269|PubMed:9266408, ECO:0000269|PubMed:9660788}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Niemann-Pick disease B (NPDB) [MIM:607616]: A late-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Clinical signs involve only visceral organs. The most constant sign is hepatosplenomegaly which can be associated with pulmonary symptoms. Patients remain free of neurologic manifestations. However, a phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. In Niemann-Pick disease type B, onset of the first symptoms occurs in early childhood and patients can survive into adulthood. {ECO:0000269|PubMed:12369017, ECO:0000269|PubMed:12556236, ECO:0000269|PubMed:1301192, ECO:0000269|PubMed:15241805, ECO:0000269|PubMed:16010684, ECO:0000269|PubMed:1618760, ECO:0000269|PubMed:16472269, ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:1885770, ECO:0000269|PubMed:19050888, ECO:0000269|PubMed:19405096, ECO:0000269|PubMed:20386867, ECO:0000269|PubMed:21098024, ECO:0000269|PubMed:21621718, ECO:0000269|PubMed:22613662, ECO:0000269|PubMed:22818240, ECO:0000269|PubMed:23252888, ECO:0000269|PubMed:23430512, ECO:0000269|PubMed:25920558, ECO:0000269|PubMed:26084044, ECO:0000269|PubMed:26499107, ECO:0000269|PubMed:27338287, ECO:0000269|PubMed:27659707, ECO:0000269|PubMed:8051942, ECO:0000269|PubMed:8664904}. The disease is caused by variants affecting the gene represented in this entry.

DB08163; DB00118; DB01917

P17707; Q96A98; Q8WY91

EC 4.1.1.50

3D-structure; Alternative splicing; Autocatalytic cleavage; Decarboxylase; Direct protein sequencing; Lyase; Phosphoprotein; Polyamine biosynthesis; Proteomics identification; Pyruvate; Reference proteome; S-adenosyl-L-methionine; Schiff base; Spermidine biosynthesis; Zymogen

A,B

35790.5

311

0.14

39.47

6.03

-2.01

-5.46

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

MAP2K2

Homo sapiens (Human)

NA

MEK2;MKK2;PRKMK2

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

Transferase

ATP binding.MAP kinase kinase activity.Metal ion binding.PDZ domain binding.Protein serine/threonine/tyrosine kinase activity.Protein serine/threonine kinase activator activity.Protein serine/threonine kinase activity.Protein tyrosine kinase activity.Scaffold protein binding.

Cardiofaciocutaneous syndrome 4 (CFC4) [MIM:615280]: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. {ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:18042262, ECO:0000269|PubMed:20358587}. The disease is caused by variants affecting the gene represented in this entry.

DB11967; DB06616; DB12010; DB14904; DB11689; DB08911

P05067; P10398; Q96II5; P15056; O95273; Q12959; P61978-2; Q8IVT5; P00540; P04049

2.7.12.2

3D-structure; Acetylation; ATP-binding; Cardiomyopathy; Cytoplasm; Direct protein sequencing; Disease variant; Ectodermal dysplasia; Intellectual disability; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase

B

41918.9

364

0.1

40.94

7.34

0.91

-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

-5.45

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

SMO

Homo sapiens (Human)

Smo-D473H; SMOH; Protein Gx

G-protein coupled receptor Fz/Smo family

GPCR frizzled

Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia. Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation. G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal.

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

DB01047; DB11978; DB06786; DB09143; DB08828

NA

NA

3D-structure; Cell membrane; Cell projection; Developmental protein; Disease variant; Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix

A,B

37420.1

333

0.16

25.17

6.65

-0.76

-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

-5.46

TK1

Homo sapiens (Human)

Thymidine kinase, cytosolic

Thymidine kinase family

Kinase

cytosol, identical protein binding, thymidine kinase activity, zinc ion binding, DNA metabolic process, nucleobase-containing compound metabolic process, protein homotetramerization, pyrimidine nucleoside salvage, thymidine metabolic process

