CDK4

Homo sapiens (Human)

NA

NA

Protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily

Cell cycle

ATP binding.Cyclin binding.Cyclin-dependent protein serine/threonine kinase activity.Cyclin-dependent protein serine/threonine kinase regulator activity.Protein complex binding.

Melanoma, cutaneous malignant 3 (CMM3) [MIM:609048]: A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites. {ECO:0000269|PubMed:7652577, ECO:0000269|PubMed:8528263, ECO:0000269|PubMed:9311594, ECO:0000269|PubMed:9425228}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB12001; DB03496; DB12010; DB09073; DB02733; DB11730; DB15442

Q9UH17; P24385; P30279; P30281; Q16543; P50613; P38936; P46527; P49918; P42771; P42772; P42773; P55273; Q9UJC3; P08238; Q9UKT9; Q0VD86; P01106; Q9ULD0; P28749; Q08999; P09936; Q8N720

2.7.11.22

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle; Cell division; Cytoplasm; Disease variant; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase

B

30138.4

267

0.09

36.2

5.78

-5.83

-7.61

N/A

Plasmodium falciparum (isolate HB3)

NA

NA

Peptidase A1 family

Hydrolase

Aspartic-type endopeptidase activity.

Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) [MIM:610006]: Autosomal recessive disorder and consists of a defect in catabolism of L-isoleucine which is characterized by an increase of 2-methylbutyrylglycine and 2-methylbutyrylcarnitine in blood and urine. Affected individuals have seizures and psychomotor delay as the main clinical features. {ECO:0000269|PubMed:10832746, ECO:0000269|PubMed:11013134, ECO:0000269|PubMed:16317551}. The disease is caused by variants affecting the gene represented in this entry.

DB04378; DB04373; DB11638; DB01218; DB02505; DB03063

NA

3.4.23.39

3D-structure; Aspartyl protease; Direct protein sequencing; Disulfide bond; Hydrolase; Membrane; Protease; Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix; Vacuole; Zymogen

A

36923.5

329

0.13

44.31

4.67

-17.94

-7.59

cocE

Rhodococcus sp. (strain MB1 Bresler)

NA

NA

CocE/NonD hydrolase family

Hydrolase

Carboxylic ester hydrolase activity.Dipeptidyl-peptidase activity.

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

DB03793; DB01795

NA

3.1.1.84

3D-structure; Cytoplasm; Direct protein sequencing; Hydrolase; Serine esterase

A

62127.9

574

0.09

26.62

4.56

-33.24

-7.58

HPD

Homo sapiens (Human)

NA

PPD

4HPPD family

Oxidoreductase

4-hydroxyphenylpyruvate dioxygenase activity.Metal ion binding.

Tyrosinemia 3 (TYRSN3) [MIM:276710]: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild intellectual disability. {ECO:0000269|PubMed:10942115, ECO:0000269|PubMed:11073718}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hawkinsinuria (HWKS) [MIM:140350]: An inborn error of tyrosine metabolism characterized by failure to thrive, persistent metabolic acidosis, fine and sparse hair, and excretion of the unusual cyclic amino acid metabolite, hawkinsin, in the urine. {ECO:0000269|PubMed:11073718}. The disease is caused by variants affecting the gene represented in this entry.

DB02850; DB00348

NA

1.13.11.27

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Dioxygenase; Disease variant; Endoplasmic reticulum; Golgi apparatus; Intellectual disability; Iron; Membrane; Metal-binding; Oxidoreductase; Phenylalanine catabolism; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Tyrosine catabolism

A

43164.8

376

0.11

32.38

6.73

-1.04

-7.56

CHRNA2

Homo sapiens (Human)

NA

NA

Ligand-gated ion channel (TC 1.A.9) family, Acetylcholine receptor (TC 1.A.9.1) subfamily, Alpha-2/CHRNA2 sub-subfamily

NA

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane."

Epilepsy, nocturnal frontal lobe, 4 (ENFL4) [MIM:610353]: An autosomal dominant focal epilepsy characterized by nocturnal seizures associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. {ECO:0000269|PubMed:16826524}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Seizures, benign familial infantile, 6 (BFIS6) [MIM:610353]: A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS6 inheritance is autosomal dominant. {ECO:0000269|PubMed:25847220}. The disease may be caused by variants affecting the gene represented in this entry.

