CDK8

Homo sapiens (Human)

Protein kinase K35; Mediator of RNA polymerase II transcription subunit CDK8; Mediator complex subunit CDK8; Cell division protein kinase 8

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

Kinase

Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation. Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes.

Intellectual developmental disorder with hypotonia and behavioral abnormalities (IDDHBA) [MIM:618748]: An autosomal dominant neurodevelopmental disorder with onset in infancy. IDDHBA is characterized by hypotonia, global developmental delay, learning disability, and behavioral abnormalities, such as autistic features and attention deficit-hyperactivity disorder. Additional variable features may include non-specific facial dysmorphism, congenital heart defects, ocular anomalies, and poor feeding. {ECO:0000269|PubMed:30905399}. The disease is caused by variants affecting the gene represented in this entry.

DB03496

P24863; Q01094; P02489; Q14204; Q92876

EC 2.7.11.22

3D-structure; Activator; Alternative splicing; ATP-binding; Autism spectrum disorder; Disease variant; Intellectual disability; Kinase; Nucleotide-binding; Nucleus; Proteomics identification; Reference proteome; Repressor; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase

A

37655.2

321

0.11

37.04

8.56

5.13

-8.28

TRBC1

Homo sapiens (Human)

TCRBC1; BV05S1J2.2

NA

NA

Alpha-beta T cell receptors are antigen specific receptors which are essential to the immune response and are present on the cell surface of T lymphocytes. Recognize peptide-major histocompatibility (MH) (pMH) complexes that are displayed by antigen presenting cells (APC), a prerequisite for efficient T cell adaptive immunity against pathogens. Binding of alpha-beta TR to pMH complex initiates TR-CD3 clustering on the cell surface and intracellular activation of LCK that phosphorylates the ITAM motifs of CD3G, CD3D, CD3E and CD247 enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NF-kappa-B (NF-kB) pathways, leading to the mobilization of transcription factors that are critical for gene expression and essential for T cell growth and differentiation. The T cell repertoire is generated in the thymus, by V-(D)-J rearrangement. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MH restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TR with the pMH complexes shapes TR structural and functional avidity. Constant region of T cell receptor (TR) alpha chain.

Immunodeficiency 57 with autoinflammation (IMD57) [MIM:618108]: An autosomal recessive primary immunodeficiency characterized by lymphopenia and recurrent viral, bacterial, and fungal infections. Patients exhibit early-onset inflammatory bowel disease involving the upper and lower gastrointestinal tract, and develop progressive polyarthritis. {ECO:0000269|PubMed:30026316}. The disease is caused by variants affecting the gene represented in this entry. RIPK1-deficient immune cells from IMD57 patients have impaired proinflammatory signaling leading to dysregulated cytokine secretion and are prone to necroptosis. {ECO:0000269|PubMed:30026316}.; DISEASE: Autoinflammation with episodic fever and lymphadenopathy (AIEFL) [MIM:618852]: An autosomal dominant immunologic disorder characterized by early onset of recurrent episodes of unexplained fever, lymphadenopathy, hepatosplenomegaly, and increased levels of inflammatory cytokines and chemokines in patient serum. {ECO:0000269|PubMed:31827280, ECO:0000269|PubMed:31827281}. The disease is caused by variants affecting the gene represented in this entry.

DB02740

NA

NA

3D-structure; Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Membrane; Proteomics identification; Receptor; Reference proteome; T cell receptor; Transmembrane; Transmembrane helix

C,B,A

84668.2

736

0.13

39.96

5.8

-14.36

-8.28

xylA

Arthrobacter sp. (strain NRRL B3728)

NA

NA

Xylose isomerase family

Isomerase(intramolecular oxidoreductase)

Metal ion binding.Xylose isomerase activity.

