qacR

Staphylococcus aureus

NA

SAP104C_022;SAP100B_005

NA

Transcription

DNA binding.Transcription factor activity, sequence-specific DNA binding.

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.

DB04209; DB03608; DB03808; DB01123

NA

NA

3D-structure; Direct protein sequencing; DNA-binding; Plasmid; Repressor; Transcription; Transcription regulation

A,B,D,E

43715

372

0.13

34.92

8.24

2.33

-6.88

NPPB

Homo sapiens (Human)

NA

NA

Natriuretic peptide family

Hormone / growth factor receptor

Diuretic hormone activity.Hormone activity.Peptide hormone receptor binding.Receptor binding.

Multiple fibroadenomas of the breast (MFAB) [MIM:615554]: A benign breast disease marked by lobuloalveolar growth with abnormally high proliferation of the epithelium, and characterized by the presence of more than 3 fibroadenomas in one breast. Fibroadenomas are adenomas containing fibrous tissue. {ECO:0000269|PubMed:18779591}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hyperprolactinemia (HPRL) [MIM:615555]: A disorder characterized by increased levels of prolactin in the blood not associated with gestation or the puerperium. HPRL may result in infertility, hypogonadism, and galactorrhea. {ECO:0000269|PubMed:24195502}. The disease is caused by variants affecting the gene represented in this entry.

DB01136; DB06412

A8MQ03; P57678; Q6A162; P60411; Q7Z3S9; P25788; Q9UJW9

NA

3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein; Hormone; Pharmaceutical; Proteoglycan; Proteomics identification; Reference proteome; Secreted; Signal; Vasoactive; Vasodilator

E

46353.1

415

0.1

37.91

5.51

-12.09

-6.89

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

-6.89

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

-6.88

SDHB

Sus scrofa (Pig)

NA

NA

Succinate dehydrogenase/fumarate reductase iron-sulfur protein family

NA

Iron-sulfur protein (IP) subunit of the succinate dehydrogenase complex (mitochondrial respiratory chain complex II), responsible for transferring electrons from succinate to ubiquinone (coenzyme Q) (PubMed:15989954). SDH also oxidizes malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate. Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerized into keto-oxaloacetate (By similarity). {ECO:0000250|UniProtKB:Q3T189, ECO:0000269|PubMed:15989954}."

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

NA

1.1.5.-; 1.3.5.1

2Fe-2S; 3D-structure; 3Fe-4S; 4Fe-4S; Acetylation; Electron transport; Iron; Iron-sulfur; Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; Oxidoreductase; Reference proteome; Transit peptide; Transport; Tricarboxylic acid cycle

A,B,C,D

120840

1092

0.09

39.34

7.64

4.11

-6.89

PTK6

Homo sapiens (Human)

Protein-tyrosine kinase 6; Breast tumor kinase; BRK

Protein kinase superfamily, Tyr protein kinase family, BRK/PTK6/SIK subfamily

Kinase

Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Associates also with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage-independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways.