DB00732; DB00237; DB00411; DB00565; DB01245; DB00514; DB01135; DB07720; DB00898; DB00472; DB00483; DB08960; DB00657; DB01336; DB00416; DB01226; DB00184; DB01337; DB01338; DB00721; DB00728; DB05740; DB00202; DB01199; DB01339

NA

NA

3D-structure; Alternative splicing; Cell membrane; Disease variant; Disulfide bond; Epilepsy; Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel; Membrane; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix; Transport

A,B,C,D,E

120584

1031

0.14

32.21

5.62

-17.58

-7.55

MT-CO2

Homo sapiens (Human)

NA

MTCO2;COXII;COII;COX2

Cytochrome c oxidase subunit 2 family

Immune system

Copper ion binding.Cytochrome-c oxidase activity.

Mitochondrial complex IV deficiency (MT-C4D) [MIM:220110]: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and intellectual disability. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh syndrome. {ECO:0000269|PubMed:10486321}. The disease is caused by variants affecting the gene represented in this entry.

DB02659; DB04464; DB05412

Q9NZ94-2; P49281-3

7.1.1.9

3D-structure; Copper; Disease variant; Electron transport; Magnesium; Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; Primary mitochondrial disease; Proteomics identification; Reference proteome; Respiratory chain; Translocase; Transmembrane; Transmembrane helix; Transport

C

21687.9

189

0.11

38

5.68

-3.26

-7.53

cumD

Pseudomonas fluorescens

NA

NA

NA

Hydrolase

Hydrolase activity.

Intellectual developmental disorder, autosomal dominant 62 (MRD62) [MIM:618793]: An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD62 is characterized by mild to moderately impaired intellectual development. {ECO:0000269|PubMed:27479843, ECO:0000269|PubMed:29460436}. The disease is caused by variants affecting the gene represented in this entry.

DB03741; DB03793; DB03568; DB02531; DB03750; DB02406; DB03766

NA

NA

3D-structure; Hydrolase

A

30307.9

271

0.1

37.49

5.02

-11.58

-7.53

pab

Finegoldia magna (Peptostreptococcus magnus)

NA

NA

NA

Protein binding

Binds serum albumin.

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}.

DB03600; DB00788

NA

NA

3D-structure; Cell wall; Peptidoglycan-anchor; Secreted; Signal

B

21751.6

189

0.1

49.17

5.44

-6.7

-7.52

CRBN

Homo sapiens (Human)

Protein cereblon

CRBN family

NA

Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2. Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. May play a role in memory and learning by regulating the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1. Binding of pomalidomide and other thalidomide-related drugs changes the substrate specificity of the human protein, leading to decreased degradation of MEIS2 and other target proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3.

Intellectual developmental disorder, autosomal recessive 2 (MRT2) [MIM:607417]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT2 patients display mild intellectual disability with a standard IQ ranged from 50 to 70. IQ scores are lower in males than females. Developmental milestones are mildly delayed. There are no dysmorphic or autistic features. {ECO:0000269|PubMed:15557513, ECO:0000269|PubMed:28143899}. The disease is caused by variants affecting the gene represented in this entry.

DB00480; DB08910; DB01041

Q96A83-2; P48729; Q16531; O14901; Q8IVT2; Q9P286; A0A6Q8PF08; Q93062; Q16531; Q13422-7

NA

3D-structure; Alternative splicing; Cytoplasm; Disease variant; Intellectual disability; Membrane; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation; Ubl conjugation pathway; Zinc

B,E

38245.7

337

0.08

40.62

5.7

-6.53

-7.53

LTA4H

Homo sapiens (Human)

Leukotriene A4 hydrolase; Leukotriene A(4)Leukotriene A-4 hydrolase hydrolase; Leukotriene A(4) hydrolase; LTA4; LTA-H; LTA-4hydrolase; LTA-4 hydrolase

Peptidase M1 family

Ether bond hydrolase

Has also aminopeptidase activity. Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4.

