Stap-coc fabI

Staphylococcus aureus (strain NCTC 8325 / PS 47)

NADPHdependent enoylACP reductase; Enoyl[acylcarrierprotein] reductase [NADPH] FabI

Short-chain dehydrogenases/reductases (SDR) family, FabI subfamily

Short-chain dehydrogenases reductase

Catalyzes the reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). It has a preference for a long chain (C12) substrate compared to the shorter (C4) acyl group. Involved in the elongation cycle of fatty acid which are used in the lipid metabolism.

Amyloidosis, hereditary systemic 4, Finnish type (AMYLD4) [MIM:105120]: A form of hereditary systemic amyloidosis, a disorder characterized by amyloid deposition in multiple tissues resulting in a wide clinical spectrum. AMYLD4 is due to gelsolin amyloid deposition and is typically characterized by cranial neuropathy and lattice corneal dystrophy. Most patients have modest involvement of internal organs, but severe systemic disease can develop in some individuals causing peripheral polyneuropathy, amyloid cardiomyopathy, and nephrotic syndrome leading to renal failure. AMYLD4 is usually inherited in an autosomal dominant pattern. However, homozygotes with a more severe phenotype have also been reported. {ECO:0000269|PubMed:1338910, ECO:0000269|PubMed:19666512, ECO:0000269|PubMed:2176481}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

NA

3D-structure; Fatty acid biosynthesis; Fatty acid metabolism; Lipid biosynthesis; Lipid metabolism; NAD; NADP; Oxidoreductase; Reference proteome

A,C

55674.6

510

0.07

33.86

5.64

-9.3

-6.97

SSTR4

Homo sapiens (Human)

SSTR4; SS4R

G-protein coupled receptor 1 family

GPCR rhodopsin

Receptor for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. It is functionally coupled not only to inhibition of adenylate cyclase, but also to activation of both arachidonate release and mitogen-activated protein (MAP) kinase cascade. Mediates antiproliferative action of somatostatin in tumor cells.

Oocyte/zygote/embryo maturation arrest 21 (OZEMA21) [MIM:620610]: An autosomal dominant, female infertility disorder characterized by zygote development arrest due to failure of pronuclei fusion. {ECO:0000269|PubMed:33948904, ECO:0000269|PubMed:33953335}. The disease is caused by variants affecting the gene represented in this entry.

DB13985; DB09099

P35346

NA

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

R

29548.3

265

0.12

45.65

9.78

14.03

-6.96

HPD

Homo sapiens (Human)

NA

PPD

4HPPD family

Oxidoreductase

4-hydroxyphenylpyruvate dioxygenase activity.Metal ion binding.

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

DB02850; DB00348

NA

1.13.11.27

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

A

43164.8

376

0.11

32.38

6.73

-1.04

-6.96

ASPH

Homo sapiens (Human)

Peptideaspartate betadioxygenase; Aspartyl/asparaginyl betahydroxylase; ASPH; ASP betahydroxylase

Aspartyl/asparaginyl beta-hydroxylase family

Paired donor oxygen oxidoreductase

Isoform 8: membrane-bound Ca(2+)-sensing protein, which is a structural component of the ER-plasma membrane junctions. Isoform 8 regulates the activity of Ca(+2) released-activated Ca(+2) (CRAC) channels in T-cells. {ECO:0000269|PubMed:22586105}.

Facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebs (FDLAB) [MIM:601552]: A syndrome characterized by dislocated crystalline lenses and anterior segment abnormalities in association with a distinctive facies involving flat cheeks and a beaked nose. Some affected individuals develop highly unusual non-traumatic conjunctival cysts (filtering blebs). {ECO:0000269|PubMed:24768550}. The disease is caused by variants affecting the gene represented in this entry.

DB00128; DB00139

O43681; O95994; P02818; P01037; Q5JRM2; P81605; P60022; Q8N5I4; Q14204; Q6UWR7; Q8NFU4; Q14512; Q9Y680; P22466; P01350; O43681; Q8NBJ4; Q8TDV5; Q96SL4; Q8TED1; O15499; Q02747; P42858; Q9HBE4; Q9Y5Q6; Q9NZI2-2; Q9Y2W7; Q6PIL6; Q92876; P80188; P30533; P01374; Q9NX40; Q6UW60; P04085-2; Q9NWW9; Q9H8W4; Q59EV6; Q96NZ9; A5D903; P02812; P01270; P21246; Q15293; Q8NC24; O60930; P0DMR2; P34741; Q15428; Q96EQ0; Q3SXP7; Q86UW2; P58511; Q96E16; P08294; P00995; Q9NRX6; Q9Y320; O14763; A0A384ME17; Q96J42; O75310; Q8WWY7; Q8TCV5; O60844; A0A087WZY1; A0A1U9X8X8; P42858

