Persius/hicric huggingface dataset:
COPII
COPII is a coatomer, a type of vesicle coat protein that transports proteins from the rough endoplasmic reticulum to the Golgi apparatus. This process is termed anterograde transport, in contrast to the retrograde transport associated with the COPI protein. The name "COPII" refers to the specific coat protein complex that initiates the budding process.  The coat consists of large protein subcomplexes that are made of four different protein subunits.

# Coat proteins
There are two protein heterodimers that form the coat complex.  These proteins are
- Sec23p/Sec24p Heterodimer
- Sec13p/Sec31p Heterotetramer
These proteins alone are not able to cause the budding of the vesicle or direct the vesicle to the correct target membrane.  SNARE, cargo, and other proteins are also needed for these processes to occur.  The CopII protein does, however, cause the binding that forms vesicle coat, and thereby causes the release from the ER.  The exact process of how the vesicle is brought to a particular location, or how that location is determined is not yet known.

# Budding process
The GTPase Sar1p is a protein that hydrolyzes GTP and acts like a molecular "switch" that flips between an activated and membrane embedded GTP-bound form, and inactive and soluble GDP-bound form. Inactive GDP-bound Sar1p is attracted to the cytosolic side of the endoplasmic reticulum. Sec12, a transmembrane protein found in the ER acts as a Guanine nucleotide exchange factor by stimulating the release of GDP to allow the binding of GTP. Now in a GTP bound state, Sar1p undergoes a conformational change which exposes a hydrophobic tail that can be inserted into the lipid bilayer, binding it to the membrane.  Membrane-bound Sar1p recruits the Sec23p/24p complex to form what is collectively known as the pre-budding complex. The pre-budding complex recruits the long, flexible Sec13p/31p complex.  Sec13p/31p complexes polymerizes on the cytosolic side of the membrane to form a convex mesh structure.  The assembling mesh causes the membrane to bulge outward until a vesicle buds off. Some proteins are found to be responsible for selectively packaging cargos into COPII vesicles. For example, Erv29p in Saccharomyces cerevisiae is found to be necessary for packaging glycosylated pro--factor.

# Conformational changes
CopII has three specific binding sites that can each be complexed.  The adjacent picture (Sed5) uses the Sec22 t-SNARE complex to bind.  This site is more strongly bound, and therefore is more favored. (Embo)
- Conformation of the CopII protein complexed with the snare protein Bet1 (PDB: 1PCX).
Conformation of the CopII protein complexed with the snare protein Bet1 (PDB: 1PCX).
- Conformation of the CopII protein that is complexed with the snare protein Sed5 (PDB: 1PD0).
Conformation of the CopII protein that is complexed with the snare protein Sed5 (PDB: 1PD0).
CORIN
Corin, also called atrial natriuretic peptide-converting enzyme, is a protein that in humans is encoded by the CORIN gene.

# Protein
Human corin, a polypeptide of 1042 amino acids, consists of an N-terminal cytoplasmic domain, a transmembrane domain and an extracellular region with two frizzled-like domains, eight LDL receptor-like domains, a scavenger receptor-like domain and a C-terminal trypsin-like serine protease domain. Corin is synthesized as a zymogen that is activated by PCSK6.
Corin exhibits a trypsin-like catalytic activity favoring basic residues at the P1 position.
Human corin contains 19 N-glycosylation sites.  N-glycans promote corin expression on the cell surface and protect corin from metalloproteinase-mediated shedding.

# Function
Corin converts the atrial natriuretic peptide (ANP) precursor, pro-ANP, to mature ANP, a cardiac hormone that regulates salt-water balance and blood pressure.  In mice, corin deficiency prevents pro-ANP processing and causes salt-sensitive hypertension.
Corin may also function as a pro-brain-type natriuretic peptide convertase.
Corin-mediated ANP production in the pregnant uterus promotes spiral artery remodeling and trophoblast invasion.  CORIN mutations have been reported in patients with preeclampsia.
In mice, corin functions in the dermal papilla to regulate coat color in an Agouti-dependent pathway.

