PFF0160c

Plasmodium falciparum (isolate 3D7)

NA

NA

Dihydroorotate dehydrogenase family, Type 2 subfamily

Oxidoreductase

Dihydroorotate dehydrogenase activity.

Combined oxidative phosphorylation deficiency 33 (COXPD33) [MIM:617713]: An autosomal recessive disorder caused by multiple mitochondrial respiratory chain defects and impaired mitochondrial energy metabolism. Clinical manifestations are highly variable. Affected infants present with cardiomyopathy accompanied by multisystemic features involving liver, kidney, and brain. Death in infancy is observed in some patients. Children and adults present with myopathy and progressive external ophthalmoplegia. {ECO:0000269|PubMed:28942965}. The disease is caused by variants affecting the gene represented in this entry.

DB01117

NA

1.3.5.2

3D-structure; Flavoprotein; FMN; Membrane; Mitochondrion; Mitochondrion inner membrane; Oxidoreductase; Pyrimidine biosynthesis; Reference proteome; Transit peptide; Transmembrane; Transmembrane helix

A,B

42573.5

378

0.1

36.63

8.21

3.17

-6.21

STK38

Homo sapiens (Human)

Serine/threonine-protein kinase 38; Nuclear Dbf2-related kinase 1; NDR1

Protein kinase superfamily, AGC Ser/Thr protein kinase family

Kinase

Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2. Negative regulator of MAP3K1/2 signaling.

Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. {ECO:0000269|PubMed:8955068}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages. {ECO:0000269|PubMed:17332249}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Noonan syndrome 3 (NS3) [MIM:609942]: 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:16474405, ECO:0000269|PubMed:16773572, ECO:0000269|PubMed:17056636, ECO:0000269|PubMed:17468812, ECO:0000269|PubMed:19396835, ECO:0000269|PubMed:20949621}. 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:14534542, ECO:0000269|PubMed:3034404, ECO:0000269|PubMed:7773929}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. {ECO:0000269|PubMed:16247081}.; DISEASE: Cardiofaciocutaneous syndrome 2 (CFC2) [MIM:615278]: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. CFC2 patients often do not have the skin abnormalities, such as ichthyosis, hyperkeratosis, and hemangioma observed in CFC1. {ECO:0000269|PubMed:16474404, ECO:0000269|PubMed:16474405, ECO:0000269|PubMed:17056636, ECO:0000269|PubMed:20949621, ECO:0000269|PubMed:21797849}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: KRAS mutations are involved in cancer development. {ECO:0000269|PubMed:14534542, ECO:0000269|PubMed:1553789, ECO:0000269|PubMed:16533793, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:3034404, ECO:0000269|PubMed:3627975, ECO:0000269|PubMed:6092920, ECO:0000269|PubMed:6695174, ECO:0000269|PubMed:7773929}.; DISEASE: Oculoectodermal syndrome (OES) [MIM:600268]: A syndrome characterized by the association of epibulbar dermoids and aplasia cutis congenita. Affected individuals show multiple, asymmetric, atrophic, non-scarring and hairless regions that may be associated with hamartomas. Ectodermal changes include linear hyperpigmentation that may follow the lines of Blaschko and rarely epidermal nevus-like lesions. Epibulbar dermoids may be uni-or bilateral. Additional ocular anomalies such as skin tags of the upper eyelid, rarely optic nerve or retinal changes, and microphthalmia can be present. The phenotypic expression is highly variable, and various other abnormalities have occasionally been reported including growth failure, lymphedema, cardiovascular defects, as well as neurodevelopmental symptoms like developmental delay, epilepsy, learning difficulties, and behavioral abnormalities. Benign tumor-like lesions such as nonossifying fibromas of the long bones and giant cell granulomas of the jaws have repeatedly been observed and appear to be age-dependent, becoming a common manifestation in individuals aged 5 years or older. {ECO:0000269|PubMed:25808193, ECO:0000269|PubMed:26970110, ECO:0000269|PubMed:30891959}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:163200]: A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis. {ECO:0000269|PubMed:30891959}. The disease is caused by variants affecting the gene represented in this entry.

DB12010

P49407; P32121; Q8N9N5-2; Q03135; P08238; Q9H8S9; Q70IA6; P16333; P30086; P02638

EC 2.7.11.1

3D-structure; Acetylation; ATP-binding; Chromosome; Cytoplasm; Direct protein sequencing; DNA damage; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation

A

38701.1

333

0.11

38.05

5.69

-7.8

-6.21

PRKAR1A

Homo sapiens (Human)

cAMP-dependent protein kinase type I-alpha regulatory subunit; Tissue-specific extinguisher 1; TSE1; PRKAR1; PKR1

CAMP-dependent kinase regulatory chain family

Kinase

Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.

Carney complex 1 (CNC1) [MIM:160980]: CNC is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas. {ECO:0000269|PubMed:15371594, ECO:0000269|PubMed:18241045, ECO:0000269|PubMed:22785148, ECO:0000269|PubMed:23323113, ECO:0000269|PubMed:26405036}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Intracardiac myxoma (INTMYX) [MIM:255960]: Inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Primary pigmented nodular adrenocortical disease 1 (PPNAD1) [MIM:610489]: A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. PPNAD1 is most often diagnosed in patients with Carney complex, a multiple neoplasia syndrome. However it can also be observed in patients without other manifestations. {ECO:0000269|PubMed:12213893}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Acrodysostosis 1, with or without hormone resistance (ACRDYS1) [MIM:101800]: A form of skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and obesity. Laboratory studies show resistance to multiple hormones, including parathyroid, thyrotropin, calcitonin, growth hormone-releasing hormone, and gonadotropin. However, not all patients show endocrine abnormalities. {ECO:0000269|PubMed:21651393, ECO:0000269|PubMed:22464250, ECO:0000269|PubMed:22464252, ECO:0000269|PubMed:22723333, ECO:0000269|PubMed:23043190, ECO:0000269|PubMed:23425300, ECO:0000269|PubMed:26405036}. The disease is caused by variants affecting the gene represented in this entry.