Periodic paralysis hypokalemic 1 (HOKPP1) [MIM:170400]: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. {ECO:0000269|PubMed:17418573, ECO:0000269|PubMed:18162704, ECO:0000269|PubMed:19118277, ECO:0000269|PubMed:7987325, ECO:0000269|PubMed:8004673}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Malignant hyperthermia 5 (MHS5) [MIM:601887]: Autosomal dominant disorder that is potentially lethal in susceptible individuals on exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants. {ECO:0000269|PubMed:9199552}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Thyrotoxic periodic paralysis 1 (TTPP1) [MIM:188580]: A sporadic muscular disorder characterized by episodic weakness and hypokalemia during a thyrotoxic state. It is clinically similar to hereditary hypokalemic periodic paralysis, except for the fact that hyperthyroidism is an absolute requirement for disease manifestation. The disease presents with recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest. Thyrotoxic periodic paralysis can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves disease. {ECO:0000269|PubMed:15001631}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy 18 (CMYO18) [MIM:620246]: A congenital myopathy of variable severity, ranging from severe fetal akinesia to milder forms of muscle weakness. Most affected individuals show delayed motor development with generalized hypotonia and progressive axial and limb muscle weakness beginning soon after birth or in infancy. Additional features may include swallowing difficulties, external ophthalmoplegia, ptosis, high-arched palate, and respiratory insufficiency. Muscle biopsy shows variable morphologic abnormalities, including alveolar changes in the intermyofibrillar network, fiber size variability, focal disorganization, internal nuclei, and dilated sarcoplasmic reticulum and T-tubules. CMYO18 inheritance is autosomal dominant or recessive. {ECO:0000269|PubMed:28012042, ECO:0000269|PubMed:31227654, ECO:0000269|PubMed:33060286}. The disease is caused by variants affecting the gene represented in this entry.

DB12010; DB11800; DB05294; DB15035

Q08043; Q3KP44; Q13191; Q16543; Q92841; Q8N9I9; Q5JST6; P04626; O00471; O14526; Q13480; P08238; P42858; Q9UKT9; Q5VWX1; Q5T5P2-6; P10721; O14770-4; Q13064; Q8TDC0; P78337; Q9NQX0; Q13882; Q04864; P23246; Q13239-3; O00401; Q9BYN7

EC 2.7.10.2

3D-structure; Alternative splicing; ATP-binding; Cell projection; Cytoplasm; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase

A

30240.6

264

0.09

46.88

6.95

-0.14

-6.89

HNF4A

Homo sapiens (Human)

Transcription factor HNF-4; Transcription factor 14; TCF14; TCF-14; Nuclear receptor subfamily 2 group A member 1; NR2A1; HNF4; HNF-4-alpha

Nuclear hormone receptor family, NR2 subfamily

Nuclear hormone receptor

Activates the transcription of CYP2C38. Represses the CLOCK-ARNTL/BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells. Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes.

Maturity-onset diabetes of the young 1 (MODY1) [MIM:125850]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. {ECO:0000269|PubMed:10389854, ECO:0000269|PubMed:17407387, ECO:0000269|PubMed:9243109, ECO:0000269|PubMed:9313765}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Type 2 diabetes mellitus (T2D) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:9449683}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young (FRTS4) [MIM:616026]: An autosomal dominant disease characterized by Fanconi syndrome associated with a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes. Fanconi syndrome is a proximal tubulopathy resulting in generalized aminoaciduria, low molecular weight proteinuria, glycosuria, hyperphosphaturia and hypouricemia. Some FRTS4 patients have nephrocalcinosis, renal impairment, hypercalciuria with relative hypocalcemia, and hypermagnesemia. {ECO:0000269|PubMed:22802087, ECO:0000269|PubMed:24285859}. The disease is caused by variants affecting the gene represented in this entry.

DB05447; DB03017; DB08231

Q99967; A8MYZ6; P04150; Q9UBK2; Q92786; P23246; Q12772; P04637; P11532; O14602; O43688

NA

3D-structure; Acetylation; Activator; Alternative promoter usage; Alternative splicing; Biological rhythms; Diabetes mellitus; Disease variant; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

B

23446.1

205

0.08

39.17

5.05

-6.97

-6.88

TK1

Homo sapiens (Human)

Thymidine kinase, cytosolic

Thymidine kinase family

Kinase

cytosol, identical protein binding, thymidine kinase activity, zinc ion binding, DNA metabolic process, nucleobase-containing compound metabolic process, protein homotetramerization, pyrimidine nucleoside salvage, thymidine metabolic process

