SIGMAR1

Homo sapiens (Human)

hSigmaR1; Sigma1R; Sigma1-receptor; Sigma non-opioid intracellular receptor 1; Sigma 1-type opioid receptor; SRBP; SR31747-binding protein; SR31747 binding protein 1; SR-BP; SIG-1R; Opioid receptor, s

ERG2 family

GPCR rhodopsin

Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration. Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria. Plays a role in protecting cells against oxidative stress-induced cell death via its interaction with RNF112. Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane.

Amyotrophic lateral sclerosis 16, juvenile (ALS16) [MIM:614373]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269|PubMed:21842496}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neuronopathy, distal hereditary motor, autosomal recessive 2 (HMNR2) [MIM:605726]: A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMNR2 is characterized by onset of distal muscle weakness and wasting affecting the lower and upper limbs in the first decade. {ECO:0000269|PubMed:26078401, ECO:0000269|PubMed:27629094}. The disease is caused by variants affecting the gene represented in this entry.

DB00321; DB09014; DB00907; DB00514; DB01488; DB00574; DB00502; DB00956; DB00704; DB00540; DB06174; DB00652; DB11186; DB03575; DB05316; DB01708; DB00409; DB01104

Q92847-1; Q99720-1; O00213-2; P17612; P50454; P37173

NA

3D-structure; Alternative splicing; Amyotrophic lateral sclerosis; Cell junction; Cell membrane; Cell projection; Cytoplasmic vesicle; Direct protein sequencing; Disease variant; Endoplasmic reticulum; Lipid droplet; Lipid transport; Membrane; Neurodegeneration; Neuropathy; Nucleus; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Synapse; Transmembrane; Transmembrane helix; Transport

A

23901

212

0.14

33.12

5.61

-5.6

-10.54

CYP1B1

Homo sapiens (Human)

CYPIB1

Cytochrome P450 family

Paired donor oxygen oxidoreductase

In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression. Cytochromes P450 are a group of heme-thiolate monooxygenases.

Anterior segment dysgenesis 6 (ASGD6) [MIM:617315]: A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD6 patients predominantly manifest Peters anomaly. Peters anomaly consists of corneal leukoma, defects in the posterior structures of the cornea such as absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iridocorneal and/or keratolenticular adhesions. Over 50% of patients develop glaucoma in childhood. {ECO:0000269|PubMed:11403040}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Glaucoma 3, primary congenital, A (GLC3A) [MIM:231300]: An autosomal recessive form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor. {ECO:0000269|PubMed:10227395, ECO:0000269|PubMed:10655546, ECO:0000269|PubMed:11184479, ECO:0000269|PubMed:11527932, ECO:0000269|PubMed:11774072, ECO:0000269|PubMed:11980847, ECO:0000269|PubMed:12036985, ECO:0000269|PubMed:12525557, ECO:0000269|PubMed:14635112, ECO:0000269|PubMed:14640114, ECO:0000269|PubMed:15255109, ECO:0000269|PubMed:15342693, ECO:0000269|PubMed:15475877, ECO:0000269|PubMed:16490498, ECO:0000269|PubMed:16688110, ECO:0000269|PubMed:16735994, ECO:0000269|PubMed:16862072, ECO:0000269|PubMed:18470941, ECO:0000269|PubMed:9463332, ECO:0000269|PubMed:9497261}. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry.; DISEASE: Glaucoma 1, open angle, A (GLC1A) [MIM:137750]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. {ECO:0000269|PubMed:11774072}. The gene represented in this entry acts as a disease modifier. Digenic mutations in CYP1B1 and MYOC have been found in a family segregating both primary adult-onset and juvenile forms of open angle glaucoma (PubMed:11774072). All affected family members with mutations in both MYOC and CYP1B1 had juvenile glaucoma, whereas those with only the MYOC mutation had the adult-onset form (PubMed:11774072). {ECO:0000269|PubMed:11774072}.

