F10

Homo sapiens (Human)

Fxa; Factor Xa; F10; Activated coagulation factor X

Peptidase S1 family

Peptidase

Factor Xa is avitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.

Factor X deficiency (FA10D) [MIM:227600]: A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis. {ECO:0000269|PubMed:10468877, ECO:0000269|PubMed:10739379, ECO:0000269|PubMed:10746568, ECO:0000269|PubMed:11248282, ECO:0000269|PubMed:11728527, ECO:0000269|PubMed:12574802, ECO:0000269|PubMed:12945883, ECO:0000269|PubMed:15075089, ECO:0000269|PubMed:15650540, ECO:0000269|PubMed:17393015, ECO:0000269|PubMed:19135706, ECO:0000269|PubMed:1973167, ECO:0000269|PubMed:1985698, ECO:0000269|PubMed:25313940, ECO:0000269|PubMed:26222694, ECO:0000269|PubMed:2790181, ECO:0000269|PubMed:7669671, ECO:0000269|PubMed:7860069, ECO:0000269|PubMed:8529633, ECO:0000269|PubMed:8845463, ECO:0000269|PubMed:8910490}. The disease is caused by variants affecting the gene represented in this entry.

DB07211; DB08746; DB07974; DB07277; DB07605; DB08487; DB08495; DB04673; DB08745; DB08488; DB07804; DB08174; DB08173; DB07872; DB07843; DB07848; DB07875; DB08143; DB07847; DB07844; DB13884; DB06552; DB13151; DB13192; DB00025; DB11166; DB06605; DB09258; DB12364; DB00100; DB13152; DB13150; DB00036; DB09075; DB16662; DB13923; DB01225; DB06920; DB00569; DB03847; DB07278; DB01109; DB06406; DB09332; DB06245; DB13998; DB05713; DB13999; DB07630; DB07629; DB07973; DB07800; DB12598; DB13933; DB06635; DB09141; DB13149; DB11311; DB06228; DB05362; DB07261; DB08426; DB09109; DB14738

P0DPK4; Q9UK55; Q9UHD9

EC 3.4.21.6

3D-structure; Blood coagulation; Calcium; Cleavage on pair of basic residues; Direct protein sequencing; Disease variant; Disulfide bond; EGF-like domain; Gamma-carboxyglutamic acid; Glycoprotein; Hemostasis; Hydrolase; Hydroxylation; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Serine protease; Signal; Zymogen

A

31315.2

280

0.09

38.33

6.36

-1.82

-10.68

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

-10.42

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

-8.58

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

-10.78

HPN

Homo sapiens (Human)

Transmembrane protease, serine 1; HPN; HEPSIN

Peptidase S1 family

Peptidase

Plays an essential role in cell growth and maintenance of cell morphology. May mediate the activating cleavage of HGF and MST1/HGFL. Plays a role in the proteolytic processing of ACE2.

Immunodeficiency, common variable, 5 (CVID5) [MIM:613495]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. {ECO:0000269|PubMed:20038800}. The disease is caused by variants affecting the gene represented in this entry.

DB03865; DB00522; DB03297; DB03643

Q12983; P11686; O00526

EC 3.4.21.106

3D-structure; Cell membrane; Disulfide bond; Glycoprotein; Hydrolase; Membrane; Protease; Proteomics identification; Reference proteome; Serine protease; Signal-anchor; Transmembrane; Transmembrane helix

B

26606.9

247

0.1

34.55

7.11

0.2

-9.38

F12

Homo sapiens (Human)

Hageman factor; HAF

Peptidase S1 family

Peptidase

NA

Factor XII deficiency (FA12D) [MIM:234000]: An asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. Factor XII deficiency is divided into two categories, a cross-reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection). {ECO:0000269|PubMed:10361128, ECO:0000269|PubMed:11776307, ECO:0000269|PubMed:15205584, ECO:0000269|PubMed:15617741, ECO:0000269|PubMed:2510163, ECO:0000269|PubMed:2882793, ECO:0000269|PubMed:8049433, ECO:0000269|PubMed:8528215, ECO:0000269|PubMed:9354665}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Angioedema, hereditary, 3 (HAE3) [MIM:610618]: A hereditary angioedema occurring only in women. Hereditary angioedema is an autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema type 3 differs from types 1 and 2 in that both concentration and function of C1 esterase inhibitor are normal. Hereditary angioedema type 3 is precipitated or worsened by high estrogen levels (e.g., during pregnancy or treatment with oral contraceptives). {ECO:0000269|PubMed:16638441, ECO:0000269|PubMed:17186468}. The disease is caused by variants affecting the gene represented in this entry.

