ponA

Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

NA

SP_0369

Glycosyltransferase 51 family; Transpeptidase family

Biosynthetic protein

Penicillin binding.Peptidoglycan glycosyltransferase activity.Serine-type D-Ala-D-Ala carboxypeptidase activity.

Aminoacylase-1 deficiency (ACY1D) [MIM:609924]: An enzymatic deficiency resulting in encephalopathy, unspecific psychomotor delay, psychomotor delay with atrophy of the vermis and syringomyelia, marked muscular hypotonia or normal clinical features. Epileptic seizures are a frequent feature. All affected individuals exhibit markedly increased urinary excretion of several N-acetylated amino acids. {ECO:0000269|PubMed:16274666, ECO:0000269|PubMed:16465618, ECO:0000269|PubMed:17562838, ECO:0000269|PubMed:21414403}. The disease is caused by variants affecting the gene represented in this entry.

DB01150; DB05659

NA

2.4.99.28; 3.4.16.4

3D-structure; Antibiotic resistance; Carboxypeptidase; Cell shape; Cell wall biogenesis/degradation; Glycosyltransferase; Hydrolase; Multifunctional enzyme; Peptidoglycan synthesis; Protease; Reference proteome; Secreted; Transferase

A,C

44805.1

400

0.12

31.82

4.88

-14.68

-6.46

KDM4C

Homo sapiens (Human)

KIAA0780; Jumonji domain-containing protein 2C; JmjC domain-containing histone demethylation protein 3C; JMJD2C; JHDM3C; Gene amplified in squamous cell carcinoma 1 protein; GASC1; GASC-1 protein

JHDM3 histone demethylase family

Paired donor oxygen oxidoreductase

Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code.

Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype. {ECO:0000269|PubMed:20054297, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:23792563, ECO:0000269|PubMed:25728682}. The disease may be caused by variants affecting the gene represented in this entry. Defects of SETD2 are associated with loss of DNA methylation at non-promoter regions (PubMed:23792563). SETD2 defects lead to aberrant and reduced nucleosome compaction and chromatin association of key replication proteins, such as MCM7 and DNA polymerase delta, leading to hinder replication fork progression and prevent loading of RAD51 homologous recombination repair factor at DNA breaks (PubMed:25728682). {ECO:0000269|PubMed:23792563, ECO:0000269|PubMed:25728682}.; DISEASE: Luscan-Lumish syndrome (LLS) [MIM:616831]: An autosomal dominant syndrome with a variable phenotype. Clinical features include macrocephaly, distinctive facial appearance, postnatal overgrowth, various degrees of learning difficulties, autism spectrum disorder, and intellectual disability. {ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:24852293, ECO:0000269|PubMed:26084711, ECO:0000269|PubMed:27317772}. The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Leukemia, acute lymphoblastic (ALL) [MIM:613065]: A subtype of acute leukemia, a cancer of the white blood cells. ALL is a malignant disease of bone marrow and the most common malignancy diagnosed in children. The malignant cells are lymphoid precursor cells (lymphoblasts) that are arrested in an early stage of development. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymphnodes. {ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24662245}. The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry.; DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. {ECO:0000269|PubMed:16314571, ECO:0000269|PubMed:24509477}. The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry.; DISEASE: Intellectual developmental disorder, autosomal dominant 70 (MRD70) [MIM:620157]: An autosomal dominant disorder characterized by mild global developmental delay, moderately impaired intellectual disability with speech difficulties, and behavioral abnormalities. {ECO:0000269|PubMed:32710489}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Rabin-Pappas syndrome (RAPAS) [MIM:620155]: An autosomal dominant neurodevelopmental disorder characterized by severely impaired global development, intellectual disability, microcephaly, facial dysmorphism, and variable congenital anomalies affecting the skeletal, genitourinary, cardiac, and other organ systems. {ECO:0000269|PubMed:32710489}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 1.14.11.-

3D-structure; Alternative splicing; Chromatin regulator; Dioxygenase; Iron; Metal-binding; Nucleus; Oxidoreductase; Proteomics identification; Reference proteome; Repeat; Transcription; Transcription regulation; Zinc; Zinc-finger

A

39355.6

338

0.14

38.34

8.04

2.41

-6.46

ACADM

Homo sapiens (Human)

NA

NA

Acyl-CoA dehydrogenase family

Oxidoreductase

Acyl-CoA dehydrogenase activity.Flavin adenine dinucleotide binding.Identical protein binding.Medium-chain-acyl-CoA dehydrogenase activity.