DB01790; DB02527; DB02315; DB05798

Q9GZX7; P24588; O43687-2; Q9BSF0; Q9H6J7-2; Q86Y01; P0C7A2-2; Q9H0R8; Q9H8W4; P17612; P31321; P51817; P35250; Q86UC2; Q01105; Q8N0X7; O96006; P03259-2

NA

3D-structure; Acetylation; Alternative splicing; cAMP; cAMP-binding; Cell membrane; Cushing syndrome; Direct protein sequencing; Disease variant; Disulfide bond; Membrane; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Repeat

A

17007.4

149

0.08

49.36

6.36

-0.52

-6.21

NAPEPLD

Homo sapiens (Human)

NAPE-PLD; N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D; N-acyl phosphatidylethanolamine phospholipase D; C7orf18

NAPE-PLD family

NA

Hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce N-acylethanolamines (NAEs) and phosphatidic acid. Responsible for the generation of these bioactive fatty acid ethanolamides (FAEs), including anandamide (N-arachidonoylethanolamine), the ligand of cannabinoid and vanilloid receptors. As a regulator of lipid metabolism in the adipose tissue, mediates the crosstalk between adipocytes, gut microbiota and immune cells to control body temperature and weight. In particular, regulates energy homeostasis by promoting cold-induced brown or beige adipocyte differentiation program to generate heat from fatty acids and glucose (By similarity).

Glioma (GLM) [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:22286061, ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23539269}. The gene represented in this entry is involved in disease pathogenesis. H3F3A mutations affecting residues involved in post-translational modifications of histone H3.3 are recurrent in malignant, aggressive gliomas including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG) (PubMed:22286061, PubMed:22286216). The mechanism through which mutations lead to tumorigenesis involves altered histones methylation, impaired regulation of Polycomb repressive complex 2 (PRC2) activity, and aberrant epigenetic regulation of gene expression (PubMed:23539183, PubMed:23539269, PubMed:23603901). {ECO:0000269|PubMed:22286061, ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23539183, ECO:0000269|PubMed:23539269, ECO:0000269|PubMed:23603901}.; DISEASE: Bryant-Li-Bhoj neurodevelopmental syndrome 1 (BRYLIB1) [MIM:619720]: An autosomal dominant disorder predominantly characterized by global developmental delay, impaired intellectual development, poor or absent speech, and delayed motor milestones. Clinical manifestations are highly variable, including abnormal head shape, dysmorphic facial features, oculomotor abnormalities, feeding problems, and non-specific brain imaging abnormalities. Additional features may include hearing loss, seizures, short stature, and mild skeletal defects. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}. The disease is caused by variants affecting the gene represented in this entry. BRYLIB1 is caused by variants in H3-3A. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}.; DISEASE: Bryant-Li-Bhoj neurodevelopmental syndrome 2 (BRYLIB2) [MIM:619721]: An autosomal dominant disorder predominantly characterized by global developmental delay, impaired intellectual development, poor or absent speech, and delayed motor milestones. Clinical manifestations are highly variable, including abnormal head shape, dysmorphic facial features, oculomotor abnormalities, feeding problems, and non-specific brain imaging abnormalities. Additional features may include hearing loss, seizures, short stature, and mild skeletal defects. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}. The disease is caused by variants affecting the gene represented in this entry. BRYLIB2 is caused by variants in H3-3B. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}.; DISEASE: H3F3A and H3F3B mutations affecting residues involved in post-translational modifications of histone H3.3 are implicated in the pathogenesis of some bone and cartilage neoplasms. Mutations have been found with high prevalence in chondroblastoma and giant cell tumors of bone, and with low frequency in osteosarcoma, conventional chondrosarcoma and clear cell chondrosarcoma. Chondroblastoma samples frequently carry a H3F3B mutation affecting residue Lys-37 (H3K36), although H3F3A is mutated in some cases. Most giant cell tumors of bone harbor H3F3A mutations affecting residue Gly-35 (H3G34). {ECO:0000269|PubMed:24162739}.

DB14009

Q6IQ20

EC 3.1.4.54

3D-structure; Acetylation; Endosome; Golgi apparatus; Hydrolase; Lipid degradation; Lipid metabolism; Membrane; Metal-binding; Nucleus; Phospholipid degradation; Phospholipid metabolism; Proteomics identification; Reference proteome; Zinc

A,B

74256.5

643

0.13

48.34

5.65

-17.61

-6.22

PEBP1

Homo sapiens (Human)

Raf kinase inhibitor protein; RKIP; Prostatic-binding protein; PEBP-1; PEBP; PBP; Neuropolypeptide h3; Hippocampal cholinergic neurostimulating peptide; HCNPpp; HCNP

Phosphatidylethanolamine-binding protein family

Phosphatidylethanolamine-binding protein family

Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase. Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation.

Retinitis pigmentosa 49 (RP49) [MIM:613756]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:15570217, ECO:0000269|PubMed:7479749}. The disease is caused by variants affecting the gene represented in this entry.