Seizures, benign familial infantile, 3 (BFIS3) [MIM:607745]: 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. BFIS3 inheritance is autosomal dominant. {ECO:0000269|PubMed:11371648, ECO:0000269|PubMed:12243921, ECO:0000269|PubMed:15048894, ECO:0000269|PubMed:16417554, ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:17386050, ECO:0000269|PubMed:18479388, ECO:0000269|PubMed:20371507, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23360469, ECO:0000269|PubMed:23758435, ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 11 (DEE11) [MIM:613721]: An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. {ECO:0000269|PubMed:19783390, ECO:0000269|PubMed:19786696, ECO:0000269|PubMed:20956790, ECO:0000269|PubMed:22677033, ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:23550958, ECO:0000269|PubMed:23662938, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:23935176, ECO:0000269|PubMed:23988467, ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:24579881, ECO:0000269|PubMed:24659627, ECO:0000269|PubMed:24710820, ECO:0000269|PubMed:25457084, ECO:0000269|PubMed:25459969, ECO:0000269|PubMed:25772804, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:29625812, ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217, ECO:0000269|PubMed:30415926}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Defects in SCN2A are associated with genetic epilepsy with febrile seizures plus (GEFS+), a familial autosomal dominant epilepsy syndrome, a clinical subset of febrile seizures, characterized by frequent episodes after 6 years of age and various types of subsequent epilepsy. {ECO:0000269|PubMed:29635106}.; DISEASE: Defects in SCN2A are associated with autism spectrum disorders (ASD). It seems that mutations resulting in sodium channel gain of function and increased neuron excitability lead to infantile seizures, whereas variants resulting in sodium channel loss of function and decrease neuron excitability are associated with ASD. {ECO:0000269|PubMed:28256214}.; DISEASE: Episodic ataxia 9 (EA9) [MIM:618924]: An autosomal dominant neurologic disorder characterized by episodic ataxia manifesting in the first years of life, early-onset seizures, difficulty walking, dizziness, slurred speech, headache, vomiting, and pain. The duration of ataxic episodes is heterogeneous. Most patients show episodes lasting minutes to maximum several hours, but periods lasting days up to weeks have been reported. Some patients have mildly delayed development with speech delay and/or autistic features or mildly impaired intellectual development. {ECO:0000269|PubMed:26645390, ECO:0000269|PubMed:27159988, ECO:0000269|PubMed:27328862, ECO:0000269|PubMed:28065826}. The disease is caused by variants affecting the gene represented in this entry.

DB01692; DB04485; DB02452; DB00432; DB00495

P05067; A0A087WZT3; Q92993; Q1RN33; P04183

EC 2.7.1.21

3D-structure; Acetylation; ATP-binding; Cytoplasm; DNA synthesis; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Transferase; Ubl conjugation; Zinc

A

19373.5

174

0.09

36.21

8.63

3.88

-6.89

MAP2K1

Homo sapiens (Human)

PRKMK1; Mitogen-activated protein kinase kinase 1; MKK1; MEK 1; MAPKK 1; MAPK/ERKkinase 1; MAPK/ERK kinase 1; MAP kinase kinase 1; Dual specificity mitogen-activated protein kinase kinase 1

Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase subfamily

Kinase

Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway.

Cardiofaciocutaneous syndrome 3 (CFC3) [MIM:615279]: 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. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures. {ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:18042262}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melorheostosis, isolated (MEL) [MIM:155950]: A sclerosing bone disorder characterized by hyperostosis of the cortex of tubular bones, frequently involving one limb. The lesions may be accompanied by abnormalities of adjacent soft tissue, joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangioma. {ECO:0000269|PubMed:29643386}. The disease is caused by variants affecting the gene represented in this entry.