DB02342; DB00613; DB06732; DB00443; DB00121; DB01222; DB00201; DB09061; DB14737; DB01254; DB00694; DB01248; DB00997; DB00470; DB00530; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB00655; DB07776; DB00499; DB01645; DB01381; DB00741; DB01064; DB01026; DB00448; DB14009; DB01065; DB00170; DB00959; DB01204; DB14011; DB03467; DB00338; DB01229; DB14631; DB00635; DB01087; DB00396; DB00818; DB04216; DB02709; DB00675; DB00624; DB13946; DB00277; DB12245; DB11155

Q02763

EC 1.14.14.-

3D-structure; Disease variant; Endoplasmic reticulum; Fatty acid metabolism; Glaucoma; Heme; Iron; Lipid metabolism; Lyase; Membrane; Metal-binding; Microsome; Mitochondrion; Monooxygenase; Oxidoreductase; Peters anomaly; Proteomics identification; Reference proteome; Steroid metabolism

A

51875.9

459

0.1

34.16

8.64

4.89

-10.55

mop

Megalodesulfovibrio gigas (Desulfovibrio gigas)

NA

NA

Xanthine dehydrogenase family

Oxidoreductase

2 iron, 2 sulfur cluster binding.Aldehyde dehydrogenase (FAD-independent) activity.Electron carrier activity.Metal ion binding.

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

DB02137

NA

1.2.99.7

2Fe-2S; 3D-structure; FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding; Molybdenum; NAD; Oxidoreductase

A

96930.4

907

0.07

29.17

5.69

-17.56

-10.54

LCMT1

Homo sapiens (Human)

NA

CGI-68;LCMT

Methyltransferase superfamily, LCMT family

Transferase

Protein C-terminal carboxyl O-methyltransferase activity.Protein C-terminal leucine carboxyl O-methyltransferase activity.S-adenosylmethionine-dependent methyltransferase activity.

Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS) [MIM:617710]: An autosomal recessive, mitochondrial disorder with a broad phenotypic spectrum ranging from severe neonatal lactic acidosis, encephalomyopathy and early death to an attenuated course with milder manifestations. Clinical features include delayed psychomotor development, intellectual disability, hypotonia, dystonia, ataxia, and spasticity. Severe combined respiratory chain deficiency may be found in severely affected individuals. {ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:28650581, ECO:0000269|PubMed:28905505, ECO:0000269|PubMed:30920170, ECO:0000269|PubMed:35074316}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Parkinsonism-dystonia 3, childhood-onset (PKDYS3) [MIM:619738]: An autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances. {ECO:0000269|PubMed:29120065, ECO:0000269|PubMed:31970218, ECO:0000269|PubMed:34890876}. The disease is caused by variants affecting the gene represented in this entry.

DB00149

P51116

2.1.1.233

3D-structure; Alternative splicing; Methyltransferase; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Transferase

A,B,C,D,E,F,G,H

35803

310

0.08

42.77

6.13

-3.58

-10.52

THRA

Homo sapiens (Human)

V-erbA-related protein 7; THRA2; THRA1; Nuclear receptor subfamily 1 group A member 1; NR1A1; ERBA1; EAR7; EAR-7; C-erbA-alpha; C-erbA-1

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription.

Hypothyroidism, congenital, non-goitrous, 6 (CHNG6) [MIM:614450]: A disease characterized by growth retardation, developmental retardation, skeletal dysplasia, borderline low thyroxine levels and high triiodothyronine levels. There is differential sensitivity to thyroid hormone action, with retention of hormone responsiveness in the hypothalamic pituitary axis and liver but skeletal, gastrointestinal, and myocardial resistance. {ECO:0000269|PubMed:22168587, ECO:0000269|PubMed:24969835, ECO:0000269|PubMed:25670821, ECO:0000269|PubMed:26037512}. The disease is caused by variants affecting the gene represented in this entry.