Acyl-CoA dehydrogenase medium-chain deficiency (ACADMD) [MIM:201450]: An inborn error of mitochondrial fatty acid beta-oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy. {ECO:0000269|PubMed:10767181, ECO:0000269|PubMed:11349232, ECO:0000269|PubMed:11409868, ECO:0000269|PubMed:11486912, ECO:0000269|PubMed:1363805, ECO:0000269|PubMed:1671131, ECO:0000269|PubMed:1684086, ECO:0000269|PubMed:1902818, ECO:0000269|PubMed:2251268, ECO:0000269|PubMed:2393404, ECO:0000269|PubMed:2394825, ECO:0000269|PubMed:7603790, ECO:0000269|PubMed:7929823, ECO:0000269|PubMed:8198141, ECO:0000269|PubMed:9158144, ECO:0000269|PubMed:9882619}. The disease is caused by variants affecting the gene represented in this entry.

DB03415; DB03147; DB02910

PRO_0000000502 [P11310]

1.3.8.7

3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; Disease variant; FAD; Fatty acid metabolism; Flavoprotein; Lipid metabolism; Mitochondrion; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Transit peptide

A,B,C,D

85080.3

773

0.09

30.55

5.71

-7.7

-6.41

UCHL3

Homo sapiens (Human)

Ubiquitin carboxyl-terminal hydrolase isozyme L3; UCH-L3

Peptidase C12 family

Peptidase

Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3", and exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders. Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins.

Epilepsy, familial focal, with variable foci 4 (FFEVF4) [MIM:617935]: An autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy, frontal lobe epilepsy, and nocturnal frontal lobe epilepsy. Some patients may have intellectual disability or autism spectrum disorders. Seizure onset usually occurs in the first or second decades, although later onset has been reported, and there is phenotypic variability within families. A subset of patients have structural brain abnormalities. Penetrance of the disorder is incomplete. FFEVF4 is characterized by onset of focal seizures in the first years of life. {ECO:0000269|PubMed:24157691, ECO:0000269|PubMed:28235671}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 62 (DEE62) [MIM:617938]: A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE62 is characterized by onset of seizures in the first year of life. {ECO:0000269|PubMed:29466837}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9H078; G5E9A7; Q15797; Q7Z699

EC 3.4.19.12

3D-structure; Cytoplasm; Hydrolase; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Thiol protease; Ubl conjugation pathway

A,B

34540.8

304

0.07

39.91

5.01

-17.24

-6.39

RRM2

Homo sapiens (Human)

NA

RR2

Ribonucleoside diphosphate reductase small chain family

Oxidoreductase

Metal ion binding.Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor.

Pyruvate kinase hyperactivity (PKHYP) [MIM:102900]: Autosomal dominant phenotype characterized by increase of red blood cell ATP. {ECO:0000269|PubMed:9090535}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Pyruvate kinase deficiency of red cells (PKRD) [MIM:266200]: A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia. {ECO:0000269|PubMed:10087985, ECO:0000269|PubMed:10772876, ECO:0000269|PubMed:11328279, ECO:0000269|PubMed:11960989, ECO:0000269|PubMed:1536957, ECO:0000269|PubMed:1896471, ECO:0000269|PubMed:19085939, ECO:0000269|PubMed:2018831, ECO:0000269|PubMed:21794208, ECO:0000269|PubMed:7706479, ECO:0000269|PubMed:8161798, ECO:0000269|PubMed:8180378, ECO:0000269|PubMed:8476433, ECO:0000269|PubMed:8481523, ECO:0000269|PubMed:8483951, ECO:0000269|PubMed:8664896, ECO:0000269|PubMed:8807089, ECO:0000269|PubMed:9075576, ECO:0000269|PubMed:9482576, ECO:0000269|PubMed:9827908, ECO:0000269|PubMed:9886305, ECO:0000269|Ref.24}. The disease is caused by variants affecting the gene represented in this entry.