DB06892; DB07046; DB08208; DB03115; DB11967; DB06616; DB05239; DB02152; DB07101; DB08130; DB14904; DB11689; DB08911

Q8N9N5; Q8N9N5-2; Q9NR09; P15056; Q9Y297; O15519-1; P28482; P27361; Q13526; Q9H8W4; P04049; Q8WWU5-7; Q86Y07; Q86Y07-1; P46937

EC 2.7.12.2

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cardiomyopathy; Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease variant; Ectodermal dysplasia; Intellectual disability; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase

B

34785.9

311

0.07

46.58

6.29

-2.54

-6.89

EPCAM

Homo sapiens (Human)

hEGP314; TROP1; TACSTD1; Major gastrointestinal tumor-associated protein GA733-2; MIC18; M4S1; M1S2; KSA; KS 1/4 antigen; Gastrointestinal carcinoma antigen GA733; GA733-2; Epithelial glycoprotein 314

EPCAM family

NA

Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E. May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection.

Diarrhea 5, with tufting enteropathy, congenital (DIAR5) [MIM:613217]: An intractable diarrhea of infancy characterized by villous atrophy and absence of inflammation, with intestinal epithelial cell dysplasia manifesting as focal epithelial tufts in the duodenum and jejunum. {ECO:0000269|PubMed:18572020, ECO:0000269|PubMed:24142340}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Lynch syndrome 8 (LYNCH8) [MIM:613244]: A form of Lynch syndrome, an autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. Lynch syndrome is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, it is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical Lynch syndrome is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected Lynch syndrome' or 'incomplete Lynch syndrome' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. {ECO:0000269|PubMed:19098912}. The disease is caused by variants affecting the gene represented in this entry. LYNCH8 results from heterozygous deletion of 3-prime exons of EPCAM and intergenic regions directly upstream of MSH2, resulting in transcriptional read-through and epigenetic silencing of MSH2 in tissues expressing EPCAM.

DB06607; DB11075; DB05831; DB05319; DB09336

P27797; P12830; Q15078; P36957; Q8TDX7

NA

3D-structure; Cell junction; Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Hereditary nonpolyposis colorectal cancer; Membrane; Proteomics identification; Reference proteome; Repeat; Signal; Tight junction; Transmembrane; Transmembrane helix; Tumor antigen

A

27439.8

243

0.07

33.77

6.03

-1.99

-6.89

SLC22A3

Homo sapiens (Human)

Solute carrier family 22 member 3; Extraneuronal monoamine transporter; EMTH

Major facilitator (TC 2.A.1) superfamily, Organic cation transporter (TC 2.A.1.19) family

NA

Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.

Deafness, autosomal dominant, 2A (DFNA2A) [MIM:600101]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:10025409, ECO:0000269|PubMed:10369879, ECO:0000269|PubMed:10571947, ECO:0000269|PubMed:10925378, ECO:0000269|PubMed:21242547}. The disease is caused by variants affecting the gene represented in this entry.

DB00718; DB08838; DB00182; DB00122; DB14006; DB00501; DB00575; DB00363; DB01151; DB00988; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB00983; DB00536; DB05381; DB00458; DB00762; DB00709; DB00448; DB08882; DB01042; DB01577; DB00331; DB08893; DB00184; DB00368; DB00526; DB00925; DB00413; DB00457; DB01035; DB00396; DB00938; DB00391; DB13943; DB13944; DB08837; DB08841; DB00541

P00519

NA

3D-structure; Cell membrane; Glycoprotein; Ion transport; Membrane; Mitochondrion; Nucleus; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix; Transport

A

53067.4

478

0.13

38.82

9.07

10.54

-6.88

KMT5C

Homo sapiens (Human)

Lysine N-methyltransferase 5C; Lysine-specific methyltransferase 5C; Suppressor of variegation 4-20 homolog 2; Su(var)4-20 homolog 2; Suv4-20h2; [histone H4]-N-methyl-L-lysine20 N-methyltransferase KM

Class V-like SAM-binding methyltransferase superfamily, Histone-lysine methyltransferase family, Suvar4-20 subfamily

NA

Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity. In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes. H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5C is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4. May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity).

