BUB1

Homo sapiens (Human)

hBUB1; Mitotic checkpoint serine/threonine-protein kinase BUB1; BUB1L; BUB1A

Protein kinase superfamily, Ser/Thr protein kinase family, BUB1 subfamily

Kinase

Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment.

Microcephaly 30, primary, autosomal recessive (MCPH30) [MIM:620183]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH30 is characterized by small head, poor overall growth, and global developmental delay with variably impaired intellectual development. Affected individuals may also have variable congenital anomalies, including atrial septal defect, dysmorphic facial features, tracheal stenosis, and anomalies of the skin and teeth. {ECO:0000269|PubMed:35044816}. The disease is caused by variants affecting the gene represented in this entry.

NA

O95376; O60566; O43684; P46108; Q8NG31; Q8NG31-2; Q9GZQ8; P03070

EC 2.7.11.1

3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell cycle; Cell division; Centromere; Chromosome; Chromosome partition; Host-virus interaction; Intellectual disability; Kinase; Kinetochore; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Primary microcephaly; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation

A

39564.8

343

0.12

31.17

8.49

4.7

-7.85

RBP4

Homo sapiens (Human)

Retinol-binding protein 4; RBP4; RBP; Plasma retinol-binding protein(1-176); PRBP

Calycin superfamily, Lipocalin family

Calycin family

Delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, this prevents its loss by filtration through the kidney glomeruli.

Retinal dystrophy, iris coloboma, and comedogenic acne syndrome (RDCCAS) [MIM:615147]: A disease characterized by retinal degeneration, ocular colobomas involving both the anterior and posterior segment, impaired night vision and loss of visual acuity. Additional characteristic features include developmental abnormalities and severe acne. {ECO:0000269|PubMed:10232633, ECO:0000269|PubMed:23189188, ECO:0000269|PubMed:9888420}. The disease is caused by variants affecting the gene represented in this entry. Loss of functional RBP4 protein results in serum retinol deficiency. Lack of normal levels of retinol impairs the visual cycle leading to night blindness at early stages; prolonged deficiency may lead to retinal degeneration. Additionally, retinol deficiency may result in dry skin, increased susceptibility to infection and acne (PubMed:23189188). {ECO:0000269|PubMed:23189188}.; DISEASE: Microphthalmia/Coloboma 10 (MCOPCB10) [MIM:616428]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). {ECO:0000269|PubMed:25910211}. The disease is caused by variants affecting the gene represented in this entry.

DB06985; DB06755; DB05076; DB03917; DB00755; DB00162

Q9UBX0; P02766; O55245

NA

3D-structure; Direct protein sequencing; Disease variant; Disulfide bond; Methylation; Microphthalmia; Proteomics identification; Reference proteome; Retinol-binding; Secreted; Sensory transduction; Signal; Transport; Vision; Vitamin A

A

20030.2

174

0.13

28.54

5.24

-4.02

-7.85

PNMT

Homo sapiens (Human)

PNMTase; PENT; Noradrenaline N-methyltransferase

Class I-like SAM-binding methyltransferase superfamily, NNMT/PNMT/TEMT family

NA

Converts noradrenaline to adrenaline.

A chromosomal aberration involving TRIM24/TIF1 is found in papillary thyroid carcinomas (PTCs). Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene. {ECO:0000269|PubMed:10439047}.

DB08129; DB08128; DB07739; DB07798; DB07747; DB03468; DB08550; DB03824; DB04273; DB07906; DB07597; DB09571; DB00968; DB08631; DB01752; DB08654

Q9P2G9-2; Q8TBB1

EC 2.1.1.28

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

A

29198.9

264

0.09

54.33

5.91

-3.69

-7.86

sch PNP

Schistosoma mansoni (Blood fluke)

sch Purine nucleoside phosphorylase; sch Inosine-guanosine phosphorylase

PNP/MTAP phosphorylase family

NA

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.

Hemolytic anemia, non-spherocytic, due to glucose phosphate isomerase deficiency (HA-GPID) [MIM:613470]: A form of anemia in which there is no abnormal hemoglobin or spherocytosis. It is caused by glucose phosphate isomerase deficiency. {ECO:0000269|PubMed:28803808, ECO:0000269|PubMed:7989588, ECO:0000269|PubMed:8499925, ECO:0000269|PubMed:8822952, ECO:0000269|PubMed:8822954, ECO:0000269|PubMed:9446754, ECO:0000269|PubMed:9856489}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 2.4.2.1

3D-structure; Glycosyltransferase; Transferase

A,B

61140.6

564

0.06

29.8

7.6

1.82

-7.86

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

-7.86

FSCN1

Homo sapiens (Human)

Singed-like protein; SNL; HSN; FAN1; 55 kDa actin-bundling protein; 55 kDa actin bundling protein

Fascin family

NA

Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers. Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration. Organizes filamentous actin into bundles with a minimum of 4. 1:1 actin/fascin ratio.