Seizures, benign familial infantile, 3 (BFIS3) [MIM:607745]: A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS3 inheritance is autosomal dominant. {ECO:0000269|PubMed:11371648, ECO:0000269|PubMed:12243921, ECO:0000269|PubMed:15048894, ECO:0000269|PubMed:16417554, ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:17386050, ECO:0000269|PubMed:18479388, ECO:0000269|PubMed:20371507, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23360469, ECO:0000269|PubMed:23758435, ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 11 (DEE11) [MIM:613721]: An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. {ECO:0000269|PubMed:19783390, ECO:0000269|PubMed:19786696, ECO:0000269|PubMed:20956790, ECO:0000269|PubMed:22677033, ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:23550958, ECO:0000269|PubMed:23662938, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:23935176, ECO:0000269|PubMed:23988467, ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:24579881, ECO:0000269|PubMed:24659627, ECO:0000269|PubMed:24710820, ECO:0000269|PubMed:25457084, ECO:0000269|PubMed:25459969, ECO:0000269|PubMed:25772804, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:29625812, ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217, ECO:0000269|PubMed:30415926}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Defects in SCN2A are associated with genetic epilepsy with febrile seizures plus (GEFS+), a familial autosomal dominant epilepsy syndrome, a clinical subset of febrile seizures, characterized by frequent episodes after 6 years of age and various types of subsequent epilepsy. {ECO:0000269|PubMed:29635106}.; DISEASE: Defects in SCN2A are associated with autism spectrum disorders (ASD). It seems that mutations resulting in sodium channel gain of function and increased neuron excitability lead to infantile seizures, whereas variants resulting in sodium channel loss of function and decrease neuron excitability are associated with ASD. {ECO:0000269|PubMed:28256214}.; DISEASE: Episodic ataxia 9 (EA9) [MIM:618924]: An autosomal dominant neurologic disorder characterized by episodic ataxia manifesting in the first years of life, early-onset seizures, difficulty walking, dizziness, slurred speech, headache, vomiting, and pain. The duration of ataxic episodes is heterogeneous. Most patients show episodes lasting minutes to maximum several hours, but periods lasting days up to weeks have been reported. Some patients have mildly delayed development with speech delay and/or autistic features or mildly impaired intellectual development. {ECO:0000269|PubMed:26645390, ECO:0000269|PubMed:27159988, ECO:0000269|PubMed:27328862, ECO:0000269|PubMed:28065826}. The disease is caused by variants affecting the gene represented in this entry.

DB01692; DB04485; DB02452; DB00432; DB00495

P05067; A0A087WZT3; Q92993; Q1RN33; P04183

EC 2.7.1.21

3D-structure; Acetylation; ATP-binding; Cytoplasm; DNA synthesis; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Transferase; Ubl conjugation; Zinc

A

19373.5

174

0.09

36.21

8.63

3.88

-5.46

GAPDH

Homo sapiens (Human)

Peptidyl-cysteine S-nitrosylase GAPDH; OK/SW-cl.12; GAPD; D-glyceraldehyde-3-phosphate dehydrogenase; CDABP0047

Glyceraldehyde-3-phosphate dehydrogenase family

Aldehyde/oxo donor oxidoreductase

Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules. Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively.

Bone marrow failure and diabetes mellitus syndrome (BMFDMS) [MIM:620044]: A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFDMS is an autosomal recessive form characterized by various degrees of bone marrow failure, ranging from dyserythropoiesis to bone marrow aplasia, with onset in infancy or early childhood, and non-autoimmune insulin-dependent diabetes mellitus appearing in the first or second decades. Many patients show pigmentary skin abnormalities and short stature. {ECO:0000269|PubMed:28073829, ECO:0000269|PubMed:35611808, ECO:0000269|PubMed:35931051}. The disease is caused by variants affecting the gene represented in this entry.

DB07347; DB02059; DB11638; DB09130; DB00157; DB03893; DB09092

Q6UY14-3; Q9UIJ7; P05067; Q9UQM7; Q14194; P35222; Q9BPW9-4; P00533; O00471; O75344; P06241; P04406; O14556; Q8NEA9; P42858; Q92993-2; P42695; P35228; P12004; P00558; P48147; P17612; Q8WUY3; Q9UHX1-2; P15927; P05109; Q96GZ6; P00441; Q9BSI4; P10599

EC 1.2.1.12

3D-structure; Acetylation; ADP-ribosylation; Alternative splicing; Apoptosis; Cytoplasm; Cytoskeleton; Direct protein sequencing; Glycolysis; Glycoprotein; Immunity; Innate immunity; Isopeptide bond; Membrane; Methylation; NAD; Nucleus; Oxidation; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; S-nitrosylation; Transferase; Translation regulation; Ubl conjugation