Bachmann-Bupp syndrome (BABS) [MIM:619075]: An autosomal dominant disorder characterized by global developmental delay, alopecia, absolute or relative macrocephaly, and facial dysmorphism. Neuroimaging shows white matter abnormalities, prominent Virchow-Robin spaces, periventricular cysts, and abnormalities of the corpus callosum. {ECO:0000269|PubMed:30239107, ECO:0000269|PubMed:30475435}. The disease is caused by variants affecting the gene represented in this entry. BABS is due to truncating variants that lead to a gain of function. This phenomenon apparently results from truncation proximal to or involving the C-terminal region of ODC1 protein, distal enough to allow escape from nonsense-mediated decay. A gain of function is corroborated by elevated plasma levels of N-acetylputrescine, with otherwise normal polyamine levels, in affected individuals. {ECO:0000269|PubMed:30475435}.

DB02172; DB03206; DB11195

NA

5.3.1.5

3D-structure; Carbohydrate metabolism; Cytoplasm; Direct protein sequencing; Isomerase; Magnesium; Metal-binding; Xylose metabolism

A,B

35700.7

325

0.11

20.63

5.19

-14.16

-8.26

KDR

Homo sapiens (Human)

VEGFR2; VEGFR-2; VEGF-2 receptor; Protein-tyrosine kinase receptor flk-1; Kinase insert domain receptor; Fetal liver kinase 1; FLK1; FLK-1; CD309

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

Kinase

Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD.

Hemangioma, capillary infantile (HCI) [MIM:602089]: A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. {ECO:0000269|PubMed:11807987, ECO:0000269|PubMed:18931684}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.

DB04727; DB07514; DB07528; DB06938; DB07326; DB06626; DB08875; DB04849; DB05198; DB12147; DB12307; DB12010; DB11679; DB06101; DB09078; DB06080; DB06595; DB07537; DB07183; DB07333; DB07334; DB07274; DB09079; DB08519; DB08042; DB16265; DB06589; DB05931; DB08901; DB15822; DB05984; DB05578; DB08896; DB14840; DB06436; DB00398; DB01268; DB05075; DB11800; DB04879; DB05146; DB05014

P35916; O60565; P98160; PRO_0000391621 [P98160]; PRO_0000391622 [P98160]; P17301; P35968; P09382; P08581; P16333; O14786; O75340; P09619; P29350; Q12913; P12931; P15692; P15692-4; P49767; Q9MYV3-3

EC 2.7.10.1

3D-structure; Alternative splicing; Angiogenesis; ATP-binding; Cell junction; Cell membrane; Cytoplasm; Cytoplasmic vesicle; Developmental protein; Differentiation; Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein; Host-virus interaction; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation

A

33863.9

296

0.1

40.01

8.5

4.59

-8.27

SMS

Homo sapiens (Human)

NA

NA

Spermidine/spermine synthase family

Transferase

Spermine synthase activity.

Intellectual developmental disorder, X-linked, syndromic, Snyder-Robinson type (MRXSSR) [MIM:309583]: An X-linked intellectual disability syndrome characterized by a collection of clinical features including facial asymmetry, marfanoid habitus, hypertonia, osteoporosis and unsteady gait. {ECO:0000269|PubMed:14508504, ECO:0000269|PubMed:18550699, ECO:0000269|PubMed:19206178, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23696453, ECO:0000269|PubMed:23897707}. The disease is caused by variants affecting the gene represented in this entry.

DB00127

NA

2.5.1.22

3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; Intellectual disability; Phosphoprotein; Polyamine biosynthesis; Proteomics identification; Reference proteome; Transferase

A,B,C,D

27177.1

238

0.11

41.31

4.82

-9.19

-8.26

TNKS2

Homo sapiens (Human)

Tankyrase-related protein; Tankyrase-like protein; Tankyrase II; TRF1-interacting ankyrin-related ADP-ribose polymerase 2; TNKL; TANK2; Protein poly-ADP-ribosyltransferase tankyrase-2; Poly [ADP-ribos

ARTD/PARP family

Glycosyltransferases

Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. Stimulates 26S proteasome activity. Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.

Intellectual developmental disorder with macrocephaly, seizures, and speech delay (IDDMSSD) [MIM:618158]: An autosomal dominant neurodevelopmental disorder characterized by impaired intellectual development, poor speech, postnatal macrocephaly, and seizures. {ECO:0000269|PubMed:30290153}. The disease is caused by variants affecting the gene represented in this entry.