EC 1.14.11.16

3D-structure; Alternative splicing; Calcium; Dioxygenase; Disease variant; Disulfide bond; Endoplasmic reticulum; Glycoprotein; Iron; Membrane; Metal-binding; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Sarcoplasmic reticulum; Signal-anchor; TPR repeat; Transmembrane; Transmembrane helix

A

22760.8

196

0.1

41.41

8.51

2.96

-6.95

Pseudo LasR

Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)

NA

Autoinducer-regulated transcriptional regulatory protein family

NA

Transcriptional activator of elastase structural gene (LasB). Binds to the PAI autoinducer.

Growth hormone deficiency, isolated, 1A (IGHD1A) [MIM:262400]: An autosomal recessive, severe deficiency of growth hormone leading to dwarfism. Patients often develop antibodies to administered growth hormone. {ECO:0000269|PubMed:8364549}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 1B (IGHD1B) [MIM:612781]: An autosomal recessive deficiency of growth hormone leading to short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:12655557}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Kowarski syndrome (KWKS) [MIM:262650]: A syndrome clinically characterized by short stature associated with bioinactive growth hormone, normal or slightly increased growth hormone secretion, pathologically low insulin-like growth factor 1 levels, and normal catch-up growth on growth hormone replacement therapy. {ECO:0000269|PubMed:17519310, ECO:0000269|PubMed:8552145, ECO:0000269|PubMed:9276733}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 2 (IGHD2) [MIM:173100]: An autosomal dominant deficiency of growth hormone leading to short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:11502836, ECO:0000269|PubMed:9152628}. The disease is caused by variants affecting the gene represented in this entry.

DB08324

NA

NA

3D-structure; Activator; DNA-binding; Quorum sensing; Reference proteome; Transcription; Transcription regulation

A

18305.5

163

0.12

46.52

5.19

-6.78

-6.95

MAP2K1

Homo sapiens (Human)

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

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

Kinase

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

Cardiofaciocutaneous syndrome 3 (CFC3) [MIM:615279]: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures. {ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:18042262}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melorheostosis, isolated (MEL) [MIM:155950]: A sclerosing bone disorder characterized by hyperostosis of the cortex of tubular bones, frequently involving one limb. The lesions may be accompanied by abnormalities of adjacent soft tissue, joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangioma. {ECO:0000269|PubMed:29643386}. The disease is caused by variants affecting the gene represented in this entry.

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

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

EC 2.7.12.2

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

B

34785.9

311

0.07

46.58

6.29

-2.54

-6.96

MSH2

Homo sapiens (Human)

hMSH2; MutS protein homolog 2; Mismatch repair gene Msh2

DNA mismatch repair MutS family

NA

Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. Recruits DNA helicase MCM9 to chromatin which unwinds the mismatch containg DNA strand. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis. Component of the post-replicative DNA mismatch repair system (MMR).