A

35818.4

333

0.08

13.69

8.64

3.64

-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

FURIN

Homo sapiens (Human)

Paired basic amino acid residuecleaving enzyme; Paired basic amino acid residue-cleaving enzyme; PCSK3; PACE; FUR; Dibasicprocessing enzyme

Peptidase S8 family, Furin subfamily

Peptidase

Mediates processing of TGFB1, an essential step in TGF-beta-1 activation. Ubiquitous endoprotease within constitutive secretory pathways capable of cleavage at the RX(K/R)R consensus motif.

Brachydactyly A2 (BDA2) [MIM:112600]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type A2 shortening of the middle phalanges is confined to the index finger and the second toe, all other digits being more or less normal. Because of a rhomboid or triangular shape of the affected middle phalanx, the end of the second finger usually deviates radially. {ECO:0000269|PubMed:19327734, ECO:0000269|PubMed:21357617}. The gene represented in this entry is involved in disease pathogenesis. Duplications of a cis-regulatory element located approximately 110 kb downstream of BMP2 have been found in BDA2 families. They likely cause altered BMP2 expression with pathological consequences. {ECO:0000269|PubMed:19327734, ECO:0000269|PubMed:21357617}.; DISEASE: Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 (SSFSC1) [MIM:617877]: An autosomal dominant disorder characterized by short stature, facial dysmorphism, skeletal anomalies, and variable cardiac defects. Distinctive facial features include midface retrusion, short upturned nose, long philtrum, high-arched or cleft palate, and variable degrees of micrognathia and dental crowding. Skeletal anomalies include patterning defects of the axial skeleton, characterized by 11 pairs of ribs and brachydactyly of the fifth ray. Congenital heart defects are variably observed and appear to involve primarily the cardiac outflow tract. {ECO:0000269|PubMed:29198724}. The disease is caused by variants affecting the gene represented in this entry.

DB03600

P05067; P50281; Q9H239; O14793; K9N5Q8; P0DTC2; Q91QT1

EC 3.4.21.75

3D-structure; Autocatalytic cleavage; Calcium; Cell membrane; Cleavage on pair of basic residues; Disulfide bond; Endosome; Glycoprotein; Golgi apparatus; Heparin-binding; Host-virus interaction; Hydrolase; Membrane; Metal-binding; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Serine protease; Signal; Transmembrane; Transmembrane helix; Zymogen

A

51029.8

470

0.08

26.23

5.23

-16.94

-5.46

TKT

Homo sapiens (Human)

TKT1; SDDHD; HEL107; HEL-S-48

Transketolase family

Transketolase

Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.

Short stature, developmental delay, and congenital heart defects (SDDHD) [MIM:617044]: An autosomal recessive syndrome characterized by short stature, developmental delay, intellectual disability and congenital heart defects including ventricular septal defect, atrial septal defect and patent foramen ovale. Cataract and uveitis are observed in some patients. {ECO:0000269|PubMed:27259054}. The disease is caused by variants affecting the gene represented in this entry.

DB09130

P54274

EC 2.2.1.1

3D-structure; Acetylation; Alternative splicing; Calcium; Direct protein sequencing; Disease variant; Dwarfism; Isopeptide bond; Magnesium; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome; Thiamine pyrophosphate; Transferase; Ubl conjugation

A

67546.4

620

0.07

35.53

7.37

1.28

-5.45

LANCL1

Homo sapiens (Human)

p40; LanC-like protein 1; GPR69A; 40 kDa erythrocyte membrane protein

LanC-like protein family

NA

Functions as glutathione transferase. Catalyzes conjugation of the glutathione (GSH) to artificial substrates 1-chloro-2,4-dinitrobenzene (CDNB) and p-nitrophenyl acetate. Mitigates neuronal oxidative stress during normal postnatal development and in response to oxidative stresses probably through GSH antioxidant defense mechanism (By similarity). May play a role in EPS8 signaling. Binds glutathione.

