112-468: 1P97 , 2A24 , 3F1N , 3F1O , 3F1P , 3H7W , 3H82 , 4GHI , 4GS9 , 4PKY , 4XT2 2034 13819 ENSG00000116016 ENSMUSG00000024140 Q99814 P97481 NM_001430 NM_010137 NP_001421 NP_034267 Endothelial PAS domain-containing protein 1 ( EPAS1 , also known as hypoxia-inducible factor-2alpha (HIF-2α)) is a protein that is encoded by the EPAS1 gene in mammals. It
224-520: A carboxyl group, and a variable side chain are bonded . Only proline differs from this basic structure as it contains an unusual ring to the N-end amine group, which forces the CO–NH amide moiety into a fixed conformation. The side chains of the standard amino acids, detailed in the list of standard amino acids , have a great variety of chemical structures and properties; it is the combined effect of all of
336-639: A gene flow of 16% from Chinese indigenous dogs and 2% of the dingo's genome. It probably recolonised the Tibetan Plateau. The Himalayan wolf contrasts with the wolves living at lower elevations in Inner Mongolia , Mongolia , and Xinjiang province. Some wolves in China and Mongolia also fall within the Himalayan wolf clade, indicating a common maternal ancestor and a wide distribution. There
448-470: A gene may be duplicated before it can mutate freely. However, this can also lead to complete loss of gene function and thus pseudo-genes . More commonly, single amino acid changes have limited consequences although some can change protein function substantially, especially in enzymes . For instance, many enzymes can change their substrate specificity by one or a few mutations. Changes in substrate specificity are facilitated by substrate promiscuity , i.e.
560-404: A phylogenetic tree that represents evolutionary relationships, with each branch point representing the divergence of two lineages from a common ancestor. On this tree, the term “basal” is used to describe a lineage that forms a branch diverging nearest to the common ancestor. In 2021, a study compared both the mitochondrial DNA and the nuclear DNA (from the cell nucleus) from the wolves of
672-552: A combination of sequence, structure and function, and they can be combined in many different ways. In an early study of 170,000 proteins, about two-thirds were assigned at least one domain, with larger proteins containing more domains (e.g. proteins larger than 600 amino acids having an average of more than 5 domains). Most proteins consist of linear polymers built from series of up to 20 different L -α- amino acids. All proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group,
784-403: A defined conformation . Proteins can interact with many types of molecules, including with other proteins , with lipids , with carbohydrates , and with DNA . It has been estimated that average-sized bacteria contain about 2 million proteins per cell (e.g. E. coli and Staphylococcus aureus ). Smaller bacteria, such as Mycoplasma or spirochetes contain fewer molecules, on
896-851: A detailed review of the vegetable proteins at the Connecticut Agricultural Experiment Station . Then, working with Lafayette Mendel and applying Liebig's law of the minimum , which states that growth is limited by the scarcest resource, to the feeding of laboratory rats, the nutritionally essential amino acids were established. The work was continued and communicated by William Cumming Rose . The difficulty in purifying proteins in large quantities made them very difficult for early protein biochemists to study. Hence, early studies focused on proteins that could be purified in large quantities, including those of blood, egg whites, and various toxins, as well as digestive and metabolic enzymes obtained from slaughterhouses. In
1008-482: A domain found in signal transduction proteins which respond to oxygen levels. EPAS1 is involved in the development of the embryonic heart and is expressed in endothelial cells that line the walls of blood vessels in the umbilical cord . EPAS1 is also essential for the maintenance of catecholamine homeostasis and protection against heart failure during early embryonic development. Catecholamines regulated by EPAS1 include epinephrine and norepinephrine . It
1120-478: A little ambiguous and can overlap in meaning. Protein is generally used to refer to the complete biological molecule in a stable conformation , whereas peptide is generally reserved for a short amino acid oligomers often lacking a stable 3D structure. But the boundary between the two is not well defined and usually lies near 20–30 residues. Polypeptide can refer to any single linear chain of amino acids, usually regardless of length, but often implies an absence of
1232-410: A particular cell or cell type is known as its proteome . The chief characteristic of proteins that also allows their diverse set of functions is their ability to bind other molecules specifically and tightly. The region of the protein responsible for binding another molecule is known as the binding site and is often a depression or "pocket" on the molecular surface. This binding ability is mediated by