NA

O15084; Q7Z6K5-1; O15169; Q9NWV8; P11274; Q13698; Q9NRI5; Q6V0I7; Q9NWT6; P14652; Q9UIQ6; Q14980; Q9BZL4; Q92698; P78314; O43815; P54274; Q9C0C2; Q9UHP3; Q06649

EC 2.4.2.30

3D-structure; ADP-ribosylation; ANK repeat; Chromosome; Cytoplasm; Glycosyltransferase; Golgi apparatus; Hydroxylation; Membrane; Metal-binding; NAD; Nucleotidyltransferase; Nucleus; Proteomics identification; Reference proteome; Repeat; Telomere; Transferase; Ubl conjugation; Wnt signaling pathway; Zinc

A

23695.5

208

0.11

47.61

8.28

2.88

-8.26

PIK3CG

Homo sapiens (Human)

p120-PI3K; p110gamma; Serine/threonine protein kinase PIK3CG; PtdIns-3-kinase subunit p110-gamma; PtdIns-3-kinase subunit gamma; PtdIns-3-kinase p110; Phosphoinositol-3 kinase; Phosphoinositide-3-kina

PI3/PI4-kinase family

Kinase

Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.

Immunodeficiency 97 with autoinflammation (IMD97) [MIM:619802]: An autosomal recessive disorder with variable features. Affected individuals have childhood-onset antibody defects, cytopenias, and T lymphocytic pneumonitis and colitis. Some patients may have features of hemophagocytic lymphohistiocytosis. {ECO:0000269|PubMed:31554793, ECO:0000269|PubMed:33054089}. The disease is caused by variants affecting the gene represented in this entry.

DB07503; DB08300; DB06831; DB07335; DB07073; DB04769; DB12483; DB11952; DB12010; DB02656; DB02375; DB06836; DB04216; DB02010; DB05552; DB08059; DB05241

P05067; Q13370; P48736; O02696; Q3U6Q4; P68404-2

EC 2.7.1.153

3D-structure; Angiogenesis; ATP-binding; Cell membrane; Chemotaxis; Cytoplasm; Disease variant; Endocytosis; Immunity; Inflammatory response; Kinase; Lipid metabolism; Membrane; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase

A

94934.7

823

0.1

41.86

6.23

-8.39

-8.26

MKNK2

Homo sapiens (Human)

Mnk2; MAPK signal-integrating kinase 2

Protein kinase superfamily, CAMK Ser/Thr protein kinase family

Protein kinase superfamily. CAMK Ser/Thr protein kinase family

Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.

Charcot-Marie-Tooth disease, X-linked dominant, 6 (CMTX6) [MIM:300905]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies characterized by severely reduced motor nerve conduction velocities (NCVs) (less than 38m/s) and segmental demyelination and remyelination, and primary peripheral axonal neuropathies characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy. {ECO:0000269|PubMed:23297365}. The disease is caused by variants affecting the gene represented in this entry.

DB12010

Q16539; P46379-2; O14901; Q14696; P25786

EC 2.7.11.1

3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cytoplasm; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Translation regulation; Zinc

A

30812.8

271

0.1

60.57

5.48

-10.33

-8.27

CHRM4

Homo sapiens (Human)

M4 receptor; CHRM4

G-protein coupled receptor 1 family, Muscarinic acetylcholine receptor subfamily, CHRM4 sub-subfamily

GPCR rhodopsin

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.

Leukodystrophy, hypomyelinating, 15 (HLD15) [MIM:617951]: An autosomal recessive disorder characterized by hypomyelinating leukodystrophy with thinning of the corpus callosum. Clinical features include motor and cognitive impairment appearing in the first or second decade of life, dystonia, ataxia, spasticity, and dysphagia. Most patients develop severe optic atrophy, and some have hearing loss. {ECO:0000269|PubMed:29576217}. The disease may be caused by variants affecting the gene represented in this entry.

