Persius/hicric huggingface dataset:
GLRX5
Glutaredoxin 5, also known as GLRX5, is a protein which in humans is encoded by the GLRX5 gene located on chromosome 14. This gene encodes a mitochondrial protein, which is evolutionarily conserved. It is involved in the biogenesis of iron- sulfur clusters, which are required for normal iron homeostasis. Mutations in this gene are associated with autosomal recessive pyridoxine-refractory sideroblastic anemia.

# Structure
The GLRX5 gene contains 2 exons and encodes for a protein that is 13 kDa in size. The protein is highly expressed in erythroid cells. Crystal structure of the GLRX5 protein reveals that the protein likely exists as a tetramer with two Fe-S clusters buried in the interior.

# Function
GLRX5 is a mitochondrial protein is conserved evolutionarily and plays a role in the formation of iron-sulfur clusters, which function to maintain iron homeostasis within the mitochondria and in the cell. GLRX5 is required for the steps in haem synthesis that involves mitochondrial enzymes, and is therefore involved in hematopoiesis. GLRX5 activity is required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1. The function of GLRX5 is highly conserved evolutionarily.

# Clinical significance
Mutations in the GLRX5 gene have been associated with sideroblastic anemia, variant glycine encephalopathy (also known as non-ketotic hyperglycinemia, NKH). as well as pyridoxine-refractory, autosomal recessive anemia (PRARSA). Cells with mutations in GLRX5 activity show deficiency in Fe-S cluster synthesis, which is likely causative of the observed symptoms.
GLUT8
GLUT8 also known as SLC2A8 is the eighth member of glucose transporter superfamily.
It is characterized by the presence of  two leucine residues in its N-terminal intracellular domain, which influences intracellular trafficking.

# Discovery
GLUT8, originally named GLUTX1, was cloned almost simultaneously by two different groups.

# Tissue distribution
GLUT8 is expressed mostly in neurons and testis, although expression in most other tissues has also been shown at lower levels.  GLUT8 is expressed at moderate levels in the brain, most strikingly in hippocampus. Whether the glucose transporter plays any role in these cells remains to be shown.

# Subcellular localization
Contrary to GLUT4, GLUT8 (previously known as GLUTX1) is not insulin-sensitive. In other words, insulin does not promote GLUT8 translocation to the cell surface in neurons as well as in transfected cell lines.
Where in the cell GLUT8 is localized in not yet clear. Most GLUT8 is not present at the cell surface. Some co-localization with both the endoplasmic reticulum and late endosomes/lysosomes has been published.
When the N-terminal di-leucine motif is mutated into a di-alanine motif, GLUT8 is located mostly at the cell surface in Xenopus oocytes and mammalian cells such as HEK 293 cells and differentiated PC12 cells.

# Physiological role
GLUT8 function in vivo remains to be defined, despite suggestions that it may play a role in fertility, being expressed at high levels in testes and in the acrosomal part of spermatozoa. Furthermore, GLUT8 appears to play an important role in the energy metabolism of sperm cells.
The recent description of GLUT8 expression in kidneys and liver suggest that the transporter may play a role in glucose uptake in these organs.
GLUT8, when expressed in Xenopus oocytes, mediates glucose uptake with high affinity. Other hexoses are not good substrates of the transporter. Whether the transporter actually mediates glucose uptake in vivo in the brain has not been evaluated yet.
Mice devoid of both copies of the SLC2A8 gene are viable, fertile and do not show any obvious phenotype. They are not diabetic, showing that GLUT8 is unlikely to play major roles in glucose homeostasis.
GLYAT
Glycine-N-acyltransferase, also known as GLYAT, is an enzyme which in humans is encoded by the GLYAT gene.