DB00242; DB05260; DB05801; DB05003; DB05428

P41002; Q9UM11; P23921; O00560

1.17.4.1

3D-structure; Alternative splicing; Cytoplasm; Deoxyribonucleotide synthesis; Iron; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation

A,B,C,D

33579.4

286

0.14

43.7

5.12

-12.86

-6.39

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

-6.39

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

-6.37

NOS3

Homo sapiens (Human)

Nitric oxide synthase, endothelial; NOSIII; NOS,type III; NOS type III; Endothelial nitric oxide synthase; Endothelial NOS; ENOS; EC-NOS; Constitutive NOS; CNOS

NOS family

Paired donor oxygen oxidoreductase

NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway.

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

DB07001; DB02048; DB02911; DB02335; DB01997; DB03332; DB04534; DB07244; DB03100; DB03918; DB02207; DB03065; DB00125; DB02994; DB01833; DB00155; DB00997; DB07388; DB03974; DB02077; DB01821; DB09237; DB01110; DB03144; DB03305; DB01686; DB04559; DB02044; DB08019; DB08018; DB02027; DB02979; DB00435; DB04223; DB06154; DB03910; DB02141; DB03963; DB03707; DB02234; DB04018; DB00360; DB02589

P60709; P63010-2; Q8N6T3-3; Q9Y575-3; Q96FT7-4; Q5SZD1; Q16543; Q9UNS2; Q8IUI8; P35222; Q05193; O15287; Q08379; Q71DI3; P69905; P61978; Q12891; Q9UKT9; Q9Y2M5; Q14525; Q6DKI2; P43364-2; Q8N6F8; O94851; A4FUJ8; Q8N594; Q8IVI9; Q6X4W1-6; O15381-5; Q9NV79; Q16549; Q5T2W1; O75925; Q96I34; Q6ZMI0-5; P57052; Q9GZR2; Q96D59; Q8N6K7-2; Q9GZS3; Q8IUW3; Q7Z699; Q7Z698; P50502; Q9BR01-2; Q9NVV9; Q86WT6-2; Q9H347; P58304; Q9NZC7-5; Q9UNY5; P14079

EC 1.14.13.39

3D-structure; Alternative splicing; Calcium; Calmodulin-binding; Cell membrane; Cytoplasm; Cytoskeleton; Direct protein sequencing; FAD; Flavoprotein; FMN; Golgi apparatus; Heme; Iron; Lipoprotein; Membrane; Metal-binding; Myristate; NADP; Oxidoreductase; Palmitate; Phosphoprotein; Proteomics identification; Reference proteome; Zinc

A,B

90790.1

803

0.11

50.67

6.03

-9.56

-6.37

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

-6.37

IKZF2

Homo sapiens (Human)

Ikaros family zinc finger protein 2

Ikaros C2H2-type zinc-finger protein family

NA

Associates with Ikaros at centromeric heterochromatin.

Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta (DEE25) [MIM:615905]: An autosomal recessive disease characterized by subclinical seizures appearing in the first days of life, evolving to severe epileptic disease. Affected individuals have profound or severe delayed development with lack of speech, and most patients do not acquire the ability to sit. Additional variable features include axial hypotonia, peripheral hypertonia, and abnormal involuntary movements such as dystonia and choreoathetosis. Dental abnormalities, including delayed eruption, hypodontia, tooth hypoplasia, yellow discoloration, thin enamel, and enamel chipping are observed in most patients. {ECO:0000269|PubMed:24995870, ECO:0000269|PubMed:26384929, ECO:0000269|PubMed:30054523}. The disease is caused by variants affecting the gene represented in this entry.