Lynch syndrome 1 (LYNCH1) [MIM:120435]: A form of Lynch syndrome, an autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. Lynch syndrome is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, it is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical Lynch syndrome is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected Lynch syndrome' or 'incomplete Lynch syndrome' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. {ECO:0000269|PubMed:10375096, ECO:0000269|PubMed:10386556, ECO:0000269|PubMed:10528862, ECO:0000269|PubMed:10573010, ECO:0000269|PubMed:10612836, ECO:0000269|PubMed:10777691, ECO:0000269|PubMed:10829038, ECO:0000269|PubMed:11726306, ECO:0000269|PubMed:11870161, ECO:0000269|PubMed:11920458, ECO:0000269|PubMed:12112654, ECO:0000269|PubMed:12124176, ECO:0000269|PubMed:12132870, ECO:0000269|PubMed:12200596, ECO:0000269|PubMed:12362047, ECO:0000269|PubMed:12373605, ECO:0000269|PubMed:12655564, ECO:0000269|PubMed:12655568, ECO:0000269|PubMed:12658575, ECO:0000269|PubMed:14635101, ECO:0000269|PubMed:15046096, ECO:0000269|PubMed:15300854, ECO:0000269|PubMed:15342696, ECO:0000269|PubMed:15365995, ECO:0000269|PubMed:15613555, ECO:0000269|PubMed:15870828, ECO:0000269|PubMed:15896463, ECO:0000269|PubMed:15991316, ECO:0000269|PubMed:15996210, ECO:0000269|PubMed:16451135, ECO:0000269|PubMed:17101317, ECO:0000269|PubMed:17128465, ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:18625694, ECO:0000269|PubMed:18781619, ECO:0000269|PubMed:18822302, ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22102614, ECO:0000269|PubMed:22371642, ECO:0000269|PubMed:7874129, ECO:0000269|PubMed:8261515, ECO:0000269|PubMed:8700523, ECO:0000269|PubMed:8797773, ECO:0000269|PubMed:8872463, ECO:0000269|PubMed:9048925, ECO:0000269|PubMed:9240418, ECO:0000269|PubMed:9298827, ECO:0000269|PubMed:9311737, ECO:0000269|PubMed:9419403, ECO:0000269|PubMed:9559627, ECO:0000269|PubMed:9621522, ECO:0000269|PubMed:9718327, ECO:0000269|PubMed:9889267}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy. {ECO:0000269|PubMed:7713503}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. {ECO:0000305|PubMed:11306449, ECO:0000305|PubMed:21642682}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Mismatch repair cancer syndrome 2 (MMRCS2) [MIM:619096]: An autosomal recessive form of mismatch repair cancer syndrome, a childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. {ECO:0000269|PubMed:12549480, ECO:0000269|PubMed:16372347}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:12792735, ECO:0000269|PubMed:14504054, ECO:0000269|PubMed:15996210, ECO:0000269|PubMed:9559627}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

NA

Q92624; Q9UQ84-1; P09429; P20585; P52701; Q8IY92; P39875

NA

3D-structure; Acetylation; Alternative splicing; ATP-binding; Chromosome; Disease variant; DNA damage; DNA repair; DNA-binding; Hereditary nonpolyposis colorectal cancer; Isopeptide bond; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Tumor suppressor; Ubl conjugation

A

97883.4

868

0.08

36.78

5.79

-10.09

-6.96

MKNK1

Homo sapiens (Human)

Mnk1; MAP kinase signal-integrating kinase 1

Protein kinase superfamily, CAMK Ser/Thr protein kinase family

Protein kinase superfamily. CAMK Ser/Thr protein kinase family

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.

Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.

DB12010

P54253; Q03060-25; P42858; P28482; Q16539; Q96CV9

EC 2.7.11.1

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

A

27536.2

241

0.11

50.42

6.02

-3.43

-6.96

FABP2

Homo sapiens (Human)

NA

FABPI

Calycin superfamily, Fatty-acid binding protein (FABP) family

Transport protein

Fatty acid binding.Transporter activity.

Usher syndrome 3B (USH3B) [MIM:614504]: A syndrome characterized by progressive vision and hearing loss during early childhood. Some patients have the so-called 'Charles Bonnet syndrome,' involving decreased visual acuity and vivid visual hallucinations. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life. {ECO:0000269|PubMed:22279524}. The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, axonal, 2W (CMT2W) [MIM:616625]: An autosomal dominant, axonal 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 (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2W patients manifest a peripheral neuropathy mainly affecting the lower limbs and resulting in gait difficulties and distal sensory impairment. Most patients also have upper limb involvement. {ECO:0000269|PubMed:22930593, ECO:0000269|PubMed:26072516, ECO:0000269|PubMed:29235198}. The disease is caused by variants affecting the gene represented in this entry.

DB04557; DB09213; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB01050; DB08231; DB03796; DB01138

O95994; Q9NYB0

NA

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

A,B,C,D

15075.9

131

0.11

32.01

6.88

-0.09

-6.94

CHRNA3

Homo sapiens (Human)

NA

NACHRA3

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

Acetylcholine binding protein

Acetylcholine binding.Acetylcholine-gated cation-selective channel activity.Acetylcholine receptor activity.Ligand-gated ion channel activity.Serotonin-gated cation-selective channel activity.

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

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

NA

NA

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

A,B,C,D,E

46391.5

408

0.12

30.23

4.6

-22.73

-6.95

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

-6.94

BCAT1

Homo sapiens (Human)

Protein ECA39; ECA39; Branched-chain-amino-acid aminotransferase, cytosolic; BCT1; BCAT(c)

Class-IV pyridoxal-phosphate-dependent aminotransferase family

Transaminase

Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine.