Pigmentary disorder, reticulate, with systemic manifestations, X-linked (PDR) [MIM:301220]: An X-linked recessive disorder characterized by recurrent infections and sterile inflammation in various organs. Diffuse skin hyperpigmentation with a distinctive reticulate pattern is universally evident by early childhood. This is later followed in many patients by hypohidrosis, corneal inflammation and scarring, enterocolitis that resembles inflammatory bowel disease, and recurrent urethral strictures. Melanin and amyloid deposition is present in the dermis. Affected males also have a characteristic facies with frontally upswept hair and flared eyebrows. Female carriers have only restricted pigmentary changes along Blaschko's lines. {ECO:0000269|PubMed:27019227}. The disease is caused by variants affecting the gene represented in this entry. XLPDR is caused by a recurrent intronic mutation that results in missplicing and reduced POLA1 expression. This leads to a decrease in cytosolic RNA:DNA hybrids and constitutive activation of type I interferon responses, but has no effect on cell replication. {ECO:0000269|PubMed:27019227}.; DISEASE: Van Esch-O'Driscoll syndrome (VEODS) [MIM:301030]: An X-linked recessive syndrome characterized by different degrees of intellectual disability, moderate to severe short stature, microcephaly, hypogonadism, and variable congenital malformations. {ECO:0000269|PubMed:31006512}. The disease is caused by variants affecting the gene represented in this entry.

DB07102; DB06917; DB07258; DB07094; DB07259; DB02352; DB07292; DB07104; DB06828; DB08466; DB01197; DB05177; DB03366; DB08040; DB06851; DB02062; DB07099; DB07260; DB07196; DB11781; DB03424; DB07237

Q9BSI4

EC 3.3.2.6

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing; Hydrolase; Leukotriene biosynthesis; Lipid metabolism; Metal-binding; Metalloprotease; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Zinc

A

68927

608

0.1

38.84

5.87

-9.86

-7.51

FLT3

Homo sapiens (Human)

Stem cell tyrosine kinase 1; STK1; STK-1; Receptor-type tyrosine-protein kinase FLT3; Fetal liver kinase-2; FLT-3; FLK2; FLK-2; FL cytokine receptor; CD135

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

Kinase

Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.

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:11090077, ECO:0000269|PubMed:11290608, ECO:0000269|PubMed:11442493, ECO:0000269|PubMed:14504097, ECO:0000269|PubMed:16266983, ECO:0000269|PubMed:18305215, ECO:0000269|PubMed:8946930, ECO:0000269|PubMed:9737679}. The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase.

DB12742; DB12267; DB12500; DB12010; DB12141; DB06469; DB06080; DB06595; DB11763; DB09079; DB11697; DB12978; DB08901; DB15822; DB12874; DB00398; DB01268; DB05465; DB11800; DB05014

P00519; P42684; P46108; P46109; P06241; Q13322; Q9Y6K9; P06239; P27986; P20936; P43405; Q8R4L0

EC 2.7.10.1

3D-structure; Alternative splicing; ATP-binding; Disease variant; Disulfide bond; Endoplasmic reticulum; Glycoprotein; Host-virus interaction; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; Reference proteome; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation

A

34209.2

298

0.14

39.68

5.57

-4.02

-7.52

ACC1

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

NA

MTR7;YNR016C;N3175;ABP2;FAS3

NA

NA

Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in the synthesis of very-long-chain fatty acid synthesis which is required to maintain a functional nuclear envelope. Required for acylation and vacuolar membrane association of VAC8 which is necessary to maintain a normal morphology of the vacuole. {ECO:0000269|PubMed:10757783, ECO:0000269|PubMed:12730220, ECO:0000269|PubMed:6103540, ECO:0000269|PubMed:6108218, ECO:0000269|PubMed:8943372}."

A chromosomal aberration involving NFKB2 is found in a case of B-cell non Hodgkin lymphoma (B-NHL). Translocation t(10;14)(q24;q32) with IGHA1. The resulting oncogene is also called Lyt-10C alpha variant.; DISEASE: A chromosomal aberration involving NFKB2 is found in a cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement produces the p80HT gene which codes for a truncated 80 kDa protein (p80HT).; DISEASE: In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions.; DISEASE: Immunodeficiency, common variable, 10 (CVID10) [MIM:615577]: A primary immunodeficiency characterized by childhood-onset of recurrent infections, hypogammaglobulinemia, and decreased numbers of memory and marginal zone B-cells. Some patients may develop autoimmune features and have circulating autoantibodies. An unusual feature is central adrenal insufficiency. {ECO:0000269|PubMed:24140114, ECO:0000269|PubMed:25524009}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q00955