Familial adenomatous polyposis 2 (FAP2) [MIM:608456]: A condition characterized by the development of multiple colorectal adenomatous polyps, benign neoplasms derived from glandular epithelium. Some affected individuals may develop colorectal carcinoma. {ECO:0000269|PubMed:11818965, ECO:0000269|PubMed:12606733, ECO:0000269|PubMed:12853198, ECO:0000269|PubMed:15366000, ECO:0000269|PubMed:16134147, ECO:0000269|PubMed:16287072, ECO:0000269|PubMed:16557584, ECO:0000269|PubMed:16941501, ECO:0000269|PubMed:18091433, ECO:0000269|PubMed:18515411, ECO:0000269|PubMed:19953527, ECO:0000269|PubMed:20418187, ECO:0000269|PubMed:20848659, ECO:0000269|PubMed:25820570, ECO:0000269|PubMed:26694661}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gastric cancer (GASC) [MIM:613659]: A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. {ECO:0000269|PubMed:15273732, ECO:0000269|PubMed:25820570}. The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations contribute to the development of a sub-set of sporadic gastric cancers in carriers of Helicobacter pylori (PubMed:15273732). {ECO:0000269|PubMed:15273732}.

NA

Q9BXW9; P40692; Q9ULL4; P63104

NA

3D-structure; Acetylation; Actin-binding; Cell junction; Cell projection; Cytoplasm; Cytoskeleton; Direct protein sequencing; Isopeptide bond; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation

A

53682.4

484

0.1

34.21

7.24

0.65

-7.86

xylA

Arthrobacter sp. (strain NRRL B3728)

NA

NA

Xylose isomerase family

Isomerase(intramolecular oxidoreductase)

Metal ion binding.Xylose isomerase activity.

Bachmann-Bupp syndrome (BABS) [MIM:619075]: An autosomal dominant disorder characterized by global developmental delay, alopecia, absolute or relative macrocephaly, and facial dysmorphism. Neuroimaging shows white matter abnormalities, prominent Virchow-Robin spaces, periventricular cysts, and abnormalities of the corpus callosum. {ECO:0000269|PubMed:30239107, ECO:0000269|PubMed:30475435}. The disease is caused by variants affecting the gene represented in this entry. BABS is due to truncating variants that lead to a gain of function. This phenomenon apparently results from truncation proximal to or involving the C-terminal region of ODC1 protein, distal enough to allow escape from nonsense-mediated decay. A gain of function is corroborated by elevated plasma levels of N-acetylputrescine, with otherwise normal polyamine levels, in affected individuals. {ECO:0000269|PubMed:30475435}.

DB02172; DB03206; DB11195

NA

5.3.1.5

3D-structure; Carbohydrate metabolism; Cytoplasm; Direct protein sequencing; Isomerase; Magnesium; Metal-binding; Xylose metabolism

A,B

35700.7

325

0.11

20.63

5.19

-14.16

-7.85

ACHE

Homo sapiens (Human)

YT; N-ACHE; ARACHE

Type-B carboxylesterase/lipase family

Carboxylic ester hydrolase

Role in neuronal apoptosis. Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft.

Phosphoribosylaminoimidazole carboxylase deficiency (PAICSD) [MIM:619859]: An autosomal recessive inborn error of purine metabolism, clinically characterized by multiple congenital anomalies and early neonatal death. {ECO:0000269|PubMed:31600779}. The disease is caused by variants affecting the gene represented in this entry.

