ECE1

Homo sapiens (Human)

ECE-1

Peptidase M13 family

Peptidase

Converts big endothelin-1 to endothelin-1.

Hirschsprung disease, cardiac defects, and autonomic dysfunction (HCAD) [MIM:613870]: A disorder characterized by skip-lesions Hirschsprung disease, craniofacial abnormalities and other dysmorphic features, cardiac defects including ductus arteriosus, small subaortic ventricular septal defect, small atrial septal defect, and autonomic dysfunction. {ECO:0000269|PubMed:9915973}. The disease is caused by variants affecting the gene represented in this entry.

DB07171

P49760; A8MQ03; Q8IUG1; P60370; P60410

EC 3.4.24.71

3D-structure; Alternative splicing; Cell membrane; Disease variant; Disulfide bond; Glycoprotein; Hirschsprung disease; Hydrolase; Membrane; Metal-binding; Metalloprotease; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix; Zinc

A

75247.9

660

0.12

46.29

5.33

-18.3

-8.35

CYP51A1

Homo sapiens (Human)

Cytochrome P450LI; Cytochrome P45014DM; Cytochrome P450-14DM; Cytochrome P450 51A1

Cytochrome P450 family

Cytochrome P450 family

Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.

Spondyloepimetaphyseal dysplasia, short limb-hand type (SEMD-SL) [MIM:271665]: A bone disease characterized by short-limbed dwarfism, a narrow chest with pectus excavatum, brachydactyly in the hands and feet, a characteristic craniofacial appearance and premature calcifications. The radiological findings are distinctive and comprise short long bones throughout the skeleton with striking epiphyses that are stippled, flattened and fragmented and flared, irregular metaphyses. Platyspondyly in the spine with wide intervertebral spaces is observed and some vertebral bodies are pear-shaped with central humps, anterior protrusions and posterior scalloping. {ECO:0000269|PubMed:19110212, ECO:0000269|PubMed:20223752, ECO:0000269|PubMed:26463668}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Warburg-Cinotti syndrome (WRCN) [MIM:618175]: An autosomal dominant disease characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acro-osteolysis. {ECO:0000269|PubMed:30449416}. The disease is caused by variants affecting the gene represented in this entry.

DB07705; DB05667; DB01110; DB01007

NA

EC 1.14.14.154

3D-structure; Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum; Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix

A,B,C,D

53013.3

462

0.11

47.66

8.8

7

-8.99

CYP1A2

Homo sapiens (Human)

NA

NA

Cytochrome P450 family

Oxidoreductase

Aromatase activity.Caffeine oxidase activity.Demethylase activity.Electron carrier activity.Enzyme binding.Heme binding.Iron ion binding.Monooxygenase activity.Oxidoreductase activity.Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen.Oxygen binding.

Myeloperoxidase deficiency (MPOD) [MIM:254600]: A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis. {ECO:0000269|PubMed:37198333, ECO:0000269|PubMed:7904599, ECO:0000269|PubMed:8142659, ECO:0000269|PubMed:8621627, ECO:0000269|PubMed:9354683, ECO:0000269|PubMed:9637725}. The disease is caused by variants affecting the gene represented in this entry.