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#17327647856931344-500: A protein carries out its function: for example, enzyme kinetics studies explore the chemical mechanism of an enzyme's catalytic activity and its relative affinity for various possible substrate molecules. By contrast, in vivo experiments can provide information about the physiological role of a protein in the context of a cell or even a whole organism . In silico studies use computational methods to study proteins. Proteins may be purified from other cellular components using
1456-411: A protein is defined by the sequence of a gene, which is encoded in the genetic code . In general, the genetic code specifies 20 standard amino acids; but in certain organisms the genetic code can include selenocysteine and—in certain archaea — pyrrolysine . Shortly after or even during synthesis, the residues in a protein are often chemically modified by post-translational modification , which alters
1568-542: A protein that fold into distinct structural units. Domains usually also have specific functions, such as enzymatic activities (e.g. kinase ) or they serve as binding modules (e.g. the SH3 domain binds to proline-rich sequences in other proteins). Short amino acid sequences within proteins often act as recognition sites for other proteins. For instance, SH3 domains typically bind to short PxxP motifs (i.e. 2 prolines [P], separated by two unspecified amino acids [x], although
1680-486: A role in biological recognition phenomena involving cells and proteins. Receptors and hormones are highly specific binding proteins. Transmembrane proteins can also serve as ligand transport proteins that alter the permeability of the cell membrane to small molecules and ions. The membrane alone has a hydrophobic core through which polar or charged molecules cannot diffuse . Membrane proteins contain internal channels that allow such molecules to enter and exit
1792-406: A series of purification steps may be necessary to obtain protein sufficiently pure for laboratory applications. To simplify this process, genetic engineering is often used to add chemical features to proteins that make them easier to purify without affecting their structure or activity. Here, a "tag" consisting of a specific amino acid sequence, often a series of histidine residues (a " His-tag "),
1904-627: A single expansion from one region within the last 100,000 years. However, the study indicated that the Himalayan wolf had separated from this lineage 496,000 years ago, and the Indian lowland wolf 200,000 years ago. The Tibetan mastiff breed was able to adapt to the extreme highland conditions of the Tibetan Plateau very quickly, comparably to other mammals such as the yak , Tibetan antelope , snow leopard , and wild boar . The Tibetan mastiff's ability to avoid hypoxia in high elevations due to its higher hemoglobin levels compared to low-altitude dogs,
2016-432: A solution known as a crude lysate . The resulting mixture can be purified using ultracentrifugation , which fractionates the various cellular components into fractions containing soluble proteins; membrane lipids and proteins; cellular organelles , and nucleic acids . Precipitation by a method known as salting out can concentrate the proteins from this lysate. Various types of chromatography are then used to isolate
2128-451: A specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide . A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides . The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residues in
2240-441: A variety of techniques such as ultracentrifugation , precipitation , electrophoresis , and chromatography ; the advent of genetic engineering has made possible a number of methods to facilitate purification. To perform in vitro analysis, a protein must be purified away from other cellular components. This process usually begins with cell lysis , in which a cell's membrane is disrupted and its internal contents released into
2352-432: A vast array of functions within organisms, including catalysing metabolic reactions , DNA replication , responding to stimuli , providing structure to cells and organisms , and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes , and which usually results in protein folding into
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#17327647856932464-552: Is agouti , in which the upperside of the body has banded hairs and the underside exhibits lighter shading. The colour yellow is dominant to the colour black and is found in dogs across much of the world and the dingo in Australia. In 2021, a study of whole genome sequences taken from dogs and wolves focused on the genetic relationships between them based on coat colour. The study found that most dog colour haplotypes were similar to most wolf haplotypes, however dominant yellow in dogs
2576-760: Is a canine of debated taxonomy. It is distinguished by its genetic markers , with mitochondrial DNA indicating that it is genetically basal to the Holarctic grey wolf , genetically the same wolf as the Tibetan and Mongolian wolf , and has an association with the African wolf ( Canis lupaster ). No striking morphological differences are seen between the wolves from the Himalayas and those from Tibet. The Himalayan wolf lineage can be found living in Ladakh in