# Function
The glycine-N-acyltransferase protein conjugates glycine with acyl-CoA substrates in the mitochondria primarily in liver and kidney. The glycine N-acyltransferase enzyme is involved in the detoxification of a wide range of xenobiotic and endogenous metabolites. These include benzoic acid, a compound found in fruits and vegetables and used in medicine and foodstuffs as a preservative; salicylic acid, a metabolite of aspirin; and several endogenous metabolites. The diversity is demonstrated by the wide range of acylglycines excreted in the urines of patients with defects of organic acid metabolism. No defect of glycine N-acyltransferase has yet been described, but it has been demonstrated that there is significant inter individual variation in glycine conjugation capacity. Human glycine N-acyltransferase isoform a is a 296 amino acid protein translated from mRNA transcript splice variant 1. It is encoded by exons 2 to 6 of the mRNA transcript.

# Molecular weight
The literature reports it to be approximately 30 kDa, or approximately 27 kDa. The predicted size is 33.9 KDa. For the bovine enzyme a range of sizes between approximately 33 kDa and about 36 KDa is reported (Nandi, 1979, Vessey, 1992, van der Westhuizen, 2000). The predicted size of bovine GLYAT based on its sequence (accession number nm: 177486), is 33.9 kDa. This compares well to the experimentally determined sizes
GNAI1
Guanine nucleotide-binding protein G(i), alpha-1 subunit is a protein that in humans is encoded by the GNAI1 gene.

# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.
-  The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}

# Interactions
GNAI1 has been shown to interact with:
- GPR143,
- RGS12,
- RGS14,
- RGS19,
- RIC8A,  and
- S1PR1.
GOLM1
Golgi membrane protein 1 (GOLM1) also known as Golgi phosphoprotein 2 or Golgi membrane protein GP73 is a protein that in humans is encoded by the GOLM1 gene.  Two alternatively spliced transcript variants encoding the same protein have been described for this gene.

# Function
The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is a type II Golgi transmembrane protein. It processes protein synthesized in the rough endoplasmic reticulum and assists in the transport of protein cargo through the Golgi apparatus. The expression of this encoded protein has been observed to be upregulated in response to viral infection.

# Clinical significance
Golgi membrane protein 1 is overexpressed in prostate cancer and lung adenocarcinoma tissue.
Blood levels of GP73 are higher in patients with liver cancer than in healthy individuals. In addition, levels were not significantly higher in patients with diseases other than liver disease. The current blood test used to screen for early tumors in people at high risk for liver cancer involves the alpha-fetoprotein (AFP). Patients who are at risk for non-metastatic, or primary, liver cancer typically have chronic liver disease such as cirrhosis. Such cases of cirrhosis are usually due to infection caused by infectious hepatitis (usually hepatitis B or hepatitis C, though there are other strains), or because of degenerative fatty liver disease (which can be especially severe in those with alcoholism). However, the AFP test is not usually sensitive enough to detect liver cancer in time and it often generates false positives. So far, the blood samples of more than 1,000 patients with various stages of liver and non-liver disease have been tested for the presence of GP73 in several studies. Several medical diagnostic companies are in the process of developing automated serum tests for the protein that could be performed in routine hospital laboratories.
GOSR1
Golgi SNAP receptor complex member 1 is a protein that in humans is encoded by the GOSR1 gene.
This gene encodes a trafficking membrane protein which transports proteins among the endoplasmic reticulum and the Golgi apparatus and between Golgi compartments. This protein is considered an essential component of the Golgi SNAP receptor (SNARE) complex. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

# Interactions
GOSR1 has been shown to interact with USO1, BET1L and STX5.
GPD1L
GPD1L is a human gene. The protein encoded by this gene contains a glycerol-3-phosphate dehydrogenase (NAD+) motif and shares 72% sequence identity with GPD1.

# Structure
GPD1L contains the following domains:
- N-terminal  NAD+ consensus binding site
- a site homologous to the cardiac sodium channel SCN5A
- C-terminal lysine-206 residue

# Tissue distribution
Northern blot analysis detected a single GPD1L transcript in all tissues examined except liver. Highest expression was in heart and skeletal muscle.