Charcot-Marie-Tooth disease, dominant intermediate C (CMTDIC) [MIM:608323]: 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. The dominant intermediate type C is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. {ECO:0000269|PubMed:16429158}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2 (IMNEPD2) [MIM:619418]: An autosomal recessive disorder with variable clinical manifestations and severity. Main features include cholestatic hepatitis, poor feeding, poor overall growth, and hypoglycemia apparent from infancy. Most patients have variable global developmental delay, sensorineural deafness, retinal abnormalities with visual defects, and hypotonia. Some patients have endocrine abnormalities. Brain imaging often shows dysmyelination, thin corpus callosum, cerebral atrophy, and white matter abnormalities. Death in early childhood may occur. {ECO:0000269|PubMed:27633801, ECO:0000269|PubMed:29232904, ECO:0000269|PubMed:30304524}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Defects in YARS1 may be the cause of proximal-predominant motor neuropathy. Affected individuals may develop tremors, cramping of hands, asymmetric weakness in the upper and lower extremities, and present with elevated creatine kinase levels. {ECO:0000269|PubMed:36307205}.

DB00996; DB00142; DB00167; DB00149; DB07544; DB00114; DB00161

P55212; O75190-2; O14645; P22607; P06396; O14901; P13473-2; O75400-2

EC 2.6.1.42

3D-structure; Acetylation; Alternative splicing; Amino-acid biosynthesis; Aminotransferase; Branched-chain amino acid biosynthesis; Cytoplasm; Lipid metabolism; Proteomics identification; Pyridoxal phosphate; Reference proteome; Transferase

A,B

40123.7

356

0.1

32.34

5.39

-9

-6.94

OGDH

Homo sapiens (Human)

NA

NA

Alpha-ketoglutarate dehydrogenase family

Immune system

Chaperone binding.Heat shock protein binding.Metal ion binding.Oxoglutarate dehydrogenase (NAD+) activity.Oxoglutarate dehydrogenase (succinyl-transferring) activity.Thiamine pyrophosphate binding.

Postaxial acrofacial dysostosis (POADS) [MIM:263750]: POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases. {ECO:0000269|PubMed:19915526}. The disease is caused by variants affecting the gene represented in this entry.

DB00157; DB00313; DB09092

P54253; P42858

1.2.4.2

3D-structure; Acetylation; Alternative splicing; Calcium; Glycolysis; Isopeptide bond; Magnesium; Metal-binding; Mitochondrion; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Thiamine pyrophosphate; Transit peptide; Ubl conjugation

P,Q

18311.1

158

0.15

37.26

5.64

-2.98

-6.94

ITK

Homo sapiens (Human)

Tyrosine kinase ITK; Inducible T cell kinase; EMT

Protein kinase superfamily, Tyr protein kinase family, TEC subfamily

Kinase

Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3. Tyrosine kinase that plays an essential role in regulation of the adaptive immune response.

Lymphoproliferative syndrome 1 (LPFS1) [MIM:613011]: A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma. {ECO:0000269|PubMed:19425169}. The disease is caused by variants affecting the gene represented in this entry.

DB12010; DB06589; DB14924; DB02010; DB15035

P04626; P48023; P08238; Q13094; P31947; P62258; P10686

EC 2.7.10.2

3D-structure; Adaptive immunity; ATP-binding; Cytoplasm; Direct protein sequencing; Disease variant; Immunity; Kinase; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation; Zinc; Zinc-finger

A

30116.1

263

0.11

37.47

5.03

-11.73

-6.94

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

-6.94

ADRA2A

Homo sapiens (Human)

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

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

GPCR rhodopsin

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

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

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

NA

NA

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

R

30303.9

263

0.16

35.08

9.66

16.82

-6.94

ZUP1

Homo sapiens (Human)

Zinc finger with UFM1-specific peptidase domain protein; ZUFSP; Lys-63-specific deubiquitinase ZUFSP; DUB; C6orf113

Peptidase C78 family, ZUFSP subfamily

Peptidase

Shows only weak activity against 'Lys-11' and 'Lys-48'-linked chains. Plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage. Modulates the ubiquitination status of replication protein A (RPA) complex proteins in response to replication stress. Deubiquitinase with endodeubiquitinase activity that specifically interacts with and cleaves 'Lys-63'-linked long polyubiquitin chains.

