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

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

TF

Homo sapiens (Human)

Siderophilin; Serotransferrin; PRO1400; Beta-1 metal-binding globulin

Transferrin family

Transferrin

It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation. Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.

Atransferrinemia (ATRAF) [MIM:209300]: A rare autosomal recessive disorder characterized by abnormal synthesis of transferrin leading to iron overload and microcytic hypochromic anemia. {ECO:0000269|PubMed:11110675, ECO:0000269|PubMed:15466165}. The disease is caused by variants affecting the gene represented in this entry.

DB01370; DB14517; DB14518; DB01294; DB14526; DB14527; DB11136; DB14528; DB14529; DB14530; DB00515; DB09130; DB11397; DB13949; DB14490; DB14491; DB14488; DB14501; DB14489; DB13257; DB06215; DB06784; DB05260; DB01592; DB00893; DB00677; DB06757; DB11182; DB14520; DB01593; DB14487; DB14533; DB14548

O43315; O00501; Q7Z7G2; Q9GZR5; Q9Y282; Q96KR6; P01350; P08034; Q8NBJ4; O15529; Q8TED1; Q7Z5P4; A8MZ59; O15173; Q96TC7; Q3KNW5; Q9BXS9-3; Q99523; O43278-2; Q8N9I0; P02786; Q4KMG9; Q9K0U9; Q09057; Q9K0V0; P02786

NA

3D-structure; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Ion transport; Iron; Iron transport; Metal-binding; Methylation; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Secreted; Signal; Transport

A

35854.5

324

0.1

34.17

7.58

1.42

-5.44

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

-5.44

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

-5.45

penA

Streptococcus pneumoniae (strain ATCC BAA-255 / R6)

NA

spr1517;pbp2b

Transpeptidase family

Peptide binding protein

Penicillin 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.

DB01163; DB00415; DB08795; DB01140; DB00456; DB01066; DB00493; DB01331; DB01212; DB00567; DB03313; DB00485; DB00739; DB01603; DB00607; DB00713; DB00319

NA

NA

3D-structure; Antibiotic resistance; Cell membrane; Cell shape; Cell wall biogenesis/degradation; Membrane; Peptidoglycan synthesis; Reference proteome; Transmembrane; Transmembrane helix

A,B,C

65444.4

607

0.08

30.15

4.95

-20.68

-5.44

AMY2A

Homo sapiens (Human)

PA; 1,4-alpha-D-glucan glucanohydrolase

Glycosyl hydrolase 13 family

Glycosylase

Hydrolyses alpha bonds of large, alpha-linked polysaccharides, such as starch and glycogen, yielding glucose and maltose.

Congenital insensitivity to pain with anhidrosis (CIPA) [MIM:256800]: Characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and intellectual disability. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II. {ECO:0000269|PubMed:10090906, ECO:0000269|PubMed:10233776, ECO:0000269|PubMed:10330344, ECO:0000269|PubMed:10567924, ECO:0000269|PubMed:10861667, ECO:0000269|PubMed:10982191, ECO:0000269|PubMed:11159935, ECO:0000269|PubMed:11310631, ECO:0000269|PubMed:18077166, ECO:0000269|PubMed:22302274, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:28177573, ECO:0000269|PubMed:28328124, ECO:0000269|PubMed:8696348}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Chromosomal aberrations involving NTRK1 are found in papillary thyroid carcinomas (PTCs) (PubMed:1532241, PubMed:2869410, PubMed:7565764). Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1 (PubMed:7565764). A rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1 (PubMed:2869410). An intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the C-terminus of the NTRK1 protein (PubMed:1532241). {ECO:0000269|PubMed:1532241, ECO:0000269|PubMed:2869410, ECO:0000269|PubMed:7565764}.

DB03439; DB03495; DB04618; DB02889; DB04453; DB03092; DB00284; DB03971; DB03773; DB02379; DB00702; DB01922; DB00491; DB02218; DB03088

NA

EC 3.2.1.1

3D-structure; Alternative splicing; Calcium; Carbohydrate metabolism; Chloride; Disulfide bond; Glycoprotein; Glycosidase; Hydrolase; Metal-binding; Proteomics identification; Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal

A

55758.8

496

0.13

23.97

6.45

-2.34

-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

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

-5.44

MTHFD2

Homo sapiens (Human)

NA

NMDMC

Tetrahydrofolate dehydrogenase/cyclohydrolase family

Oxidoreductase

Magnesium ion binding.Methenyltetrahydrofolate cyclohydrolase activity.Methylenetetrahydrofolate dehydrogenase (NAD+) activity.Methylenetetrahydrofolate dehydrogenase (NADP+) activity.Phosphate ion binding.