Brachydactyly A2 (BDA2) [MIM:112600]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type A2 shortening of the middle phalanges is confined to the index finger and the second toe, all other digits being more or less normal. Because of a rhomboid or triangular shape of the affected middle phalanx, the end of the second finger usually deviates radially. {ECO:0000269|PubMed:19327734, ECO:0000269|PubMed:21357617}. The gene represented in this entry is involved in disease pathogenesis. Duplications of a cis-regulatory element located approximately 110 kb downstream of BMP2 have been found in BDA2 families. They likely cause altered BMP2 expression with pathological consequences. {ECO:0000269|PubMed:19327734, ECO:0000269|PubMed:21357617}.; DISEASE: Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 (SSFSC1) [MIM:617877]: An autosomal dominant disorder characterized by short stature, facial dysmorphism, skeletal anomalies, and variable cardiac defects. Distinctive facial features include midface retrusion, short upturned nose, long philtrum, high-arched or cleft palate, and variable degrees of micrognathia and dental crowding. Skeletal anomalies include patterning defects of the axial skeleton, characterized by 11 pairs of ribs and brachydactyly of the fifth ray. Congenital heart defects are variably observed and appear to involve primarily the cardiac outflow tract. {ECO:0000269|PubMed:29198724}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q13185

EC 2.1.1.361

3D-structure; Alternative splicing; Chromatin regulator; Chromosome; Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repressor; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase; Zinc

A

27285.8

240

0.1

42.74

8.32

3.24

-6.88

CHRNA3-CHRNB4

Homo sapiens (Human)

Neuronal acetylcholine receptor

Ligand-gated ion channel (TC 1.A.9) family, Acetylcholine receptor (TC 1.A.9.1) subfamily, Alpha-3/CHRNA3 sub-subfamily

Neurotransmitter receptor

A type of nicotinic acetylcholine receptor, consisting of 3 and 4 subunits.

Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT (BAIPRCK) [MIM:191800]: An autosomal recessive disease characterized by impaired innervation and autonomic dysfunction of the urinary bladder, hydronephrosis, vesicoureteral reflux, small kidneys, recurrent urinary tract infections, and progressive renal insufficiency. Additional autonomic features are impaired pupillary reflex and orthostatic hypotension. The disease manifests in utero or early childhood. {ECO:0000269|PubMed:31708116}. The disease is caused by variants affecting the gene represented in this entry.

DB00915; DB01156; DB00237; DB00565; DB09028; DB00514; DB07720; DB00898; DB00472; DB05710; DB01227; DB00848; DB00333; DB00184; DB01090; DB00202; DB01273

NA

NA

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

A,B

89661.2

775

0.12

35.11

6.07

-5.67

-6.88

ASL

Homo sapiens (Human)

NA

NA

Lyase 1 family, Argininosuccinate lyase subfamily

Lyase

Argininosuccinate lyase activity.Identical protein binding.

Argininosuccinic aciduria (ARGINSA) [MIM:207900]: An autosomal recessive disorder of the urea cycle. The disease is characterized by mental and physical retardation, liver enlargement, skin lesions, dry and brittle hair showing trichorrhexis nodosa microscopically and fluorescing red, convulsions, and episodic unconsciousness. {ECO:0000269|PubMed:11747432, ECO:0000269|PubMed:11747433, ECO:0000269|PubMed:12408190, ECO:0000269|PubMed:1705937, ECO:0000269|PubMed:17326097, ECO:0000269|PubMed:19703900, ECO:0000269|PubMed:22081021, ECO:0000269|PubMed:2263616, ECO:0000269|PubMed:24166829, ECO:0000269|PubMed:9045711}. The disease is caused by variants affecting the gene represented in this entry. The phenotype heterogeneity among patients is associated with interallelic complementation resulting in either complete loss of activity or partial regeneration of functional active sites in the heterotetrameric mutant protein. {ECO:0000269|PubMed:11747433}.