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

NA

Q9UHR4; P42858; Q08509

EC 2.5.1.18

3D-structure; Acetylation; Cell membrane; Cytoplasm; Direct protein sequencing; Membrane; Metal-binding; Proteomics identification; Reference proteome; Transferase; Zinc

A

46005.4

405

0.14

33.7

7.13

0.4

-5.46

nadE

Bacillus subtilis (strain 168)

NA

outB;BSU03130

NAD synthetase family

Ligase

ATP binding.Metal ion binding.NAD+ synthase (glutamine-hydrolyzing) activity.NAD+ synthase activity.

Leukodystrophy, hypomyelinating, 15 (HLD15) [MIM:617951]: An autosomal recessive disorder characterized by hypomyelinating leukodystrophy with thinning of the corpus callosum. Clinical features include motor and cognitive impairment appearing in the first or second decade of life, dystonia, ataxia, spasticity, and dysphagia. Most patients develop severe optic atrophy, and some have hearing loss. {ECO:0000269|PubMed:29576217}. The disease may be caused by variants affecting the gene represented in this entry.

DB02596; DB04099; DB00798

NA

6.3.1.5

3D-structure; ATP-binding; Direct protein sequencing; Ligase; Magnesium; Metal-binding; NAD; Nucleotide-binding; Phosphoprotein; Reference proteome; Sporulation; Stress response

A,B

60509.3

542

0.08

31.96

5.07

-19.73

-5.44

MME

Homo sapiens (Human)

NA

EPN

Peptidase M13 family

Hydrolase

Endopeptidase activity.Exopeptidase activity.Metalloendopeptidase activity.Metallopeptidase activity.Peptide binding.Zinc ion binding.

Charcot-Marie-Tooth disease, axonal, 2T (CMT2T) [MIM:617017]: An 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:26991897, ECO:0000269|PubMed:27588448}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spinocerebellar ataxia 43 (SCA43) [MIM:617018]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA43 is a slowly progressive, autosomal dominant form. {ECO:0000269|PubMed:27583304}. The disease is caused by variants affecting the gene represented in this entry.

DB08575; DB02597; DB00616; DB11623; DB05796; DB06655; DB02558; DB02062; DB00886; DB02557; DB09292; DB13928; DB08626

P05067; P21926; Q06787-7; P08107; P04792

3.4.24.11

3D-structure; Cell membrane; Charcot-Marie-Tooth disease; Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Lipoprotein; Membrane; Metal-binding; Metalloprotease; Myristate; Neurodegeneration; Neuropathy; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Signal-anchor; Spinocerebellar ataxia; Transmembrane; Transmembrane helix; Zinc

A

79435.8

696

0.11

37.5

5.53

-11.46

-5.44

putA

Escherichia coli (strain K12)

NA

b1014;poaA;JW0999

Proline dehydrogenase family; Aldehyde dehydrogenase family

Oxidoreductase

1-pyrroline-5-carboxylate dehydrogenase activity.Bacterial-type RNA polymerase core promoter proximal region sequence-specific DNA binding.DNA binding.Flavin adenine dinucleotide binding.Identical protein binding.Proline dehydrogenase activity.Sequence-specific DNA binding.Transcriptional repressor activity, bacterial-type RNA polymerase core promoter proximal region sequence-specific binding.

Fructose-1,6-bisphosphatase deficiency (FBP1D) [MIM:229700]: An autosomal recessive metabolic disorder characterized by impaired gluconeogenesis, and episodes of hypoglycemia and metabolic acidosis that can be lethal in newborn infants or young children. {ECO:0000269|PubMed:12126934, ECO:0000269|PubMed:25601412, ECO:0000269|PubMed:9382095}. The disease is caused by variants affecting the gene represented in this entry.

DB03051; DB03147; DB04398

P09546

1.2.1.88; 1.5.5.2

3D-structure; DNA-binding; FAD; Flavoprotein; Multifunctional enzyme; NAD; Oxidoreductase; Proline metabolism; Reference proteome; Repressor; Transcription; Transcription regulation

A

45567.7

407

0.08

33.2

7.22

0.47

-5.44

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

-5.44

ribC

Escherichia coli (strain K12)

NA

JW1654;ribE;b1662

NA

Transferase

Riboflavin synthase 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.

DB00140

NA

2.5.1.9

3D-structure; Reference proteome; Repeat; Riboflavin biosynthesis; Transferase

A,B

19023.5

174

0.05

2.85

5.13

-9.8

-5.44