DB03128; DB08897; DB05752; DB00321; DB00543; DB01238; DB14185; DB00572; DB00767; DB01019; DB00835; DB00411; DB01239; DB00568; DB00363; DB00496; DB01151; DB09167; DB01142; DB00366; DB09194; DB06702; DB00986; DB06787; DB11181; DB00725; DB00424; DB00458; DB01625; DB01221; DB00408; DB00934; DB00454; DB06709; DB00940; DB01403; DB00340; DB00622; DB00540; DB00334; DB00715; DB01085; DB00387; DB01069; DB00777; DB12278; DB01224; DB11855; DB13581; DB00747; DB01591; DB00342; DB11235; DB01409; DB01036; DB00376; DB09089; DB00726; DB00809; DB09076; DB09185; DB00246

NA

NA

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

A,B

32545.4

287

0.14

30.63

9.34

11.91

-8.26

por

Desulfocurvibacter africanus (Desulfovibrio africanus)

NA

NA

Pyruvate:ferredoxin/flavodoxin oxidoreductase family

Oxidoreductase

4 iron, 4 sulfur cluster binding.Iron ion binding.Pyruvate synthase activity.Thiamine pyrophosphate binding.

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.

DB02410; DB01987; DB00507

NA

1.2.7.1

3D-structure; 4Fe-4S; Calcium; Cytoplasm; Direct protein sequencing; Disulfide bond; Electron transport; Iron; Iron-sulfur; Magnesium; Metal-binding; Oxidoreductase; Pyruvate; Thiamine pyrophosphate; Transport

A,B

115569

1065

0.09

31.51

6.32

-5.62

-8.26

P2RY12

Homo sapiens (Human)

NA

HORK3

G-protein coupled receptor 1 family

Membrane protein

ADP receptor activity.G-protein coupled adenosine receptor activity.Guanyl-nucleotide exchange factor activity.

Bleeding disorder, platelet-type, 8 (BDPLT8) [MIM:609821]: A condition characterized by mild to moderate mucocutaneous bleeding, and excessive bleeding after surgery or trauma. The defect is due to severe impairment of platelet response to ADP resulting in defective platelet aggregation. {ECO:0000269|PubMed:11196645, ECO:0000269|PubMed:12578987, ECO:0000269|PubMed:25428217}. The disease is caused by variants affecting the gene represented in this entry.

DB06441; DB00758; DB06350; DB01240; DB06209; DB01069; DB05553; DB15163; DB08816; DB00208; DB00374; DB16349

NA

NA

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

A

28830.4

248

0.17

24.19

9.39

10.55

-8.25

GHRL

Homo sapiens (Human)

UNQ524/PRO1066; Motilin-related peptide; M46 protein; Growth hormone secretagogue; Growth hormone releasing peptide; Gastric peptide ghrelin; GHRL

Motilin family

NA

Specific ligand for the growth hormone secretagogue receptor type 1 (ghsr) inducing the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion.Involved in growth regulation.

Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (NEDBAF) [MIM:618577]: An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, severe intellectual disability, poor language, seizures, dysmorphic features, and thin corpus callosum. {ECO:0000269|PubMed:29276006, ECO:0000269|PubMed:30293988}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9UMX0; Q9UMX0-2; Q9UHD9

NA

3D-structure; Alternative splicing; Amidation; Direct protein sequencing; Hormone; Lipoprotein; Proteomics identification; Reference proteome; Secreted; Signal

C,R

34053.1

300

0.14

38.34

9.3

11.02

-8.25

NR1H3

Homo sapiens (Human)

Nuclear receptor subfamily 1 group H member 3; Nuclear receptor LXRalpha; Nuclear orphan receptor LXR-alpha; Liver X receptor alpha; LXRalpha; LXRA

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

Interaction with retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism. Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity.

Okur-Chung neurodevelopmental syndrome (OCNDS) [MIM:617062]: An autosomal dominant neurodevelopmental disorder characterized by developmental delay, intellectual disability, behavioral problems, hypotonia, speech problems, microcephaly, pachygyria and variable dysmorphic features. {ECO:0000269|PubMed:27048600}. The disease is caused by variants affecting the gene represented in this entry.

