Persius/hicric huggingface dataset:
SORBS1
CAP/Ponsin protein, also known as Sorbin and SH3 domain-containing protein 1 is a protein that in humans is encoded by the SORBS1 gene. CAP/Ponsin is part of a small family of adaptor proteins that regulate cell adhesion, growth factor signaling and cytoskeletal formation. CAP/Ponsin is mainly expressed in heart, skeletal muscle, liver, adipose tissue, and macrophages; in striated muscle tissue, CAP/Ponsin is localized to costamere structures.

# Structure
CAP/Ponsin may exist as thirteen alternatively-spliced isoforms, ranging from 81 kDa to 142 kDa. CAP/Ponsin is part of an adaptor protein family, of which ArgBP2 and vinexin are also a part. These proteins contain a conserved sorbin homology (SOHO) domain and three SH3 domains, and CAP/Ponsin is expressed in heart, skeletal muscle, liver, adipose tissue, and macrophages.

# Function
In muscle, CAP/Ponsin plays a role in the formation of mature costameres from focal adhesion-like contacts during assembly of the contractile apparatus, as overexpression of CAP/Ponsin disrupted normal cell-matrix contact morphology. In a mouse model of viral myocarditis due to Coxsackievirus infection, CAP/Ponsin stabilized antiviral type I interferon production and was protective against apoptosis and cytotoxicity. CAP/Ponsin has also been shown to be a major regulator of insulin-stimulated signaling and regulation of glucose uptake, by potentiating insulin-induced phosphorylation and recruitment of CBL to a lipid raft signaling complex involving flotillin. A role for CAP/Ponsin in macrophage function was illuminated by the finding that mice harboring SORBS1-deficient macrophages in bone marrow was protective against high-fat diet-induced insulin resistance and showed reduced inflammation. In non-muscle cells, CAP/Ponsin inhibits cell spreading and focal adhesion turnover, as its siRNA-mediated knockdown resulted in enhanced PAK/MEK/ERK activation and cell migration.

# Clinical Significance
CAP/Ponsin was demonstrated to be down-regulated in end-stage heart failure patients; an effect that was restored upon mechanical unloading. A single nucleotide polymorphism in SORBS1 was found to be associated with type 2 diabetes and obesity.

# Interactions
SORBS1 has been shown to interact with:
- CBL,
- FLOT1,
- INPPL1,
- INSM1,
- MLLT4,
- PXN, and
- Vinculin.
SORBS2
ArgBP2 protein, also referred to as Sorbin and SH3 domain-containing protein 2 is a protein that in humans is encoded by the SORBS2 gene. ArgBP2 belongs to the a small family of adaptor proteins having sorbin homology (SOHO) domains. ArgBP2 is highly abundant in cardiac muscle cells at sarcomeric Z-disc structures, and is expressed in other cells at actin stress fibers and the nucleus.

# Structure
ArgBP2 may exist in as many as 9 unique isoforms ranging from 52 kDa to 117 kDa (492 to 1100 amino acids). ArgBP2 belongs to the a small family of adaptor proteins having sorbin homology (SOHO) domains and three SH3 domains, which regulate cell adhesion, cytoskeletal organization and growth factor signaling; other members include CAP/ponsin and vinexin. The three SH3 domains are C-terminal, a serine-threonine rich domain resides in the middle, and the sorbin homology (SoHo) domain is N-terminal.  The SH3 domains interact with Arg/Abl, vinculin. The SOHO domain interacts with flotillin found in lipid rafts.

# Function
The subcellular localization of this protein in epithelial and cardiac muscle cells suggests that ArgBP2 functions as an adapter protein to assemble signaling complexes in stress fibers, and that it is a potential link between Abl family kinases and the actin cytoskeleton. ArgBP2 contains several potential Abl phosphorylation sites; Arg and c-Abl represent the mammalian members of the Abelson family of non-receptor protein-tyrosine kinases. In non-muscle cells, ArgBP2 bids Cbl which enhances the degradation of c-Abl; and also Pyk2 which promotes cytoskeletal remodeling. ArgBP2 binding with flotillin at lipid rafts may indicate a role for ArgBP2 in vesicle trafficking and signal transduction. flotillin in skeletal muscle cells exhibits a striated pattern suggesting localization to T-tubules or sarcoplasmic reticular cisternae, though no precise role has been determined in cardiac cells. In cardiac muscle cells, pull-down experiments discovered ArgBP2 in complex with alpha actinin-2, vinculin, spectrin, paxillin, Pyk2 and flotillin, suggesting that ArgBP2 may be involved in myofibril assembly and Z-band signaling in cardiomyocytes, though functional studies are necessary to elucidate specific mechanisms. ArgBP2 has been linked to hyertrophic signaling, as a potent paracrine-acting RNA molecule shown to induce cardiac hypertrophy in mice, miR-21, acts on both ArgBP2 and PDLIM5 to trigger the hypertrophic response.