DB08496; DB01667; DB14132; DB04356; DB02489; DB11932; DB12001; DB05812; DB13573; DB01418; DB00316; DB15568; DB06594; DB00518; DB05396; DB00969; DB07453; DB01424; DB01223; DB01118; DB00321; DB00261; DB01217; DB01435; DB06605; DB05676; DB06413; DB06216; DB01072; DB15011; DB06442; DB06626; DB00993; DB00972; DB13203; DB05015; DB16703; DB06769; DB01086; DB06770; DB06771; DB06732; DB00195; DB04889; DB11967; DB13975; DB00188; DB12151; DB01558; DB14018; DB13812; DB00201; DB09061; DB14737; DB11791; DB06774; DB00564; DB06016; DB01136; DB12814; DB00477; DB00356; DB01166; DB00501; DB01012; DB00568; DB00827; DB00537; DB00215; DB12499; DB14025; DB00349; DB01242; DB00575; DB00758; DB00363; DB00286; DB11672; DB14635; DB00924; DB08912; DB00851; DB06292; DB01254; DB01609; DB01151; DB16650; DB12161; DB01191; DB00633; DB11994; DB00586; DB11511; DB12945; DB00280; DB01184; DB09167; DB05928; DB01142; DB09273; DB00470; DB00476; DB00625; DB15444; DB06210; DB13874; DB11718; DB00467; DB11404; DB00530; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB00655; DB04574; DB13592; DB00330; DB00898; DB00977; DB00773; DB01628; DB00927; DB04854; DB01482; DB00574; DB12265; DB15669; DB01195; DB08972; DB04841; DB00544; DB00472; DB00499; DB00176; DB01320; DB00998; DB14029; DB06160; DB01044; DB01241; DB01155; DB01645; DB01381; DB00986; DB00365; DB00400; DB05708; DB00629; DB00502; DB01094; DB14999; DB04076; DB11737; DB00619; DB00458; DB11564; DB01306; DB09456; DB09564; DB01307; DB00047; DB01309; DB00030; DB00046; DB11567; DB00071; DB11568; DB05258; DB00034; DB00105; DB15131; DB00011; DB00018; DB00069; DB00060; DB00068; DB00033; DB00951; DB11757; DB09570; DB01026; DB01097; DB16217; DB09078; DB01002; DB05667; DB00281; DB12406; DB09198; DB04948; DB00978; DB06448; DB16220; DB01601; DB00455; DB04871; DB06077; DB01283; DB00772; DB00934; DB06234; DB14009; DB00784; DB01065; DB00170; DB00454; DB00532; DB00333; DB00763; DB00553; DB01028; DB09241; DB01233; DB00379; DB06148; DB01388; DB06595; DB00370; DB16236; DB00745; DB11763; DB00218; DB06510; DB14011; DB00461; DB00607; DB00779; DB00788; DB06600; DB00238; DB06803; DB00184; DB01115; DB11793; DB00435; DB05115; DB00717; DB01059; DB00540; DB05990; DB01165; DB00334; DB16267; DB00338; DB00904; DB11632; DB11443; DB01173; DB11837; DB09330; DB01303; DB11697; DB00377; DB00715; DB06589; DB11774; DB00487; DB00008; DB00022; DB09122; DB13634; DB00806; DB11198; DB08883; DB00850; DB03783; DB01174; DB00388; DB00252; DB11450; DB01100; DB13823; DB04951; DB17472; DB11642; DB08910; DB15822; DB01058; DB01087; DB00794; DB00420; DB09288; DB01182; DB06479; DB00818; DB00571; DB13449; DB11892; DB04216; DB00908; DB00468; DB01129; DB00980; DB09290; DB00863; DB01367; DB00409; DB02709; DB13174; DB01045; DB11753; DB00740; DB14924; DB00503; DB00533; DB01656; DB15119; DB00268; DB00296; DB00412; DB00817; DB12332; DB13772; DB06654; DB11491; DB00418; DB01037; DB11689; DB06290; DB13261; DB15093; DB00052; DB00398; DB01208; DB09118; DB00428; DB06820; DB00382; DB00675; DB06083; DB09071; DB05488; DB09256; DB01079; DB01405; DB00857; DB08880; DB11712; DB01412; DB00277; DB00730; DB01623; DB00208; DB06137; DB00697; DB01056; DB06264; DB00752; DB00384; DB12245; DB00831; DB15442; DB00440; DB00685; DB08867; DB14989; DB13609; DB06235; DB00313; DB08881; DB00661; DB09185; DB12026; DB00682; DB02134; DB00549; DB00744; DB00315; DB00425; DB09225; DB09120

O95870

1.14.14.1; 4.2.1.152

3D-structure; Direct protein sequencing; Endoplasmic reticulum; Fatty acid metabolism; Glycoprotein; Heme; Iron; Lipid metabolism; Lyase; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Steroid metabolism; Sterol metabolism

A

54475

480

0.1

40.43

9.16

9.89

-9.61

ECE1

Homo sapiens (Human)

ECE-1

Peptidase M13 family

Peptidase

Converts big endothelin-1 to endothelin-1.