DB09228; DB06689; DB06404; DB12598; DB01593; DB14487

P05067; Q07021; P13473-2

EC 3.4.21.38

3D-structure; Blood coagulation; Direct protein sequencing; Disease variant; Disulfide bond; EGF-like domain; Fibrinolysis; Glycoprotein; Hemostasis; Hydrolase; Kringle; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Serine protease; Signal; Zymogen

A

26038

241

0.08

50.34

5.25

-11.38

-8.57

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

-9.36

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

-9.86

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

-11.82

FASN

Homo sapiens (Human)

Yeast fatty acid synthase; Fatty-acyl-CoA synthase; Fatty acyl-CoA synthetase enzyme; FAS

NA

Acyltransferase

Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities as an acyl carrier protein.

Glycine encephalopathy 2 (GCE2) [MIM:620398]: A form of glycine encephalopathy, a metabolic disorder characterized by a high concentration of glycine in the body fluids. Affected individuals typically have severe neurological symptoms, including seizure, lethargy, and muscular hypotonia soon after birth. Most of them die within the neonatal period. Atypical cases have later disease onset and less severely affected psychomotor development. {ECO:0000269|PubMed:10873393, ECO:0000269|PubMed:11286506, ECO:0000269|PubMed:16051266, ECO:0000269|PubMed:26371980, ECO:0000269|PubMed:28244183, ECO:0000269|PubMed:8005589, ECO:0000269|PubMed:9600239, ECO:0000269|PubMed:9621520}. The disease is caused by variants affecting the gene represented in this entry.

DB01034; DB01083

Q15848; Q16665; P42858; Q8IV20; Q8TBB1; PRO_0000045603 [Q99IB8]

EC 2.3.1.85

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Fatty acid biosynthesis; Fatty acid metabolism; Hydrolase; Isopeptide bond; Lipid biosynthesis; Lipid metabolism; Lyase; Multifunctional enzyme; NAD; NADP; Oxidoreductase; Phosphopantetheine; Phosphoprotein; Proteomics identification; Pyridoxal phosphate; Reference proteome; S-nitrosylation; Transferase; Ubl conjugation

A

30174.9

275

0.09

43.28

5.92

-5.4

-12.19

folP

Bacillus anthracis

NA

GBAA_0071

DHPS family

NA

Catalyzes the condensation of para-aminobenzoate (pABA) with 6-hydroxymethyl-7,8-dihydropterin diphosphate (DHPt-PP) to form 7,8-dihydropteroate (H2Pte), the immediate precursor of folate derivatives. {ECO:0000256|RuleBase:RU361205}."

Pentosuria (PNTSU) [MIM:260800]: An inborn error of metabolism characterized by excessive urinary excretion of L-xylulose. {ECO:0000269|PubMed:11882650, ECO:0000269|PubMed:22042873, ECO:0000269|PubMed:4392213}. The disease is caused by variants affecting the gene represented in this entry.

DB04047; DB03705; DB03592; DB04196

NA

2.5.1.15

3D-structure; Folate biosynthesis; Magnesium; Metal-binding; Reference proteome; Transferase

A,B

59575.9

538

0.05

41.43

5.08

-24.21

-8.36

TEK

Homo sapiens (Human)

hTIE2; VMCM1; VMCM; Tyrosine-protein kinase receptor TIE-2; Tyrosine-protein kinase receptor TEK; Tyrosine kinase with Ig and EGF homology domains-2; Tunica interna endothelial cell kinase; TIE2; P140

Protein kinase superfamily, Tyr protein kinase family, Tie subfamily

Kinase

Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1. Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence.