# Disease linkage
Mutations in the GPD1L gene are associated with the Brugada syndrome and sudden infant death syndrome.
GPLD1
Phosphatidylinositol-glycan-specific phospholipase D is an enzyme that in humans is encoded by the GPLD1 gene.
Many proteins are tethered to the extracellular face of eukaryotic plasma membranes by a glycosylphosphatidylinositol (GPI) anchor. The GPI-anchor is a glycolipid found on many blood cells. The protein encoded by this gene is a GPI degrading enzyme. Glycosylphosphatidylinositol specific phospholipase D1 hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby releasing the attached protein from the plasma membrane.

# Interactions
GPLD1 has been shown to interact with Apolipoprotein A1 and APOA4.
GPNMB
Transmembrane glycoprotein NMB is a protein that in humans is encoded by the GPNMB gene. Two transcript variants encoding 560 and 572 amino acid isoforms have been characterized for this gene in humans.  The mouse and rat orthologues of GPNMB are known as DC-HIL and Osteoactivin (OA), respectively.
GPNMB is a type I transmembrane glycoprotein which shows homology to the pmel17 precursor, a melanocyte-specific protein.
GPNMB has been reported to be expressed in various cell types, including: melanocytes, osteoclasts, osteoblasts, dendritic cells, and it is overexpressed in various cancer types. In melanocytic cells and osteoclasts the GPNMB gene is transcriptionally regulated by Microphthalmia-associated transcription factor.

# Function
In osteoblast progenitor cells, Osteoactivin works as a positive regulator of osteoblast differentiation during later stages of matrix maturation and mineralization  that is mediated at least in part by BMP-2 in a SMAD1 dependent manner to promote osteoblast differentiation. In addition, using a rat fracture model, Osteoactivin (OA) enhances the repairing process in bone fracture, demonstrated by its high expression during chondrogenesis (soft callus) and osteogenesis (hard callus) compared to the intact femurs  that is why Osteoactivin (OA) could be a novel therapeutic agent used to treat generalized osteoporosis or localized osteopenia during fracture repair by stimulating bone growth and regeneration.  Similarly, Osteoactivin expression increases during osteoclast differentiation and it is functionally implicated in this process, possibly by promoting the fusion of osteoclast progenitor cells.

# Clinical and functional significance in cancer
GPNMB was originally identified as  a gene that was expressed in poorly metastatic human melanoma cell lines and xenografts and not expressed in highly metastatic cell lines. However, several recent studies have identified high GPNMB expression in aggressive melanoma, glioma, and breast cancer specimens.

## Breast cancer
Based on Immunohistochemical analysis, two studies have shown that GPNMB is commonly expressed in breast tumors. In the first study, GPNMB was detected in 71% (10/14) of breast tumors. In the second study, 64% of human breast tumors express GPNMB in the tumor stroma and an additional 10% of tumors express GPNMB in the tumor epithelium. In this study it was reported that GPNMB expression in the tumor epithelium was an independent prognostic indicator of breast cancer recurrence. Moreover, epithelial GPNMB expression was most abundant in triple negative breast cancers and it was found to be a prognostic marker for shorter metastasis-free survival times within this breast cancer subtype. Finally, GPNMB expression in breast cancer cells is capable of promoting cell migration, invasion, and  metastasis both in vitro and in vivo.

# GPNMB as a target for therapy
GPNMB is the target of the antibody glembatumumab (CR011) which is used in the antibody-drug conjugate glembatumumab vedotin (CDX-011, CR011-vcMMAE) which is in clinical trials for melanoma and breast cancer. (See glembatumumab vedotin)
GPR32
G protein-coupled receptor 32, also known as GPR32 or the RvD1 receptor, is a human Receptor (biochemistry) belonging to the rhodopsin-like subfamily of G protein-coupled receptors.