Hirschsprung disease, cardiac defects, and autonomic dysfunction (HCAD) [MIM:613870]: A disorder characterized by skip-lesions Hirschsprung disease, craniofacial abnormalities and other dysmorphic features, cardiac defects including ductus arteriosus, small subaortic ventricular septal defect, small atrial septal defect, and autonomic dysfunction. {ECO:0000269|PubMed:9915973}. The disease is caused by variants affecting the gene represented in this entry.

DB07171

P49760; A8MQ03; Q8IUG1; P60370; P60410

EC 3.4.24.71

3D-structure; Alternative splicing; Cell membrane; Disease variant; Disulfide bond; Glycoprotein; Hirschsprung disease; Hydrolase; Membrane; Metal-binding; Metalloprotease; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix; Zinc

A

75247.9

660

0.12

46.29

5.33

-18.3

-8.41

TMPRSS15

Homo sapiens (Human)

Transmembrane protease serine 15; TMPRSS15; Serine protease 7; Enterokinase

Peptidase S1 family

Peptidase

Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A). It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases.

Enterokinase deficiency (ENTKD) [MIM:226200]: Life-threatening intestinal malabsorption disorder characterized by diarrhea and failure to thrive. {ECO:0000269|PubMed:11719902}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 3.4.21.9

3D-structure; Disulfide bond; Glycoprotein; Hydrolase; Lipoprotein; Membrane; Myristate; Protease; Proteomics identification; Reference proteome; Repeat; Serine protease; Signal-anchor; Transmembrane; Transmembrane helix; Zymogen

A

26220.3

234

0.1

50.13

4.82

-9.93

-7.54

HIV PR

Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1)

HIV Retropepsin; HIV PR

NA

Peptidase

Gag-Pol polyprotein: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation.

Sitosterolemia 2 (STSL2) [MIM:618666]: A form of sitosterolemia, an autosomal recessive metabolic disorder characterized by unregulated intestinal absorption of cholesterol, phytosterols and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. {ECO:0000269|PubMed:11138003, ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:11668628, ECO:0000269|PubMed:15054092, ECO:0000269|PubMed:35557526}. The disease is caused by variants affecting the gene represented in this entry.

DB07035; DB02704; DB07806; DB02785; DB01824; DB01732; DB06874; DB08034; DB07961; DB07451; DB08212; DB08372; DB02972; DB04190; DB04042; DB08428; DB03076; DB03141; DB08457; DB07343; DB07337; DB07018; DB07332; DB05398; DB07578; DB08639; DB06414; DB04255; DB04547; DB02683; DB02009; DB03908; DB02629; DB01887; DB03803; DB02033; DB08281; DB08282; DB08284; DB08414; DB08598; DB07327; DB07885; DB02768; DB08600; DB01891; DB05871

NA

EC 3.4.23.16

3D-structure; Activation of host caspases by virus; AIDS; Aspartyl protease; Capsid protein; Direct protein sequencing; DNA integration; DNA recombination; DNA-binding; DNA-directed DNA polymerase; Endonuclease; Eukaryotic host gene expression shutoff by virus; Eukaryotic host translation shutoff by virus; Host cell membrane; Host cytoplasm; Host endosome; Host gene expression shutoff by virus; Host membrane; Host nucleus; Host-virus interaction; Hydrolase; Lipid-binding; Lipoprotein; Magnesium; Membrane; Metal-binding; Methylation; Modulation of host cell apoptosis by virus; Multifunctional enzyme; Myristate; Nuclease; Nucleotidyltransferase; Phosphoprotein; Protease; Repeat; Ribosomal frameshifting; RNA-binding; RNA-directed DNA polymerase; Transferase; Viral genome integration; Viral nucleoprotein; Viral penetration into host nucleus; Viral release from host cell; Virion; Virion maturation; Virus entry into host cell; Zinc; Zinc-finger

A,B

21934.7

202

0.06

48.65

9.66

6.15

-7.85

KLK5

Homo sapiens (Human)

UNQ570/PRO1132; Stratum corneum tryptic enzyme; SCTE; Kallikrein-like protein 2; KLK-L2

Peptidase S1 family, Kallikrein subfamily

Peptidase

May be involved in desquamation.