# Variants and mutations
Variants encoded by alternative exons were reported in human and mouse corin. A variant allele (T555I/Q568P) was found in African Americans with hypertension and cardiac hypertrophy.  The amino acid substitutions impaired corin activity. An insertion variant in exon 1 alters the cytoplasmic tail.  This variant appeared more frequently in hypertensive patients. CORIN mutations were found in patients with hypertension.
CORO6
Coronin-6 also known as coronin-like protein E (Clipin-E) is a protein that in humans is encoded by the CORO6 gene.
Coronin-6 is belongs to coronin family which is an actin binding protein. Human CORO6 gene is located on chromosome 17 on the cytogenetic band 17 p11.2. Gene CORO6 is well conserved across domain of eukaryotic organisms from animal to fungi.

# Expression

## EST profile
Based on the EST profile, CORO6 expressed in high level at the larynx, nerve and muscle. CORO6 has also been shown to be expressed in high levels in the breast (mammary gland) tumor. During the human development stage,the higher level of CORO6 expressed at blastocyst and adult.

## Transcript Variant
Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron. Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript .  CORO6 contains 21 distinct gt-ag introns. Transcription produces 10 alternatively spliced mRNA. There are 3 probable alternative promoters, and validated alternative polyadenylation sites.

# Structure
CORO6 protein sequence contains WD-40 repeats.  WD40 domain is a structural motif found in Eukaryotes and cover variety of functions, such as adaptor or regulatory modules in signal transduction, pre-mRNA processing and cytoskeletal assembly.  It usually terminating at WD dipeptide at its C-terminus and is about 40 residues long, so called WD40.
The structure of CORO6 is predicted by using Phyre2 program. It is similar to the crystal structure of murine coronin-1. 390 residues ( 83% of CORO6 protein sequence) have been modelled with 100.0% confidence by the single highest scoring template. Image coloured by rainbow N  C terminus

# Homology

## Paralogs
Human proteins which are the paralogs to CORO6,
CORO1A,
CORO1B,
CORO1C,
CORO2A,
CORO2B,
CORO7
The table compared Homo sapiens protein CORO6 to its paralogs
By comparing its paralogs we found that CORO1A and CORO1B are most related to CORO6.

## Orthologs
CORO6 is highly conserved throughout the organisms from vertebrate to fungus, the organisms listed in the table are some representatives.

# Clinical significance
There are several clinical studies about that have been performed by using microarray indicating that CORO6 is positively related to allergic nasal epithelium response to house dust mite allergen in vitro.

# Model organisms
Model organisms have been used in the study of CORO6 function. A conditional knockout mouse line called Coro6tm1e(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
COTL1
Coactosin-like protein (COTL1 or CLP) is a protein that in humans is encoded by the COTL1 gene.

# Function
This gene encodes one of the numerous actin-binding proteins which regulate the actin cytoskeleton. This protein binds F-actin, and also interacts with and thereby stabilizes 5-lipoxygenase (ALOX5). Although this gene has been reported to map to chromosome 17 in the Smith-Magenis syndrome region, the best alignments for this gene are to chromosome 16. The Smith-Magenis syndrome region is the site of two related pseudogenes.