NA

P29972; P56545; P56545-3; Q17RB8; P09022; Q8N8B7-2

NA

3D-structure; Acetylation; Activator; Alternative splicing; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

B,C

47006.6

410

0.09

44.28

7.23

0.69

-6.36

NT5E

Homo sapiens (Human)

NT5; CD73 antigen; 5'-nucleotidase; 5'-NT

5'-nucleotidase family

Phosphoric monoester hydrolase

Exhibits AMP-, NAD-, and NMN-nucleosidase activities. Hydrolyzes extracellular nucleotides into membrane permeable nucleosides.

Calcification of joints and arteries (CALJA) [MIM:211800]: A condition characterized by adult-onset calcification of the lower extremity arteries, including the iliac, femoral and tibial arteries, and hand and foot capsule joints. Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands. {ECO:0000269|PubMed:21288095, ECO:0000269|PubMed:24887587}. The disease is caused by variants affecting the gene represented in this entry.

DB00987; DB00806

Q9Y225-2; Q8WWF5

EC 3.1.3.5

3D-structure; Alternative splicing; Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; Membrane; Metal-binding; Nucleotide-binding; Proteomics identification; Reference proteome; Signal; Zinc

A

24417.6

219

0.09

40.43

5.49

-5.75

-6.34

CUL4A/CUL4B-DDB1-CRBN

Homo sapiens (Human)

NA

Cullin family

NA

NA

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

P54253; Q86VP6; Q16531; Q92466; P08238; O94888; P55072

NA

3D-structure; Alternative splicing; Biological rhythms; DNA damage; DNA repair; Host-virus interaction; Isopeptide bond; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation; Ubl conjugation pathway

B

42669.7

368

0.1

44.94

8.72

6.58

-6.34

MMP13

Homo sapiens (Human)

Matrix metalloproteinase 13; Collagenase-3; Collagenase 3

Peptidase M10A family

Peptidase

Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CTGF. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CTGF. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion. Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN.

Spondyloepimetaphyseal dysplasia, Missouri type (SEMDM) [MIM:602111]: A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age. {ECO:0000269|PubMed:16167086}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Metaphyseal anadysplasia 1 (MANDP1) [MIM:602111]: A bone development disorder characterized by skeletal anomalies that resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia. {ECO:0000269|PubMed:19615667}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Metaphyseal dysplasia, Spahr type (MDST) [MIM:250400]: An autosomal recessive, rare disease characterized by moderate short stature, mild genua vara, and radiographic signs of metaphyseal dysplasia, but no biochemical signs of rickets. {ECO:0000269|PubMed:24648384, ECO:0000269|PubMed:24781753}. The disease is caused by variants affecting the gene represented in this entry.

DB02049; DB01996; DB03033; DB07827; DB08388; DB08561; DB08490; DB06423; DB02697; DB00786; DB04759; DB04760; DB04761; DB07013; DB02071

NA

EC 3.4.24.-

3D-structure; Calcium; Collagen degradation; Direct protein sequencing; Disease variant; Disulfide bond; Dwarfism; Extracellular matrix; Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen

A

18757.8

167

0.15

9.97

5.47

-7.44

-6.34

PRKDC

Homo sapiens (Human)

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

PI3/PI4-kinase family

Kinase

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

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

DB00201; DB05210

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

EC 2.7.11.1

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

A

437836

3852

0.09

47.88

6.63

-10.35

-6.34

HMGCS2

Homo sapiens (Human)

HMGCS2; HMG-CoAsynthase; 3-hydroxy-3-methylglutaryl coenzyme A synthase 2

Thiolase-like superfamily, HMG-CoA synthase family

Acyltransferase

This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.