2688-560: Is a type of hypoxia-inducible factor , a group of transcription factors involved in the physiological response to oxygen concentration. The gene is active under hypoxic conditions. It is also important in the development of the heart, and for maintaining the catecholamine balance required for protection of the heart. Mutation often leads to neuroendocrine tumors . However, several characterized alleles of EPAS1 contribute to high-altitude adaptation in humans . One such allele, which has been inherited from Denisovan archaic hominins ,
2800-861: Is also evidence that certain variants of this gene provide protection for people living at high altitude such as in Tibet. The effect is most profound among the Tibetans living in the Himalayas at an altitude of about 4,000 metres above sea level, the environment of which is intolerable to other human populations due to 40% less atmospheric oxygen. A study by UC Berkeley identified more than 30 genetic factors that make Tibetans' bodies well-suited for high-altitudes, including EPAS1. Tibetans suffer no health problems associated with altitude sickness , but instead produce low levels of blood pigment ( haemoglobin ) sufficient for less oxygen, more elaborate blood vessels, have lower infant mortality, and are heavier at birth. EPAS1
2912-490: Is also found in the extinct Denisovan genome, suggesting that it arose in them and entered the modern human population through hybridization . The Himalayan wolf and the Tibetan mastiff have inherited an altitude-adaptive allele of the gene from interbreeding with a ghost population of an unknown wolf-like canid. The EPAS1 allele is known to confer an adaptive advantage to animals living at high-altitudes. Mutations in
3024-539: Is an obstacle for developing a conservation plan. In Nepal, it is protected under Schedule I of the National Parks and Wildlife Conservation Act, 2029 (1973) prohibiting hunting it. In China, the wolf is listed as vulnerable in the Red List of China’s Vertebrates , and hunting it is banned. In 2007, 18 Himalayan wolves were kept for breeding in two Indian zoos. They were captured in the wild and were kept at
3136-446: Is attached to one terminus of the protein. As a result, when the lysate is passed over a chromatography column containing nickel , the histidine residues ligate the nickel and attach to the column while the untagged components of the lysate pass unimpeded. A number of different tags have been developed to help researchers purify specific proteins from complex mixtures. Himalayan wolf The Himalayan wolf ( Canis lupus chanco )
3248-430: Is critical that the production of catecholamines remain in homeostatic conditions so that both the delicate fetal heart and the adult heart do not overexert themselves and induce heart failure. Catecholamine production in the embryo is related to control of cardiac output by increasing the fetal heart rate . A high percentage of Tibetans carry an allele of EPAS1 that improves oxygen transport. The beneficial allele
3360-530: Is essential. Other recorded prey species are Bactrian deer , Yarkand deer , Tibetan red deer , Siberian roe deer , Siberian ibex , Tibetan wild ass , Przewalski's horse , wild yak , markhor , argali and urial . Historical sources indicate that wolves occasionally killed children in Ladakh and Lahaul . Within the proposed Gya-Miru Wildlife Sanctuary in Ladakh, the intensity of livestock depredation assessed in three villages found that Tibetan wolves were
3472-628: Is found in hard or filamentous structures such as hair , nails , feathers , hooves , and some animal shells . Some globular proteins can also play structural functions, for example, actin and tubulin are globular and soluble as monomers, but polymerize to form long, stiff fibers that make up the cytoskeleton , which allows the cell to maintain its shape and size. Other proteins that serve structural functions are motor proteins such as myosin , kinesin , and dynein , which are capable of generating mechanical forces. These proteins are crucial for cellular motility of single celled organisms and
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3584-469: Is higher in prokaryotes than eukaryotes and can reach up to 20 amino acids per second. The process of synthesizing a protein from an mRNA template is known as translation . The mRNA is loaded onto the ribosome and is read three nucleotides at a time by matching each codon to its base pairing anticodon located on a transfer RNA molecule, which carries the amino acid corresponding to the codon it recognizes. The enzyme aminoacyl tRNA synthetase "charges"
3696-461: Is inefficient for polypeptides longer than about 300 amino acids, and the synthesized proteins may not readily assume their native tertiary structure . Most chemical synthesis methods proceed from C-terminus to N-terminus, opposite the biological reaction. Most proteins fold into unique 3D structures. The shape into which a protein naturally folds is known as its native conformation . Although many proteins can fold unassisted, simply through
3808-399: Is known to confer increased athletic performance in some people, and has therefore been referred to as the "super athlete gene". The EPAS1 gene encodes one subunit of a transcription factor involved in the induction of genes regulated by oxygen, and which is induced as oxygen concentration falls (hypoxia). The protein contains a basic helix-loop-helix protein dimerization domain as well as