# Clinical Significance
Elevated levels of serum ArgBP2 and coordinate decreases in ArgBP2 in myocardial tissue were detected  in the very early phase from patients post-myocardial infarction who died within 7 hours of the insult. Chromosome 4 pericentric inversion has been observed in 10 patients, with associated cardiac defects linked to terminal 4q35.1 deletions, which may affect SORBS2.

# Interactions
ArgBP2 has been shown to interact with:
- ABL,
- ABL2,
- ACTC1,
- CBL,
- FLOT1,
- PTK2B,
- PLDN, and
- VCL.
SPRED1
Sprouty-related, EVH1 domain-containing protein 1 (Spread-1) is a protein that in humans is encoded by the SPRED1 gene located on chromosome 15q13.2 and has seven coding exons.

# Function
Spread-1 is a member of the Sprouty family of proteins and is phosphorylated by tyrosine kinase in response to several growth factors. The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade.

# Clinical associations
Defects in this gene are a cause of neurofibromatosis type 1-like syndrome (NFLS).
Mutations in this gene are associated with
- Legius syndrome.
- Childhood leukemia

# Mutations
The following mutations have been observed:
- An exon 3 c.46C>T mutation leading to p.Arg16Stop.  This mutation may result in a truncated nonfunctional protein.  Blast cells analysis displayed the same abnormality as germline mutation with one mutated allele (no somatic SPRED1 single-point mutation or loss of heterozygosity was found). The M4/M5 phenotype of AML are most closely associated with Ras pathway mutations.  Ras pathway mutations are also associated with monosomy 7.
- 3 Nonsense (R16X, E73X, R262X)
- 2 Frameshift (c.1048_c1049 delGG, c.149_1152del 4 bp)
- Missense (V44D)
- p.R18X and p.Q194X with phenotype altered pigmentation without tumoriginesis.

# Disease Database
SPRED1 gene variant database
SPTBN1
Spectrin beta chain, brain 1 is a protein that in humans is encoded by the SPTBN1 gene.

# Function
Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. This gene is one member of a family of beta-spectrin genes. The encoded protein contains an N-terminal actin-binding domain, and 17 spectrin repeats that are involved in dimer formation. Multiple transcript variants encoding different isoforms have been found for this gene.

# Interactions
SPTBN1 has been shown to interact with Merlin.

# Model organisms
Model organisms have been used in the study of spectrin function. A conditional knockout mouse line, called Spnb2tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program  a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty seven tests were carried out on mutant mice and four significant abnormalities were observed. Few homozygous mutant embryos were identified during gestation and those that were present displayed oedema. None survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice. These animals had a decreased length of long bones, while males also displayed hypoalbuminemia .
SRD5A1
3-oxo-5-steroid 4-dehydrogenase 1 is an enzyme that in humans is encoded by the SRD5A1 gene. It is one of three forms of 5-reductase.
Steroid 5-reductase (EC 1.3.99.5) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT). There are 3 isoforms of the enzyme: SRD5A1, SRD5A2, and SRD5A3.

# Regulation
ETV4 family members bind to ETS DNA-binding sites and both regulate their own expression and the transcription of a subset of genes that are dependent upon testicular luminal fluid factors, including Ggt_pr4, SRD5A1, and Gpx5.
6-month dietary vitamin E (VE) deficiency in rats resulted in a twofold increase in the mRNA level of SRD5A1 gene and a twofold decrease in the mRNA level of GCLM gene but is not directly mediated by changes in promoter DNA methylation.
Insulin increases the expression of 5-reductase type 1 mRNA via Akt signalling suggest that elevated levels of 5-reduced androgens seen in hyperinsulinemic conditions might be explained on the basis of a stimulatory effect of insulin on 5-reductase in granulosa cells leading to impaired follicle growth and ovulation.