DB03814; DB00125; DB02267

P04424; Q9BTE3-2; Q96HA8; O75382

4.3.2.1

3D-structure; Acetylation; Alternative splicing; Amino-acid biosynthesis; Arginine biosynthesis; Disease variant; Lyase; Proteomics identification; Reference proteome; Urea cycle

A,B

51364.1

459

0.08

35.82

6.66

-1.25

-6.87

MMP16

Homo sapiens (Human)

Membrane-type-3 matrix metalloproteinase; Membrane-type matrix metalloproteinase 3; MTMMP3; MT3MMP; MT3-MMP; MT-MMP 3; MMPX2; MMP-X2; C8orf57

Peptidase M10A family

Peptidase

Activates progelatinase A. Involved in the matrix remodeling of blood vessels. Isoform short cleaves fibronectin and also collagen type III, but at lower rate. It has no effect on type I, II, IV and V collagen. However, upon interaction with CSPG4, it may be involved in degradation and invasion of type I collagen by melanoma cells. Endopeptidase that degrades various components of the extracellular matrix, such as collagen type III and fibronectin.

Cerebral creatine deficiency syndrome 3 (CCDS3) [MIM:612718]: An autosomal recessive disorder characterized by developmental delay/regression, intellectual disability, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain. Most patients develop a myopathy characterized by muscle weakness and atrophy later in life. {ECO:0000269|PubMed:11555793, ECO:0000269|PubMed:20682460, ECO:0000269|PubMed:22386973, ECO:0000269|PubMed:23660394, ECO:0000269|PubMed:23770102, ECO:0000269|PubMed:26490222, ECO:0000269|PubMed:27233232}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Fanconi renotubular syndrome 1 (FRTS1) [MIM:134600]: A form of Fanconi renotubular syndrome, a disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. FRTS1 inheritance is autosomal dominant. {ECO:0000269|PubMed:29654216}. The disease is caused by variants affecting the gene represented in this entry.

DB03880; DB00786

NA

EC 3.4.24.-

3D-structure; Alternative splicing; Calcium; Cell membrane; Cleavage on pair of basic residues; Collagen degradation; Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Signal; Transmembrane; Transmembrane helix; Zinc; Zymogen

A

18853.6

169

0.12

33.65

4.88

-12.42

-6.88

MAP2K1

Homo sapiens (Human)

NA

PRKMK1;MEK1

Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase subfamily

Transferase

ATP binding.MAP kinase kinase activity.Protein C-terminus binding.Protein kinase activity.Protein N-terminus binding.Protein serine/threonine/tyrosine kinase activity.Protein serine/threonine kinase activator activity.Protein serine/threonine kinase activity.Protein tyrosine kinase activity.Signal transducer, downstream of receptor, with protein tyrosine phosphatase activity.

Cardiofaciocutaneous syndrome 3 (CFC3) [MIM:615279]: 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. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures. {ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:18042262}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melorheostosis, isolated (MEL) [MIM:155950]: A sclerosing bone disorder characterized by hyperostosis of the cortex of tubular bones, frequently involving one limb. The lesions may be accompanied by abnormalities of adjacent soft tissue, joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangioma. {ECO:0000269|PubMed:29643386}. The disease is caused by variants affecting the gene represented in this entry.

DB06892; DB07046; DB08208; DB03115; DB11967; DB06616; DB05239; DB02152; DB07101; DB08130; DB14904; DB11689; DB08911

Q8N9N5; Q8N9N5-2; Q9NR09; P15056; Q9Y297; O15519-1; P28482; P27361; Q13526; Q9H8W4; P04049; Q8WWU5-7; Q86Y07; Q86Y07-1; P46937

2.7.12.2

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cardiomyopathy; Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease variant; Ectodermal dysplasia; Intellectual disability; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase

A

34949.2

312

0.07

45.3

5.96

-4.47

-6.87

PDE4C

Homo sapiens (Human)

NA

DPDE1

Cyclic nucleotide phosphodiesterase family, PDE4 subfamily

Hydrolase

3',5'-cyclic-AMP phosphodiesterase activity.Metal ion binding.