DB01118; DB00509; DB04855; DB05035; DB03176; DB00451; DB00279; DB01583; DB05235; DB09100

Q9Y2J4; Q9Y2J4-4; O95971; Q8TAP6; Q96JM7; Q15648; Q6FHY5; P31321; Q96A49; O75410-7; Q9JLI4

NA

3D-structure; Alternative splicing; Congenital hypothyroidism; Cytoplasm; Disease variant; DNA-binding; Metal-binding; Nucleus; Proteomics identification; Receptor; Reference proteome; Transcription; Transcription regulation; Zinc; Zinc-finger

A

29910.1

267

0.07

52.75

5.31

-11.32

-10.51

JAK2

Homo sapiens (Human)

Tyrosine-protein kinase JAK2

Protein kinase superfamily, Tyr protein kinase family, JAK subfamily

Kinase

Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. 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, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin. Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications.

Chromosomal aberrations involving JAK2 are found in both chronic and acute forms of eosinophilic, lymphoblastic and myeloid leukemia. Translocation t(8;9)(p22;p24) with PCM1 links the protein kinase domain of JAK2 to the major portion of PCM1. Translocation t(9;12)(p24;p13) with ETV6.; DISEASE: Budd-Chiari syndrome (BDCHS) [MIM:600880]: A syndrome caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava. Obstructions are generally caused by thrombosis and lead to hepatic congestion and ischemic necrosis. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain and abdominal ascites. Budd-Chiari syndrome is associated with a combination of disease states including primary myeloproliferative syndromes and thrombophilia due to factor V Leiden, protein C deficiency and antithrombin III deficiency. Budd-Chiari syndrome is a rare but typical complication in patients with polycythemia vera. {ECO:0000269|PubMed:16707754}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Polycythemia vera (PV) [MIM:263300]: A myeloproliferative disorder characterized by abnormal proliferation of all hematopoietic bone marrow elements, erythroid hyperplasia, an absolute increase in total blood volume, but also by myeloid leukocytosis, thrombocytosis and splenomegaly. {ECO:0000269|PubMed:15781101, ECO:0000269|PubMed:15793561, ECO:0000269|PubMed:15858187, ECO:0000269|PubMed:16603627, ECO:0000269|PubMed:25644777}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thrombocythemia 3 (THCYT3) [MIM:614521]: A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes. {ECO:0000269|PubMed:16325696, ECO:0000269|PubMed:22397670}. The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Myelofibrosis (MYELOF) [MIM:254450]: A disorder characterized by replacement of the bone marrow by fibrous tissue, occurring in association with a myeloproliferative disorder. Clinical manifestations may include anemia, pallor, splenomegaly, hypermetabolic state, petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, portal hypertension. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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:16247455}. The disease is caused by variants affecting the gene represented in this entry.

DB04716; DB07162; DB08067; DB07161; DB14973; DB11817; DB11986; DB12500; DB12010; DB11763; DB11697; DB15822; DB08877; DB08895; DB05243; DB15035

P32927; Q01344; P23458; O60674; P40238; P16333; P18031; O75116; P29597; Q9JHI9

EC 2.7.10.2

3D-structure; Adaptive immunity; ATP-binding; Chromatin regulator; Chromosomal rearrangement; Cytoplasm; Disease variant; Immunity; Innate immunity; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Proto-oncogene; Reference proteome; Repeat; SH2 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation

A

32174.5

274

0.1

50.94

7.78

1.46

-10.51

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

-10.51

DHODH

Homo sapiens (Human)

Dihydroorotate oxidase; Dihydroorotate dehydrogenase (quinone), mitochondrial; DHOdehase; DHODH

Dihydroorotate dehydrogenase family, Type 2 subfamily

CH-CH donor oxidoreductase

Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.

Postaxial acrofacial dysostosis (POADS) [MIM:263750]: POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases. {ECO:0000269|PubMed:19915526}. The disease is caused by variants affecting the gene represented in this entry.