# Clinical significance
Hyperinsulinemia acutely enhances ACTH effects on both the androgen and glucocorticoid pathways leading to changes in steroid metabolites molar ratios that suggest insulin stimulation of 5 -reductase activity. 
PCOS is associated with enhanced androgen and cortisol metabolite excretion and increased 5-reductase activity that cannot be explained by obesity alone. Increased adrenal corticosteroid production represents an important pathogenic pathway in PCOS.
Progression to castration-resistant prostate cancer (CRPC) is accompanied by increased expression of SRD5A1 over SRD5A2, which is otherwise the dominant isoenzyme expressed in the prostate. The dominant route of DHT synthesis in human CRPC bypasses testosterone, and instead requires 5-reduction of androstenedione by SRD5A1 to 5-androstanedione, which is then converted to DHT fuelling cancer growth.
SRD5A2
3-oxo-5-steroid 4-dehydrogenase 2 is an enzyme that in humans is encoded by the SRD5A2 gene. It is one of three forms of 5-reductase.
Steroid 5-reductase catalyzes the conversion of the male sex hormone testosterone into the more potent androgen, dihydrotestosterone.
This gene encodes a microsomal protein expressed at high levels in androgen-sensitive tissues such as the prostate. The encoded protein is active at acidic pH and is sensitive to the 4-azasteroid inhibitor finasteride. Deficiencies in this gene can result in male pseudohermaphroditism, specifically pseudovaginal perineoscrotal hypospadias (PPSH).
SRGAP2
SLIT-ROBO Rho GTPase-activating protein 2 (srGAP2) also known as formin-binding protein 2 (FNBP2) is a protein that in humans is encoded by the SRGAP2 gene.
SRGAP2 is involved in neuronal migration and neuronal differentiation. SRGAP2 also plays a critical role in synaptic development, brain mass and the number of cortical neurons.
SRGAP2C slows maturation of some neurons and increases neuronal spine density.
Downregulation of srGAP2 inhibits cell-cell repulsion and enhances cell-cell contact duration.

# Gene duplication
This gene is one of the 23 genes that are duplicated in humans but not in other primates.
This protein in humans has been duplicated three times in the human genome in the past 3.4 million years:  one duplication 3.4 million years ago (mya) called SRGAP2B, a second duplication 2.4 mya (called SRGAP2C), and one final duplication ~1 mya (SRGAP2D).  The ancestral gene SRGAP2 is found in all mammals and the human copy has been renamed SRGAP2A. The 2.4 million year-old duplication (SRGAP2C) expresses a shortened version that 100% of humans possess.  This shortened version SRGAP2C inhibits the function of the ancestral copy SRGAP2A and (1) allows faster migration of neurons by interfering with filopodia production and (2) slows the rate of synaptic maturation and increases the density of synapses in the cerebral cortex.
SS18L1
SS18-like protein 1 is a protein that in humans is encoded by the SS18L1 gene.

# Function
Synovial sarcomas occur most frequently in the extremities around large joints. More than 90% of cases have a recurrent and specific chromosomal translocation, t(X;18)(p11.2;q11.2), in which the 5-prime end of the SS18 gene is fused in-frame to the 3-prime end of the SSX1, SSX2, or SSX4 gene. The SS18L1 gene is homologous to SS18.

# Interactions
SS18L1 has been shown to interact with CREB-binding protein. Biochemical pull down assays reveal SS18L1 to interact with several components of the human SWI/SNF chromatin remodeling complex.
SSMEM1
Serine-rich single pass membrane protein 1 is a protein that in humans is encoded by the SSMEM1 gene.

# Gene
The gene and intron-exon structure were first predicted through analysis of the complete sequence of human chromosome 7, its initial designation being C7orf45.  Human mRNA transcripts were identified through two large scale cDNA cloning efforts, an American effort run out of the Dana-Farber Cancer Institute and Harvard Medical School, and full-length long Japan effort.   Later assigned the official symbol SSMEM1, the gene is located on the long arm of chromosome 7 (7q32.2) on the sense strand in humans. The human mRNA transcript is 1171 bp long with three exons.