DB08175; DB08063; DB11994; DB07929; DB13174; DB07080

O60869; O60341; Q99750; Q15788; O75376; Q07869; Q07869-1; Q03181; P37231; P19793; P28702; P48443; O43463; P42858; Q99750; O95817; G5E9A7; O95872; P02545; Q99750; P28702; P28702-3; P48443; Q7Z699

NA

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

A

25389.9

220

0.09

46.42

5.51

-6.58

-8.26

EHMT2

Homo sapiens (Human)

Protein G9a; NG36; Lysine N-methyltransferase 1C; KMT1C; Histone H3-K9 methyltransferase 3; HLA-B-associated transcript 8; H3-K9-HMTase 3; G9A; Euchromatic histone-lysine N-methyltransferase 2; C6orf3

Class V-like SAM-binding methyltransferase superfamily, Histone-lysine methyltransferase family, Suvar3-9 subfamily

Methyltransferase

H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself. Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin.

Pseudohypoaldosteronism 2C (PHA2C) [MIM:614492]: An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in some cases, and correction of physiologic abnormalities by thiazide diuretics. {ECO:0000269|PubMed:11498583}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neuropathy, hereditary sensory and autonomic, 2A (HSAN2A) [MIM:201300]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2A is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation, onset of symptoms in infancy or early childhood, occurrence of distal extremity pathologies (paronychia, whitlows, ulcers, and Charcot joints), frequent amputations, sensory loss that affects all modalities of sensation (lower and upper limbs and perhaps the trunk as well), absence or diminution of tendon reflexes (usually in all limbs), minimal autonomic dysfunction, absence of sensory nerve action potentials, and virtual absence of myelinated fibers with decreased numbers of unmyelinated fibers in sural nerves. {ECO:0000269|PubMed:15060842, ECO:0000269|PubMed:15911806, ECO:0000269|PubMed:18521183}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q6VMQ6-2; Q6P1J9; Q9UBC3; P38919; Q9UM22; P23771; Q99684; Q13547; Q96JB3; Q92831; O60341-1; Q9Y4X4; P57682; Q13330; O94776; Q9BTC8; P20592; Q9BSU3; Q99801-1; O60568; Q9NQX1; Q5JSZ5; Q7Z3Z2; Q9P2R6; Q14119; Q96GT9; O60315; Q9NWS9-2; Q96JM2; A0A0S2Z5X4; Q96BV0; Q96EG3; Q07120; O60341-1

EC 2.1.1.-

3D-structure; Acetylation; Alternative splicing; ANK repeat; Chromatin regulator; Chromosome; Isopeptide bond; Metal-binding; Methylation; Methyltransferase; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; S-adenosyl-L-methionine; Transferase; Ubl conjugation; Zinc

A

31010.9

269

0.1

47.49

5.16

-9.31

-8.25

IRAK1

Homo sapiens (Human)

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

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

Kinase

Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3. Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens.

Anemia, non-spherocytic hemolytic, due to G6PD deficiency (NSHA) [MIM:300908]: A disease characterized by G6PD deficiency, acute hemolytic anemia, fatigue, back pain, and jaundice. In most patients, the disease is triggered by an exogenous agent, such as some drugs, food, or infection. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. Although G6PD deficiency can be life-threatening, most patients are asymptomatic throughout their life. {ECO:0000269|PubMed:12524354, ECO:0000269|PubMed:1303180, ECO:0000269|PubMed:1303182, ECO:0000269|PubMed:1536798, ECO:0000269|PubMed:1611091, ECO:0000269|PubMed:1889820, ECO:0000269|PubMed:1945893, ECO:0000269|PubMed:20007901, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:2836867, ECO:0000269|PubMed:2912069, ECO:0000269|PubMed:30988594, ECO:0000269|PubMed:38066190, ECO:0000269|PubMed:7858267, ECO:0000269|PubMed:7959695, ECO:0000269|PubMed:8193373, ECO:0000269|PubMed:8490627, ECO:0000269|PubMed:8533762, ECO:0000269|PubMed:8733135, ECO:0000269|PubMed:9452072}. The disease is caused by variants affecting the gene represented in this entry. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of NSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.