DB07846; DB02673; DB04617; DB04614; DB04615; DB07756; DB07701; DB02404; DB03814; DB08615; DB02343; DB02226; DB03005; DB04114; DB03128; DB01122; DB03283; DB00411; DB00122; DB14006; DB01245; DB00944; DB08357; DB08996; DB00449; DB00843; DB01010; DB01364; DB00898; DB00674; DB00483; DB06525; DB04864; DB03348; DB07555; DB00677; DB04924; DB03359; DB00358; DB00940; DB02825; DB02845; DB08167; DB04021; DB00805; DB01805; DB03740; DB04556; DB01400; DB04892; DB00981; DB00733; DB02166; DB00545; DB00863; DB00989; DB00382; DB04616; DB12816; DB01199; DB13503; DB04859

Q9Y215; P06733; P63244

EC 3.1.1.7

3D-structure; Alternative splicing; Blood group antigen; Cell membrane; Direct protein sequencing; Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; Membrane; Neurotransmitter degradation; Nucleus; Proteomics identification; Reference proteome; Secreted; Serine esterase; Signal; Synapse

A,B

58804.1

537

0.11

40.85

5.73

-8.18

-7.84

mmaA2

Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

NA

Rv0644c;mma2

CFA/CMAS family

Transferase

Cyclopropane-fatty-acyl-phospholipid synthase activity.Methyltransferase 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.

DB01718; DB01752

NA

2.1.1.79

3D-structure; Acetylation; Lipid biosynthesis; Lipid metabolism; Methyltransferase; Reference proteome; S-adenosyl-L-methionine; Transferase

A

32493.6

285

0.1

43.61

5.53

-10.17

-7.85

NR1H4

Homo sapiens (Human)

NA

HRR1;BAR;RIP14;FXR

Nuclear hormone receptor family, NR1 subfamily

Transcription

Bile acid binding.Bile acid receptor activity.Chenodeoxycholic acid binding.Ligand-dependent nuclear receptor binding.Retinoid X receptor binding.RNA polymerase II distal enhancer sequence-specific DNA binding.RNA polymerase II regulatory region sequence-specific DNA binding.RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding.Sequence-specific DNA binding.Steroid hormone receptor activity.Thyroid hormone receptor activity.Transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding.Transcriptional activator activity, RNA polymerase II transcription factor binding.Transcription coactivator activity.Transcription corepressor activity.Transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding.Transcription factor activity, sequence-specific DNA binding.Transcription regulatory region sequence-specific DNA binding.Zinc ion binding.

May be involved in intrahepatic cholestasis of pregnancy. {ECO:0000305|PubMed:17681172}.; DISEASE: May be involved in cholesterol cholelithiasis. {ECO:0000305|PubMed:17931734}.; DISEASE: Cholestasis, progressive familial intrahepatic, 5 (PFIC5) [MIM:617049]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC5 is an autosomal recessive, severe form characterized by onset of intralobular cholestasis in the neonatal period. {ECO:0000269|PubMed:26888176}. The disease is caused by variants affecting the gene represented in this entry.

DB08220; DB00132; DB04557; DB06777; DB02659; DB03619; DB02509; DB02545; DB11605; DB16255; DB05990; DB04348; DB16343; DB01586

Q15788; O75151; Q8WTS6; P28702; P28702-3; P48443; Q15788; P78527; P03372

NA

3D-structure; Acetylation; Activator; Alternative promoter usage; Alternative splicing; Disease variant; DNA-binding; Immunity; Inflammatory response; Innate immunity; Intrahepatic cholestasis; Isopeptide bond; Metal-binding; Methylation; Nucleus; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A

28271.2

241

0.08

47.06

5.39

-11.24

-7.84

JAK3

Homo sapiens (Human)

Tyrosine-protein kinase JAK3; Leukocyte janus kinase; L-JAK

Protein kinase superfamily, Tyr protein kinase family, JAK subfamily

Kinase

Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion. Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation.

Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:600802]: A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. {ECO:0000269|PubMed:10982185, ECO:0000269|PubMed:14615376, ECO:0000269|PubMed:7659163, ECO:0000269|PubMed:9354668, ECO:0000269|PubMed:9753072}. The disease is caused by variants affecting the gene represented in this entry.

DB04716; DB14973; DB11817; DB12010; DB11763; DB06321; DB14924; DB08877; DB08895; DB15035

Q07666; Q9UNF1; P55209

EC 2.7.10.2

3D-structure; Adaptive immunity; Alternative splicing; ATP-binding; Cytoplasm; Disease variant; Immunity; Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; SCID; SH2 domain; Transferase; Tyrosine-protein kinase

A

31742.2

279

0.1

57.69

6.99

-0.03

-7.85

NR1I2

Homo sapiens (Human)

Steroid and xenobiotic receptor; SXR; PXR; Orphan nuclear receptor PXR; Orphan nuclear receptor PAR1; Nuclear receptor subfamily 1 group I member 2

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes. Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds.