Lipodystrophy, familial partial, 8 (FPLD8) [MIM:620679]: An autosomal dominant form of partial lipodystrophy, a disorder characterized by abnormal subcutaneous fat distribution. FPLD8 patients show selective loss of subcutaneous adipose tissue from the limbs, beginning around 13 to 15 years of age, and abnormal accumulation of subcutaneous adipose tissue in the dorsal neck and face, as well as in the posterior thoracic and abdominal regions. The disorder is associated with metabolic abnormalities, including diabetes mellitus and hyperlipidemia. {ECO:0000269|PubMed:27376152}. The disease may be caused by variants affecting the gene represented in this entry.

NA

P20930; Q9NQG1

EC 3.4.21.-

3D-structure; Disulfide bond; Glycoprotein; Hydrolase; Protease; Proteomics identification; Reference proteome; Secreted; Serine protease; Signal

A,B

50299.2

454

0.07

40.74

9.25

23.09

-9.61

GP6

Homo sapiens (Human)

Glycoprotein 6; GPVI

NA

NA

Collagen receptor involved in collagen-induced platelet adhesion and activation. Plays a key role in platelet procoagulant activity and subsequent thrombin and fibrin formation. This procoagulant function may contribute to arterial and venous thrombus formation. The signaling pathway involves the FcR gamma-chain, the Src kinases (likely FYN or LYN) and SYK, the adapter protein LAT and leads to the activation of PLCG2.

Bleeding disorder, platelet-type, 11 (BDPLT11) [MIM:614201]: A mild to moderate bleeding disorder caused by defective platelet activation and aggregation in response to collagen. {ECO:0000269|PubMed:19549989, ECO:0000269|PubMed:19552682}. The disease is caused by variants affecting the gene represented in this entry.

NA

P06241; P07948; P06241; P07948

NA

3D-structure; Alternative splicing; Blood coagulation; Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Hemostasis; Immunoglobulin domain; Membrane; Proteomics identification; Receptor; Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix

A

19027.4

173

0.11

37.14

8.68

2.52

-7.61

pol

Human immunodeficiency virus type 1 (HIV-1)

NA

NA

NA

Hydrolase / hydrolase inhibitor

Aspartic-type endopeptidase activity.

Oocyte/zygote/embryo maturation arrest 16 (OZEMA16) [MIM:617234]: A rare cause of female primary infertility. In affected women, ovulation and fertilization proceed normally but embryos are arrested at early stages of development. Inheritance is autosomal recessive. {ECO:0000269|PubMed:27545678}. The disease is caused by variants affecting the gene represented in this entry.

DB00701; DB01072; DB04887; DB01264; DB01319; DB00224; DB01601; DB00503; DB01232; DB00932

NA

NA

3D-structure; Aspartyl protease; Hydrolase; Protease

A,B

21411

198

0.05

42.78

9.45

4.15

-8.89

NQO1

Homo sapiens (Human)

Qui reductase 1; QR1; Phylloquinone reductase; Phylloqui reductase; NMOR1; NAD(P)H:quinone oxidoreductase 1; NAD(P)H dehydrogenase [quinone] 1; Menadione reductase; DTD; DT-diaphorase 1; DT-diaphorase

NAD(P)H dehydrogenase (quinone) family

NADH/NADPH oxidoreductase

The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.

