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

-8.19

SLC5A2

Homo sapiens (Human)

Solute carrier family 5 member 2; Na(+)/glucose cotransporter 2; Low affinity sodium-glucose cotransporter

Sodium:solute symporter (SSF) (TC 2.A.21) family

Solute:sodium symporter

Has a Na(+) to glucose coupling ratio of 1:1. Sodium-dependent glucose transporter.

Renal glucosuria (GLYS) [MIM:233100]: A disorder characterized by persistent isolated glucosuria, normal fasting serum glucose concentration, decreased renal tubular resorption of glucose from the urine, and absence of any other signs of tubular dysfunction. {ECO:0000269|PubMed:14614622}. The disease is caused by variants affecting the gene represented in this entry.

DB12236; DB08907; DB01914; DB06292; DB09038; DB11827; DB12713

O14556; Q13113

NA

3D-structure; Alternative splicing; Cell membrane; Disease variant; Disulfide bond; Glycoprotein; Ion transport; Membrane; Metal-binding; Proteomics identification; Reference proteome; Sodium; Sodium transport; Sugar transport; Symport; Transmembrane; Transmembrane helix; Transport

A

63858.9

586

0.12

39.46

8.62

7.41

-8.19

GPR119

Homo sapiens (Human)

GPR119; G-protein coupled receptor 119

G-protein coupled receptor 1 family

GPCR rhodopsin

Receptor for the endogenous fatty-acid ethanolamide oleoylethanolamide (OEA) and lysophosphatidylcholine (LPC). Functions as a glucose-dependent insulinotropic receptor. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Seems to act through a G(s) mediated pathway.

Developmental and epileptic encephalopathy 24 (DEE24) [MIM:615871]: A disease characterized by early-onset seizures, intellectual disability of varying degrees, and behavioral disturbances or autistic features in most individuals. {ECO:0000269|PubMed:24747641, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:30351409}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Generalized epilepsy with febrile seizures plus 10 (GEFSP10) [MIM:618482]: An autosomal dominant neurologic disorder with incomplete penetrance, characterized by variable types of seizures including absence, tonic-clonic, febrile, focal, and eyelid myoclonia. Some patients have normal neurologic development. Others have mild-to-moderate intellectual disability or autism spectrum disorder. {ECO:0000269|PubMed:29936235, ECO:0000269|PubMed:30351409}. The disease is caused by variants affecting the gene represented in this entry.

DB05166

Q12797-6

NA

3D-structure; Cell membrane; G-protein coupled receptor; Lipid-binding; Membrane; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

R

32134.1

292

0.12

34.96

9.12

8.03

-8.19

DAO

Homo sapiens (Human)

Daminoacid oxidase; DAMOX; DAAO

DAMOX/DASOX family

CH-NH(2) donor oxidoreductase

Regulates the level of the neuromodulator D-serine in the brain. Has high activity towards D-DOPA and contributes to dopamine synthesis. Could act as a detoxifying agent which removes D-amino acids accumulated during aging. Acts on a variety of D-amino acids with a preference for those having small hydrophobic side chains followed by those bearing polar, aromatic, and basic groups. Does not act on acidic amino acids.

Schizophrenia (SCZD) [MIM:181500]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:12364586}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Amyotrophic lateral sclerosis (ALS) [MIM:105400]: 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:20368421, ECO:0000269|PubMed:20538972, ECO:0000269|PubMed:22203986, ECO:0000269|PubMed:23219954, ECO:0000269|PubMed:24138986, ECO:0000269|PubMed:25701391, ECO:0000269|PubMed:37558109, ECO:0000269|PubMed:38035964, ECO:0000269|PubMed:38134563}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

DB07979; DB02838; DB04166; DB03793; DB03225; DB03147; DB03531; DB02988

Q9P2K6; O43741

EC 1.4.3.3

3D-structure; Amyotrophic lateral sclerosis; Cell projection; Cytoplasm; Disease variant; FAD; Flavoprotein; Neurodegeneration; Oxidoreductase; Peroxisome; Phosphoprotein; Proteomics identification; Reference proteome; S-nitrosylation; Schizophrenia; Secreted; Synapse

A,B

38654.6

340

0.11

29.13

6.18

-4.45

-8.16

MAOA

Homo sapiens (Human)

Monoamine oxidase A; Amine oxidase [flavin-containing] A

Flavin monoamine oxidase family

CH-NH(2) donor oxidoreductase

MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine. Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues.