DB09130; DB09568

P16050; Q9NRD5; P04049; Q15208; Q9NS68; Q9JLL3

NA

3D-structure; ATP-binding; Cytoplasm; Direct protein sequencing; Disulfide bond; Lipid-binding; Nucleotide-binding; Phosphoprotein; Protease inhibitor; Proteomics identification; Reference proteome; Serine protease inhibitor

A

20928.3

186

0.1

24.05

6.59

-0.98

-6.22

LANCL1

Homo sapiens (Human)

p40; LanC-like protein 1; GPR69A; 40 kDa erythrocyte membrane protein

LanC-like protein family

NA

Functions as glutathione transferase. Catalyzes conjugation of the glutathione (GSH) to artificial substrates 1-chloro-2,4-dinitrobenzene (CDNB) and p-nitrophenyl acetate. Mitigates neuronal oxidative stress during normal postnatal development and in response to oxidative stresses probably through GSH antioxidant defense mechanism (By similarity). May play a role in EPS8 signaling. Binds glutathione.

Spermatogenic failure 5 (SPGF5) [MIM:243060]: An infertility disorder caused by spermatogenesis defects. Semen from affected men show close to 100% morphologically abnormal multiflagellar spermatozoa with low motility, oversized irregular heads, and abnormal midpiece and acrosome. {ECO:0000269|PubMed:17435757, ECO:0000269|PubMed:21733974}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9UHR4; P42858; Q08509

EC 2.5.1.18

3D-structure; Acetylation; Cell membrane; Cytoplasm; Direct protein sequencing; Membrane; Metal-binding; Proteomics identification; Reference proteome; Transferase; Zinc

A

46005.4

405

0.14

33.7

7.13

0.4

-6.22

cpo

Kitasatospora aureofaciens (Streptomyces aureofaciens)

NA

cpoT

AB hydrolase superfamily, Bacterial non-heme haloperoxidase / perhydrolase family

Haloperoxidase

Chloride peroxidase activity.

Hypervalinemia and hyperleucine-isoleucinemia (HVLI) [MIM:618850]: An autosomal recessive metabolic disorder characterized by highly elevated plasma concentrations of valine and leucine/isoleucine. Affected individuals suffer from headache and mild memory impairment. {ECO:0000269|PubMed:25653144}. The disease is caused by variants affecting the gene represented in this entry. A patient with hypervalinemia and hyperleucine-isoleucinemia was identified as compound heterozygote for Gln-170 (inherited from his father) and Lys-264 (inherited from his mother), both variants reduced the catalytic activity of the enzyme. After treatment with vitamin B6, a precursor of pyridoxal 5'-phosphate, a BCAT2 cofactor, the blood levels of branched chain amino acids, especially valine, were decreased and brain lesions were improved. {ECO:0000269|PubMed:25653144}.

DB03793

NA

1.11.1.-

3D-structure; Chloride; Oxidoreductase; Peroxidase

A,B

60428.4

554

0.13

31.26

4.65

-32.72

-6.21

top6B

Saccharolobus shibatae (strain ATCC 51178 / DSM 5389 / JCM 8931 / NBRC 15437 / B12) (Sulfolobus shibatae)

NA

J5U23_02508

TOP6B family

NA

Relaxes both positive and negative supercoils and exhibits a strong decatenase and unknotting activity; it cannot introduce DNA supercoils (PubMed:7961685). ATP is absolutely required for DNA cleavage; the nonhydrolyzable analog AMP-PNP generates nicked or linear products from a supercoiled dsDNA substrate. Generates staggered two-nucleotide long 5' overhangs. The enzyme is covalently attached transiently to the 5'-ends of the cleaved strands (PubMed:11485995). {ECO:0000269|PubMed:11485995, ECO:0000269|PubMed:7961685}."

Neuropathy, hereditary motor and sensory, 6C, with optic atrophy (HMSN6C) [MIM:618511]: An autosomal recessive neurologic disorder characterized by childhood onset of axonal, sensorimotor polyneuropathy affecting mainly the lower limbs, and adult-onset optic atrophy. Clinical features include progressive distal muscle weakness and atrophy, significant standing and walking difficulties, areflexia, neurogenic pain and progressive visual impairment. {ECO:0000269|PubMed:31187503}. The disease is caused by variants affecting the gene represented in this entry.

NA

O05208; O05207

5.6.2.2

3D-structure; ATP-binding; Direct protein sequencing; DNA-binding; Isomerase; Nucleotide-binding; Topoisomerase

A

52553.8

461

0.09

38.32

8.62

4.35

-6.2

ADRB2

Homo sapiens (Human)

Beta-2 adrenoreceptor; Beta-2 adrenoceptor; Beta-2 adrenergic receptor; B2AR; ADRB2R

G-protein coupled receptor 1 family, Adrenergic receptor subfamily, ADRB2 sub-subfamily

GPCR rhodopsin

The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine. Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins.

Cortical dysplasia, complex, with other brain malformations 6 (CDCBM6) [MIM:615771]: A disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have microcephaly, ataxia, and severe delayed psychomotor development. Brain imaging shows variable malformations of cortical development, including white matter streaks, dysmorphic basal ganglia, corpus callosum abnormalities, brainstem and cerebellar hypoplasia, cortical dysplasia, polymicrogyria. {ECO:0000269|PubMed:23246003}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Skin creases, congenital symmetric circumferential, 1 (CSCSC1) [MIM:156610]: An autosomal dominant disease characterized by multiple, symmetric, circumferential rings of folded skin, affecting primarily the limbs. Affected individuals also exhibit intellectual disability, cleft palate, and dysmorphic features. {ECO:0000269|PubMed:26637975}. The disease is caused by variants affecting the gene represented in this entry.