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.

DB01427; DB00201; DB05219; DB00651; DB06246; DB05266; DB01088; DB01791; DB01656; DB01954; DB09283

Q96D03; O15499; P26718; P50221; Q6FHY5; Q9UJX0; P26367; P30626; P59817; P30626

3.1.4.53

3D-structure; Alternative splicing; cAMP; Cell projection; Cilium; Hydrolase; Manganese; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome; Zinc

A

33042.2

291

0.08

23.45

4.91

-18.1

-6.87

GLTP

Homo sapiens (Human)

NA

NA

GLTP family

Lipid transport

Glycolipid binding.Glycolipid transporter activity.Identical protein binding.Intermembrane lipid transfer activity.Lipid binding.

Brugada syndrome 7 (BRGDA7) [MIM:613120]: 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:20031595}. The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Atrial fibrillation, familial, 16 (ATFB16) [MIM:613120]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:20558140, ECO:0000269|PubMed:21051419}. The disease is caused by variants affecting the gene represented in this entry.

DB03600; DB04465; DB03017; DB03203

Q96DZ9; Q9NZD2

NA

3D-structure; Acetylation; Cytoplasm; Lipid transport; Proteomics identification; Reference proteome; Repeat; Transport

A

23534.1

206

0.11

36.45

7.08

0.1

-6.87

APEX1

Homo sapiens (Human)

Redox factor-1; REF1; REF-1; HAP1; DNA-(apurinic or apyrimidinic site) lyase; Apurinic-apyrimidinic endonuclease 1; APX; APEX nuclease; APEX; APEN; APE1; APE-1; APE

DNA repair enzymes AP/ExoA family

Alpha-carbonic anhydrase

Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 are DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.

Microvascular complications of diabetes 5 (MVCD5) [MIM:612633]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Disease susceptibility is associated with variants affecting the gene represented in this entry. Homozygosity for the Leu-55 allele is strongly associated with the development of retinal disease in diabetic patients.

DB04967

Q09472; Q8N4N3; Q16236; Q96EB6; O88846

EC 3.1.-.-

3D-structure; Acetylation; Activator; Cleavage on pair of basic residues; Cytoplasm; Direct protein sequencing; Disulfide bond; DNA damage; DNA recombination; DNA repair; DNA-binding; Endonuclease; Endoplasmic reticulum; Exonuclease; Hydrolase; Magnesium; Metal-binding; Mitochondrion; Nuclease; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repressor; RNA-binding; S-nitrosylation; Transcription; Transcription regulation; Ubl conjugation

A,D

31820.9

285

0.1

42.58

8.35

3.27

-6.87

MGLL

Homo sapiens (Human)

Monoacylglycerol lipase; MGL; Lysophospholipaselike; Lysophospholipase-like; Lysophospholipase homolog; HUK5; HU-K5

AB hydrolase superfamily, Monoacylglycerol lipase family

Carboxylic ester hydrolase

Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain. Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth. Converts monoacylglycerides to free fatty acids and glycerol.

Systemic lupus erythematosus 9 (SLEB9) [MIM:610927]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:17360460}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency, common variable, 7 (CVID7) [MIM:614699]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. {ECO:0000269|PubMed:22035880}. The disease is caused by variants affecting the gene represented in this entry.

NA

P07550; P37235

EC 3.1.1.23

3D-structure; Alternative splicing; Cytoplasm; Fatty acid biosynthesis; Fatty acid metabolism; Hydrolase; Lipid biosynthesis; Lipid degradation; Lipid metabolism; Membrane; Nitration; Phosphoprotein; Proteomics identification; Reference proteome; Serine esterase

A

31808.4

289

0.08

29.7

6.73

-0.91

-6.87