6.3.4.14; 6.4.1.2

3D-structure; Acetylation; ATP-binding; Biotin; Cytoplasm; Direct protein sequencing; Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism; Ligase; Lipid biosynthesis; Lipid metabolism; Manganese; Membrane; Metal-binding; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; Reference proteome

B,C

145619

1328

0.1

30.31

5.32

-26.79

-7.5

AGTR1

Homo sapiens (Human)

Type-1 angiotensin II receptor; Angiotensin II type-1 receptor; Angiotensin II receptor 1; Angiotensin 1 receptor; AT2R1B; AT2R1; AT1BR; AT1AR; AT1; AGTR1B; AGTR1A

G-protein coupled receptor 1 family

GPCR rhodopsin

Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Receptor for angiotensin II.

Renal tubular dysgenesis (RTD) [MIM:267430]: Autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype). {ECO:0000269|PubMed:16116425}. The disease is caused by variants affecting the gene represented in this entry.

DB11842; DB08822; DB13919; DB00796; DB05739; DB00876; DB09279; DB01342; DB01029; DB00678; DB00275; DB01347; DB01349; DB00966; DB00177

PRO_0000032458 [P01019]; P35414; P05026; Q6ZMG9; O75937; P54368

NA

3D-structure; Cell membrane; Disease variant; Disulfide bond; G-protein coupled receptor; Glycoprotein; Host-virus interaction; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

A

30770.7

271

0.16

28.86

8.09

2.1

-7.48

NSD1

Homo sapiens (Human)

Nuclear receptor-binding SET domain-containing protein 1; NR-binding SET domain-containing protein; NR-binding SET domain containing protein; KMT3B; Hypothetical protein FLJ22263 similar to nuclear re

Class V-like SAM-binding methyltransferase superfamily

Methyltransferase

Preferentially methylates 'Lys-36' of histone H3 and 'Lys-20' of histone H4 (in vitro). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. Histone methyltransferase.

Sotos syndrome (SOTOS) [MIM:117550]: An autosomal dominant, childhood overgrowth syndrome characterized by pre- and postnatal overgrowth, developmental delay, intellectual disability, advanced bone age, and abnormal craniofacial morphology including macrodolichocephaly with frontal bossing, frontoparietal sparseness of hair, apparent hypertelorism, downslanting palpebral fissures, and facial flushing. Common oral findings include: premature eruption of teeth; high, arched palate; pointed chin and, more rarely, prognathism. {ECO:0000269|PubMed:11896389, ECO:0000269|PubMed:12464997, ECO:0000269|PubMed:12807965, ECO:0000269|PubMed:14997421}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Beckwith-Wiedemann syndrome (BWS) [MIM:130650]: A disorder characterized by anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumors. {ECO:0000269|PubMed:14997421}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: A chromosomal aberration involving NSD1 is found in childhood acute myeloid leukemia. Translocation t(5;11)(q35;p15.5) with NUP98.; DISEASE: A chromosomal aberration involving NSD1 is found in an adult form of myelodysplastic syndrome (MDS). Insertion of NUP98 into NSD1 generates a NUP98-NSD1 fusion product. {ECO:0000269|PubMed:15382262}.

NA

Q13283; Q16778; Q04206; O95994; Q86Z20; A8MQ03; Q3LI66; Q99750

EC 2.1.1.43

3D-structure; Activator; Alternative splicing; Chromatin regulator; Chromosomal rearrangement; Chromosome; Disease variant; Isopeptide bond; Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; Proteomics identification; Proto-oncogene; Reference proteome; Repeat; Repressor; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase; Ubl conjugation; Zinc; Zinc-finger

A

26487.9

232

0.08

37.29

8.1

2.69

-7.49

HRH1

Homo sapiens (Human)

HH1R; H1R

G-protein coupled receptor 1 family

GPCR rhodopsin

In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.

Hypertriglyceridemia, transient infantile (HTGTI) [MIM:614480]: An autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis. {ECO:0000269|PubMed:22226083, ECO:0000269|PubMed:24549054}. The disease is caused by variants affecting the gene represented in this entry.