DB07543; DB01193; DB00866; DB01118; DB00182; DB01102; DB01274; DB01238; DB09204; DB06216; DB00335; DB01408; DB05590; DB09013; DB00195; DB00217; DB01295; DB00612; DB00901; DB08807; DB06726; DB08808; DB00248; DB00521; DB01136; DB04846; DB01407; DB00785; DB01151; DB11273; DB13345; DB00449; DB11278; DB00841; DB09273; DB06262; DB01363; DB01364; DB00668; DB01049; DB11587; DB01288; DB00983; DB05039; DB00221; DB01064; DB00598; DB01210; DB13139; DB01365; DB13624; DB01214; DB00264; DB01203; DB05849; DB04861; DB00368; DB00540; DB00334; DB09080; DB00816; DB01580; DB00715; DB01359; DB00925; DB00397; DB00960; DB01291; DB01366; DB01182; DB00571; DB06814; DB00852; DB01917; DB11124; DB00867; DB01001; DB00938; DB00489; DB03566; DB00127; DB00871; DB00373; DB00726; DB12248; DB09082; DB09185

P30542; P07550; P32121; Q96B67; Q9UII2; Q9ULD4-2; Q9NSI6-4; Q5M9N0-2; A0AVK6; Q658K8; O00472; Q15910-2; Q15486; P61978; Q5TCQ9; Q99685; O14745; Q9NR21-5; Q8WVD3; Q9H0X6; Q13573; P12931; Q5T0J7-2; Q8N0U2

NA

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

A

32266.1

282

0.15

36.1

8.02

2.1

-6.2

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

-6.2

PAICS

Homo sapiens (Human)

NA

ADE2;PAIS;AIRC

SAICAR synthetase family; AIR carboxylase family, Class II subfamily

Ligase

ATP binding.Cadherin binding.Identical protein binding.Phosphoribosylaminoimidazole carboxylase activity.Phosphoribosylaminoimidazolesuccinocarboxamide synthase activity.

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.

DB00128

Q16543; P51116; Q969R5; Q8TBB1; Q6ZVK8; P22234; O75928-2; C9JJ79; Q9Y4B4; P78317; Q7KZS0; Q9UBW7

4.1.1.21; 6.3.2.6

3D-structure; Acetylation; Alternative splicing; ATP-binding; Decarboxylase; Direct protein sequencing; Disease variant; Ligase; Lyase; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; Proteomics identification; Purine biosynthesis; Reference proteome

A

41862.7

386

0.08

34.99

7.02

0.04

-6.2

RET

Homo sapiens (Human)

RET51 M918T mutant; Proto-oncogene tyrosine-protein kinase receptor Ret M918T mutant; Proto-oncogene c-Ret M918T mutant; PTC M918T mutant; Cadherin family member 12 M918T mutant; CDHR16 M918T mutant;

Protein kinase superfamily, Tyr protein kinase family

Kinase

Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e. g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways. Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL. Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands.