Congenital disorder of glycosylation 2D (CDG2D) [MIM:607091]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:11901181, ECO:0000269|PubMed:30653653, ECO:0000269|PubMed:32157688}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Combined low LDL and fibrinogen (CLDLFIB) [MIM:620364]: An autosomal recessive condition characterized by low plasma LDL-cholesterol and fibrinogen levels, and associated with a decreased risk of coronary artery disease. {ECO:0000269|PubMed:34855475}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

DB07385; DB02395; DB03626; DB14001; DB04392; DB09061; DB00958; DB02633; DB00515; DB14002; DB00266; DB00997; DB01927; DB02400; DB03147; DB00170; DB00526; DB00252; DB04090; DB00163

P07902; Q9UK53; P15559

EC 1.6.5.2

3D-structure; Alternative splicing; Cytoplasm; FAD; Flavoprotein; Isopeptide bond; NAD; NADP; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation

A,B,C,D

61454.1

546

0.12

36.74

8.99

8.99

-9.45

ST14

Homo sapiens (Human)

Tumor-associated differentially-expressed gene 15 protein; Tumor associated differentially-expressed gene-15 protein; TADG15; Serine protease TADG-15; Serine protease 14; SNC19; Prostamin; PRSS14; Mem

Peptidase S1 family

Peptidase

Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. Involved in the terminal differentiation of keratinocytes through prostasin (PRSS8) activation and filaggrin (FLG) processing. Degrades extracellular matrix.

Ichthyosis, congenital, autosomal recessive 11 (ARCI11) [MIM:602400]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269|PubMed:17273967, ECO:0000269|PubMed:18843291}. The disease is caused by variants affecting the gene represented in this entry.

DB03127; DB13729; DB00013

NA

EC 3.4.21.109

3D-structure; Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Hypotrichosis; Ichthyosis; Membrane; Protease; Proteomics identification; Reference proteome; Repeat; Serine protease; Signal-anchor; Transmembrane; Transmembrane helix

A

26451.5

241

0.1

30.45

5.6

-5.69

-7.96

ABCB4

Homo sapiens (Human)

PGY3; MDR3; ATP-binding cassette sub-family B member 4; ABCB4

ABC transporter superfamily, ABCB family, Multidrug resistance exporter (TC 3.A.1.201) subfamily

Acid anhydrides hydrolase

Mediates ATP-dependent export of organic anions and drugs from the cytoplasm. Hydrolyzes ATP with low efficiency. Not capable of conferring drug resistance. Mediates the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte.

Cholestasis, progressive familial intrahepatic, 3 (PFIC3) [MIM:602347]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC3 inheritance is autosomal recessive. {ECO:0000269|PubMed:11313315, ECO:0000269|PubMed:12671900, ECO:0000269|PubMed:17726488, ECO:0000269|PubMed:21119540, ECO:0000269|PubMed:24045840, ECO:0000269|PubMed:24594635, ECO:0000269|PubMed:24806754, ECO:0000269|PubMed:28012258, ECO:0000269|PubMed:9419367}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cholestasis of pregnancy, intrahepatic 3 (ICP3) [MIM:614972]: A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimester of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. It causes fetal distress, spontaneous premature delivery and intrauterine death. Patients have spontaneous and progressive disappearance of cholestasis after delivery. Cholestasis results from abnormal biliary transport from the liver into the small intestine. {ECO:0000269|PubMed:10767346, ECO:0000269|PubMed:12746424, ECO:0000269|PubMed:15077010}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gallbladder disease 1 (GBD1) [MIM:600803]: One of the major digestive diseases. Gallstones composed of cholesterol (cholelithiasis) are the common manifestations in western countries. Most people with gallstones, however, remain asymptomatic through their lifetimes. {ECO:0000269|PubMed:11313316, ECO:0000269|PubMed:12891548, ECO:0000269|PubMed:22331132, ECO:0000269|PubMed:23533021, ECO:0000269|PubMed:24723470, ECO:0000269|PubMed:28012258, ECO:0000269|PubMed:28587926, ECO:0000269|Ref.2}. The disease is caused by variants affecting the gene represented in this entry.

DB06414; DB06207

NA

EC 7.6.2.1

3D-structure; Alternative splicing; ATP-binding; Cell membrane; Cytoplasm; Cytoplasmic vesicle; Disease variant; Glycoprotein; Intrahepatic cholestasis; Lipid transport; Membrane; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Translocase; Transmembrane; Transmembrane helix; Transport

A

123919

1128

0.1

29.44

8.78

11.08

-8.3

GAST

Homo sapiens (Human)

Gastrin6; GAST; G52; G34; G14

Gastrin/cholecystokinin family

Gastrin cholecystokinin

Gastrin stimulates the stomach mucosa to produce and secrete hydrochloric acid and the pancreas to secrete its digestive enzymes. It also stimulates smooth muscle contraction and increases blood circulation and water secretion in the stomach and intestine.