Acute hepatic porphyria (AHEPP) [MIM:612740]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralyses and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. {ECO:0000269|PubMed:10706561, ECO:0000269|PubMed:1309003, ECO:0000269|PubMed:1569184, ECO:0000269|PubMed:17236137, ECO:0000269|PubMed:2063868}. The disease is caused by variants affecting the gene represented in this entry.

DB00157; DB00116

Q9UJ70-2

1.5.1.15; 3.5.4.9

3D-structure; Acetylation; Alternative splicing; Hydrolase; Isopeptide bond; Magnesium; Mitochondrion; Multifunctional enzyme; NAD; NADP; One-carbon metabolism; Oxidoreductase; Proteomics identification; Reference proteome; Transit peptide; Ubl conjugation

A

31600.3

292

0.03

27.9

8

1.64

-5.44

poxB

Escherichia coli (strain K12)

NA

b0871;JW0855

TPP enzyme family

Oxidoreductase

Flavin adenine dinucleotide binding.Identical protein binding.Lipid binding.Magnesium ion binding.Pyruvate dehydrogenase (quinone) activity.Thiamine pyrophosphate binding.

Glycogen storage disease 6 (GSD6) [MIM:232700]: A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected. {ECO:0000269|PubMed:9529348}. The disease is caused by variants affecting the gene represented in this entry.

NA

P07003

1.2.5.1

3D-structure; Cell inner membrane; Cell membrane; Direct protein sequencing; FAD; Flavoprotein; Lipid-binding; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Oxidoreductase; Pyruvate; Reference proteome; Thiamine pyrophosphate; Ubiquinone

A,B,C,D,E,F,G,H,I,J,K,L

113027

1046

0.07

35.99

5.75

-24.38

-5.44

SMPD1

Homo sapiens (Human)

NA

ASM

Acid sphingomyelinase family

Hydrolase

Acid sphingomyelin phosphodiesterase activity.Hydrolase activity, acting on glycosyl bonds.Sphingomyelin phosphodiesterase activity.Zinc ion binding.

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.

DB00381; DB12151; DB00477; DB01151; DB14009

P55210

3.1.4.12; 3.1.4.3

3D-structure; Alternative splicing; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Glycosidase; Host-virus interaction; Hydrolase; Lipid droplet; Lipid metabolism; Lysosome; Metal-binding; Neurodegeneration; Niemann-Pick disease; Phosphoprotein; Proteomics identification; Reference proteome; Secreted; Signal; Zinc

A

58913.8

528

0.11

46.93

6.48

-3.6

-5.45

RRM2

Homo sapiens (Human)

NA

RR2

Ribonucleoside diphosphate reductase small chain family

Oxidoreductase

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

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

DB00242; DB05260; DB05801; DB05003; DB05428

P41002; Q9UM11; P23921; O00560

1.17.4.1

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

A,B,C,D

33579.4

286

0.14

43.7

5.12

-12.86

-5.44

NOS1

Homo sapiens (Human)

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

NOS family

Paired donor oxygen oxidoreductase

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

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

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

Q08AM6

EC 1.14.13.39

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

A,B

34875.7

299

0.1

42.94

5.96

-6.25

-5.45

GATM

Homo sapiens (Human)

NA

AGAT

Amidinotransferase family

Transferase

Glycine amidinotransferase activity.

Cerebral creatine deficiency syndrome 3 (CCDS3) [MIM:612718]: An autosomal recessive disorder characterized by developmental delay/regression, intellectual disability, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain. Most patients develop a myopathy characterized by muscle weakness and atrophy later in life. {ECO:0000269|PubMed:11555793, ECO:0000269|PubMed:20682460, ECO:0000269|PubMed:22386973, ECO:0000269|PubMed:23660394, ECO:0000269|PubMed:23770102, ECO:0000269|PubMed:26490222, ECO:0000269|PubMed:27233232}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Fanconi renotubular syndrome 1 (FRTS1) [MIM:134600]: A form of Fanconi renotubular syndrome, a disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. FRTS1 inheritance is autosomal dominant. {ECO:0000269|PubMed:29654216}. The disease is caused by variants affecting the gene represented in this entry.