# Interactions
COTL1 has been shown to interact with ALOX5.  ALOX5 is the first committed enzyme in the metabolism of arachidonic acid to an array of biologically important cell signaling agents: a) the pro-inflammatory mediator, leukotriene B4 (LTB4); b) the airways constrictors, LTC4, LTD4, and LTE4; c) the 5-hydroxyeicosatetraenoic acid family of pro-inflammatory and pro-allergic reactions mediators, 5-HETE and 5-oxo-eicosatetraenoic acid. ALOX5 also contributes to the metabolism of arachidonic acid and other polyunsaturated fatty acids to agents which act block inflammation and allergic reactions, the specialized pro-resolving mediators of the lipoxin and resolvin subclasses. Based on in vitro studies, COTL1 serves to stabilize ALOX5, acting as a chaperone or scaffold, to avert the enzyme's inactivation and thereby to promote its metabolic activity.
COX10
Protoheme IX farnesyltransferase, mitochondrial is an enzyme that in humans is encoded by the COX10 gene. Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear  genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene, COX10, encodes heme A: farnesyltransferase, which is not a structural subunit but required for the expression of functional COX and functions in the maturation of the heme A prosthetic group of COX. A gene mutation, which results in the substitution of a lysine for an asparagine (N204K), is identified to be responsible for cytochrome c oxidase deficiency. In addition, this gene is disrupted in patients with CMT1A (Charcot-Marie-Tooth type 1A) duplication and with HNPP (hereditary neuropathy with liability to pressure palsies) deletion.

# Structure
The COX10 gene is located on the p arm of chromosome 17 in position 12 and spans 139,277 base pairs. The gene produces a 48.9 kDa protein composed of 443 amino acids. This gene has an unusually long 3' untranslated region measuring 1426 base pairs, compared to a 1329 base pair open reading frame. The COX10 gene has 7 exons totaling 135 kilobases in length. This protein is predicted to contain 7-9 transmembrane domains localized in the mitochondrial inner membrane. There are hydrophilic loops between transmembrane domains II/III and VI/VII. This protein is considered a constituent of the mitochondrial inner membrane.

# Function
The protein encoded by COX10 is an assembly factor essential to COX synthesis, participating in the first step of the mitochondrial heme A biosynthetic pathway. It catalyzes the farnesylation of the vinyl group at position C2 of protoheme (heme B) and converts it to heme O.

# Clinical Significance
Mutations in the COX10 gene can result in numerous clinical phenotypes, from tubulopathy and leukodystrophy to Leigh syndrome to fatal infantile cardiomyopathy to a French Canadian form of Leigh Syndrome. A wide variety of symptoms encompassing the entire range of COX deficiency symptoms have been reported, including ataxia, hypotonia, ptosis, lactic acidosis, proximal tubulopathy, anemia, myopathy, hypertrophic cardiomyopathy, sensorineural hearing loss, and leukodystrophy.
In addition, this gene is disrupted in patients with CMT1A (Charcot-Marie-Tooth type 1A) duplication and with HNPP (hereditary neuropathy with liability to pressure palsies) deletion.

# Interactions
This protein interacts with FAM136A.
COX14
Cytochrome c oxidase assembly factor COX14 is a protein that in humans is encoded by the COX14 gene. This gene encodes a small single-pass transmembrane protein that localizes to mitochondria. This protein may play a role in coordinating the early steps of cytochrome c oxidase (COX; also known as complex IV) subunit assembly and, in particular, the synthesis and assembly of the COX I subunit of the holoenzyme. Mutations in this gene have been associated with mitochondrial complex IV deficiency. Alternative splicing results in multiple transcript variants.

# Structure
The COX14 gene is located on the q arm of chromosome 12 at position 13.12 and it spans 8,476 base pairs. The COX14 gene produces a 6.6 kDa protein composed of 57 amino acids. COX14 is a component of the enzyme MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, and the structure contains a central transmembrane domain.

# Function
The COX14 gene encodes for a core protein component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, which is required for the proper regulation of complex IV assembly. Complex IV of the mitochondrial respiratory chain is essential in catalyzing the oxidation of cytochrome c by molecular oxygen. COX14 has been shown to contribute to the early stages of complex IV assembly by coelution with COX1 and COX4 for nucleation of the assembly. The protein participates in the coupling synthesis of COX1 followed by an assembly of nascent subunits into the holoenzyme complex IV. The knockdown of the protein COX14 involving small interfering RNA in regular human fibroblast has been shown to result in a complex IV defect with reduced activity.