3920-575: Is listed on CITES Appendix I . In India, the wolf is protected under Schedule I of the Wildlife Protection Act, 1972 , which prohibits hunting; a zoo needs a permission from the government to acquire a wolf. It is listed as endangered in Jammu and Kashmir , Himachal Pradesh, and Uttarakhand, where a large portion of the wolf population lives outside the protected area network. Lack of information about its basic ecology in this landscape
4032-404: Is often enormous—as much as 10 -fold increase in rate over the uncatalysed reaction in the case of orotate decarboxylase (78 million years without the enzyme, 18 milliseconds with the enzyme). The molecules bound and acted upon by enzymes are called substrates . Although enzymes can consist of hundreds of amino acids, it is usually only a small fraction of the residues that come in contact with
4144-535: Is the code for methionine . Because DNA contains four nucleotides, the total number of possible codons is 64; hence, there is some redundancy in the genetic code, with some amino acids specified by more than one codon. Genes encoded in DNA are first transcribed into pre- messenger RNA (mRNA) by proteins such as RNA polymerase . Most organisms then process the pre-mRNA (also known as a primary transcript ) using various forms of post-transcriptional modification to form
4256-495: Is useful in high altitudes as a short term adaptive response. However, EPAS1 can also cause excessive production of red blood cells leading to chronic mountain sickness that can lead to death and inhibited reproductive abilities. Some mutations that increase its expression are associated with increased hypertension and stroke at low altitude, with symptoms similar to mountain sickness. Populations living permanently at high altitudes experience selection on EPAS1 for mutations which reduce
4368-649: The Annapurna Conservation Area also fell within the Himalayan wolf clade but formed a separate haplotype from those previously studied. The Himalayan wolf population in Tibet declined over the past 25,000 years and suffered a historical population bottleneck . Glaciation during the Last Glacial Maximum may have caused habitat loss, genetic isolation, and ancient inbreeding. The population in Qinghai had grown, though, showing
4480-602: The Himalayas , the Tibetan Plateau , and the mountains of Central Asia predominantly above 4,000 m (13,000 ft) in elevation because it has adapted to a low-oxygen environment, compared with other wolves that are found only at lower elevations. Some authors have proposed the reclassification of this lineage as a separate species. In 2019, a workshop hosted by the IUCN /SSC Canid Specialist Group noted that
4592-625: The Kanchenjunga Conservation Area . The Nepal Himalayas provide an important habitat refuge for the Himalayan wolf. The howls of the Himalayan wolf have lower frequencies, unmodulated frequencies, and are shorter in duration compared to Holarctic wolf howls. The Himalayan and North African wolves have the most acoustically distinct howls and differ significantly from each other and the Holarctic wolves. Himalayan wolves prefer wild over domestic prey. It usually prefers
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4704-635: The Padmaja Naidu Himalayan Zoological Park was analysed in 2007. Results showed that they shared a common female ancestor. As this study was based on captive-bred zoo specimens that had descended from only two females, these samples were not considered to be representative. Additionally, the wolf population in the Kashmir Valley is known to have recently arrived in that area. Subsequent genetic research showed that wolf samples from Tibet are genetically basal to
4816-492: The amino acid leucine for which he found a (nearly correct) molecular weight of 131 Da . Early nutritional scientists such as the German Carl von Voit believed that protein was the most important nutrient for maintaining the structure of the body, because it was generally believed that "flesh makes flesh." Around 1862, Karl Heinrich Ritthausen isolated the amino acid glutamic acid . Thomas Burr Osborne compiled
4928-502: The cell nucleus , indicate that the Himalayan wolf is genetically basal to the Holarctic gray wolf. Its degree of divergence from the Holarctic gray wolf is similar to the degree of divergence of the African wolf from the Holarctic wolf. The Himalayan wolf shares a maternal lineage with the African wolf. It possesses a unique paternal lineage that falls between the gray wolf and the African wolf. The results of these two studies imply that
5040-644: The muscle sarcomere , with a molecular mass of almost 3,000 kDa and a total length of almost 27,000 amino acids. Short proteins can also be synthesized chemically by a family of methods known as peptide synthesis , which rely on organic synthesis techniques such as chemical ligation to produce peptides in high yield. Chemical synthesis allows for the introduction of non-natural amino acids into polypeptide chains, such as attachment of fluorescent probes to amino acid side chains. These methods are useful in laboratory biochemistry and cell biology , though generally not for commercial applications. Chemical synthesis