## Aliases
In humans, SSMEM1 is also referred to as C7orf45. Human SSMEM1 has a clone name of FLJ40316.

## Expression
In humans, SSMEM1 is highly expressed in the testes. In mice, SSMEM1 is expressed in the brain.

# Protein
In humans, serine-rich single pass membrane protein 1 is 244 amino acids long with a transmembrane domain region spanning amino acids 35-55. This protein has a domain of unknown function (DUF4636) that spans almost all of the protein (amino acids 1-243).  DUF4636 belongs to  pfam15468 which is a part of the superfamily cl21285 that is found in eukaryotes and typically 196 to 244 amino acids long. The human protein has a molecular weight of 28036 Da and an isoelectric point of 7.64.
STARD4
StAR-related lipid transfer protein 4 (STARD4) is a soluble protein involved in cholesterol transport.  It can transfer up to 7 sterol molecules per minute between artificial membranes.

# Function
STARD4 may regulate cholesterol levels in many cells, including in the liver.  STARD4 has specifically been linked to the movement of cholesterol to the endoplasmic reticulum.  The protein is associated with the endoplasmic reticulum and lipid droplets.  Increases in the protein relate to cell stress.
High levels of STARD4 increases the synthesis of bile acids and cholesterol esters in liver hepatocytes. Reductions in cholesterol synthesis by cells increase STARD4 levels while StarD4 declines in mice fed a high cholesterol diet.
Increases in levels of either master gene regulator SREBP-1a or SREBP2, which both promote the production of proteins involved in cholesterol synthesis, increase StarD4 levels in mouse liver.  Conversely, increased STARD4 increases active SREBP2 levels.
Loss of the protein in mice has little effect.  Mice without functional STARD4 weigh less and females tend to have lower cholesterol profiles.  The most dramatic change observed to date is a reduction in NPC-1, a protein involved in bringing cholesterol into cells.

# Structure
The protein is 205 amino acids long in the human (224 in the mouse) and almost entirely consists of a StAR-related transfer (START) domain.  It also lends its name to the subgroup of START domain proteins it is part of, StarD4.  This subfamily includes STARD5 and STARD6 and is closely related to the StarD1/D3 group.
STARD5
StAR-related lipid transfer protein 5 is a protein that in humans is encoded by the STARD5 gene.  The protein is a 213 amino acids long, consisting almost entirely of a StAR-related transfer (START) domain.  It is also part of the StarD4 subfamily of START domain proteins, sharing 34% sequence identity with STARD4.

# Function
The protein is most prevalent in the kidney and the liver where it is found in Kupffer cells. STARD5 binds both cholesterol and 25-hydroxycholesterol and appears to function to redistribute cholesterol to the endoplasmic reticulum with which the protein associates and/or the plasma membrane.  Increased levels of StarD5 increase free cholesterol in the cell.
Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g., SREBP1) and by liver X receptors (e.g., LXRA). Upon sterol depletion, LXRs are inactive and SREBPs are cleaved, after which they bind promoter SREs and activate genes involved in cholesterol biosynthesis and uptake. Sterol transport is mediated by vesicles or by soluble protein carriers, such as steroidogenic acute regulatory protein (STAR). STAR is homologous to a family of proteins containing a 200- to 210-amino acid STAR-related lipid transfer (START) domain, including STARD5.

# Model organisms
Model organisms have been used in the study of STARD5 function. A conditional knockout mouse line, called Stard5tm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program  a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on homozygous mutant mice and one significant abnormality was observed: abnormal vertebral transverse processes.
STARD7
StAR-related lipid transfer domain protein 7 (STARD7) or gestational trophoblastic tumor gene-1 (GTT1) is a lipid transporter that specifically binds and transports phosphatidylcholine between membranes.

# Function and tissue distribution
StarD7 is found in the cytosol and associated with the mitochondrion.  When overproduced in the cell, mitochondrial levels of phosphatidylcholine rise.  High levels of the protein are found in tumor cells compared to normal cells, suggesting a role in cell proliferation.