DB12010

Q15306; Q92985; Q99836; Q96FA3; Q9HAT8; Q8N2H9-2; Q13526; Q86WV6; P58753; Q9Y4K3; Q8VCW4; Q5D1E7

EC 2.7.11.1

3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Direct protein sequencing; Host-virus interaction; Immunity; Innate immunity; Isopeptide bond; Kinase; Lipid droplet; Magnesium; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation

A

33681.4

301

0.09

39.86

8.6

5.09

-8.25

PGR

Homo sapiens (Human)

PR; Nuclear receptor subfamily 3 group C member 3; NR3C3

Nuclear hormone receptor family, NR3 subfamily

Nuclear hormone receptor

Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.

Butyrylcholinesterase deficiency (BCHED) [MIM:617936]: An autosomal recessive metabolic condition characterized by increased sensitivity to certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium. BCHED results in slower hydrolysis of these drugs and, consequently, a prolonged neuromuscular block, leading to apnea. The duration of the prolonged apnea varies significantly depending on the extent of the enzyme deficiency. {ECO:0000269|PubMed:10404729, ECO:0000269|PubMed:11928765, ECO:0000269|PubMed:12881446, ECO:0000269|PubMed:1306123, ECO:0000269|PubMed:1349196, ECO:0000269|PubMed:1415224, ECO:0000269|PubMed:15563885, ECO:0000269|PubMed:15781196, ECO:0000269|PubMed:1611188, ECO:0000269|PubMed:16788378, ECO:0000269|PubMed:17700357, ECO:0000269|PubMed:18075469, ECO:0000269|PubMed:18300943, ECO:0000269|PubMed:25054547, ECO:0000269|PubMed:25264279, ECO:0000269|PubMed:2915989, ECO:0000269|PubMed:7634491, ECO:0000269|PubMed:8554068, ECO:0000269|PubMed:8680411, ECO:0000269|PubMed:9110359, ECO:0000269|PubMed:9191541, ECO:0000269|PubMed:9388484, ECO:0000269|PubMed:9543549, ECO:0000269|PubMed:9694584}. The disease is caused by variants affecting the gene represented in this entry.

DB01431; DB06680; DB01406; DB12941; DB13857; DB00304; DB09123; DB01395; DB00378; DB11219; DB00823; DB00294; DB13867; DB08906; DB00588; DB06730; DB11619; DB11064; DB06789; DB00367; DB00431; DB09124; DB00603; DB00351; DB02998; DB00834; DB00648; DB00764; DB14512; DB06713; DB00717; DB00957; DB09389; DB01428; DB02746; DB00396; DB14583; DB00421; DB04787; DB05253; DB08867

Q9H467; P03372; P06401; P40763; P03372

NA

3D-structure; Alternative promoter usage; Alternative splicing; Cytoplasm; Direct protein sequencing; DNA-binding; Isopeptide bond; Lipid-binding; Lipoprotein; Membrane; Metal-binding; Mitochondrion; Mitochondrion outer membrane; Nucleus; Palmitate; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Steroid-binding; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A,B

28853.6

250

0.09

54.82

8.4

2.28

-8.23

KIT

Homo sapiens (Human)

v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; p145 c-kit; Proto-oncogene tyrosine-protein kinase Kit; Proto-oncogene c-Kit; Piebald trait protein; PBT; Mast/stem cell growth factor re

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

Kinase

In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1. Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis.