Orotic aciduria 1 (ORAC1) [MIM:258900]: A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and intellectual disability. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. {ECO:0000269|PubMed:9042911}. The disease is caused by variants affecting the gene represented in this entry.

DB12532

Q13520; O43315; Q12797-6; Q9BXK5; Q8N5K1; Q96BA8; P00387; Q9Y282; Q5JX71; Q8NBJ4; Q8TDT2; P43628; O76011; Q6ZUX7; Q15546; P15941-11; Q13113; P60201-2; Q14973; P02787; Q4KMG9

NA

3D-structure; Amidation; Cleavage on pair of basic residues; Direct protein sequencing; Hormone; Phosphoprotein; Proteomics identification; Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal; Sulfation

A,F

31827.9

280

0.08

41.06

8.84

5.56

-8.7

PNP

Homo sapiens (Human)

PNP; Inosine phosphorylase

PNP/MTAP phosphorylase family

Pentosyltransferase

The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta- (deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.

Purine nucleoside phosphorylase deficiency (PNPD) [MIM:613179]: A disorder that interrupts both the catabolism of inosine into hypoxanthine and guanosine into guanine, and leads to the accumulation of guanosine, inosine, and their deoxified by-products. The main clinical presentation is recurrent infections due to severe T-cell immunodeficiency. Some patients also have neurologic impairment. {ECO:0000269|PubMed:1384322, ECO:0000269|PubMed:3029074, ECO:0000269|PubMed:8931706}. The disease is caused by variants affecting the gene represented in this entry.

DB03881; DB03551; DB02222; DB02391; DB03609; DB01667; DB04260; DB02796; DB04753; DB00640; DB00242; DB00900; DB06185; DB02377; DB02857; DB04754; DB04757; DB04076; DB02230; DB04335; DB02568; DB03101

P05067; Q9UQM7; O14576-2; P06241; P14136; Q92993-2; Q9BXM7; P00491; P17612; P63000; Q92673; Q15583

EC 2.4.2.1

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Disease variant; Glycosyltransferase; Phosphoprotein; Proteomics identification; Purine salvage; Reference proteome; Transferase

A,B,C

31849.2

288

0.1

34.77

6.42

-1.63

-9.65

HMGCR

Homo sapiens (Human)

3-hydroxy-3-methylglutaryl-coenzyme A reductase

HMG-CoA reductase family

CH-OH donor oxidoreductase

Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.

Muscular dystrophy, limb-girdle, autosomal recessive 28 (LGMDR28) [MIM:620375]: An autosomal recessive form of limb girdle muscular dystrophy, a group of genetically heterogeneous muscular disorders that share proximal muscle weakness as the major attribute. Most limb girdle muscular dystrophies present with elevated creatinine kinase and myopathic electromyographic features. Disease is usually progressive to a variable degree, ranging from minor disability to complete inability to ambulate, and can involve the large proximal muscles, as well as axial and facial muscles. Different disease forms may exhibit skeletal muscle hypertrophy, kyphoscoliosis, and contractures or involve other muscle groups and manifest with distal weakness, cardiomyopathy, dysphagia, and respiratory difficulties. LGMDR28 is characterized by progressive muscle weakness affecting the proximal and axial muscles of the upper and lower limbs, and highly variable age at onset. Most patients have limited ambulation or become wheelchair-bound within a few decades, and respiratory insufficiency commonly occurs. {ECO:0000269|PubMed:36745799, ECO:0000269|PubMed:37167966}. The disease is caused by variants affecting the gene represented in this entry.

