Hae-influ nadR

Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)

nadR; Transcriptional regulator nadR

Bacterial NMN adenylyltransferase family; Bacterial RNK family

Nicotinamide ribonucleoside uptake permease

This enzyme has twoactivities: nicotinamide mononucleotide (NMN) adenylyltransferase and ribosylnicotinamide (RN) kinase. The RN kinase activity catalyzes the phosphorylation of RN to form nicotinamide ribonucleotide. The NMN adenylyltransferase activity catalyzes the transfer of the AMP moiety of ATP to nicotinamide ribonucleotide to form NAD(+).

Involved in the epigenetic regulation of ESR1 expression in breast cancer in a TFAP2C, IFI16 and HDAC4/5/6-dependent manner. {ECO:0000269|PubMed:24413532}.

NA

NA

NA

3D-structure; Alternative initiation; ATP-binding; Cell membrane; Cytoplasm; Kinase; Membrane; Multifunctional enzyme; NAD; Nucleotide-binding; Pyridine nucleotide biosynthesis; Reference proteome; Transferase

A

39581.5

344

0.14

41.39

6.94

-0.18

-5.47

GAD1

Homo sapiens (Human)

Glutamate decarboxylase 67 kDa isoform; Glutamate decarboxylase 1; GAD67; GAD-67; GAD; 67 kDa glutamic acid decarboxylase

Group II decarboxylase family

NA

Catalyzes the production of GABA.

Developmental and epileptic encephalopathy 89 (DEE89) [MIM:619124]: A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE89 is an autosomal recessive severe form characterized by profound global developmental delay with impaired intellectual development, absent speech, inability to sit or walk due to axial hypotonia and spastic quadriparesis, and onset of seizures in the first days or months of life. {ECO:0000269|PubMed:32282878}. The disease is caused by variants affecting the gene represented in this entry.

DB00142; DB00114

Q6RW13; Q6RW13-2; Q96DZ9; Q96DZ9-2; P46952; Q969L2; P16333; Q13188

EC 4.1.1.15

3D-structure; Alternative splicing; Decarboxylase; Disease variant; Epilepsy; Intellectual disability; Lyase; Neurotransmitter biosynthesis; Phosphoprotein; Proteomics identification; Pyridoxal phosphate; Reference proteome

A,B

112173

991

0.11

35.6

6.46

-6.01

-5.47

GALNS

Homo sapiens (Human)

N-acetylgalactosamine-6-sulfate sulfatase; N-acetylgalactosamine-6-sulfatase; Galactose-6-sulfate sulfatase; GalNAc6S sulfatase; GalN6S; Chondroitinsulfatase; Chondroitinase

Sulfatase family

Sulfuric ester hydrolase

Catalyzes the chemical reaction of cleaving off the 6-sulfate groups of the N-acetyl-D-galactosamine 6-sulfate units of the macromolecule chondroitin sulfate and, similarly, of the D-galactose 6-sulfate units of the macromolecule keratan sulfate.

Mucopolysaccharidosis 4A (MPS4A) [MIM:253000]: A form of mucopolysaccharidosis type 4, an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life. {ECO:0000269|PubMed:1522213, ECO:0000269|PubMed:16287098, ECO:0000269|PubMed:24726177, ECO:0000269|PubMed:7581409, ECO:0000269|PubMed:7633425, ECO:0000269|PubMed:7668283, ECO:0000269|PubMed:7795586, ECO:0000269|PubMed:8651279, ECO:0000269|PubMed:8826435, ECO:0000269|PubMed:9298823, ECO:0000269|PubMed:9375852, ECO:0000269|PubMed:9521421}. The disease is caused by variants affecting the gene represented in this entry.

DB09301

NA

EC 3.1.6.4

3D-structure; Calcium; Direct protein sequencing; Disease variant; Disulfide bond; Dwarfism; Glycoprotein; Hydrolase; Lysosome; Metal-binding; Mucopolysaccharidosis; Proteomics identification; Reference proteome; Signal

A

55013.8

493

0.11

35.46

6.14

-6.48

-5.47

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

-5.47

CSNK2A1

Homo sapiens (Human)

Protein kinase CK2; Casein kinase II subunit alpha; CK2A1; CK II alpha; CK II

Protein kinase superfamily, Ser/Thr protein kinase family, CK2 subfamily

Kinase

Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation. Plays an important role in the circadian clock function by phosphorylating ARNTL/BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry. Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue. Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine.