# Gene
The GPR32 was initially identified and defined by Molecular cloning in 1998 as coding for an Orphan receptor, i.e. a protein with an amino acid sequence similar to known receptors but having no known ligand(s) to which it responds and no known function. The projected amino acid sequence of GPR32, however, shared 35-39% amino acid identity with certain members of the chemotactic factor receptor family, i.e. 39% identity with Formyl peptide receptor 1, which is a receptor for N-Formylmethionine-leucyl-phenylalanine and related N-formyl peptide chemotactic factors, and 35% identity with Formyl peptide receptor 2, which likewise is also a receptor for N-formyl peptides but also a receptor for certain lipoxins which are arachidonic acid metabolites belonging to a set of specialized proresolving mediators that act to resolve or inhibit inflammatory reactions. GPR32 mapped to chromosomal 19, region q13.3. There are no mouse or orthologs of GPR32.

# Receptor
The GPR32 protein is a G protein coupled receptor although the specific G protein subtypes which it activates has not yet been reported. GPR32 is expressed in human blood neutrophils, certain types of blood lymphocytes (i.e. activated CD8+ cells, CD4+ T cells, and T helper 17 cells), tissue macrophages, small airway epithelial cells, and adipose tissue. When expressed in Chinese hamster ovary cells, GPR32 inhibits the Cyclic adenosine monophosphate signaling pathway under both baseline and forskolin-stimulated conditions indicating that it is a member of the class of orphan G protein coupled receptors that possesses constitutive signaling activity.
At least 6 members of the D series of resolvins (RvDs) viz., RvD1, RvD2m AT-RVD1, RvD3, AT-RvD3, and RvD5, activate their target cells through this receptor; these results have led to naming GPR32 the RVD1 receptor (see Resolvin#Mechanisms of Action).  RvDs are members of the specialized proresolving mediators (SPM) class of polyunsaturated fatty acid metabolites. RVDs are metabolites of the omega-3 fatty acid, docosahexaenoic acid (DHA), and, along with other SRMs contribute to the inhibition and resolution of a diverse range of inflammation and inflammation-related responses as well as to the healing of these inflammatory lesions in animals and humans. The metabolism of DHA to RVD's and the activation of GPR32 by these RVD's are proposed to be one mechanism by which omega-3 fatty acids may ameliorate inflammation as well as various inflammation-based and other diseases.
GPR35
G protein-coupled receptor 35 also known as GPR35 is a G protein-coupled receptor which in humans is encoded by the GPR35 gene. Heightened expression of GPR35 is found in immune and gastrointestinal tissues, including the crypts of Lieberkuhn.

# Ligands

## Endogenous ligands
Although GPR35 is still considered an orphan receptor, there have been attempts to deorphanize it by identifying endogenous molecules that can activate the receptor. All of the currently proposed ligands are either unselective towards GPR35, or they lack high potency, a characteristic feature of natural ligands. The following list includes the most prominent examples:
- kynurenic acid
- LPA species 
- cyclic guanosine monophosphate 
- DHICA 
- T3 
- reverse T3 

## Synthetic agonists
Other synthetic agonists of GPR35 include:
- cromoglicic acid 
- nedocromil 
- pamoic acid
- zaprinast 
- lodoxamide
- bufrolin
Zaprinast is currently the gold standard in the biochemical evaluation of novel synthetic GPR35 agonists, because it remains potent in an animal model. Most other known agonists display high selectivity towards the human GPR35 orthologue. This phenomenon is well established for other GPCRs and complicates the development of pharmaceutical drugs.

## Antagonists
Antagonists of GPR35 include:
- ML145 (CID-2286812)
- ML144 (CID-1542103)
Both ML145 and ML144 unfurl their antagonistic activity through inverse agonism. They are, however, highly species-selective, and practically inactive at the rodent receptor orthologues.

# Clinical significance
Deletion of GPR35 gene may be responsible for brachydactyly mental retardation syndrome and is mutated in 2q37 monosomy and 2q37 deletion syndrome. In one study GPR35 has been recognised as a potential oncogene in stomach cancer.
GPR37
Probable G-protein coupled receptor 37 is a protein that in humans is encoded by the GPR37 gene.