WHIM syndrome 2 (WHIMS2) [MIM:619407]: An autosomal recessive form of WHIM syndrome, a primary immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. Myelokathexis is a unique form of non-cyclic severe congenital neutropenia caused by accumulation of mature and degenerating neutrophils in the bone marrow. Monocytopenia and lymphopenia, especially B lymphopenia, also commonly occur. There is significant phenotypic variation among patients, such that some individuals may have an incomplete form of the disorder in which one or more of the classic tetrad features are not present. {ECO:0000269|PubMed:24777453}. The disease may be caused by variants affecting the gene represented in this entry.

NA

Q92619; P50281; Q8WVC2

EC 3.4.19.12

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Hydrolase; Metal-binding; Nucleus; Proteomics identification; Reference proteome; Repeat; Zinc; Zinc-finger

A,B

46930.3

410

0.07

58.67

9

9.7

-6.95

EPHB3

Homo sapiens (Human)

hEK2; Tyrosine-protein kinase TYRO6; TYRO6; Embryonic kinase 2; ETK2; EPH-like tyrosine kinase 2; EPH-like kinase 2; EK2

Protein kinase superfamily, Tyr protein kinase family, Ephrin receptor subfamily

Kinase

The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Generally has an overlapping and redundant function with EPHB2. Like EPHB2, functions in axon guidance during development regulating for instance the neurons forming the corpus callosum and the anterior commissure, 2 major interhemispheric connections between the temporal lobes of the cerebral cortex. In addition to its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and the formation of excitatory synapses. Controls other aspects of development through regulation of cell migration and positioning. This includes angiogenesis, palate development and thymic epithelium development for instance. Forward and reverse signaling through the EFNB2/EPHB3 complex also regulate migration and adhesion of cells that tubularize the urethra and septate the cloaca. Finally, plays an important role in intestinal epithelium differentiation segregating progenitor from differentiated cells in the crypt. Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.

A chromosomal aberration involving TRIM24/TIF1 is found in papillary thyroid carcinomas (PTCs). Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene. {ECO:0000269|PubMed:10439047}.

NA

P37235; O75031

EC 2.7.10.1

3D-structure; Angiogenesis; ATP-binding; Cell membrane; Cell projection; Developmental protein; Disulfide bond; Glycoprotein; Kinase; Membrane; Neurogenesis; Nucleotide-binding; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation

A

30412.9

267

0.09

37.42

7.74

1

-6.94

ALDH1L1

Homo sapiens (Human)

NA

FTHFD

GART family; Aldehyde dehydrogenase family, ALDH1L subfamily

Oxidoreductase

Aldehyde dehydrogenase (NAD) activity.Catalytic activity.Formyltetrahydrofolate dehydrogenase activity.Hydroxymethyl-, formyl- and related transferase activity.

Developmental and epileptic encephalopathy 39 with leukodystrophy (DEE39) [MIM:612949]: 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. DEE39 is characterized by global hypomyelination of the central nervous system, with the gray matter appearing relatively unaffected. Inheritance is autosomal recessive. {ECO:0000269|PubMed:19641205, ECO:0000269|PubMed:24515575}. The disease is caused by variants affecting the gene represented in this entry.

DB00116

Q3SY69; Q92624

1.5.1.6

3D-structure; Acetylation; Alternative splicing; Cytoplasm; NADP; One-carbon metabolism; Oxidoreductase; Phosphopantetheine; Phosphoprotein; Proteomics identification; Reference proteome

A

33869.5

308

0.08

30.42

6.09

-3.83

-6.93

IMPA1

Homo sapiens (Human)

NA

IMPA

Inositol monophosphatase superfamily

Hydrolase

Identical protein binding.Inositol monophosphate 1-phosphatase activity.Inositol monophosphate 3-phosphatase activity.Inositol monophosphate 4-phosphatase activity.Inositol monophosphate phosphatase activity.Lithium ion binding.Magnesium ion binding.Manganese ion binding.Protein homodimerization activity.

Intellectual developmental disorder, autosomal recessive 59 (MRT59) [MIM:617323]: 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:26416544}. The disease is caused by variants affecting the gene represented in this entry.

DB03542; DB14509; DB01356; DB14507; DB14508

P29218; O14732; P54253; G5E9A7; P42858; P29218-3; O14732; Q7Z699

3.1.3.25; 3.1.3.94

3D-structure; Alternative splicing; Cytoplasm; Hydrolase; Intellectual disability; Lithium; Magnesium; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome

A,B

59299.9

544

0.07

37.53

5.38

-11.58

-6.93