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

DB01765; DB03035; DB02170; DB08338; DB08354; DB08360; DB08353; DB07802; DB08345; DB03924; DB00171; DB03127; DB08473; DB04719; DB08846; DB07715; DB12010; DB08340; DB08362; DB04721; DB04395; DB04216; DB08660; DB02709; DB04720; DB04462

P78563; O00170; P05067; Q86V38; Q8N7W2-2; P35226; O00257-3; Q8IYX3; P68400; P19784; P67870; Q5HYN5; Q9GZR7; P35659; Q92997; P20042; O75822; Q8N9E0; A0A0C3SFZ9; Q9NW75-2; Q9NWQ4-1; O15499; Q13547; Q92769; P09017; P08238; A0A0C4DFT8; Q14145; Q5T7B8-2; O60282; Q92876; Q9UBR4-2; Q68G74; Q9NQ69; Q96GA3; Q9H063; P43364-2; P50221; Q6FHY5; Q9BU76; P19338; P23511; P23511-2; Q02548; P26367; Q5T6S3; P78356-2; P29590; Q9H307; P78424; O75400-2; Q14498; Q04864-2; Q6ZNA4; Q99496; P05386; P62269; P23396; Q01105; Q13435; Q96EB6; Q92504; O43623; P12931; Q08945; Q96MF2; Q9H7L9; O75683; Q96N21; Q9NVV9; Q9Y2W1; Q08117-2; Q8WV44; Q9H2G4; Q13360-2; Q8IYI8; Q96NG5; Q9BS34; Q6NSZ9-2

EC 2.7.11.1

3D-structure; Alternative splicing; Apoptosis; ATP-binding; Biological rhythms; Cell cycle; Disease variant; Intellectual disability; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase; Wnt signaling pathway

A

39870

334

0.12

40.91

7.28

0.88

-5.47

Trem1

Homo sapiens (Human)

Trem1; TREM-1

NA

NA

Stimulates neutrophil and monocyte-mediated inflammatory responses. Triggers release of pro-inflammatory chemokines and cytokines, as well as increased surface expression of cell activation markers. Amplifier of inflammatory responses that are triggered by bacterial and fungal infections and is a crucial mediator of septic shock.

GLUT1 deficiency syndrome 1 (GLUT1DS1) [MIM:606777]: A neurologic disorder showing wide phenotypic variability. The most severe 'classic' phenotype comprises infantile-onset epileptic encephalopathy associated with delayed development, acquired microcephaly, motor incoordination, and spasticity. Onset of seizures, usually characterized by apneic episodes, staring spells, and episodic eye movements, occurs within the first 4 months of life. Other paroxysmal findings include intermittent ataxia, confusion, lethargy, sleep disturbance, and headache. Varying degrees of cognitive impairment can occur, ranging from learning disabilities to severe intellectual disability. {ECO:0000269|PubMed:10227690, ECO:0000269|PubMed:10980529, ECO:0000269|PubMed:11136715, ECO:0000269|PubMed:11603379, ECO:0000269|PubMed:12325075, ECO:0000269|PubMed:15622525, ECO:0000269|PubMed:19901175, ECO:0000269|PubMed:20129935, ECO:0000269|PubMed:20221955, ECO:0000269|PubMed:20574033, ECO:0000269|PubMed:24847886, ECO:0000269|PubMed:25982116, ECO:0000269|PubMed:30197081}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: GLUT1 deficiency syndrome 2 (GLUT1DS2) [MIM:612126]: A clinically variable disorder characterized primarily by onset in childhood of paroxysmal exercise-induced dyskinesia. The dyskinesia involves transient abnormal involuntary movements, such as dystonia and choreoathetosis, induced by exercise or exertion, and affecting the exercised limbs. Some patients may also have epilepsy, most commonly childhood absence epilepsy. Mild intellectual disability may also occur. In some patients involuntary exertion-induced dystonic, choreoathetotic, and ballistic movements may be associated with macrocytic hemolytic anemia. {ECO:0000269|PubMed:14605501, ECO:0000269|PubMed:18451999, ECO:0000269|PubMed:19630075, ECO:0000269|PubMed:19798636, ECO:0000269|PubMed:20129935, ECO:0000269|PubMed:20574033, ECO:0000269|PubMed:20621801, ECO:0000269|PubMed:20830593, ECO:0000269|PubMed:21204808}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Epilepsy, idiopathic generalized 12 (EIG12) [MIM:614847]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. In some EIG12 patients seizures may remit with age. {ECO:0000269|PubMed:19798636, ECO:0000269|PubMed:22282645, ECO:0000269|PubMed:23280796, ECO:0000269|PubMed:25982116}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Dystonia 9 (DYT9) [MIM:601042]: An autosomal dominant neurologic disorder characterized by childhood onset of paroxysmal choreoathetosis and progressive spastic paraplegia. Most patients show some degree of cognitive impairment. Other variable features may include seizures, migraine headaches, and ataxia. {ECO:0000269|PubMed:21832227}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Stomatin-deficient cryohydrocytosis with neurologic defects (SDCHCN) [MIM:608885]: A rare form of stomatocytosis characterized by episodic hemolytic anemia, cold-induced red cells cation leak, erratic hyperkalemia, neonatal hyperbilirubinemia, hepatosplenomegaly, cataracts, seizures, intellectual disability, and movement disorder. {ECO:0000269|PubMed:21791420, ECO:0000269|PubMed:22492876}. The disease is caused by variants affecting the gene represented in this entry.