Brunner syndrome (BRNRS) [MIM:300615]: A form of X-linked non-dysmorphic mild intellectual disability. Male patients are affected by borderline intellectual deficit and exhibit abnormal behavior, including disturbed regulation of impulsive aggression. Obligate female carriers have normal intelligence and behavior. {ECO:0000269|PubMed:8211186}. The disease is caused by variants affecting the gene represented in this entry.

DB01472; DB00918; DB00182; DB06698; DB04889; DB13876; DB01445; DB06774; DB00215; DB04017; DB09130; DB05205; DB07641; DB00988; DB01363; DB00668; DB12329; DB01175; DB03147; DB14914; DB00614; DB01381; DB07919; DB04818; DB01247; DB00601; DB01577; DB00805; DB01442; DB01171; DB08804; DB00952; DB04820; DB00184; DB04821; DB06412; DB01626; DB00780; DB00191; DB00388; DB00397; DB09244; DB04850; DB00721; DB01168; DB00571; DB00852; DB09363; DB00140; DB00953; DB06654; DB01037; DB01104; DB00669; DB14569; DB09042; DB00624; DB13943; DB13944; DB13946; DB09245; DB00752; DB15328; DB09185; DB04832; DB00315; DB00909

P27338

EC 1.4.3.4

3D-structure; Acetylation; Alternative splicing; Catecholamine metabolism; Direct protein sequencing; Disease variant; FAD; Flavoprotein; Intellectual disability; Membrane; Mitochondrion; Mitochondrion outer membrane; Neurotransmitter degradation; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix

A

58195.3

513

0.11

34.97

7.98

2.87

-8.17

NOS1

Homo sapiens (Human)

Peptidyl-cysteine S-nitrosylase NOS1; Nitric oxide synthase, brain; Neuronal NOS; NOS, type I; NOS type I; NNOS; NC-NOS; N-NOS; BNOS

NOS family

Paired donor oxygen oxidoreductase

In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body.

Variation Asp-298 in NOS3 may be associated with susceptibility to coronary spasm. {ECO:0000269|PubMed:11740345, ECO:0000269|PubMed:9737779}.

DB02143; DB02727; DB01997; DB03892; DB02207; DB03710; DB00155; DB00843; DB00997; DB03147; DB03247; DB01942; DB01221; DB02077; DB01821; DB09241; DB03144; DB03449; DB02044; DB02644; DB08019; DB08018; DB02027; DB03461; DB04223; DB06096; DB02991; DB03707

Q08AM6

EC 1.14.13.39

3D-structure; Alternative splicing; Calmodulin-binding; Cell membrane; Cell projection; FAD; Flavoprotein; FMN; Heme; Iron; Membrane; Metal-binding; NADP; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Synapse; Ubl conjugation

A,B

34875.7

299

0.1

42.94

5.96

-6.25

-8.17

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

-8.17

GSK3B

Homo sapiens (Human)

Serine/threonine-protein kinase GSK3B; GSK-3 beta

Protein kinase superfamily, CMGC Ser/Thr protein kinase family, GSK-3 subfamily

Kinase

Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2. Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation. Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation. Regulates the circadian rhythmicity of hippocampal long-term potentiation and ARNTL/BMLA1 and PER2 expression. Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer. Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1.

Neuromyotonia and axonal neuropathy, autosomal recessive (NMAN) [MIM:137200]: An autosomal recessive neurologic disorder characterized by onset in the first or second decade of a peripheral axonal neuropathy predominantly affecting motor more than sensory nerves. The axonal neuropathy is reminiscent of Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy. Individuals with NMAN also have delayed muscle relaxation and action myotonia associated with neuromyotonic discharges on needle EMG resulting from hyperexcitability of the peripheral nerves. {ECO:0000269|PubMed:16835243, ECO:0000269|PubMed:22961002, ECO:0000269|PubMed:28691797, ECO:0000269|PubMed:29787766, ECO:0000269|PubMed:31088288}. The disease is caused by variants affecting the gene represented in this entry.