DB01615; DB09488; DB06766; DB01246; DB00321; DB00543; DB08799; DB01238; DB14185; DB06216; DB00637; DB00719; DB00972; DB00245; DB00767; DB04890; DB06698; DB11591; DB09128; DB01237; DB00835; DB00354; DB09016; DB00748; DB06016; DB00341; DB08936; DB08800; DB01114; DB00477; DB01239; DB00568; DB00215; DB00283; DB04837; DB00363; DB01176; DB00434; DB01151; DB00967; DB00405; DB09555; DB00985; DB08801; DB01075; DB01146; DB09167; DB01142; DB00366; DB01084; DB05492; DB00751; DB01175; DB06678; DB00950; DB04841; DB00502; DB05381; DB05079; DB00557; DB04946; DB00458; DB08802; DB00920; DB00555; DB01106; DB06282; DB00455; DB09195; DB00408; DB00934; DB00737; DB06691; DB01071; DB00902; DB01403; DB06148; DB00370; DB00540; DB05080; DB06229; DB00334; DB00768; DB01173; DB01267; DB00715; DB08922; DB01619; DB01620; DB06153; DB00433; DB00420; DB01069; DB00777; DB01224; DB00912; DB00734; DB11614; DB05345; DB00342; DB04905; DB11235; DB00797; DB00656; DB00726; DB00792; DB00427; DB09185; DB00246; DB01624

NA

NA

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

R

32298.5

275

0.15

36.59

9.54

16.01

-7.48

VDR

Homo sapiens (Human)

Vitamin D(3) receptor; Nuclear vitamin D receptor; Nuclear receptor subfamily 1 group I member 1; NR1I1; 1,25-dihydroxyvitamin D3 receptor

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes. Plays a central role in calcium homeostasis. Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells.

Rickets vitamin D-dependent 2A (VDDR2A) [MIM:277440]: A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets. {ECO:0000269|PubMed:1652893, ECO:0000269|PubMed:17970811, ECO:0000269|PubMed:2177843, ECO:0000269|PubMed:2849209, ECO:0000269|PubMed:28698609, ECO:0000269|PubMed:7828346, ECO:0000269|PubMed:8106618, ECO:0000269|PubMed:8381803, ECO:0000269|PubMed:8392085, ECO:0000269|PubMed:8675579, ECO:0000269|PubMed:8961271, ECO:0000269|PubMed:9005998}. The disease is caused by variants affecting the gene represented in this entry.

DB07530; DB08742; DB01436; DB04891; DB00146; DB02300; DB00136; DB00169; DB04540; DB05024; DB11672; DB14635; DB01070; DB06410; DB05295; DB06194; DB00153; DB04796; DB03451; DB00910; DB04258; DB11094

P35222; Q09472; Q15648; P50222; Q15788; P26045; P19793; Q13573; Q13501; P04637; Q15645; Q9JLI4; P28700; X5D778; Q96HA8; Q01804; Q96S38; P48443

NA

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

A

28781

254

0.07

47.69

6.15

-3.44

-7.48

MT-CYB

Bos taurus (Bovine)

NA

CYTB;MTCYB;COB

Cytochrome b family

NA

Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c. Contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis. {ECO:0000269|PubMed:1327781, ECO:0000269|PubMed:20025846, ECO:0000269|PubMed:9485330, ECO:0000305|PubMed:189810}."

Combined oxidative phosphorylation deficiency 6 (COXPD6) [MIM:300816]: A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy. {ECO:0000269|PubMed:20362274, ECO:0000269|PubMed:22019070, ECO:0000269|PubMed:25583628, ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:26173962, ECO:0000269|PubMed:27178839}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, X-linked recessive, 4, with or without cerebellar ataxia (CMTX4) [MIM:310490]: A neuromuscular disorder characterized by progressive sensorimotor axonal neuropathy, distal sensory impairment, difficulty walking due to peripheral neuropathy and/or cerebellar ataxia, and deafness due to auditory neuropathy. Additional features include cognitive impairment, cerebellar atrophy, dysarthria, abnormal extraocular movements, tremor, dysmetria and spasticity. The age at onset ranges from infancy to young adulthood. {ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:26004228}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Deafness, X-linked, 5, with peripheral neuropathy (DFNX5) [MIM:300614]: A form of hearing loss characterized by absent or severely abnormal auditory brainstem response, abnormal middle ear reflexes, abnormal speech discrimination, loss of outer hair cell function, and cochlear nerve hypoplasia. DFNX5 patients manifest auditory neuropathy with childhood onset, associated with distal sensory impairment affecting the peripheral nervous system. {ECO:0000269|PubMed:25986071}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy (SEMDHL) [MIM:300232]: An X-linked recessive developmental disorder characterized by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy. {ECO:0000269|PubMed:28842795}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