DB01694

NA

NA

3D-structure; Adaptive immunity; Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Innate immunity; Membrane; Proteomics identification; Receptor; Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix

A,B

28186.2

242

0.07

45.2

6.1

-3.8

-5.48

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

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

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

-5.45

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

frdA

Escherichia coli (strain K12)

NA

JW4115;b4154

FAD-dependent oxidoreductase 2 family, FRD/SDH subfamily

Oxidoreductase

Electron carrier activity.FAD binding.Fumarate reductase (menaquinone).Succinate dehydrogenase activity.

Glycogen storage disease 11 (GSD11) [MIM:612933]: A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue. {ECO:0000269|PubMed:2334430}. The disease is caused by variants affecting the gene represented in this entry.

DB07490; DB07918; DB00730

P0AC47; P0ACB4; P76111

1.3.5.1

3D-structure; Cell inner membrane; Cell membrane; Direct protein sequencing; Electron transport; FAD; Flavoprotein; Membrane; Nucleotide-binding; Oxidoreductase; Reference proteome; Transport

A,M

90370.7

820

0.08

28.88

5.86

-16.21

-5.45

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

-5.45

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

-5.45

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

LTA4H

Homo sapiens (Human)

Leukotriene A4 hydrolase; Leukotriene A(4)Leukotriene A-4 hydrolase hydrolase; Leukotriene A(4) hydrolase; LTA4; LTA-H; LTA-4hydrolase; LTA-4 hydrolase

Peptidase M1 family

Ether bond hydrolase

Has also aminopeptidase activity. Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4.

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.

DB07102; DB06917; DB07258; DB07094; DB07259; DB02352; DB07292; DB07104; DB06828; DB08466; DB01197; DB05177; DB03366; DB08040; DB06851; DB02062; DB07099; DB07260; DB07196; DB11781; DB03424; DB07237

Q9BSI4

EC 3.3.2.6

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing; Hydrolase; Leukotriene biosynthesis; Lipid metabolism; Metal-binding; Metalloprotease; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Zinc

A

68927

608

0.1

38.84

5.87

-9.86

-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

-5.45

REN

Homo sapiens (Human)

Renin; Angiotensinogenase

Peptidase A1 family

Peptidase

Renin is a highly specific endopeptidase, whose only knownfunction is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.

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: Tubulointerstitial kidney disease, autosomal dominant, 4 (ADTKD4) [MIM:613092]: A form of autosomal dominant tubulointerstitial kidney disease, a genetically heterogeneous disorder characterized by slowly progressive loss of kidney function, bland urinary sediment, hyperuricemia, absent or mildly increased albuminuria, lack of severe hypertension during the early stages, and normal or small kidneys on ultrasound. Renal histology shows variable abnormalities including interstitial fibrosis with tubular atrophy, microcystic dilatation of the tubules, thickening of tubular basement membranes, medullary cysts, and secondary glomerulosclerotic or glomerulocystic changes with abnormal glomerular tufting. There is significant variability, as well as incomplete penetrance. {ECO:0000269|PubMed:19664745}. The disease is caused by variants affecting the gene represented in this entry.

DB07113; DB04387; DB03968; DB03736; DB03024; DB02803; DB07244; DB07174; DB08099; DB06967; DB09026; DB03395; DB02296; DB00722; DB00350; DB01844; DB04379; DB06899; DB07059; DB00212; DB05203

P01019

EC 3.4.23.15

3D-structure; Alternative splicing; Aspartyl protease; Cleavage on pair of basic residues; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Membrane; Protease; Proteomics identification; Reference proteome; Secreted; Signal; Zymogen

A,B

36039.5

328

0.12

40.22

5.51

-6.69

-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

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

-5.46