3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) [MIM:605911]: A metabolic disorder characterized by severe hypoketotic hypoglycemia, encephalopathy, and hepatomegaly. {ECO:0000269|PubMed:11228257, ECO:0000269|PubMed:11479731, ECO:0000269|PubMed:12647205, ECO:0000269|PubMed:16601895, ECO:0000269|PubMed:23751782, ECO:0000269|PubMed:25511235, ECO:0000269|PubMed:29597274}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 2.3.3.10

3D-structure; Acetylation; Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism; Disease variant; Lipid biosynthesis; Lipid metabolism; Mitochondrion; Phosphoprotein; Proteomics identification; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase; Transit peptide

A,D

102499

920

0.1

33.48

6.72

-1.41

-6.34

FOLR2

Homo sapiens (Human)

Placental folate-binding protein; Folate receptor, fetal/placental; Folate receptor type-beta; Folate receptor 2; FR-beta; FOLR2

Folate receptor family

Folate receptor

Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release.

Acute hepatic porphyria (AHEPP) [MIM:612740]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralyses and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. {ECO:0000269|PubMed:10706561, ECO:0000269|PubMed:1309003, ECO:0000269|PubMed:1569184, ECO:0000269|PubMed:17236137, ECO:0000269|PubMed:2063868}. The disease is caused by variants affecting the gene represented in this entry.

DB00158; DB00563; DB05168

NA

NA

3D-structure; Cell membrane; Direct protein sequencing; Disulfide bond; Folate-binding; Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Proteomics identification; Receptor; Reference proteome; Secreted; Signal; Transport

A

23841.6

205

0.12

56.78

7.92

2.58

-6.33

cpo

Kitasatospora aureofaciens (Streptomyces aureofaciens)

NA

cpoT

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

Haloperoxidase

Chloride peroxidase activity.

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

DB03793

NA

1.11.1.-

3D-structure; Chloride; Oxidoreductase; Peroxidase

A,B

60428.4

554

0.13

31.26

4.65

-32.72

-6.33

DRD2

Homo sapiens (Human)

Dopamine receptor 2; D(2) dopamine receptor

G-protein coupled receptor 1 family

GPCR rhodopsin

Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.

Congenital sucrase-isomaltase deficiency (CSID) [MIM:222900]: Autosomal recessive intestinal disorder that is clinically characterized by fermentative diarrhea, abdominal pain, and cramps upon ingestion of sugar. The symptoms are the consequence of absent or drastically reduced enzymatic activities of sucrase and isomaltase. The prevalence of CSID is 0.02 % in individuals of European descent and appears to be much higher in Greenland, Alaskan, and Canadian native people. CSID arises due to post-translational perturbations in the intracellular transport, polarized sorting, aberrant processing, and defective function of SI. {ECO:0000269|PubMed:10903344, ECO:0000269|PubMed:11340066, ECO:0000269|PubMed:14724820, ECO:0000269|PubMed:16329100, ECO:0000269|PubMed:8609217}. The disease is caused by variants affecting the gene represented in this entry.

DB01614; DB01063; DB01425; DB00915; DB06288; DB05964; DB00543; DB00182; DB04599; DB00714; DB01238; DB14185; DB09207; DB06216; DB04889; DB04888; DB05687; DB09223; DB04857; DB09128; DB01200; DB09018; DB00490; DB00248; DB06016; DB01038; DB00477; DB01239; DB00568; DB00363; DB01151; DB11274; DB13345; DB00320; DB01184; DB00988; DB00450; DB11275; DB01049; DB00696; DB01175; DB09194; DB00875; DB00623; DB04842; DB00502; DB04946; DB00458; DB04924; DB12579; DB01221; DB00555; DB01235; DB00589; DB00408; DB06077; DB08815; DB00934; DB09224; DB01043; DB00933; DB01403; DB01233; DB06148; DB00805; DB01618; DB08804; DB05766; DB00540; DB06229; DB00334; DB01267; DB12061; DB00715; DB01186; DB08922; DB00850; DB01100; DB09286; DB01621; DB12478; DB00413; DB00433; DB00420; DB01069; DB00777; DB01224; DB09097; DB12518; DB00409; DB00734; DB01549; DB00268; DB05271; DB06454; DB06144; DB00391; DB06477; DB04844; DB12093; DB00372; DB01622; DB00679; DB01623; DB13025; DB00831; DB00508; DB00726; DB06109; DB01392; DB00246; DB09225; DB01624