5152-645: The sperm of many multicellular organisms which reproduce sexually . They also generate the forces exerted by contracting muscles and play essential roles in intracellular transport. A key question in molecular biology is how proteins evolve, i.e. how can mutations (or rather changes in amino acid sequence) lead to new structures and functions? Most amino acids in a protein can be changed without disrupting activity or function, as can be seen from numerous homologous proteins across species (as collected in specialized databases for protein families , e.g. PFAM ). In order to prevent dramatic consequences of mutations,
5264-497: The 1700s by Antoine Fourcroy and others, who often collectively called them " albumins ", or "albuminous materials" ( Eiweisskörper , in German). Gluten , for example, was first separated from wheat in published research around 1747, and later determined to exist in many plants. In 1789, Antoine Fourcroy recognized three distinct varieties of animal proteins: albumin , fibrin , and gelatin . Vegetable (plant) proteins studied in
5376-572: The 1950s, the Armour Hot Dog Company purified 1 kg of pure bovine pancreatic ribonuclease A and made it freely available to scientists; this gesture helped ribonuclease A become a major target for biochemical study for the following decades. The understanding of proteins as polypeptides , or chains of amino acids, came through the work of Franz Hofmeister and Hermann Emil Fischer in 1902. The central role of proteins as enzymes in living organisms that catalyzed reactions
5488-498: The 20,000 or so proteins encoded by the human genome, only 6,000 are detected in lymphoblastoid cells. Proteins are assembled from amino acids using information encoded in genes. Each protein has its own unique amino acid sequence that is specified by the nucleotide sequence of the gene encoding this protein. The genetic code is a set of three-nucleotide sets called codons and each three-nucleotide combination designates an amino acid, for example AUG ( adenine – uracil – guanine )
5600-519: The EC number system provides a functional classification scheme. Similarly, the gene ontology classifies both genes and proteins by their biological and biochemical function, but also by their intracellular location. Sequence similarity is used to classify proteins both in terms of evolutionary and functional similarity. This may use either whole proteins or protein domains , especially in multi-domain proteins . Protein domains allow protein classification by
5712-698: The EPAS1 gene are related to early-onset neuroendocrine tumors such as paragangliomas , somatostatinomas and/or pheochromocytomas . The mutations are commonly somatic missense mutations that locate in the primary hydroxylation site of HIF-2α, which disrupt the protein hydroxylation/degradation mechanism, and leads to protein stabilization and pseudohypoxic signaling. In addition, these neuroendocrine tumors release erythropoietin (EPO) into circulating blood, and lead to polycythemia . Mutations in this gene are associated with erythrocytosis familial type 4, pulmonary hypertension , and chronic mountain sickness . There
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#17327647856935824-564: The Himalayan wolf distribution range extends from the Himalayan range north across the Tibetan Plateau up to the Qinghai Lake region in China’s Qinghai Province. In 2018, whole genome sequencing was used to compare members of the genus Canis . The African golden wolf was found to be the descendant of a genetically admixed canid of 72% gray wolf and 28% Ethiopian wolf ancestry. The Ethiopian wolf does not share
5936-746: The Himalayan wolf genome indicates that it warrants species-level recognition under the Unified Species Concept, the Differential Fitness Species Concept, and the Biological Species Concept. It was identified as an evolutionary significant unit that warranted assignment onto the IUCN Red List for its protection. The Himalayan wolf has a thick, woolly fur that is dull earthy-brown on the back and tail, and yellowish-white on
6048-461: The Himalayan wolf mitochondrial genome indicates that the Himalayan wolf diverged between 740,000 and 691,000 years ago from the lineage that would become the Holarctic gray wolf. Between 2011 and 2015, two mDNA studies found that the Himalayan wolf and Indian gray wolf were genetically closer to the African golden wolf than they were to the Holarctic gray wolf. From 2017, two studies based on mDNA, and X-chromosome and Y-chromosome markers taken from
6160-443: The Himalayan wolf's distribution included the Himalayan range and the Tibetan Plateau. The group determined that the earliest available Latin name is Canis chanco Gray, 1863, but the geographic location of the holotype is unclear. The group recommends that this wolf lineage be known as the "Himalayan wolf" and classified as Canis lupus chanco until a genetic analysis of the holotypes is available. In 2020, more recent research on
6272-497: The Himalayan wolf's distribution included the Himalayan range and the Tibetan Plateau. The group recommends that this wolf lineage be known as the "Himalayan wolf" and be classified as Canis lupus chanco until a genetic analysis of the holotypes is available. The Himalayan wolf lacks a proper morphological analysis. The wolves in India and Nepal are listed on CITES Appendix I as endangered due to international trade. Canis chanco