DB08073; DB07149; DB07014; DB07676; DB01772; DB07859; DB07585; DB07058; DB03444; DB04014; DB01950; DB12010; DB02052; DB07947; DB14509; DB01356; DB14507; DB14508; DB07812; DB07584; DB04395; DB01793; DB02010; DB12129

P31749; P31751; PRO_0000000093 [P05067]; O15169; Q9Y2T1; Q96G01; O75952-3; O75952-5; P35222; Q5VWQ8; Q5VWQ8-2; Q9NYF0; O75398; Q13144; Q92837; P13807; O75581; Q5S007; P10636; P10636-8; Q14596; Q8N4C6; P17612; Q01201; O95863; P37840; Q6J9G0; P04637; Q14134; O95071; P63104; Q8IX07; O35625; Q14DJ8; Q02248; Q811T9; P63085; P0DTC9; P05067; P35637; P01106; Q8BMD2-1

EC 2.7.11.26

3D-structure; ADP-ribosylation; Alternative splicing; Alzheimer disease; ATP-binding; Biological rhythms; Carbohydrate metabolism; Cell membrane; Cytoplasm; Developmental protein; Diabetes mellitus; Differentiation; Glycogen metabolism; Kinase; Lipoprotein; Membrane; Neurogenesis; Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Signal transduction inhibitor; Transferase; Wnt signaling pathway

C

37917

327

0.12

29.04

5.63

-7.51

-8.17

SEC14L3

Homo sapiens (Human)

NA

TAP2

NA

Transport protein

Lipid binding.Transporter activity.

Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia (CDP-PBHM) [MIM:300863]: A disease characterized by chondrodysplasia, severe platyspondyly, hydrocephaly, and facial features with microphthalmia. Bone abnormalities include a distinctive metaphyseal cupping of the metacarpals, metatarsals, and phalanges. Affected females show a milder phenotype with small stature, sometimes associated with body asymmetry and mild intellectual disability. {ECO:0000269|PubMed:20181727}. The disease is caused by variants affecting the gene represented in this entry.

DB14003; DB14001; DB14002; DB11635; DB11251; DB00163

NA

NA

3D-structure; Alternative splicing; Lipid-binding; Proteomics identification; Reference proteome; Transport

A

46148.7

401

0.1

45.19

5.79

-5.94

-8.16

LCN2

Homo sapiens (Human)

p25; Siderocalin LCN2; Oncogene 24p3; NGAL; Lipocalin-2; LCN2; 25 kDa alpha-2-microglobulin-related subunit of MMP-9

Calycin superfamily, Lipocalin family

Calycin family

Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5- DHBA), a siderophore that shares structural similarities withbacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity, possibly by sequestrating iron, leading to limit bacterial growth. .

Pseudovaginal perineoscrotal hypospadias (PPSH) [MIM:264600]: A form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum. {ECO:0000269|PubMed:10718838, ECO:0000269|PubMed:10898110, ECO:0000269|PubMed:10999800, ECO:0000269|PubMed:12843198, ECO:0000269|PubMed:15064320, ECO:0000269|PubMed:1522235, ECO:0000269|PubMed:15528927, ECO:0000269|PubMed:15770495, ECO:0000269|PubMed:16098368, ECO:0000269|PubMed:16181229, ECO:0000269|PubMed:7554313, ECO:0000269|PubMed:8626825, ECO:0000269|PubMed:8768837, ECO:0000269|PubMed:9208814, ECO:0000269|PubMed:9745434, ECO:0000269|PubMed:9843052}. The disease is caused by variants affecting the gene represented in this entry.

DB02710; DB01672; DB01926; DB04043; DB01631; DB04476

P49419-2; Q9NXW9; Q8WXI3; Q12797-6; Q9BXY8; Q96LC9; P49069; P24863; Q9UKJ5; Q9H1P6; Q9H6B4; O14595; Q08426; Q6NZ36-4; B3EWG5; Q7Z4H3; Q6ISS4; Q5TA76; P80188; Q9UIQ6-2; Q9Y6Y9; Q96JG8; Q8IXL7-2; Q969H8; Q969S2; Q17RF5; P07237; P13667; Q96FA3; Q9NRD5; Q13526; Q9UGP5-2; Q12837; P54646; Q86Y79; O60895; Q9BWG6; P60059; O43765; Q96EQ0; Q8IYX1; Q9UL33-2; P20396; O43715; Q13049; Q99816; Q5W5X9-3; Q99757; P57075-2; Q969M7; Q9UMX0; Q9UHD9; P15692-12; Q14119; Q9Y6T4; Q9H0D6; O96006; A0A1U9X8X8

NA

3D-structure; Alternative splicing; Apoptosis; Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity; Innate immunity; Ion transport; Iron; Iron transport; Proteomics identification; Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal; Transport

A

19748.4

172

0.13

30.73

7.71

0.72

-8.18

HIV nef

Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2) (HIV-1)

nef; Nef protein; F-protein; 3'ORF; 27 kDa protein

Lentivirus primate group Nef protein family

Lentivirus primate group Nef

Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors.