# Clinical significance
Variants of COX14 have been associated with the mitochonrdial Complex IV deficiency, a deficiency in an enzyme complex of the mitochondrial respiratory chain which catalyzes the oxidation of cytochrome c utilizing molecular oxygen. The deficiency is characterized by heterogeneous phenotypes ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Other Clinical Manifestations include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation.
A mutation in the homozygous missense mutation c.88G>A in the COX14 gene has resulted in the dysfunction of complex IV assembly and an unstable nascent enzyme complex.

# Interactions
Like COA3, COX14 is a key component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex. In addition, it has interactions with proteins such as COX17, COX1, LMNA, COA3, SPPL2B, and others.
COX20
Cytochrome c oxidase assembly factor COX20 is a protein that in humans is encoded by the COX20 gene.This gene encodes a protein that plays a role in the assembly of cytochrome c oxidase, an important component of the respiratory pathway. Mutations in this gene can cause mitochondrial complex IV deficiency. There are multiple pseudogenes for this gene. Alternative splicing results in multiple transcript variants.

# Structure
The COX20 gene is located on the q arm of chromosome 1 at position 44 and it spans 9,757 base pairs. The COX20 gene produces a 13.3 kDa protein composed of 118 amino acids. It contains two transmembrane helices and localizes to the mitochondrial membrane.

# Function
The COX20 gene encodes for a protein required for the assembly of cytochrome c oxidase(complex IV). Complex IV is the terminal complex of the mitochondrial respiratory chain which is required for catalyzing the oxidation of cytochrome c by molecular oxygen. COX20 is known to act as a chaperone protein during the early stages of COX2 (cytochrome c oxidase subunit II) maturation which leads to the stabilization of the protein. By presenting COX2 to the metallochaperones SCO1 and SCO2, they help facilitate the incorporation of the mature COX2 into the complex IV holoenzyme assembly. However, it has been known that COX20 has no influence on transcription or translation of COX2 or any other genes. The knockdown of the protein COX20 has been shown to result in reduced respiratory capacity and the accumulation of respiratory chain intermediates]].

# Clinical significance
Variants of COX20 have been associated with the mitochonrdial Complex IV deficiency, a deficiency in an enzyme complex of the mitochondrial respiratory chain which catalyzes the oxidation of cytochrome c utilizing molecular oxygen. The deficiency is characterized by heterogeneous phenotypes ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Other Clinical Manifestations include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation. A homozygous mutation of c.154A-C in the COX20 gene has been found to result in reduced COX20, cytochrome c oxidase, and decreased activity. Other mutations have included a homozygous T52P.

# Interactions
COX20 has co-complex interactions with proteins such as TMEM177, COX2, SCO1, COA6, and others in a COX2 and COX18 dependent manner.
COX5A
Cytochrome c oxidase subunit 5a is a protein that in humans is encoded by the COX5A gene. Cytochrome c oxidase 5A is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain.

# Structure
The COX5A gene, located on the q arm of chromosome 15 in position 24.1, is made up of 5 exons and is 17,880 base pairs in length. The COX5A protein weighs 17 kDa and is composed of 150 amino acids. The protein is a subunit of Complex IV, which consists of 13 mitochondrial- and nuclear-encoded subunits.

# Function
Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane to drive ATP synthesis via protonmotive force.  The mitochondrially-encoded subunits perform the electron transfer of proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex.
Summary reaction:

# Clinical significance
COX5A (this gene) and COX5B are involved in the regulation of cancer cell metabolism by Bcl-2. COX5A interacts specifically with Bcl-2, but not with other members of the Bcl-2 family, such as Bcl-xL, Bax or Bak.
The Trans-activator of transcription protein (Tat) of human immunodeficiency virus (HIV) inhibits cytochrome c oxidase (COX) activity in permeabilized mitochondria isolated from both mouse and human liver, heart, and brain samples.
COX5B
Cytochrome c oxidase subunit 5B, mitochondrial is an enzyme in humans that is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain. In humans, cytochrome c oxidase subunit 5B is encoded by the COX5B gene.