DB07559; DB07561; DB08172; DB08169; DB07443; DB07978; DB07975; DB04281; DB08249; DB07977; DB07976; DB04583; DB08008; DB01117; DB03523; DB03480; DB02613; DB04147; DB03247; DB01097; DB06481; DB08006; DB02262; DB05125; DB08880; DB07646

Q6ZMZ0; P49638

EC 1.3.5.2

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

A

38341.4

353

0.05

39.27

9.28

5.52

-10.51

HRV P3C

Human rhinovirus 2 (HRV-2)

Rhinovirus P3C

Picornaviruses polyprotein family

NA

Capsid protein VP1: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome. Capsid protein VP1 mainly forms the vertices of the capsid. Capsid protein VP1 interacts with host VLDLR to provide virion attachment to target host cells. This attachment induces virion internalization. Tyrosine kinases are probably involved in the entry process. After binding to its receptor, the capsid undergoes conformational changes. Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized. Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm. After genome has been released, the channel shrinks (By similarity).

Charcot-Marie-Tooth disease, axonal, 2DD (CMT2DD) [MIM:618036]: A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:29499166}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hypomagnesemia, seizures, and impaired intellectual development 2 (HOMGSMR2) [MIM:618314]: An autosomal dominant disease characterized by generalized seizures in infancy, severe hypomagnesemia, and renal magnesium wasting. Seizures persist despite magnesium supplementation and are associated with significant intellectual disability. {ECO:0000269|PubMed:30388404}. The disease is caused by variants affecting the gene represented in this entry.

DB02313; DB03017

NA

EC 3.4.22.28

3D-structure; Activation of host autophagy by virus; ATP-binding; Autocatalytic cleavage; Capsid protein; Covalent protein-RNA linkage; DNA replication; Eukaryotic host gene expression shutoff by virus; Eukaryotic host translation shutoff by virus; Helicase; Host cytoplasm; Host cytoplasmic vesicle; Host gene expression shutoff by virus; Host membrane; Host mRNA suppression by virus; Host nucleus; Host-virus interaction; Hydrolase; Inhibition of host innate immune response by virus; Inhibition of host mRNA nuclear export by virus; Inhibition of host RIG-I by virus; Inhibition of host RLR pathway by virus; Ion channel; Ion transport; Lipoprotein; Magnesium; Membrane; Metal-binding; Myristate; Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein; Pore-mediated penetration of viral genome into host cell; Protease; Repeat; RNA-binding; RNA-directed RNA polymerase; T=pseudo3 icosahedral capsid protein; Thiol protease; Transferase; Transport; Viral attachment to host cell; Viral immunoevasion; Viral ion channel; Viral penetration into host cytoplasm; Viral RNA replication; Virion; Virus endocytosis by host; Virus entry into host cell; Zinc; Zinc-finger

1

30610.1

269

0.1

55.66

6.86

-0.38

-10.52

IRAK4

Homo sapiens (Human)

Interleukin-1 receptor-associated kinase 4; IRAK-4

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

Kinase

Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections.

Immunodeficiency 67 (IMD67) [MIM:607676]: An autosomal recessive primary immunodeficiency characterized by recurrent, life-threatening systemic and invasive bacterial infections beginning in infancy or early childhood. {ECO:0000269|PubMed:12637671, ECO:0000269|PubMed:12925671, ECO:0000269|PubMed:16950813, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:19663824, ECO:0000269|PubMed:21057262, ECO:0000269|PubMed:24316379}. The disease is caused by variants affecting the gene represented in this entry.

DB08590; DB12010

Q9UBH0; O43187; Q99836; Q99836-1; Q96FA3; Q9HAT8; P58753; Q9C029; P0DPA2; Q96LX8; Q8K4B2

EC 2.7.11.1

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm; Disease variant; Immunity; Innate immunity; Kinase; Magnesium; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase

A

30948.8

276

0.08

43.33

5.09

-13.45

-10.52

PROC

Homo sapiens (Human)

Vitamin K-dependent protein C light chain; Vitamin K-dependent protein C heavy chain; PROC; Blood coagulation factor XIV; Autoprothrombin IIA; Anticoagulant protein C; Activation peptide

Peptidase S1 family

Peptidase

Protein C is avitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids.

Thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:176860]: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency. {ECO:0000269|PubMed:1301959, ECO:0000269|PubMed:1347706, ECO:0000269|PubMed:1511989, ECO:0000269|PubMed:1868249, ECO:0000269|PubMed:2437584, ECO:0000269|PubMed:25618265, ECO:0000269|PubMed:25748729, ECO:0000269|PubMed:2602169, ECO:0000269|PubMed:7792728, ECO:0000269|PubMed:7865674, ECO:0000269|PubMed:8292730, ECO:0000269|PubMed:8398832, ECO:0000269|PubMed:8499568, ECO:0000269|PubMed:8560401, ECO:0000269|PubMed:8829639, ECO:0000269|PubMed:9798967}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:612304]: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare. {ECO:0000269|PubMed:1511988, ECO:0000269|PubMed:1593215, ECO:0000269|PubMed:1611081, ECO:0000269|PubMed:25618265, ECO:0000269|PubMed:7841323, ECO:0000269|PubMed:7841324, ECO:0000269|PubMed:7878626}. The disease is caused by variants affecting the gene represented in this entry.

DB13192; DB00025; DB09131; DB09332; DB13998; DB00170; DB13999; DB13149; DB00464; DB14738

A8MQ03; P51511

EC 3.4.21.69

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

C,D

45326

411

0.12

40.68

7.07

0.29

-10.51

OXSM

Homo sapiens (Human)

3-oxoacyl-[acyl-carrier-protein] synthase, mitochondrial

Thiolase-like superfamily, Beta-ketoacyl-ACP synthases family

Acyltransferase

May play a role in the biosynthesis of lipoic acid as well as longer chain fatty acids required for optimal mitochondrial function.

Lethal congenital contracture syndrome 2 (LCCS2) [MIM:607598]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS2 patients manifest craniofacial/ocular findings, lack of hydrops, multiple pterygia, and fractures, as well as a normal duration of pregnancy and a unique feature of a markedly distended urinary bladder (neurogenic bladder defect). The phenotype suggests a spinal cord neuropathic etiology. {ECO:0000269|PubMed:17701904}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Erythroleukemia, familial (FERLK) [MIM:133180]: An autosomal dominant myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood. Disease penetrance is incomplete. {ECO:0000269|PubMed:27416908}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Visceral neuropathy, familial, 1, autosomal recessive (VSCN1) [MIM:243180]: An autosomal recessive disorder characterized by intestinal dysmotility due to aganglionosis (Hirschsprung disease), hypoganglionosis, and/or chronic intestinal pseudoobstruction. Additional variable features are progressive peripheral neuropathy, arthrogryposis, hypoplasia or aplasia of the olfactory bulb and of the external auditory canals, microtia or anotia, and facial dysmorphism. Some patients present structural cardiac anomalies and arthrogryposis with multiple pterygia. {ECO:0000269|PubMed:33497358}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 2.3.1.41

3D-structure; Acetylation; Acyltransferase; Alternative splicing; Fatty acid biosynthesis; Fatty acid metabolism; Lipid biosynthesis; Lipid metabolism; Mitochondrion; Proteomics identification; Reference proteome; Transferase; Transit peptide

A,B

89949.3

852

0.07

35.84

6.13

-10.02

-10.5

RARA

Homo sapiens (Human)

RAR-alpha; RAR alpha; Nuclear receptor subfamily 1 group B member 1; NR1B1

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function. Receptor for retinoic acid.

Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled-coil domain functions in blocking RA-mediated transactivation and cell differentiation. {ECO:0000269|PubMed:12691149, ECO:0000269|PubMed:8302850, ECO:0000269|PubMed:8562957}.