Neurodegeneration due to cerebral folate transport deficiency (NCFTD) [MIM:613068]: An autosomal recessive neurodegenerative disorder resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy and leukodystrophy. {ECO:0000269|PubMed:19732866}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q14457; P01730

NA

3D-structure; AIDS; Apoptosis; Early protein; Host cell membrane; Host Golgi apparatus; Host membrane; Host-virus interaction; Inhibition of host adaptive immune response by virus; Inhibition of host autophagy by virus; Inhibition of host MHC class I molecule presentation by virus; Inhibition of host MHC class II molecule presentation by virus; Lipoprotein; Membrane; Myristate; Phosphoprotein; Reference proteome; Secreted; SH3-binding; Viral immunoevasion; Virion; Virulence

A,B

29232.1

245

0.16

50.97

5.71

-7.32

-8.16

NQO1

Homo sapiens (Human)

Qui reductase 1; QR1; Phylloquinone reductase; Phylloqui reductase; NMOR1; NAD(P)H:quinone oxidoreductase 1; NAD(P)H dehydrogenase [quinone] 1; Menadione reductase; DTD; DT-diaphorase 1; DT-diaphorase

NAD(P)H dehydrogenase (quinone) family

NADH/NADPH oxidoreductase

The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.

Congenital disorder of glycosylation 2D (CDG2D) [MIM:607091]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:11901181, ECO:0000269|PubMed:30653653, ECO:0000269|PubMed:32157688}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Combined low LDL and fibrinogen (CLDLFIB) [MIM:620364]: An autosomal recessive condition characterized by low plasma LDL-cholesterol and fibrinogen levels, and associated with a decreased risk of coronary artery disease. {ECO:0000269|PubMed:34855475}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

DB07385; DB02395; DB03626; DB14001; DB04392; DB09061; DB00958; DB02633; DB00515; DB14002; DB00266; DB00997; DB01927; DB02400; DB03147; DB00170; DB00526; DB00252; DB04090; DB00163

P07902; Q9UK53; P15559

EC 1.6.5.2

3D-structure; Alternative splicing; Cytoplasm; FAD; Flavoprotein; Isopeptide bond; NAD; NADP; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation

A,B,C,D

61454.1

546

0.12

36.74

8.99

8.99

-8.15

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

-8.16

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

-8.15

ABL2

Homo sapiens (Human)

Tyrosine-protein kinase ARG; Abelson-related gene protein; Abelson tyrosine-protein kinase 2; Abelson murine leukemia viral oncogene homolog 2; ARG; ABLL

Protein kinase superfamily, Tyr protein kinase family, ABL subfamily

Kinase

Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis.

Smith-Kingsmore syndrome (SKS) [MIM:616638]: An autosomal dominant syndrome characterized by intellectual disability, macrocephaly, seizures, umbilical hernia, and facial dysmorphic features. {ECO:0000269|PubMed:25851998, ECO:0000269|PubMed:26542245, ECO:0000269|PubMed:27830187}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Focal cortical dysplasia 2 (FCORD2) [MIM:607341]: A form of focal cortical dysplasia, a malformation of cortical development that results in medically refractory epilepsy in the pediatric population and in adults. FCORD2 is a severe form, with onset usually in childhood, characterized by disrupted cortical lamination and specific cytological abnormalities. It is classified in 2 subtypes: type IIA characterized by dysmorphic neurons and lack of balloon cells; type IIB with dysmorphic neurons and balloon cells. {ECO:0000269|PubMed:25799227, ECO:0000269|PubMed:25878179, ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:27830187}. The disease is caused by variants affecting the gene represented in this entry.

DB00171; DB01254; DB12010; DB07664; DB05184

Q8IZP0; P46108; P00533; P04626; P21860; Q15303; P36888; P06241; P62993; P10721; P16333; P27986; P19174; Q13671; Q15637; P12931; Q9NYB9-2; Q15642-2

EC 2.7.10.2

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell adhesion; Cytoplasm; Cytoskeleton; Kinase; Lipoprotein; Magnesium; Manganese; Metal-binding; Myristate; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation

A

30761.1

268

0.12

36.31

5.35

-8.63

-8.15

HNMT

Homo sapiens (Human)

Histamine-N-methyltransferase; HNMT; HMT

Class I-like SAM-binding methyltransferase superfamily, HNMT family

Methyltransferase

Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.