Hirschsprung disease 1 (HSCR1) [MIM:142623]: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child. {ECO:0000269|PubMed:10090908, ECO:0000269|PubMed:10484767, ECO:0000269|PubMed:10618407, ECO:0000269|PubMed:22174939, ECO:0000269|PubMed:7581377, ECO:0000269|PubMed:7633441, ECO:0000269|PubMed:7704557, ECO:0000269|PubMed:7881414, ECO:0000269|PubMed:8114938, ECO:0000269|PubMed:8114939, ECO:0000269|PubMed:9043870, ECO:0000269|PubMed:9090527, ECO:0000269|PubMed:9094028, ECO:0000269|PubMed:9259198, ECO:0000269|PubMed:9384613, ECO:0000269|PubMed:9497256, ECO:0000269|Ref.70}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Medullary thyroid carcinoma (MTC) [MIM:155240]: Rare tumor derived from the C cells of the thyroid. Three hereditary forms are known, that are transmitted in an autosomal dominant fashion: (a) multiple neoplasia type 2A (MEN2A), (b) multiple neoplasia type IIB (MEN2B) and (c) familial MTC (FMTC), which occurs in 25-30% of MTC cases and where MTC is the only clinical manifestation. {ECO:0000269|PubMed:10323403, ECO:0000269|PubMed:10826520, ECO:0000269|PubMed:11692159, ECO:0000269|PubMed:24560924, ECO:0000269|PubMed:29908090, ECO:0000269|PubMed:31118272, ECO:0000269|PubMed:7784092, ECO:0000269|PubMed:7845675, ECO:0000269|PubMed:7849720, ECO:0000269|PubMed:7874109, ECO:0000269|PubMed:7881414, ECO:0000269|PubMed:7915165, ECO:0000269|PubMed:8103403, ECO:0000269|PubMed:8557249, ECO:0000269|PubMed:8625130, ECO:0000269|PubMed:8807338, ECO:0000269|PubMed:9223675, ECO:0000269|PubMed:9259198, ECO:0000269|PubMed:9398735, ECO:0000269|PubMed:9452077, ECO:0000269|PubMed:9506724, ECO:0000269|PubMed:9621513, ECO:0000269|PubMed:9677065}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Multiple neoplasia 2B (MEN2B) [MIM:162300]: Uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophthalmic abnormalities, and ganglioneuromas of the intestine tract. Then the disease progresses rapidly with the development of metastatic MTC and a pheochromocytome in 50% of cases. {ECO:0000269|PubMed:24560924, ECO:0000269|PubMed:7906417, ECO:0000269|PubMed:7906866, ECO:0000269|PubMed:7911697, ECO:0000269|PubMed:8595427, ECO:0000269|PubMed:8807338, ECO:0000269|PubMed:9294615, ECO:0000269|PubMed:9360560}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. {ECO:0000269|PubMed:12000816}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Multiple neoplasia 2A (MEN2A) [MIM:171400]: The most frequent form of medullary thyroid cancer (MTC). It is an inherited cancer syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism. {ECO:0000269|PubMed:10522989, ECO:0000269|PubMed:7860065, ECO:0000269|PubMed:7874109, ECO:0000269|PubMed:7881414, ECO:0000269|PubMed:7915165, ECO:0000269|PubMed:8099202, ECO:0000269|PubMed:8103403, ECO:0000269|PubMed:8626834, ECO:0000269|PubMed:8807338, ECO:0000269|PubMed:9097963, ECO:0000269|PubMed:9384613, ECO:0000269|PubMed:9452064}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Various chromosomal aberrations involving RET are known. Some of them have been found in papillary thyroid carcinomas (PTCs) (PubMed:10439047, PubMed:10980597, PubMed:12787916, PubMed:2406025). Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene (PubMed:2406025). Inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene. Translocation t(10;14)(q11;q32) with GOLGA5 generates the RET/GOLGA5 (PTC5) oncogene (PubMed:2734021). Translocation t(8;10)(p21.3;q11.2) with PCM1 generates the PCM1/RET fusion (PubMed:10980597). Translocation t(6;10)(p21.3;q11.2) with TRIM27/RFP generates the Delta RFP/RET oncogene (PubMed:12787916). Translocation t(1;10)(p13;q11) with TRIM33 generates the TRIM33/RET (PTC7) oncogene (PubMed:10439047). Translocation t(7;10)(q32;q11) with TRIM24/TIF1 generates the TRIM24/RET (PTC6) oncogene (PubMed:10439047). Translocation t(6;10)(p21.3;q11.2) with TRIM27/RFP generates the TRIM27/RET oncogene (PubMed:3037315). {ECO:0000269|PubMed:10439047, ECO:0000269|PubMed:10980597, ECO:0000269|PubMed:12787916, ECO:0000269|PubMed:2406025, ECO:0000269|PubMed:2734021, ECO:0000269|PubMed:3037315}.; DISEASE: Mutations in RET have been detected in patients with renal agenesis suggesting a possible involvement of this gene in disease pathogenesis. {ECO:0000269|PubMed:18252215}.

DB01809; DB12742; DB08875; DB12147; DB12010; DB00619; DB09078; DB08901; DB15822; DB08896; DB15685; DB00398; DB05294; DB05014

Q9UM73; P22455; Q7Z3S9; P40763; Q9Y490; Q62985; Q7Z3S9

EC 2.7.10.1

3D-structure; Alternative splicing; ATP-binding; Cell adhesion; Cell membrane; Chromosomal rearrangement; Disease variant; Disulfide bond; Endosome; Glycoprotein; Hirschsprung disease; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; Reference proteome; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase

A

33472.5

295

0.09

43.68

9.07

6.3

-6.21

HCN4

Homo sapiens (Human)

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

Potassium channel HCN family

Voltage-gated ion channel

Contributes to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat. May contribute to the native pacemaker currents in neurons (Ih). May mediate responses to sour stimuli. Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions.

Sick sinus syndrome 2 (SSS2) [MIM:163800]: The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS2 onset is in utero or at birth. {ECO:0000269|PubMed:15123648, ECO:0000269|PubMed:16407510, ECO:0000269|PubMed:20662977, ECO:0000269|PubMed:23103389}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Brugada syndrome 8 (BRGDA8) [MIM:613123]: A tachyarrhythmia 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:19165230}. The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Epilepsy, idiopathic generalized 18 (EIG18) [MIM:619521]: An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. EIG18 is characterized by onset of myoclonic seizures in infancy. Although the seizures remit, some patients may have later speech or cognitive impairment. {ECO:0000269|PubMed:30127718}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

NA

O60741; Q9Y3Q4

NA

3D-structure; Brugada syndrome; cAMP; cAMP-binding; Cell membrane; Disease variant; Epilepsy; Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel; Membrane; Nucleotide-binding; Phosphoprotein; Potassium; Potassium channel; Potassium transport; Proteomics identification; Reference proteome; Sodium; Sodium channel; Sodium transport; Transmembrane; Transmembrane helix; Transport; Voltage-gated channel

A

23211.2

197

0.12

42.69

8.67

3.11

-6.2

CYP46A1

Homo sapiens (Human)

Cytochrome P450 46A1; CYP46; Cholesterol 24S-hydroxylase; Cholesterol 24-monooxygenase; CH24H

Cytochrome P450 family

Paired donor oxygen oxidoreductase

Primarily catalyzes the hydroxylation (with S stereochemistry) at C-24 of cholesterol side chain, triggering cholesterol diffusion out of neurons and its further degradation. By promoting constant cholesterol elimination in neurons, may activate the mevalonate pathway and coordinate the synthesis of new cholesterol and nonsterol isoprenoids involved in synaptic activity and learning. Further hydroxylates cholesterol derivatives and hormone steroids on both the ring and side chain of these molecules, converting them into active oxysterols involved in lipid signaling and biosynthesis. Acts as an epoxidase converting cholesta-5,24-dien-3beta-ol/desmosterol into (24S),25-epoxycholesterol, an abundant lipid ligand of nuclear NR1H2 and NR1H3 receptors shown to promote neurogenesis in developing brain. May also catalyze the oxidative metabolism of xenobiotics, such as clotrimazole. P450 monooxygenase that plays a major role in cholesterol homeostasis in the brain.