DB04454; DB02068; DB02530; DB00145; DB04185; DB00129

Q6UY14-3; Q14457; Q9Y6G5; Q9UI10; Q13322-4; Q13352; Q14693; Q96CM3; P11684; Q9P1W8; Q8NFB2; Q13829; Q6ZMY6-2

2.1.4.1

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Disease variant; Membrane; Mitochondrion; Mitochondrion inner membrane; Phosphoprotein; Proteomics identification; Reference proteome; Transferase; Transit peptide

A

41665.3

360

0.12

52.78

6.64

-1.3

-5.44

TPMT

Homo sapiens (Human)

NA

NA

Class I-like SAM-binding methyltransferase superfamily, TPMT family

Transferase

Thiopurine S-methyltransferase activity.

Cerebral creatine deficiency syndrome 3 (CCDS3) [MIM:612718]: An autosomal recessive disorder characterized by developmental delay/regression, intellectual disability, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain. Most patients develop a myopathy characterized by muscle weakness and atrophy later in life. {ECO:0000269|PubMed:11555793, ECO:0000269|PubMed:20682460, ECO:0000269|PubMed:22386973, ECO:0000269|PubMed:23660394, ECO:0000269|PubMed:23770102, ECO:0000269|PubMed:26490222, ECO:0000269|PubMed:27233232}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Fanconi renotubular syndrome 1 (FRTS1) [MIM:134600]: A form of Fanconi renotubular syndrome, a disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. FRTS1 inheritance is autosomal dominant. {ECO:0000269|PubMed:29654216}. The disease is caused by variants affecting the gene represented in this entry.

DB00993; DB00436; DB01327; DB01033; DB01250; DB01021

Q8TAP4-4; Q15047-2; P61981

2.1.1.67

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Methyltransferase; Phosphoprotein; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Transferase

A

25971.5

229

0.12

32.58

6.74

-0.6

-5.44

MAP2K1

Homo sapiens (Human)

NA

PRKMK1;MEK1

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

Transferase

ATP binding.MAP kinase kinase activity.Protein C-terminus binding.Protein kinase activity.Protein N-terminus binding.Protein serine/threonine/tyrosine kinase activity.Protein serine/threonine kinase activator activity.Protein serine/threonine kinase activity.Protein tyrosine kinase activity.Signal transducer, downstream of receptor, with protein tyrosine phosphatase activity.

Cardiofaciocutaneous syndrome 3 (CFC3) [MIM:615279]: 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. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures. {ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:18042262}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melorheostosis, isolated (MEL) [MIM:155950]: A sclerosing bone disorder characterized by hyperostosis of the cortex of tubular bones, frequently involving one limb. The lesions may be accompanied by abnormalities of adjacent soft tissue, joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangioma. {ECO:0000269|PubMed:29643386}. The disease is caused by variants affecting the gene represented in this entry.

DB06892; DB07046; DB08208; DB03115; DB11967; DB06616; DB05239; DB02152; DB07101; DB08130; DB14904; DB11689; DB08911

Q8N9N5; Q8N9N5-2; Q9NR09; P15056; Q9Y297; O15519-1; P28482; P27361; Q13526; Q9H8W4; P04049; Q8WWU5-7; Q86Y07; Q86Y07-1; P46937

2.7.12.2

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

A

34949.2

312

0.07

45.3

5.96

-4.47

-5.44

IAA7

Arabidopsis thaliana (Mouse-ear cress)

NA

AXR2;At3g23050;MXC7.8

Aux/IAA family

Signaling protein

DNA binding transcription factor activity.

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

NA

Q9LW29; Q9C5W9; Q8RYC8; Q94AH6; Q9ZR12; P49677; Q38828; Q38829; Q38830; Q38831; O24407; O24408; O24409; P49678; O24410; Q8LAL2; Q9XFM0; Q38822; Q9M1R4; Q9C5X0; Q9C8Y3; Q39255; Q570C0

NA

3D-structure; Alternative splicing; Auxin signaling pathway; Nucleus; Reference proteome; Repressor; Transcription; Transcription regulation

B,C

65385.2

581

0.09

47.83

7.46

1.23

-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

dps

Agrobacterium fabrum (strain C58 / ATCC 33970) (Agrobacterium tumefaciens (strain C58))

NA

Atu2477;AGR_C_4495

Dps family

Iron-binding protein

Ferric iron binding.Oxidoreductase activity, oxidizing metal ions.

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.

NA

NA

1.16.-.-

3D-structure; Cytoplasm; Iron; Iron storage; Metal-binding; Oxidoreductase; Reference proteome

A,B,C,D,E,F

106227

967

0.06

22.32

5.52

-34.69

-5.44