NA

3D-structure; Electron transport; Heme; Iron; Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; Reference proteome; Respiratory chain; Transmembrane; Transmembrane helix; Transport; Ubiquinone

C,D,F,G,H

99281.2

866

0.12

43.81

8.32

7.12

-7.47

RARB

Homo sapiens (Human)

RAR-epsilon; RAR-beta; Nuclear receptor subfamily 1 group B member 2; NR1B2; HBV-activated protein; HAP

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 or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function. Receptor for retinoic acid.

Microphthalmia, syndromic, 12 (MCOPS12) [MIM:615524]: A form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS12 patients manifest variable features, including diaphragmatic hernia, pulmonary hypoplasia, and cardiac abnormalities. {ECO:0000269|PubMed:24075189, ECO:0000269|PubMed:27120018}. The disease is caused by variants affecting the gene represented in this entry.

DB00459; DB00210; DB00523; DB02877; DB00926; DB05785; DB04942; DB00799; DB00755; DB12808

O95273; P50222; Q9UBK2; P62195; P28702; P28702-3; P48443; P03255

NA

3D-structure; Alternative splicing; Cytoplasm; Disease variant; DNA-binding; Metal-binding; Microphthalmia; Nucleus; Phosphoprotein; Proto-oncogene; Receptor; Reference proteome; Transcription; Transcription regulation; Zinc; Zinc-finger

A,B

25904.1

229

0.06

44.34

7.55

0.73

-7.47

ADRA2A

Homo sapiens (Human)

Alpha-2AAR; Alpha-2A adrenoreceptor; Alpha-2A adrenoceptor; Alpha-2A adrenergic receptor; Alpha-2 adrenergic receptor subtype C10; ADRAR; ADRA2R

G-protein coupled receptor 1 family, Adrenergic receptor subfamily, ADRA2A sub-subfamily

GPCR rhodopsin

The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol. Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.

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

DB01472; DB00321; DB00543; DB00182; DB00714; DB00964; DB09229; DB01238; DB14185; DB06216; DB00865; DB00217; DB00484; DB01200; DB00248; DB01136; DB04846; DB00477; DB09202; DB00575; DB00363; DB01151; DB00633; DB01576; DB11273; DB13345; DB00320; DB00449; DB11278; DB09167; DB04855; DB06262; DB01363; DB05492; DB00751; DB00668; DB01049; DB00696; DB01175; DB06678; DB09194; DB00800; DB06623; DB00629; DB01018; DB00502; DB11577; DB00555; DB06707; DB00589; DB04948; DB09195; DB00408; DB08815; DB00934; DB01365; DB01577; DB01403; DB00968; DB06148; DB00370; DB09205; DB09242; DB06711; DB01149; DB00368; DB00540; DB06229; DB00935; DB01267; DB00715; DB01186; DB01608; DB00925; DB00692; DB00397; DB09286; DB09244; DB06153; DB00413; DB00457; DB00433; DB01069; DB00852; DB01224; DB11124; DB11738; DB00268; DB09304; DB06764; DB13025; DB00697; DB00797; DB00193; DB00656; DB00726; DB11477; DB06694; DB01392; DB00246; DB01624

NA

NA

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

R

30303.9

263

0.16

35.08

9.66

16.82

-7.47

MIF

Homo sapiens (Human)

Phenylpyruvate tautomerase; MMIF; L-dopachrome tautomerase; L-dopachrome isomerase; Glycosylation-inhibiting factor; GLIF; GIF

MIF family

Intramolecular oxidoreductase

Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity. Pro-inflammatory cytokine.

Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]: An inflammatory articular disorder with systemic onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. {ECO:0000269|PubMed:11508429}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB01880; DB07888; DB08334; DB08335; DB08333; DB07718; DB08765; DB02728

O43521-2; P00533; Q92743; P14174; Q96HA8

EC 5.3.2.1

3D-structure; Acetylation; Cytokine; Cytoplasm; Direct protein sequencing; Immunity; Inflammatory response; Innate immunity; Isomerase; Proteomics identification; Reference proteome; Secreted

A,C

24671.9

228

0.09

31.45

8.37

2.26

-7.47