Dominantly inherited venous malformations (VMCM) [MIM:600195]: An error of vascular morphogenesis characterized by dilated, serpiginous channels. {ECO:0000269|PubMed:10369874, ECO:0000269|PubMed:19079259, ECO:0000269|PubMed:19888299, ECO:0000269|PubMed:8980225}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Somatic mutations of TEK are associated with solitary and multiple sporadic venous malformations. {ECO:0000269|PubMed:19079259}.; DISEASE: May play a role in a range of diseases with a vascular component, including neovascularization of tumors, psoriasis and inflammation.; DISEASE: Glaucoma 3, primary congenital, E (GLC3E) [MIM:617272]: An autosomal dominant form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor. {ECO:0000269|PubMed:27270174}. The disease is caused by variants affecting the gene represented in this entry.

DB00415; DB12010; DB08221; DB08901; DB08896; DB14840; DB11800; DB05294

Q15389; O15123; O15123-1; Q16678; Q05209; P23467; P08575; Q12913; Q15262; Q16827

EC 2.7.10.1

3D-structure; Alternative splicing; Angiogenesis; ATP-binding; Cell junction; Cell membrane; Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease variant; Disulfide bond; EGF-like domain; Glaucoma; Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation

A

34965.9

310

0.11

43.57

8.39

3.42

-9.26

KAT2B

Homo sapiens (Human)

Spermidine acetyltransferase KAT2B; PCAF; P300/CBP-associated factor; P/CAF; Lysine acetyltransferase 2B; Histone acetyltransferase PCAF; Histone acetylase PCAF

Acetyltransferase family, GCN5 subfamily

Acyltransferase

Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles. Also acetylates non-histone proteins, such as ACLY, PLK4 and TBX5. Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers. Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5. Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4. Also acetylates spermidine. Functions as a histone acetyltransferase (HAT) to promote transcriptional activation.

Defects in KAT2B has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269|PubMed:28493397}.

DB08186; DB01992; DB08291

O60566; Q92793; Q96KQ7; Q09472; Q16665; Q9Y5W3; Q96EB6; Q8IXJ6; Q7Z699; Q16594; Q15672; P22415; P28033; P03129; P02299; P84040; P0DTC9; P59595; O88898-2; P03255; P03255-2

EC 2.3.1.48

3D-structure; Activator; Acyltransferase; Biological rhythms; Bromodomain; Cell cycle; Cytoplasm; Cytoskeleton; Disease variant; Host-virus interaction; Nucleus; Proteomics identification; Reference proteome; Transcription; Transcription regulation; Transferase

A

18743.8

162

0.12

25.09

9.44

9.34

-11.49

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

-11.3

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

-9.24

OPRD1

Homo sapiens (Human)

OPRD; Delta-type opioid receptor; Delta opioid receptor; DOR-1; D-OR-1

G-protein coupled receptor 1 family

GPCR rhodopsin

Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine. G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids.

Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer. {ECO:0000269|PubMed:10394368}.; DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:9753710}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Lipodystrophy, familial partial, 3 (FPLD3) [MIM:604367]: A form of lipodystrophy characterized by marked loss of subcutaneous fat from the extremities. Facial adipose tissue may be increased, decreased or normal. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia. {ECO:0000269|PubMed:11788685, ECO:0000269|PubMed:12453919}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Glioma 1 (GLM1) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:10851250}. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.