# Interactions
GPR37 has been shown to interact with HSPA1A and Parkin (ligase).
GPR37 is a receptor for prosaposin. It was previously thought to be a receptor for head activator, a neuropeptide found in the hydra, but early reports of head activator in mammals were never confirmed.
GPR50
G protein-coupled receptor 50 is a protein which in humans is encoded by the GPR50 gene.

# Function
GPR50 is a member of the G protein-coupled receptor family of integral membrane proteins and is most closely related to the melatonin receptor.  GPR50 is able to heterodimerize with both the MT1 and MT2 melatonin receptor subtypes.  While GPR50 has no effect on MT2 function, GPR50 prevented MT1 from both binding
melatonin and coupling to G proteins. GPR50 is the mammalian ortholog of melatonin receptor Mel1c described in non-mammalian vertebrates.

# Clinical significance
Certain polymorphisms of the GPR50 gene in females are associated with increased risk of developing bipolar affective disorder, major depressive disorder, and  schizophrenia. Other GPR50 gene polymorphism are associated with higher fasting circulating triglyceride levels and lower circulating High-density lipoprotein levels.
GPR64
G protein-coupled receptor 64 also known as HE6 is a protein encoded by the ADGRG2 gene. GPR64 is a member of the adhesion GPCR family.
Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.
The adhesion GPCR, GPR64, is an orphan receptor characterized by a long N-terminus with that has been suggested to be highly glycosylated.  GPR64's N-terminus has been reported to be cleaved at the GPS domain to allow for trafficking to the plasma membrane.  After cleavage the N-terminus is believed to remain non-covalently associated with the 7TM. GPR64 expression has been mostly reported in the male reproductive organs, but more recently has been shown to be expressed in the central nervous system. GPR64 is mainly expressed in human and mouse epididymis as well as human prostate and parathyroid. GPR64, together with F-actin scaffold, locates at the nonciliated principal cells of the proximal male excurrent duct epithelia, where reabsorption of testicular fluid and concentration of sperm takes place.

# Function
Targeting of Gpr64 in mice causes reduced fertility or infertility in males; but the reproductive capacity was unaffected in females. Unchanged hormone expression in knockout males indicates that the receptor functions immediately in the male genital tract. Lack of Gpr64 expression causes sperm stasis and duct obstruction due to abnormal fluid reabsorption. In addition, expression of GPR64 has been found in fibroblast-like synovial cells obtained from osteoarthritis but not from rheumatoid arthritis.

# Clinical significance
GPR64 is significantly overexpressed in the Wnt signaling-dependent subgroup of medulloblastoma, as well as in ewing sarcomas and carcinomas derived from prostate, kidney or lung. Richter et al. demonstrated that GPR64 promotes tumor invasion and metastasis through placental growth factor and MMP1.
GPR75
Probable G-protein coupled receptor 75 is a protein that in humans is encoded by the GPR75 gene.

# Function
GPR75 is a member of the G protein-coupled receptor family. GPRs are cell surface receptors that activate guanine-nucleotide binding proteins upon the binding of a ligand.
GPR75 is currently classified as an orphan GPCR and several studies are underway to identify its ligand. In one study, the chemokine CCL5 (RANTES) has been shown to stimulate calcium mobilization and inositol triphosphate formation in GPR75-transfected cells.
Recently, 20-hydroxyeicosatetraenoic acid (20-HETE), a bioactive eicosanoid formed by -hydroxylation of arachidonic acid has been shown to mediate its prohypertensive effects on the vasculature through activation of GPR75 (Gq) signalling. This study by Dr. Schwartzman's laboratory at New York Medical college, one of the pioneers in study of 20-HETE biology, has opened new insights into the field of GPR75 pharmacology.
GPR81
G protein-coupled receptor 81, also known as GPR81, is a protein that in humans is encoded by the GPR81 gene.
G protein-coupled receptors (GPCRs, or GPRs), such as GPR81, contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins.
Lactate activates the GPR81 receptor which in turn inhibits lipolysis in fat cells.