DB03169; DB04447; DB01076; DB09061; DB00439; DB01992; DB01095; DB00227; DB14009; DB04377; DB06693; DB14011; DB00157; DB03461; DB08860; DB00175; DB01098; DB00641; DB05317; DB09270

Q9Y5Z9; Q9Y5Z9-1

EC 1.1.1.34

3D-structure; Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism; Disease variant; Endoplasmic reticulum; Glycoprotein; Isopeptide bond; Limb-girdle muscular dystrophy; Lipid biosynthesis; Lipid metabolism; Membrane; NADP; Oxidoreductase; Peroxisome; Phosphoprotein; Proteomics identification; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix; Ubl conjugation

A,B,C,D

84796.9

798

0.05

47.61

6.2

-3.71

-8.06

SLC22A3

Homo sapiens (Human)

Solute carrier family 22 member 3; Extraneuronal monoamine transporter; EMTH

Major facilitator (TC 2.A.1) superfamily, Organic cation transporter (TC 2.A.1.19) family

NA

Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.

Deafness, autosomal dominant, 2A (DFNA2A) [MIM:600101]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:10025409, ECO:0000269|PubMed:10369879, ECO:0000269|PubMed:10571947, ECO:0000269|PubMed:10925378, ECO:0000269|PubMed:21242547}. The disease is caused by variants affecting the gene represented in this entry.

DB00718; DB08838; DB00182; DB00122; DB14006; DB00501; DB00575; DB00363; DB01151; DB00988; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB00983; DB00536; DB05381; DB00458; DB00762; DB00709; DB00448; DB08882; DB01042; DB01577; DB00331; DB08893; DB00184; DB00368; DB00526; DB00925; DB00413; DB00457; DB01035; DB00396; DB00938; DB00391; DB13943; DB13944; DB08837; DB08841; DB00541

P00519

NA

3D-structure; Cell membrane; Glycoprotein; Ion transport; Membrane; Mitochondrion; Nucleus; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix; Transport

A

53067.4

478

0.13

38.82

9.07

10.54

-9.37

CSF1R

Homo sapiens (Human)

Proto-oncogene c-Fms; M-CSF-R; FMS; CSF-1R; CSF-1-R; CSF-1 receptor; CD115

Protein kinase superfamily, Tyr protein kinase family, CSF-1/PDGF receptor subfamily

Kinase

Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor. Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes.

Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.; DISEASE: Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.; DISEASE: Leukoencephalopathy, hereditary diffuse, with spheroids 1 (HDLS1) [MIM:221820]: An autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes. {ECO:0000269|PubMed:22197934, ECO:0000269|PubMed:23408870, ECO:0000269|PubMed:24336230, ECO:0000269|PubMed:24532199}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS) [MIM:618476]: An autosomal recessive disease with variable manifestations. Main features are brain malformations with calcifying leukoencephalopathy, progressive neurodegeneration, and bone sclerotic features. The age at onset ranges from infancy to early adulthood. Neurologic features include loss of previous motor and language skills, cognitive impairment, spasticity, and focal seizures. Brain imaging shows periventricular white matter abnormalities and calcifications, large cisterna magna or Dandy-Walker malformation, and sometimes agenesis of the corpus callosum. {ECO:0000269|PubMed:30982608, ECO:0000269|PubMed:30982609}. The disease is caused by variants affecting the gene represented in this entry.

DB07167; DB07202; DB12147; DB12010; DB00619; DB06080; DB12978; DB01268

P09603; Q15375; P29323; Q6ZMJ4-1

EC 2.7.10.1

3D-structure; Alternative splicing; ATP-binding; Cell membrane; Disease variant; Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Inflammatory response; Innate immunity; Kinase; Membrane; Neurodegeneration; Nucleotide-binding; Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation

A

35082.9

311

0.11

44.6

8.13

2.42

-9.32

fkbI

Streptomyces hygroscopicus subsp. ascomyceticus

NA

NA

Acyl-CoA dehydrogenase family

Oxidoreductase

Flavin adenine dinucleotide binding.Oxidoreductase activity, acting on the CH-CH group of donors.

Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (THMD5) [MIM:614458]: An autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits. {ECO:0000269|PubMed:22152682}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

NA

NA

3D-structure; FAD; Flavoprotein; Nucleotide-binding; Oxidoreductase

A

36670.3

353

0.04

22.05

6.12

-5.04

-8.07

DBH

Homo sapiens (Human)

NA

NA

Copper type II ascorbate-dependent monooxygenase family

Oxidoreductase

Catalytic activity.Copper ion binding.Dopamine beta-monooxygenase activity.L-ascorbic acid binding.

Orthostatic hypotension 1 (ORTHYP1) [MIM:223360]: A form of orthostatic hypotension due to congenital dopamine beta-hydroxylase deficiency. Orthostatic hypotension, also known as postural hypotension, is a finding defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure occurring 3 minutes after a person has risen from supine to standing. Symptoms include dizziness, blurred vision, and sometimes syncope. ORTHYP1 is an autosomal recessive condition apparent from infancy or early childhood and characterized by low plasma and urinary levels of norepinephrine and epinephrine, and episodic hypoglycemia. {ECO:0000269|PubMed:11857564}. The disease is caused by variants affecting the gene represented in this entry.

DB00126; DB06774; DB09130; DB05394; DB00822; DB00988; DB00968; DB00550

P00352; P63010-2; Q04656; Q8WUW1; Q9UNS2; Q71DI3; P61978; Q9Y2M5; Q92876; P08727; Q14693; P0DPK4; Q6GQQ9-2; P27986-2; Q9ULX5; Q96D59; Q8N6K7-2; Q9GZS3; Q8IUW3; Q86WT6-2

1.14.17.1

3D-structure; Catecholamine biosynthesis; Copper; Cytoplasmic vesicle; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Secreted; Signal-anchor; Transmembrane; Transmembrane helix; Vitamin C

A,B

123694

1094

0.1

51.85

5.84

-24.5

-9.06

Cory pafA

Corynebacterium glutamicum (strain ATCC 13032 / DSM 20300 / JCM 1318 / BCRC 11384 / CCUG 27702 / LMG 3730 / NBRC 12168 / NCIMB 10025 / NRRL B-2784 / 534)

Pup-conjugating enzyme; Pup--protein ligase; Proteasome accessory factor A

Pup ligase/Pup deamidase family, Pup-conjugating enzyme subfamily

NA

Catalyzes the covalent attachment of the prokaryotic ubiquitin-like protein modifier Pup to the proteasomal substrate proteins, thereby targeting them for proteasomal degradation. This tagging system is termed pupylation. The ligation reaction involves the side-chain carboxylate of the C-terminal glutamate of Pup and the side-chain amino group of a substrate lysine.

Anemia, non-spherocytic hemolytic, due to G6PD deficiency (NSHA) [MIM:300908]: A disease characterized by G6PD deficiency, acute hemolytic anemia, fatigue, back pain, and jaundice. In most patients, the disease is triggered by an exogenous agent, such as some drugs, food, or infection. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. Although G6PD deficiency can be life-threatening, most patients are asymptomatic throughout their life. {ECO:0000269|PubMed:12524354, ECO:0000269|PubMed:1303180, ECO:0000269|PubMed:1303182, ECO:0000269|PubMed:1536798, ECO:0000269|PubMed:1611091, ECO:0000269|PubMed:1889820, ECO:0000269|PubMed:1945893, ECO:0000269|PubMed:20007901, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:2836867, ECO:0000269|PubMed:2912069, ECO:0000269|PubMed:30988594, ECO:0000269|PubMed:38066190, ECO:0000269|PubMed:7858267, ECO:0000269|PubMed:7959695, ECO:0000269|PubMed:8193373, ECO:0000269|PubMed:8490627, ECO:0000269|PubMed:8533762, ECO:0000269|PubMed:8733135, ECO:0000269|PubMed:9452072}. The disease is caused by variants affecting the gene represented in this entry. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of NSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.

NA

NA

NA

3D-structure; ATP-binding; Ligase; Magnesium; Metal-binding; Nucleotide-binding; Reference proteome; Ubl conjugation pathway

A,B

110572

994

0.07

42.33

5.26

-34.19

-9.06