# Structure
There are two forms of StarD7: StarD7-I and StarD7-II.  The former is 295 amino acids long.  StarD7-I possesses an additional 75 amino acids at its amino-terminus, which form a signaling sequence that targets it to the outer membrane of the mitochondrion.
StarD7 contains a StAR-related transfer domain (START), from which it derives its name.  Moreover, the protein is a member of the predominantly phosphatidylcholine transporter subfamily of START proteins, the StarD2 subfamily.  It shares 25% sequence identity with StarD2.
STARD8
StAR-related lipid transfer domain protein 8 (STARD8) also known as deleted in liver cancer 3 protein (DLC-3) is a protein that in humans is encoded by the STARD8 gene and is a member of the DLC family.

# Structure and function
The protein is 1103 amino acids long, which like other DLC proteins consists of a sterile alpha motif (SAM), RhoGAP and a StAR-related lipid-transfer (START) domains.
The protein is a Rho GTPase-activating protein (GAP), a type of protein that regulates members of the Rho family of GTPases.  STARD8 is characterized as activating Rho GTPases.  Its expression inhibits the growth of human breast and prostate cancer cells in culture.

# Tissue distribution and pathology
The protein is expressed in tissues throughout the body, but is absent or reduced in many kinds of tumor cells.
While there are no known disorders caused by STARD8, partial loss of the STARD8 gene occurs in cases of craniofrontonasal syndrome where the EFNB1 gene (which causes the syndrome) is completely deleted.

# Model organisms
Model organisms have been used in the study of STARD8 function. A conditional knockout mouse line called Stard8tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed:  - In-depth immunological phenotyping
STEAP3
Metalloreductase STEAP3 is an enzyme that in humans is encoded by the STEAP3 gene.
STEAP3 is a metalloreductase, capable of coverting iron from an insoluble ferric (Fe3+) to a soluble  ferrous (Fe2+) form.
STEAP3 and other STEAP protein, with the exception of STEAP1, are predicted to contain a Di-nucleotide binding domain (Rossmann Fold). This has been shown using X-ray crystallography in the cases of STEAP3 and STEAP4 (PDB: 2VNS, 2VQ3 and 2YJZ).

# Interactions
STEAP3 has been shown to interact with BNIP3L and PKMYT1.
STXBP1
Syntaxin-binding protein 1 (also known as Munc18-1) is a protein that in humans is encoded by the STXBP1 gene. This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4.

# Structure
The STXBP1 gene is located on the q arm of chromosome 9 in position 34.11 and has 20 exons spanning 80,510 base pairs. The encoded protein is a peripheral membrane protein located in the cytosol. In the retina and cerebellum, an alternatively spliced transcript variant is expressed, containing an additional exon and totaling 603 amino acids. Alternative splicing can produce an isoform with exon 19 and an isoform without.

# Function
The encoded protein may participate in the regulation of synaptic vesicle docking and fusion, possibly through interaction with GTP-binding proteins. It is essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. It can interact with syntaxins 1, 2, and 3 but not syntaxin 4 and may play a role in determining the specificity of intracellular fusion reactions. This protein functions in a late stage of the intracellular membrane fusion process of exocytosis. Dissociation of this protein from syntaxin determines the kinetics of postfusion events. This protein is essential for presynpatic vesicle release and is rapidly phosphorylated by protein kinase C upon neuronal depolarization. The protein participates in the secretory pathway between the Golgi apparatus and cell membrane.

# Clinical Significance

## Epileptic Encephalopathy
Mutations in the STXBP1 cause Early Infantile Epileptic Encephalopathy Type 4 (EIEE4), a severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Affected individuals have neonatal or infantile onset of seizures, profound mental retardation, and MRI evidence of brain hypomyelination. Inheritance of EIEE4 is autosomal dominant.
This gene was initially discovered in 2008 as cause for Ohtahara Syndrome. Ever since, it has become one of the most prominent genes for epileptic encephalopathies so far.

## Expression
In melanocytic cells STXBP1 gene expression may be regulated by MITF.
The STXBP1 gene is expressed in the brain and spinal cord and highly enriched in axons. Expression of this protein is highest in the retina and cerebellum.

# Interactions
The encoded protein binds SYTL4. STXBP1 has been shown to interact with STX2, STX4 and STX1A.