6384-546: The Himalayan wolf's nuclear genome, and contributed the EPAS1 allele which can be found in both Himalayan wolves and dogs which allows them to live in high altitudes. Domestic dogs exhibit diverse coat colours and patterns . In many mammals, different colour patterns are the result of the regulation of the Agouti gene , which can cause hair follicles to switch from making black or brown pigments to yellow or nearly white pigments. The most common coat pattern found in modern wolves
6496-494: The Himalayas with those of the wolves from the lowlands of the Indian subcontinent . The genomic analyses indicate that the Himalayan wolf and the Indian lowland wolf were genetically distinct from one another. These wolves were also genetically distinct from – and genetically basal to – the other wolf populations across the northern hemisphere. These other wolves form a single mitochondrial clade , indicating that they originated from
6608-466: The Holarctic gray wolf. Its MT-ND4L gene commences with the base pairs G TG, whereas all other canids commence with A TG. Results of whole genome sequencing showed that it is the most genetically divergent wolf. Analysis of scat samples from two wolves collected in upper Dolpo in Nepal matched the Himalayan wolf. Fecal remains of four wolves collected in the upper Mustang region of
6720-617: The Late Pleistocene, natural selection laid the genetic foundation for modern coat colour diversity in dogs and wolves. In 2011, the Himalayan, Indian and African wolves were proposed to represent ancient wolf lineages, with the African wolf having colonised Africa prior to the Northern Hemisphere radiation of the Holarctic gray wolf. Two studies of the mitochondrial genome of both modern and extinct gray wolves ( Canis lupus ) have been conducted, but these excluded
6832-544: The Tibetan Plateau in the provinces of Gansu , Qinghai , Tibet, and western Sichuan . In northern India , it occurs in the Union Territory of Ladakh and in the Lahaul and Spiti region in northeastern Himachal Pradesh . In 2004, the Himalayan wolf population in India was estimated to consist of 350 individuals ranging across an area of about 70,000 km (27,000 sq mi). Between 2005 and 2008, it
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#17327647856936944-444: The Tibetan Plateau, and a unique population from southern China. One specimen located as far southeast as Jiangxi province shows evidence of being admixed between Tibetan-related wolves and other wolves in China. Dog [REDACTED] Holarctic gray wolf [REDACTED] Late Pleistocene wolf † [REDACTED] Indian plains wolf [REDACTED] Himalayan wolf [REDACTED] DNA sequences can be mapped to reveal
7056-709: The ability of many enzymes to bind and process multiple substrates . When mutations occur, the specificity of an enzyme can increase (or decrease) and thus its enzymatic activity. Thus, bacteria (or other organisms) can adapt to different food sources, including unnatural substrates such as plastic. Methods commonly used to study protein structure and function include immunohistochemistry , site-directed mutagenesis , X-ray crystallography , nuclear magnetic resonance and mass spectrometry . The activities and structures of proteins may be examined in vitro , in vivo , and in silico . In vitro studies of purified proteins in controlled environments are useful for learning how
7168-405: The addition of a single methyl group to a binding partner can sometimes suffice to nearly eliminate binding; for example, the aminoacyl tRNA synthetase specific to the amino acid valine discriminates against the very similar side chain of the amino acid isoleucine . Proteins can bind to other proteins as well as to small-molecule substrates. When proteins bind specifically to other copies of
7280-607: The alpha carbons are roughly coplanar . The other two dihedral angles in the peptide bond determine the local shape assumed by the protein backbone. The end with a free amino group is known as the N-terminus or amino terminus, whereas the end of the protein with a free carboxyl group is known as the C-terminus or carboxy terminus (the sequence of the protein is written from N-terminus to C-terminus, from left to right). The words protein , polypeptide, and peptide are
7392-531: The amino acid side chains in a protein that ultimately determines its three-dimensional structure and its chemical reactivity. The amino acids in a polypeptide chain are linked by peptide bonds . Once linked in the protein chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen, and oxygen atoms are known as the main chain or protein backbone. The peptide bond has two resonance forms that contribute some double-bond character and inhibit rotation around its axis, so that
7504-574: The binding of a substrate molecule to an enzyme's active site , or the physical region of the protein that participates in chemical catalysis. In solution, proteins also undergo variation in structure through thermal vibration and the collision with other molecules. Proteins can be informally divided into three main classes, which correlate with typical tertiary structures: globular proteins , fibrous proteins , and membrane proteins . Almost all globular proteins are soluble and many are enzymes. Fibrous proteins are often structural, such as collagen ,