Atrial fibrillation, familial, 14 (ATFB14) [MIM:615378]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:19808477}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Genetic variations in SCN2B may be involved in Brugada syndrome (PubMed:23559163). This tachyarrhythmia is characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:23559163}.

DB04468; DB14001; DB01393; DB00564; DB06777; DB01068; DB00257; DB00531; DB14002; DB01234; DB14649; DB00255; DB01248; DB05928; DB01127; DB00530; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB00977; DB00754; DB01039; DB13873; DB00499; DB01645; DB07931; DB01892; DB01181; DB01026; DB00431; DB00532; DB00849; DB01110; DB00834; DB11605; DB01115; DB00239; DB01229; DB00312; DB04930; DB01174; DB04824; DB00252; DB12582; DB01708; DB02789; DB11087; DB04216; DB02709; DB01045; DB01220; DB08864; DB00503; DB00421; DB04466; DB01138; DB00675; DB07080; DB08604; DB13179; DB00163; DB00682

P08238; Q15788

NA

3D-structure; Activator; Alternative splicing; DNA-binding; Metal-binding; Nucleus; Proteomics identification; Receptor; Reference proteome; Transcription; Transcription regulation; Zinc; Zinc-finger

A,B

31908.8

275

0.11

46.37

6.78

-0.54

-7.83

CNR1

Homo sapiens (Human)

Cannabinoid CB1 receptor; CNR; CB-R; CANN6

G-protein coupled receptor 1 family

GPCR rhodopsin

Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP. In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission. In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner. In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone. Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes. In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism. In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism. In response to cannabinoid anandamide, elicits a proinflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion. In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells. G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC).

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:18177726}. The protein represented in this entry may be involved in disease pathogenesis. May contribute to the development of diet-induced obesity and several obesity-associated features, such as dyslipidemia and liver steatosis, regulating peripheral lipogenesis, energy expenditure and feeding behavior. CNR1 inverse agonists have been shown to reduce body weight and improve metabolic abnormalities in obese subjects, although adverse neuropsychiatric effects, including anxiety, irritability, and depressed mood, halted their therapeutic development (PubMed:18177726). In obese mice, peripherally restricted CNR1 inverse agonists have been shown to normalize metabolic abnormalities, including insulin resistance and fatty liver, and to reverse leptin resistance. {ECO:0000269|PubMed:18177726}.; DISEASE: Dysfunction of the endogenous cannabinoid system including CNR1 has been implicated in the pathogenesis of a number of central nervous system disorders, including Huntington disease, Parkinson disease, and Alzheimer disease (PubMed:32549916). In post-mortem brains from Huntington disease patients, a progressive CNR1 loss has been observed in the caudate nucleus, putamen, and substantia nigra pars reticulata, and altered expression and abnormal endocannabinoid levels precede motor symptoms in a disease mouse model (PubMed:10828533, PubMed:19524019, PubMed:8255419). In Parkinson disease, low CNR1 expression in mid-superior frontal gyrus and mid-cingulate cortex has been associated with poor mind, poor executive functioning and poor episode memory, while patients with more severe visuospatial dysfunction showed decreased receptor availability in the precuneus, mid-cingulate, supplementary motor cortex, inferior orbitofrontal gyrus and thalamus (PubMed:31342135). In an animal model for Alzheimer disease, CNR1 heterozygous deletion has been associated with decreased levels of postsynaptic density protein 95 (DLG4/PSD95) and accelerated memory impairment, suggesting synaptic dysfunction and a crucial role for CNR1 in the progression of disease symptoms (PubMed:10828533, PubMed:19524019, PubMed:30096288, PubMed:31342135, PubMed:8255419). {ECO:0000269|PubMed:10828533, ECO:0000269|PubMed:19524019, ECO:0000269|PubMed:30096288, ECO:0000269|PubMed:31342135, ECO:0000269|PubMed:32549916, ECO:0000269|PubMed:8255419}.