DB01571; DB01439; DB05050; DB06274; DB06288; DB00321; DB01238; DB00921; DB00611; DB09173; DB09061; DB01535; DB00318; DB00514; DB00647; DB01452; DB01565; DB01444; DB01081; DB01548; DB09272; DB01497; DB00813; DB00956; DB00327; DB01221; DB06738; DB00854; DB00836; DB14146; DB14009; DB12668; DB00333; DB00295; DB06409; DB14011; DB00844; DB11691; DB06230; DB01183; DB00704; DB11130; DB00497; DB01192; DB09209; DB00899; DB12543; DB00708; DB06204; DB00193

P16615; P27824; Q4LDR2; Q5JY77; Q9NS64; Q9Y666-2; Q9UKG4; Q0VAQ4; Q96Q45-2; P11607

NA

3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate; Proteomics identification; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix; Ubl conjugation

A

32859.3

294

0.11

33.86

9.38

13.6

-9.76

KLK4

Homo sapiens (Human)

Serine protease 17; Prostase; PSTS; PRSS17; Kallikreinlike protein 1; Kallikrein4; Kallikrein-like protein 1; KLKL1; KLK-L1; Enamel matrix serine proteinase 1; EMSP1

Peptidase S1 family, Kallikrein subfamily

Peptidase

Required during the maturation stage of tooth development for clearance of enamel proteins and normal structural patterning of the crystalline matrix. Has a major role in enamel formation.

Amelogenesis imperfecta, hypomaturation type, 2A1 (AI2A1) [MIM:204700]: A defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. {ECO:0000269|PubMed:15235027}. The disease is caused by variants affecting the gene represented in this entry.

NA

P20155; Q06418

EC 3.4.21.-

3D-structure; Alternative splicing; Amelogenesis imperfecta; Biomineralization; Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase; Metal-binding; Protease; Proteomics identification; Reference proteome; Secreted; Serine protease; Signal; Zinc; Zymogen

E,I

41763.9

387

0.07

32.75

5.38

-11.36

-10.27

LONP1

Homo sapiens (Human)

Serine protease 15; Mitochondrial ATP-dependent protease Lon; Lon protease-like protein; LONP1; LONP; LONHs

Peptidase S16 family

Peptidase

ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial promoters and RNA in a single- stranded, site-specific, and strand-specific manner. May regulate mitochondrial DNA replication and/or gene expression using site- specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters. Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein.

CODAS syndrome (CODASS) [MIM:600373]: A rare syndrome characterized by the combination of cerebral, ocular, dental, auricular, and skeletal features. These include developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts. {ECO:0000269|PubMed:25574826, ECO:0000269|PubMed:25808063}. The disease is caused by variants affecting the gene represented in this entry.

NA

P02666; P36776-1

EC 3.4.21.53

3D-structure; Alternative splicing; ATP-binding; Cataract; Deafness; Disease variant; DNA-binding; Dwarfism; Hydrolase; Mitochondrion; Nucleotide-binding; Protease; Proteomics identification; Reference proteome; Serine protease; Transit peptide

A,B

118797

1070

0.07

35.44

5.72

-18.18

-10.57

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

-12.66

PDE10A

Homo sapiens (Human)

cAMP and cAMPinhibited cGMP 3',5'cyclic phosphodiesterase 10A; cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A

Cyclic nucleotide phosphodiesterase family

Phosphoric diester hydrolase

Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition. Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides.

Dyskinesia, limb and orofacial, infantile-onset (IOLOD) [MIM:616921]: An autosomal recessive, early-onset hyperkinetic movement disorder characterized by axial hypotonia, dyskinesia of the limbs and trunk, orofacial dyskinesia, drooling, and dysarthria. The severity of the hyperkinesis is variable. {ECO:0000269|PubMed:27058446}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Striatal degeneration, autosomal dominant 2 (ADSD2) [MIM:616922]: An autosomal dominant disorder characterized by striatal degeneration and dysfunction of basal ganglia, resulting in hyperkinesis. {ECO:0000269|PubMed:27058447}. The disease is caused by variants affecting the gene represented in this entry.

DB08384; DB08386; DB08383; DB08389; DB00201; DB00975; DB08387; DB01113; DB08391; DB08811; DB09283; DB08814

NA

EC 3.1.4.17

3D-structure; Allosteric enzyme; Alternative initiation; Alternative splicing; cAMP; cAMP-binding; cGMP; cGMP-binding; Cytoplasm; Disease variant; Hydrolase; Metal-binding; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Repeat

A,B

37469.9

324

0.1

48.52

6.28

-4.08

-11.14