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 (SCAN1) [MIM:607250]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAN1 is an autosomal recessive cerebellar ataxia (ARCA) associated with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. All affected individuals have normal intelligence. {ECO:0000269|PubMed:12244316, ECO:0000269|PubMed:15647511, ECO:0000269|PubMed:15920477, ECO:0000269|PubMed:16141202, ECO:0000269|PubMed:17948061}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 1.14.14.25

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

A

48977

427

0.1

49.59

9.04

6.25

-6.21

ZUP1

Homo sapiens (Human)

Zinc finger with UFM1-specific peptidase domain protein; ZUFSP; Lys-63-specific deubiquitinase ZUFSP; DUB; C6orf113

Peptidase C78 family, ZUFSP subfamily

Peptidase

Shows only weak activity against 'Lys-11' and 'Lys-48'-linked chains. Plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage. Modulates the ubiquitination status of replication protein A (RPA) complex proteins in response to replication stress. Deubiquitinase with endodeubiquitinase activity that specifically interacts with and cleaves 'Lys-63'-linked long polyubiquitin chains.

WHIM syndrome 2 (WHIMS2) [MIM:619407]: An autosomal recessive form of WHIM syndrome, a primary immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. Myelokathexis is a unique form of non-cyclic severe congenital neutropenia caused by accumulation of mature and degenerating neutrophils in the bone marrow. Monocytopenia and lymphopenia, especially B lymphopenia, also commonly occur. There is significant phenotypic variation among patients, such that some individuals may have an incomplete form of the disorder in which one or more of the classic tetrad features are not present. {ECO:0000269|PubMed:24777453}. The disease may be caused by variants affecting the gene represented in this entry.

NA

Q92619; P50281; Q8WVC2

EC 3.4.19.12

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Hydrolase; Metal-binding; Nucleus; Proteomics identification; Reference proteome; Repeat; Zinc; Zinc-finger

A,B

46930.3

410

0.07

58.67

9

9.7

-6.2

CYP2D6

Homo sapiens (Human)

P450-DB1; Cytochrome P450-DB1; Cytochrome P450 2D6; CYPIID6; CYP2DL1

Cytochrome P450 family

Paired donor oxygen oxidoreductase

It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants. Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes.

A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions. {ECO:0000269|PubMed:2875799, ECO:0000269|PubMed:3285301}.

DB01562; DB01472; DB14010; DB12001; DB05812; DB01193; DB00316; DB15568; DB00918; DB06203; DB00866; DB01424; DB01118; DB00321; DB00381; DB00613; DB00543; DB00182; DB00701; DB11785; DB01435; DB01429; DB01274; DB01238; DB14185; DB09204; DB11638; DB06216; DB00637; DB11586; DB00335; DB00289; DB01076; DB00972; DB04957; DB09013; DB16703; DB01086; DB06770; DB01244; DB15982; DB00195; DB01295; DB12236; DB01128; DB04889; DB00810; DB13975; DB08807; DB00188; DB09128; DB12151; DB12752; DB06726; DB00297; DB08808; DB00921; DB01156; DB00490; DB09173; DB00201; DB09061; DB14737; DB06016; DB00521; DB01136; DB00482; DB04846; DB00439; DB00185; DB00608; DB01114; DB00477; DB00356; DB01410; DB01166; DB00501; DB01012; DB00568; DB00604; DB00215; DB12499; DB00283; DB04920; DB14025; DB00349; DB00845; DB01242; DB00575; DB13508; DB00257; DB00363; DB09065; DB05239; DB00907; DB00318; DB11672; DB14635; DB00924; DB00091; DB11963; DB06292; DB04884; DB00496; DB01264; DB09183; DB04840; DB00705; DB06512; DB01151; DB06700; DB16650; DB12161; DB13679; DB09555; DB01191; DB00633; DB01576; DB00514; DB00647; DB11994; DB01551; DB00343; DB01093; DB01075; DB00757; DB01184; DB00843; DB09167; DB00590; DB01142; DB00997; DB00470; DB04855; DB00476; DB00625; DB11979; DB00216; DB15444; DB09039; DB13874; DB01228; DB06735; DB11718; DB00494; DB13757; DB00751; DB00530; DB13443; DB01175; DB06678; DB00187; DB00330; DB01466; DB01628; DB01590; DB12500; DB01023; DB00574; DB06702; DB12265; DB01195; DB04841; DB00472; DB00623; DB01095; DB00176; DB00983; DB02703; DB15149; DB00674; DB05087; DB00317; DB08909; DB00986; DB01218; DB00502; DB00956; DB01611; DB00557; DB09053; DB01177; DB04946; DB00619; DB00458; DB08952; DB00224; DB06370; DB13293; DB04818; DB16200; DB11633; DB06636; DB00951; DB11757; DB00602; DB09570; DB01026; DB00598; DB12212; DB00448; DB11732; DB16217; DB09078; DB00528; DB12070; DB09351; DB01210; DB08918; DB00281; DB04948; DB01206; DB00836; DB01601; DB00455; DB04871; DB09195; DB06708; DB04829; DB09238; DB00934; DB14921; DB00737; DB14009; DB09224; DB00170; DB00454; DB00532; DB13530; DB06691; DB01071; DB00933; DB01577; DB00333; DB00763; DB01403; DB01028; DB09241; DB01214; DB01233; DB00264; DB00379; DB06148; DB01388; DB01110; DB00211; DB01454; DB06595; DB00834; DB00805; DB08893; DB00370; DB12523; DB01171; DB00745; DB14011; DB09049; DB00731; DB04861; DB01149; DB00220; DB09048; DB00238; DB00627; DB00622; DB00699; DB02701; DB00184; DB01115; DB04868; DB12005; DB00540; DB00334; DB14881; DB00338; DB00904; DB11130; DB04911; DB01173; DB11837; DB04938; DB01096; DB01580; DB01062; DB00497; DB06412; DB01192; DB01267; DB00377; DB06603; DB00715; DB06589; DB00022; DB01359; DB00738; DB01074; DB08922; DB00850; DB03783; DB00780; DB00914; DB00252; DB05316; DB01100; DB00960; DB00592; DB01621; DB04951; DB17472; DB11642; DB08901; DB01297; DB15822; DB01087; DB01035; DB00433; DB00396; DB01131; DB00420; DB01069; DB09288; DB01182; DB00571; DB04216; DB01224; DB00908; DB00468; DB01129; DB00863; DB00243; DB00234; DB14761; DB00409; DB06506; DB02709; DB11855; DB13174; DB11753; DB08864; DB14840; DB00734; DB12693; DB00503; DB00953; DB09291; DB15119; DB00412; DB05271; DB12332; DB11614; DB06654; DB01232; DB01037; DB06144; DB01104; DB00203; DB00641; DB01591; DB00398; DB12713; DB00489; DB06727; DB01323; DB09118; DB06820; DB06729; DB06608; DB11770; DB00675; DB00706; DB06204; DB06083; DB01079; DB12095; DB06287; DB00857; DB00342; DB13775; DB04905; DB04844; DB11712; DB00277; DB00679; DB01623; DB00208; DB00373; DB01409; DB00932; DB06137; DB01036; DB05109; DB00193; DB00752; DB00656; DB12245; DB00726; DB00792; DB00209; DB15328; DB09076; DB13609; DB15091; DB11915; DB00862; DB08881; DB00285; DB00661; DB06217; DB06684; DB09185; DB00570; DB00361; DB11739; DB09068; DB01392; DB00549; DB15688; DB00425; DB01624