# Structure
The enzyme weighs 14 kDa and is composed of 129 amino acids. The protein is a subunit of Complex IV, which consists of 13 mitochondrial- and nuclear-encoded subunits. The sequence of subunit Vb is well conserved and includes three conserved cysteines that coordinate the zinc ion. Two of these cysteines are clustered in the C-terminal section of the subunit.

# Gene
The COX5B gene, located on the q arm of chromosome 2 in position 11.2, is made up of 4 exons and is 2,137 base pairs in length.

# Function
Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane to drive ATP synthesis via protonmotive force.  The mitochondrially-encoded subunits perform the electron transfer of proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex.
Summary reaction:

# Clinical significance
COX5A and COX5B are involved in the regulation of cancer cell metabolism by Bcl-2.
The Trans-activator of transcription protein (Tat) of human immunodeficiency virus (HIV) inhibits cytochrome c oxidase (COX) activity in permeabilized mitochondria isolated from both mouse and human liver, heart, and brain samples.

# Interactions
COX5B has been shown to interact with Androgen receptor.
COX8A
Cytochrome c oxidase subunit 8A (COX8A) is a protein that in humans is encoded by the COX8A gene. Cytochrome c oxidase 8A is a subunit of the cytochrome c oxidase complex, also known as Complex IV. Mutations in the COX8A gene have been associated with complex IV deficiency with Leigh syndrome and epilepsy.

# Structure
COX8A is a 7.6 kDa protein composed of 69 amino acids. This gene encodes the nuclear-encoded subunit 8A of the human mitochondrial respiratory chain enzyme complex cytochrome c oxidase. The complex consists of 13 mitochondrial- and nuclear-encoded subunits.

# Function
Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane. The mitochondrially-encoded subunits perform the electron transfer of proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex.

# Clinical significance
COX8A is a subunit of cytochrome c oxidase and its function is important for the efficacy of complex IV. Mutations in COX8A can affect complex IV of the electron transport chain, resulting in complex IV deficiency. This disorder can have a wide range of clinical manifestations including Leigh syndrome, leukodystrophy, and severe epilepsy.

# Interactions
COX8A has been shown to have 19 binary protein-protein interactions including 7 co-complex interactions. COX8A appears to interact with NPM1, MAGEA4, EDDM3B, BATF, AMBP, CREB1, and NCOR1.
CRADD
Death domain-containing protein CRADD is a protein that in humans is encoded by the CRADD gene.

# Function
The protein encoded by this gene is a death domain (CARD/DD)-containing protein and has been shown to induce cell apoptosis. Through its CARD domain, this protein interacts with, and thus recruits, caspase 2/ICH1 to the cell death signal transduction complex that includes tumor necrosis factor receptor 1 (TNFR1A), RIPK1/RIP kinase, and numbers of other CARD domain-containing proteins.

# Interactions
CRADD has been shown to interact with RIPK1 and Caspase 2.
CRIM1
Cysteine-rich motor neuron 1 protein is a protein that in humans is encoded by the CRIM1 gene.

# Function
Motor neurons are among the earliest neurons to appear after the commencement of cell patterning and the beginning of cell differentiation. Differentiation occurs in a ventral-to-dorsal gradient and is mediated, at least in part, by the concentration of ventrally expressed sonic hedgehog protein (SHH; MIM 600725). Dorsally expressed factors, such as members of the bone morphogenic protein (e.g., BMP4; MIM 112262) and transforming growth factor-beta (e.g., TGFB1; MIM 190180) families, can repress the induction of these neurons. CRIM1 may interact with growth factors implicated in motor neuron differentiation and survival.

# Clinical significance
Loss of Crim1 function as demonstrated by the Crim1 KST264 hypomorph mice resulted in onset of chronic kidney disease with accompanying pathology including papillary hypoplasia, functional urinary tract obstruction, ectopic collagen accumulation within the endothelium and tubulointerstitial fibrosis which was in part attributed by (endothelial) epithelialmesenchymal transition.