Q9NRI5; P14416; Q01959

NA

3D-structure; Alternative splicing; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Golgi apparatus; Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

B,C

24300.3

209

0.13

40.14

4.97

-7.83

-6.33

AMD1

Homo sapiens (Human)

SamDC; S-adenosylmethioninedecarboxylase; AdoMetDC; AMD

Eukaryotic AdoMetDC family

Carbon-carbon lyase

Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels. Essential for biosynthesis of the polyamines spermidine and spermine.

Niemann-Pick disease A (NPDA) [MIM:257200]: An early-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Niemann-Pick disease type A is a primarily neurodegenerative disorder characterized by onset within the first year of life, intellectual disability, digestive disorders, failure to thrive, major hepatosplenomegaly, and severe neurologic symptoms. The severe neurological disorders and pulmonary infections lead to an early death, often around the age of four. Clinical features are variable. A phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. {ECO:0000269|PubMed:12556236, ECO:0000269|PubMed:1391960, ECO:0000269|PubMed:15221801, ECO:0000269|PubMed:15877209, ECO:0000269|PubMed:1618760, ECO:0000269|PubMed:1718266, ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:19405096, ECO:0000269|PubMed:2023926, ECO:0000269|PubMed:20386867, ECO:0000269|PubMed:22818240, ECO:0000269|PubMed:23252888, ECO:0000269|PubMed:23430884, ECO:0000269|PubMed:26499107, ECO:0000269|PubMed:27338287, ECO:0000269|PubMed:8680412, ECO:0000269|PubMed:8693491, ECO:0000269|PubMed:9266408, ECO:0000269|PubMed:9660788}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Niemann-Pick disease B (NPDB) [MIM:607616]: A late-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Clinical signs involve only visceral organs. The most constant sign is hepatosplenomegaly which can be associated with pulmonary symptoms. Patients remain free of neurologic manifestations. However, a phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. In Niemann-Pick disease type B, onset of the first symptoms occurs in early childhood and patients can survive into adulthood. {ECO:0000269|PubMed:12369017, ECO:0000269|PubMed:12556236, ECO:0000269|PubMed:1301192, ECO:0000269|PubMed:15241805, ECO:0000269|PubMed:16010684, ECO:0000269|PubMed:1618760, ECO:0000269|PubMed:16472269, ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:1885770, ECO:0000269|PubMed:19050888, ECO:0000269|PubMed:19405096, ECO:0000269|PubMed:20386867, ECO:0000269|PubMed:21098024, ECO:0000269|PubMed:21621718, ECO:0000269|PubMed:22613662, ECO:0000269|PubMed:22818240, ECO:0000269|PubMed:23252888, ECO:0000269|PubMed:23430512, ECO:0000269|PubMed:25920558, ECO:0000269|PubMed:26084044, ECO:0000269|PubMed:26499107, ECO:0000269|PubMed:27338287, ECO:0000269|PubMed:27659707, ECO:0000269|PubMed:8051942, ECO:0000269|PubMed:8664904}. The disease is caused by variants affecting the gene represented in this entry.

DB08163; DB00118; DB01917

P17707; Q96A98; Q8WY91

EC 4.1.1.50

3D-structure; Alternative splicing; Autocatalytic cleavage; Decarboxylase; Direct protein sequencing; Lyase; Phosphoprotein; Polyamine biosynthesis; Proteomics identification; Pyruvate; Reference proteome; S-adenosyl-L-methionine; Schiff base; Spermidine biosynthesis; Zymogen

A,B

35790.5

311

0.14

39.47

6.03

-2.01

-6.32

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

-6.32