NA

EC 1.14.14.-

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

A

51898.1

464

0.09

43.83

6.76

-0.99

-6.21

TOR1A

Homo sapiens (Human)

Torsin family 1 member A; Torsin ATPase-1A; TORA; TA; Dystonia 1 protein; DYT1; DQ2

ClpA/ClpB family, Torsin subfamily

Acid anhydride hydrolase

Involved in the regulation of synaptic vesicle recycling, controls STON2 protein stability in collaboration with the COP9 signalosome complex (CSN). In the nucleus, may link the cytoskeleton with the nuclear envelope, this mechanism seems to be crucial for the control of nuclear polarity, cell movement and, specifically in neurons, nuclear envelope integrity. Participates in the cellular trafficking and may regulate the subcellular location of multipass membrane proteins such as the dopamine transporter SLC6A3, leading to the modulation of dopamine neurotransmission. In the endoplasmic reticulum, plays a role in the quality control of protein folding by increasing clearance of misfolded proteins such as SGCE variants or holding them in an intermediate state for proper refolding. May have a redundant function with TOR1B in non-neural tissues. Protein with chaperone functions important for the control of protein folding, processing, stability and localization as well as for the reduction of misfolded protein aggregates.

Dystonia 1, torsion, autosomal dominant (DYT1) [MIM:128100]: A primary torsion dystonia, and the most common and severe form. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 1 is characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body, in the absence of other neurological symptoms. Typically, symptoms develop first in an arm or leg in middle to late childhood and progress in approximately 30% of patients to other body regions (generalized dystonia) within about five years. 'Torsion' refers to the twisting nature of body movements observed in DYT1, often affecting the trunk. Distribution and severity of symptoms vary widely between affected individuals, ranging from mild focal dystonia to severe generalized dystonia, even within families. {ECO:0000269|PubMed:14970196, ECO:0000269|PubMed:15505207, ECO:0000269|PubMed:16361107, ECO:0000269|PubMed:17428918, ECO:0000269|PubMed:18167355, ECO:0000269|PubMed:18477710, ECO:0000269|PubMed:18827015, ECO:0000269|PubMed:19955557, ECO:0000269|PubMed:20169475, ECO:0000269|PubMed:21102408, ECO:0000269|PubMed:24930953, ECO:0000269|PubMed:27490483, ECO:0000269|PubMed:9288096}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Arthrogryposis multiplex congenita 5 (AMC5) [MIM:618947]: A form of arthrogryposis multiplex congenita, a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. AMC5 is an autosomal recessive form characterized by severe congenital contractures, developmental delay, strabismus and tremor. {ECO:0000269|PubMed:28516161, ECO:0000269|PubMed:29053766, ECO:0000269|PubMed:30244176}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q6PCB6; P05067; Q96FT7-4; Q9UNS2; P22692; P60409; Q99750; Q5JTV8; Q8NFQ8; Q6PCB6; P63010-2; P05067; Q9UII2; Q9UJX2; Q53EZ4; Q96FZ7; Q92478; P35222; Q9NR90-2; Q9UHI6; Q14154; Q9H147; O75616; Q9UI08-2; Q6PIV2; Q9H4A5; P0C0S5; Q6DN90-2; Q8NA54; Q92993; Q8IUB9; A2RU56; Q8TDB4; P41218; Q9Y605; O43196-2; O00746; Q96CV9-2; Q99497; Q13113; P27986-2; P12273; O75626-3; P57729; Q96QF0-7; Q9BY12-3; Q15019-3; Q9NQ40; Q12824; Q05C28; Q7Z6I5; O75558; P21980-2; Q9BUZ4; Q9NX07-2; Q5JTY5