7616-570: The body of a multicellular organism. These proteins must have a high binding affinity when their ligand is present in high concentrations, but must also release the ligand when it is present at low concentrations in the target tissues. The canonical example of a ligand-binding protein is haemoglobin , which transports oxygen from the lungs to other organs and tissues in all vertebrates and has close homologs in every biological kingdom . Lectins are sugar-binding proteins which are highly specific for their sugar moieties. Lectins typically play
7728-558: The cell is as enzymes , which catalyse chemical reactions. Enzymes are usually highly specific and accelerate only one or a few chemical reactions. Enzymes carry out most of the reactions involved in metabolism , as well as manipulating DNA in processes such as DNA replication , DNA repair , and transcription . Some enzymes act on other proteins to add or remove chemical groups in a process known as posttranslational modification. About 4,000 reactions are known to be catalysed by enzymes. The rate acceleration conferred by enzymatic catalysis
7840-436: The cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change detected by other proteins within the cell. Antibodies are protein components of an adaptive immune system whose main function is to bind antigens , or foreign substances in the body, and target them for destruction. Antibodies can be secreted into the extracellular environment or anchored in
7952-752: The cell's machinery through the process of protein turnover . A protein's lifespan is measured in terms of its half-life and covers a wide range. They can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal or misfolded proteins are degraded more rapidly either due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids , proteins are essential parts of organisms and participate in virtually every process within cells . Many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism . Proteins also have structural or mechanical functions, such as actin and myosin in muscle and
8064-450: The cell. Many ion channel proteins are specialized to select for only a particular ion; for example, potassium and sodium channels often discriminate for only one of the two ions. Structural proteins confer stiffness and rigidity to otherwise-fluid biological components. Most structural proteins are fibrous proteins ; for example, collagen and elastin are critical components of connective tissue such as cartilage , and keratin
8176-621: The chemical properties of their amino acids, others require the aid of molecular chaperones to fold into their native states. Biochemists often refer to four distinct aspects of a protein's structure: Proteins are not entirely rigid molecules. In addition to these levels of structure, proteins may shift between several related structures while they perform their functions. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as " conformations ", and transitions between them are called conformational changes. Such changes are often induced by
8288-441: The chief actors within the cell, said to be carrying out the duties specified by the information encoded in genes. With the exception of certain types of RNA , most other biological molecules are relatively inert elements upon which proteins act. Proteins make up half the dry weight of an Escherichia coli cell, whereas other macromolecules such as DNA and RNA make up only 3% and 20%, respectively. The set of proteins expressed in
8400-418: The classification was for conservation purposes only, and did not "reflect the latest state of taxonomic knowledge". Further fieldwork was called for. This genetic lineage shows a 3.9% divergence in the mDNA cytochrome b gene when compared with the Holarctic grey wolf, which may justify it being classified as a distinct species. In 2019, a workshop hosted by the IUCN /SSC Canid Specialist Group noted that
8512-600: The collection of the Natural History Museum, London . In 2005, W. Christopher Wozencraft also listed C. l. niger , C. l. filchneri , C. l. karanorensis , and C. l. tschiliensis as synonyms for C. l. chanco . Canis himalayensis was proposed by Aggarwal et al. in 2007 for wolf specimens from the Indian Himalayas that differed in mitochondrial DNA from specimens collected in other parts of India. In April 2009, Canis himalayensis
8624-490: The construction of enormously complex signaling networks. As interactions between proteins are reversible, and depend heavily on the availability of different groups of partner proteins to form aggregates that are capable to carry out discrete sets of function, study of the interactions between specific proteins is a key to understand important aspects of cellular function, and ultimately the properties that distinguish particular cell types. The best-known role of proteins in