DB00459; DB00210; DB00523; DB00926; DB00982; DB05785; DB04942; DB00799; DB00755; DB12808

O43707-1; O15296; Q15699; Q96RK4; O95273; P51946; Q15910; P50148; Q9UKP3; Q96EZ8; Q15648; Q71SY5; Q15788; Q9Y6Q9; O75376; Q9Y618; Q16236; P13056-2; P48552; Q9UPP1-2; Q9H8W4; P37231; P78527; P19793; P28702; P28702-3; P48443; Q96EB6; P63165; Q8WW24; Q2M1K9; Q91XC0; P59598; Q14457; P48552; Q96CV9; P28702; P48443; Q8WW24

NA

3D-structure; Alternative splicing; Chromosomal rearrangement; Cytoplasm; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; Reference proteome; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A

27724.1

244

0.05

50.8

5.82

-3.61

-10.49

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

-10.48

XDH

Homo sapiens (Human)

Xanthine oxidase; Xanthine dehydrogenase; XDHA

Xanthine dehydrogenase family

CH/CH(2) oxidoreductase

Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro). Key enzyme in purine degradation.

Xanthinuria 1 (XAN1) [MIM:278300]: A disorder characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. XAN1 is due to isolated xanthine dehydrogenase deficiency. Patients can metabolize allopurinol. {ECO:0000269|PubMed:10844591, ECO:0000269|PubMed:11379872, ECO:0000269|PubMed:14551354, ECO:0000269|PubMed:9153281}. The disease is caused by variants affecting the gene represented in this entry.

DB00640; DB00041; DB00437; DB00993; DB00958; DB01136; DB00856; DB00515; DB00746; DB03328; DB00997; DB03516; DB12466; DB04854; DB03147; DB04335; DB01020; DB00583; DB00170; DB01033; DB00157; DB03841; DB00336; DB01250; DB05262; DB06478; DB01168; DB00339; DB00127; DB01685; DB00831

Q9Y3R0-3

NA

2Fe-2S; 3D-structure; Cytoplasm; Disease variant; Disulfide bond; FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding; Molybdenum; NAD; Oxidoreductase; Peroxisome; Proteomics identification; Reference proteome; Secreted

A,B,C,D

143697

1307

0.08

37.9

8.01

7.07

-10.47

GRM5

Homo sapiens (Human)

MGLUR5; GPRC1E

G-protein coupled receptor 3 family

GPCR glutamate

G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity.

Charcot-Marie-Tooth disease, axonal, 2D (CMT2D) [MIM:601472]: A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:12690580, ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:17101916, ECO:0000269|PubMed:17663003, ECO:0000269|PubMed:20169446, ECO:0000269|PubMed:24604904, ECO:0000269|PubMed:25168514, ECO:0000269|PubMed:26244500, ECO:0000269|PubMed:26503042, ECO:0000269|PubMed:31173493}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neuronopathy, distal hereditary motor, autosomal dominant 5 (HMND5) [MIM:600794]: A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:12690580, ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:23279345, ECO:0000269|PubMed:24627108, ECO:0000269|PubMed:26503042}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spinal muscular atrophy, infantile, James type (SMAJI) [MIM:619042]: An autosomal dominant form of spinal muscular atrophy, a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAJI is a severe disease characterized by hypotonia manifesting in the first weeks or months of life, delayed motor development, motor regression, and muscle weakness and atrophy primarily affecting distal muscles. Additional variable features include feeding difficulties, poor overall growth, foot deformities, kyphosis, hyperlordosis, scoliosis, vocal cord dysfunction, and respiratory insufficiency. {ECO:0000269|PubMed:32181591}. The disease is caused by variants affecting the gene represented in this entry.

DB00659; DB05070; DB12733; DB06201

P41594; Q7Z6G3

NA

3D-structure; Alternative splicing; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; Methylation; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix

A

27065.4

247

0.13

42.92

9.24

11.34

-10.46

CALCRL

Homo sapiens (Human)

Calcitonin receptor-like receptor; Calcitonin gene-related peptide type 1 receptor; CGRPR; CGRP type 1 receptor

G-protein coupled receptor 2 family

GPCR secretin

Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.