EC 3.6.4.-

3D-structure; Alternative splicing; ATP-binding; Cell projection; Chaperone; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Disease variant; Dystonia; Endoplasmic reticulum; Glycoprotein; Hydrolase; Membrane; Nucleotide-binding; Nucleus; Proteomics identification; Reference proteome; Signal; Synapse

A,B

58238.4

512

0.12

39.75

5.81

-11.04

-6.21

HCN2

Homo sapiens (Human)

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2; Brain cyclic nucleotide-gated channel 2; BCNG2; BCNG-2

Potassium channel HCN family

Voltage-gated ion channel

Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages. Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions.

Epilepsy, idiopathic generalized 17 (EIG17) [MIM:602477]: A form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. Both autosomal dominant and autosomal recessive EIG17 inheritance have been reported. {ECO:0000269|PubMed:22131395, ECO:0000269|PubMed:29064616}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Febrile seizures, familial, 2 (FEB2) [MIM:602477]: Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. FEB2 transmission pattern is consistent with autosomal dominant inheritance. {ECO:0000269|PubMed:24324597}. The disease is caused by variants affecting the gene represented in this entry.

DB02527; DB02315; DB09083

Q9UL51; Q4ACU6-1

NA

3D-structure; Ammonia transport; cAMP; cAMP-binding; Cell membrane; Disease variant; Epilepsy; Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel; Lipoprotein; Membrane; Methylation; Nucleotide-binding; Palmitate; Phosphoprotein; Potassium; Potassium channel; Potassium transport; Proteomics identification; Reference proteome; Sodium; Sodium channel; Sodium transport; Transmembrane; Transmembrane helix; Transport; Voltage-gated channel

A

23672.9

202

0.12

38.05

8.85

4.11

-6.2

HSPA5

Homo sapiens (Human)

Immunoglobulin heavy chainbinding protein; Immunoglobulin heavy chain-binding protein; Heat shock protein family A member 5; Heat shock protein 70 family protein 5; Heat shock 70 kDa protein 5; HSP70

Heat shock protein 70 family

Acid anhydride hydrolase

Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate. Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1. Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1. Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen.

Autoantigen in rheumatoid arthritis. {ECO:0000269|PubMed:11160188}.

DB00945; DB00025; DB09130; DB13998; DB13999

Q9BYF1; P05067; P18850; Q9ULD4-2; Q6E0U4; Q9UBS4; Q9UBS3; P49184; Q92874; Q9NZJ5; P04626; O75460; O75460-1; P62993; Q15486; P14625; Q9Y4L1; P01721; O95868; Q9Y328; Q96IZ0; Q15084; P04049; P61619; P36955; Q9H173; Q9UHI5; Q13573; Q6URK8; Q6PF05; Q13404; Q9NYU1; P09544; Q6T424; Q9QXT0; Q91YW3; Q9Z2B5; Q62627; K0BRG7; P0DTC2

EC 3.6.4.10

3D-structure; Acetylation; ATP-binding; Chaperone; Cytoplasm; Direct protein sequencing; Endoplasmic reticulum; Host-virus interaction; Hydrolase; Isopeptide bond; Methylation; Nitration; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Signal; Ubl conjugation

A

67147.3

606

0.06

32.09

5.22

-15.9

-6.2

PRKDC

Homo sapiens (Human)

p460; HYRC1; HYRC; DNPK1; DNA-dependent protein kinase catalytic subunit; DNA-PKcs; DNA-PK catalytic subunit

PI3/PI4-kinase family

Kinase

Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Required to protect and align broken ends of DNA. May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. Also involved in modulation of transcription. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism. Phosphorylates DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, XRCC1, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2. Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA. Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D. Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.

Immunodeficiency 26 with or without neurologic abnormalities (IMD26) [MIM:615966]: A form of severe combined immunodeficiency characterized by reduced or absent T and B cells, recurrent candidiasis, and lower respiratory tract infections. Some patients show dysmorphic features, severe growth failure, microcephaly, seizures, and impaired neurological functions. {ECO:0000269|PubMed:19075392, ECO:0000269|PubMed:23722905}. The disease is caused by variants affecting the gene represented in this entry.

DB00201; DB05210

O43918; P10275; Q96SD1; P14921; P50549; P09629; Q9BPZ7; Q96RI1-2; P10276; P17947; P13010; P12956; P25490

EC 2.7.11.1

3D-structure; Acetylation; Alternative splicing; ATP-binding; Biological rhythms; Disease variant; DNA damage; DNA recombination; DNA repair; DNA-binding; Immunity; Innate immunity; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Ribosome biogenesis; SCID; Serine/threonine-protein kinase; TPR repeat; Transferase; Ubl conjugation

A

437836

3852

0.09

47.88

6.63

-10.35

-6.21