Piebald trait (PBT) [MIM:172800]: Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. {ECO:0000269|PubMed:11074500, ECO:0000269|PubMed:1370874, ECO:0000269|PubMed:1376329, ECO:0000269|PubMed:1717985, ECO:0000269|PubMed:7687267, ECO:0000269|PubMed:8680409, ECO:0000269|PubMed:9450866, ECO:0000269|PubMed:9699740}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gastrointestinal stromal tumor (GIST) [MIM:606764]: Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery. {ECO:0000269|PubMed:11505412, ECO:0000269|PubMed:15824741, ECO:0000269|PubMed:9438854, ECO:0000269|PubMed:9697690}. The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. The gene represented in this entry may be involved in disease pathogenesis.; 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. The gene represented in this entry is involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the kinase domain can result in a constitutively activated kinase.; DISEASE: Mastocytosis, cutaneous (MASTC) [MIM:154800]: A form of mastocytosis, a heterogeneous group of disorders associated with abnormal proliferation and accumulation of mast cells in various tissues, especially in the skin and hematopoietic organs. MASTC is an autosomal dominant form characterized by macules, papules, nodules, or diffuse infiltration of the skin, often associated with localized hyperpigmentation. Gentle rubbing of the lesions induces histamine release from mechanically activated mast cells, causing local wheals, erythema, and often pruritus, a phenomenon termed Darier sign. {ECO:0000269|PubMed:15173254, ECO:0000269|PubMed:19865100, ECO:0000269|PubMed:21689725, ECO:0000269|PubMed:24289326, ECO:0000269|PubMed:9990072}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mastocytosis, systemic (MASTSYS) [MIM:154800]: A severe form of mastocytosis characterized by abnormal proliferation and accumulation of mast cells in several organs, resulting in a systemic disease that may affect bone, gastrointestinal tract, lymphatics, spleen, and liver. In some cases, it is associated with a clonal hematologic non-mast-cell lineage disease, such as a myelodysplastic or myeloproliferative disorder. It can also lead to mast cell leukemia, which carries a high risk of mortality. {ECO:0000269|PubMed:9990072}. The disease is caused by variants affecting the gene represented in this entry.

DB12742; DB09103; DB15233; DB01254; DB12147; DB12010; DB00619; DB09078; DB06080; DB06595; DB04868; DB05913; DB06589; DB12978; DB01962; DB08901; DB08896; DB14840; DB00398; DB01268; DB11800; DB05146

P00519; P42684; O75815; P51451; Q8WV28; P46108; P07332; P09769; O75791; P62993; Q14451; P08631; Q96JZ2; P21583; P06239; P07948; P16333; O43639; P27986; O00459; Q92569; P19174; P16885; Q13882; Q06124; Q92729; P20936; Q9UQQ2; O14796; Q9NP31; Q8N5H7; P78314; Q15464; P29353; P98077; Q92529; Q9H6Q3; O14508; O14543; O14544; P12931; Q9ULZ2; Q9HBL0; Q63HR2; Q68CZ2; P42681; P07947; P43403; Q8VBX6; P35235

EC 2.7.10.1

3D-structure; Alternative splicing; ATP-binding; Cell membrane; Cytoplasm; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Immunoglobulin domain; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation

A

33575.6

297

0.11

45.37

8.37

3.24

-8.24

N/A

Plasmodium falciparum (isolate HB3)

NA

NA

Peptidase A1 family

Hydrolase

Aspartic-type endopeptidase activity.

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

DB04378; DB04373; DB11638; DB01218; DB02505; DB03063

NA

3.4.23.39

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

A

36923.5

329

0.13

44.31

4.67

-17.94

-8.24

SULT1E1

Homo sapiens (Human)

NA

STE

Sulfotransferase 1 family

Transferase

Aryl sulfotransferase activity.Estrone sulfotransferase activity.Flavonol 3-sulfotransferase activity.Steroid binding.Steroid sulfotransferase activity.Sulfotransferase activity.

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.

DB02902; DB03346; DB01812; DB00714; DB14635; DB01176; DB00977; DB09288; DB00675; DB09100

O76083; O76083-2

2.8.2.4

3D-structure; Cytoplasm; Lipid metabolism; Lipid-binding; Proteomics identification; Reference proteome; Steroid-binding; Transferase

A,B

34022.7

285

0.15

32.76

6.33

-2.75

-8.24