DB05750; DB09061; DB00470; DB14009; DB00486; DB14011; DB11745; DB09288; DB02955; DB06155; DB05077; DB11755; DB05201

P29274; P21554

NA

3D-structure; Alternative splicing; Cell membrane; Cell projection; G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Mitochondrion; Mitochondrion outer membrane; Neurodegeneration; Obesity; Palmitate; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Synapse; Transducer; Transmembrane; Transmembrane helix

A

32070.3

282

0.13

40.15

9.16

9.36

-7.83

OGFOD1

Homo sapiens (Human)

NA

TPA1;KIAA1612

TPA1 family

Oxidoreductase / oxidoreductase inhibitor

Iron ion binding.L-ascorbic acid binding.Peptidyl-proline 3-dioxygenase activity.Peptidyl-proline dioxygenase activity.

Long QT syndrome 10 (LQT10) [MIM:611819]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269|PubMed:17592081}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Atrial fibrillation, familial, 17 (ATFB17) [MIM:611819]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:23604097}. The disease is caused by variants affecting the gene represented in this entry.

DB00126

Q9BSK4; P62266

1.14.11.-

3D-structure; Alternative splicing; Cytoplasm; Dioxygenase; Iron; Metal-binding; Nucleus; Oxidoreductase; Proteomics identification; Reference proteome; Vitamin C

A,B,C,D

54223.9

461

0.13

56.42

5.23

-23.5

-7.83

PTPRZ1

Homo sapiens (Human)

Receptor protein tyrosine phosphatase zeta; R-PTP-zeta; PTPRZ1

Protein-tyrosine phosphatase family, Receptor class 5 subfamily

Phosphoric monoester hydrolase

Protein tyrosine phosphatase that negatively regulates oligodendrocyte precursor proliferation in the embryonic spinal cord. Required for normal differentiation of the precursor cells into mature, fully myelinating oligodendrocytes. May play a role in protecting oligondendrocytes against apoptosis. May play a role in the establishment of contextual memory, probably via the dephosphorylation of proteins that are part of important signaling cascades.

Optic atrophy 1 (OPA1) [MIM:165500]: A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA1 is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disk pallor, color vision deficits, and centrocecal scotoma of variable density. {ECO:0000269|PubMed:11017079, ECO:0000269|PubMed:11017080, ECO:0000269|PubMed:11440988, ECO:0000269|PubMed:11440989, ECO:0000269|PubMed:11810270, ECO:0000269|PubMed:12036970, ECO:0000269|PubMed:12566046, ECO:0000269|PubMed:14961560, ECO:0000269|PubMed:15948788, ECO:0000269|PubMed:16513463, ECO:0000269|PubMed:16617242, ECO:0000269|PubMed:18204809, ECO:0000269|PubMed:18360822, ECO:0000269|PubMed:19319978, ECO:0000269|PubMed:19325939, ECO:0000269|PubMed:19969356, ECO:0000269|PubMed:20185555, ECO:0000269|PubMed:22382025, ECO:0000269|PubMed:22857269, ECO:0000269|PubMed:23401657}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Dominant optic atrophy plus syndrome (DOA+) [MIM:125250]: A neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia. There appears to be a wide range of intermediate phenotypes. {ECO:0000269|PubMed:15531309, ECO:0000269|PubMed:16240368, ECO:0000269|PubMed:18065439, ECO:0000269|PubMed:18158317, ECO:0000269|PubMed:18195150, ECO:0000269|PubMed:20185555, ECO:0000269|PubMed:21112924, ECO:0000269|PubMed:23387428}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Behr syndrome (BEHRS) [MIM:210000]: An autosomal recessive syndrome characterized by optic atrophy beginning in early childhood associated with ataxia, pyramidal signs, spasticity, intellectual disability, and posterior column sensory loss. The ataxia, spasticity, and muscle contractures, mainly of the hip adductors, hamstrings, and soleus, are progressive and become more prominent in the second decade. {ECO:0000269|PubMed:21636302, ECO:0000269|PubMed:25012220, ECO:0000269|PubMed:25146916}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mitochondrial DNA depletion syndrome 14, cardioencephalomyopathic type (MTDPS14) [MIM:616896]: An autosomal recessive mitochondrial disorder characterized by lethal infantile encephalopathy, hypertrophic cardiomyopathy and optic atrophy. Skeletal muscle biopsies show significant mtDNA depletion and abnormal mitochondria. {ECO:0000269|PubMed:26561570}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9UM73; Q12860

EC 3.1.3.48

3D-structure; Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein; Hydrolase; Membrane; Phosphoprotein; Protein phosphatase; Proteoglycan; Proteomics identification; Reference proteome; Repeat; Secreted; Signal; Transmembrane; Transmembrane helix

A

32208.1

282

0.11

38.98

7.35

0.89

-7.82

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

-7.82

DYRK3

Homo sapiens (Human)

Regulatory erythroid kinase; REDK; Dual specificity tyrosine-phosphorylation-regulated kinase 3

Protein kinase superfamily, CMGC Ser/Thr protein kinase family, MNB/DYRK subfamily

Kinase

Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues. Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1. Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3. Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis. Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling. When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling. Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis. Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells. Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis. Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material.

Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.

NA

Q9H8Y8

EC 2.7.12.1

3D-structure; Alternative splicing; ATP-binding; Cell cycle; Cell division; Cytoplasm; Cytoskeleton; Kinase; Magnesium; Metal-binding; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase; Ubl conjugation

A

44821.5

395

0.1

49.38

9.52

21.08

-7.82

MKNK1

Homo sapiens (Human)

Mnk1; MAP kinase signal-integrating kinase 1

Protein kinase superfamily, CAMK Ser/Thr protein kinase family

Protein kinase superfamily. CAMK Ser/Thr protein kinase family

May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap.

Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.

DB12010

P54253; Q03060-25; P42858; P28482; Q16539; Q96CV9

EC 2.7.11.1

3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Translation regulation

A

27536.2

241

0.11

50.42

6.02

-3.43

-7.82

murA

Aquifex aeolicus (strain VF5)

NA

aq_1023

Histone deacetylase family

Lyase

UDP-N-acetylglucosamine 1-carboxyvinyltransferase activity.

Atrial fibrillation, familial, 14 (ATFB14) [MIM:615378]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:19808477}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Genetic variations in SCN2B may be involved in Brugada syndrome (PubMed:23559163). This tachyarrhythmia is characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:23559163}.

DB04297; DB02546

NA

NA

3D-structure; Acetoin catabolism; Metal-binding; Reference proteome; Zinc

A,B

42338.9

372

0.12

35.74

5.77

-6.5

-7.82

BRAF

Homo sapiens (Human)

V-Raf murine sarcoma viral oncogene homolog B1; RAFB1; Proto-oncogene B-Raf; P94; BRAF1; BRAF(V599E); BRAF serine/threonine kinase; B-raf protein; B-Raf

Protein kinase superfamily, TKL Ser/Thr protein kinase family, RAF subfamily

Kinase

May play a role in the postsynaptic responses of hippocampal neuron. Phosphorylates MAP2K1, and thereby contributes to the MAP kinase signal transduction pathway. Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.

Defects in BRAF are found in a wide range of cancers. {ECO:0000269|PubMed:18974108}.; DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:12198537, ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:23263490, ECO:0000269|PubMed:24455489}. The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. {ECO:0000269|PubMed:12460919}. The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Familial non-Hodgkin lymphoma (NHL) [MIM:605027]: Cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss. {ECO:0000269|PubMed:14612909}. The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Cardiofaciocutaneous syndrome 1 (CFC1) [MIM:115150]: A multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. {ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:16474404, ECO:0000269|PubMed:18042262, ECO:0000269|PubMed:19206169}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Noonan syndrome 7 (NS7) [MIM:613706]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. {ECO:0000269|PubMed:19206169}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: LEOPARD syndrome 3 (LPRD3) [MIM:613707]: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness. {ECO:0000269|PubMed:19206169}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: A chromosomal aberration involving BRAF is found in pilocytic astrocytomas. A tandem duplication of 2 Mb at 7q34 leads to the expression of a KIAA1549-BRAF fusion protein with a constitutive kinase activity and inducing cell transformation. {ECO:0000269|PubMed:18974108}.

DB08553; DB08912; DB11718; DB12010; DB07000; DB06999; DB05984; DB08896; DB14840; DB00398; DB08881; DB05190

P15056; P01112; P08238; P46940; Q02750; P36507; Q13233; P01111; Q02156; P04049; Q15349; P31947; Q13114; P31946; P62258; P63104; Q61097; P29678; Q99N57; Q8CGE9

EC 2.7.11.1

3D-structure; Acetylation; Allosteric enzyme; ATP-binding; Cardiomyopathy; Cell membrane; Chromosomal rearrangement; Cytoplasm; Deafness; Direct protein sequencing; Disease variant; Ectodermal dysplasia; Intellectual disability; Isopeptide bond; Kinase; Membrane; Metal-binding; Methylation; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Proto-oncogene; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation; Zinc; Zinc-finger

A,B

28819.9

252

0.08

46.62

9.15

6.46

-7.81