Lymphatic malformation 8 (LMPHM8) [MIM:618773]: A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Adult patients with lymphedema may suffer from recurrent local infections. Impaired lymphatic drainage in the fetus can develop into hydrops fetalis, a severe condition characterized by excessive fluid accumulation in more than two fetal extra-vascular compartments and body cavities, placental enlargement and edema, pericardial or pleural effusion, or ascites. LMPHM8 is an autosomal recessive form characterized by onset in utero and fetal death due to non-immune hydrops fetalis. {ECO:0000269|PubMed:30115739}. The disease may be caused by variants affecting the gene represented in this entry.

DB16098; DB14039; DB04869; DB12457; DB12228; DB15328; DB15688

P06881; O60894; O60895

NA

3D-structure; Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix

D,A,C

31335.1

269

0.14

29.06

5.22

-7.93

-10.47

SMO

Homo sapiens (Human)

Smo-D473H; SMOH; Protein Gx

G-protein coupled receptor Fz/Smo family

GPCR frizzled

Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia. Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation. G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal.

Curry-Jones syndrome (CRJS) [MIM:601707]: A multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. {ECO:0000269|PubMed:24859340, ECO:0000269|PubMed:27236920}. The disease is caused by variants affecting the gene represented in this entry. 8 individuals have been identified with the disease-causing mutation Phe-412 and all were mosaic. The mutation could not be reliably detected in blood, greatest success rates were obtained with affected tissues obtained by invasive procedures. It is thought that the mutation has arisen postzygotically early during embryonic development (PubMed:27236920). This mutation has also been identified in ameloblastoma, medulloblastoma, meningioma, and basal cell carcinoma, and has been reported as the oncogenic driver in some of these tumors (PubMed:24859340). {ECO:0000269|PubMed:24859340, ECO:0000269|PubMed:27236920}.

DB01047; DB11978; DB06786; DB09143; DB08828

NA

NA

3D-structure; Cell membrane; Cell projection; Developmental protein; Disease variant; Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix

A,B

37420.1

333

0.16

25.17

6.65

-0.76

-10.45

pchF

Pseudomonas putida (Arthrobacter siderocapsulatus)

NA

NA

NA

Oxidoreductase

4-cresol dehydrogenase (hydroxylating) activity.Flavin adenine dinucleotide binding.Oxidoreductase activity, acting on CH-OH group of donors.

Dihydrolipoamide dehydrogenase deficiency (DLDD) [MIM:246900]: An autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. {ECO:0000269|PubMed:10448086, ECO:0000269|PubMed:11687750, ECO:0000269|PubMed:12925875, ECO:0000269|PubMed:15712224, ECO:0000269|PubMed:16442803, ECO:0000269|PubMed:16770810, ECO:0000269|PubMed:17404228, ECO:0000269|PubMed:20160912, ECO:0000269|PubMed:8506365, ECO:0000269|PubMed:8968745, ECO:0000269|PubMed:9540846, ECO:0000269|PubMed:9934985}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

NA

1.17.9.1

3D-structure; Direct protein sequencing; FAD; Flavoprotein; Oxidoreductase; Plasmid

A

57240.8

515

0.1

30.94

6.06

-4.42

-10.43

Malaria ht1

Plasmodium falciparum (malaria parasite P. falciparum)

ht1; Putative sugar transporter; Hexose transporter

Major facilitator superfamily, Sugar transporter (TC 2.A.1.1) family

NA

High-affinity glucose transporter.

Nivelon-Nivelon-Mabille syndrome (NNMS) [MIM:600092]: An autosomal recessive syndrome characterized by progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Additional variable features include early infantile-onset seizures, intrauterine and postnatal growth retardation, generalized chondrodysplasia, and micromelia. 46,XY gonadal dysgenesis may be present. {ECO:0000269|PubMed:24784881, ECO:0000269|PubMed:30912300}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

NA

3D-structure; Cell membrane; Disulfide bond; Membrane; Sugar transport; Transmembrane; Transmembrane helix; Transport

A

53412.5

476

0.14

28.88

8.51

4.43

-10.41