Intellectual developmental disorder, autosomal recessive 51 (MRT51) [MIM:616739]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:26206890}. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry.

DB00613; DB13875; DB05381; DB04655; DB01103; DB01752; DB07106

NA

EC 2.1.1.8

3D-structure; Alternative splicing; Cytoplasm; Disease variant; Intellectual disability; Methyltransferase; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Transferase

A,B

32712

288

0.1

36.38

5.18

-9.97

-8.15

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

-8.16

DPP8

Homo sapiens (Human)

Prolyl dipeptidase DPP8; MSTP141; MSTP135; MSTP097; Dipeptidyl peptidase VIII; Dipeptidyl peptidase IV-related protein 1; DPRP1; DPRP-1; DPP VIII; DP8

Peptidase S9B family, DPPIV subfamily

Peptidase

Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2.

Orotic aciduria 1 (ORAC1) [MIM:258900]: A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and intellectual disability. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. {ECO:0000269|PubMed:9042911}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 3.4.14.5

3D-structure; Alternative splicing; Aminopeptidase; Apoptosis; Cytoplasm; Hydrolase; Protease; Proteomics identification; Reference proteome; Serine protease

A,D

97764.9

849

0.12

47.71

5.69

-21.66

-8.16

Bact ilvA

Escherichia coli (strain K12)

ilvA; Putative threonine dehydratase

Serine/threonine dehydratase family

Carbon-nitrogen lyases

Catalyzes the anaerobic formation of alpha-ketobutyrate and ammonia from threonine in a two-step reaction. The first step involved a dehydration of threonine and a production of enamine intermediates (aminocrotonate), which tautomerizes to its imine form(iminobutyrate). Both intermediates are unstable and short- lived. The second step is the nonenzymatic hydrolysis of the enamine/imine intermediates to form 2-ketobutyrate and free ammonia. In the low water environment of the cell, the second step is accelerated by RidA.

Familial male precocious puberty (FMPP) [MIM:176410]: In FMPP the receptor is constitutively activated. {ECO:0000269|PubMed:11134146, ECO:0000269|PubMed:11391350, ECO:0000269|PubMed:7629248, ECO:0000269|PubMed:7692306, ECO:0000269|PubMed:7714085, ECO:0000269|PubMed:7757065, ECO:0000269|PubMed:8281137, ECO:0000269|PubMed:8829636, ECO:0000269|PubMed:8929952, ECO:0000269|PubMed:9467560, ECO:0000269|PubMed:9661624}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Luteinizing hormone resistance (LHR) [MIM:238320]: An autosomal recessive disorder characterized by unresponsiveness to luteinizing hormone, defective sexual development in males, and defective follicular development and ovulation, amenorrhea and infertility in females. Two forms of the disorder have been defined in males. Type 1 is a severe form characterized by complete 46,XY male pseudohermaphroditism, low testosterone and high luteinizing hormone levels, total lack of responsiveness to luteinizing and chorionic gonadotropin hormones, lack of breast development, and absent development of secondary male sex characteristics. Type 2, a milder form, displays a broader range of phenotypic expression ranging from micropenis to severe hypospadias. {ECO:0000269|PubMed:12050206, ECO:0000269|PubMed:15372531, ECO:0000269|PubMed:15472221, ECO:0000269|PubMed:19551906, ECO:0000269|PubMed:7719343, ECO:0000269|PubMed:8559204, ECO:0000269|PubMed:9215288, ECO:0000269|PubMed:9514160, ECO:0000269|PubMed:9626144, ECO:0000269|PubMed:9626653}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 4.3.1.19

3D-structure; Allosteric enzyme; Amino-acid biosynthesis; Branched-chain amino acid biosynthesis; Isoleucine biosynthesis; Lyase; Pyridoxal phosphate; Reference proteome; Repeat

A

53966.2

494

0.08

41.16

5.88

-8.91

-8.15

mtnN

Escherichia coli (strain K12)

NA

pfs;b0159;yadA;JW0155;mtn

PNP/UDP phosphorylase family, MtnN subfamily

hydrolase / hydrolase inhibitor

Adenosylhomocysteine nucleosidase activity.Identical protein binding.Methylthioadenosine nucleosidase activity.

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.

DB02158; DB08606; DB02933; DB00173; DB02281

P0AF12

3.2.2.9

3D-structure; Amino-acid biosynthesis; Hydrolase; Methionine biosynthesis; Reference proteome

A

24353.7

232

0.05

22.1

5.09

-9.9

-8.14