8736-408: The derivative unit kilodalton (kDa). The average size of a protein increases from Archaea to Bacteria to Eukaryote (283, 311, 438 residues and 31, 34, 49 kDa respectively) due to a bigger number of protein domains constituting proteins in higher organisms. For instance, yeast proteins are on average 466 amino acids long and 53 kDa in mass. The largest known proteins are the titins , a component of
8848-451: The erroneous conclusion that they might be composed of a single type of (very large) molecule. The term "protein" to describe these molecules was proposed by Mulder's associate Berzelius; protein is derived from the Greek word πρώτειος ( proteios ), meaning "primary", "in the lead", or "standing in front", + -in . Mulder went on to identify the products of protein degradation such as
8960-426: The face, tummy, and limbs. It has closely spaced black speckles on the muzzle, below the eyes, and on the upper cheeks and ears. Larger than the Indian and common European wolves , it reaches 110 to 180 cm (45 to 70 in) in length, 68 to 76 cm (27 to 30 in) tall at the shoulder, and weighs around 30 to 55 kg (66 to 121 lb) on average. The heart of the Himalayan wolf can withstand
9072-416: The genetically divergent lineages of the Himalayan wolf and the Indian wolf. The ancient specimens were radiocarbon dated and stratigraphically dated, and together with DNA sequences, a time-based phylogenetic tree was generated for wolves. The study inferred that the most recent common ancestor for all other Canis lupus specimens – modern and extinct – was 80,000 years before present. An analysis of
9184-534: The late 1700s and early 1800s included gluten , plant albumin , gliadin , and legumin . Proteins were first described by the Dutch chemist Gerardus Johannes Mulder and named by the Swedish chemist Jöns Jacob Berzelius in 1838. Mulder carried out elemental analysis of common proteins and found that nearly all proteins had the same empirical formula , C 400 H 620 N 100 O 120 P 1 S 1 . He came to
9296-764: The low oxygen level at high elevations. It has a strong selection for RYR2 , a gene that initiates cardiac excitation. The mitochondrial DNA of 27 wolves from the Himalayas and the Tibetan Plateau was compared in 2004. Results indicate that five related haplotypes formed a clade that is basal to all other wolves. This clade included one sample from Ladakh , nine from the Spiti Valley in Himachal Pradesh , four from Nepal , and two from Tibet . The Himalayan wolf clade diverged from other canids 800,000 years ago. Seven wolves from Kashmir did not fall into this clade. The mtDNA of 18 captive wolves in
9408-478: The major component of connective tissue, or keratin , the protein component of hair and nails. Membrane proteins often serve as receptors or provide channels for polar or charged molecules to pass through the cell membrane . A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own dehydration , are called dehydrons . Many proteins are composed of several protein domains , i.e. segments of
9520-443: The mature mRNA, which is then used as a template for protein synthesis by the ribosome . In prokaryotes the mRNA may either be used as soon as it is produced, or be bound by a ribosome after having moved away from the nucleoid . In contrast, eukaryotes make mRNA in the cell nucleus and then translocate it across the nuclear membrane into the cytoplasm , where protein synthesis then takes place. The rate of protein synthesis
9632-405: The membranes of specialized B cells known as plasma cells . Whereas enzymes are limited in their binding affinity for their substrates by the necessity of conducting their reaction, antibodies have no such constraints. An antibody's binding affinity to its target is extraordinarily high. Many ligand transport proteins bind particular small biomolecules and transport them to other locations in
9744-456: The most prevalent predators, accounting for 60% of the total livestock losses, followed by the snow leopard and Eurasian lynx. The most frequent prey were domestic goats (32%), followed by sheep (30%), yaks (15%), and horses (13%). The wolves killed horses significantly more, and goats less, than would be expected from their relative abundance. The wolf in Bhutan, India, Nepal, and Pakistan
9856-597: The negative fitness consequences of excessive red blood cell production. EPAS1 has been shown to interact with aryl hydrocarbon receptor nuclear translocator and ARNTL . This article incorporates text from the United States National Library of Medicine , which is in the public domain . Protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues . Proteins perform
9968-496: The nobel prize in 1972, solidified the thermodynamic hypothesis of protein folding, according to which the folded form of a protein represents its free energy minimum. With the development of X-ray crystallography , it became possible to determine protein structures as well as their sequences. The first protein structures to be solved were hemoglobin by Max Perutz and myoglobin by John Kendrew , in 1958. The use of computers and increasing computing power also supported
10080-500: The order of 50,000 to 1 million. By contrast, eukaryotic cells are larger and thus contain much more protein. For instance, yeast cells have been estimated to contain about 50 million proteins and human cells on the order of 1 to 3 billion. The concentration of individual protein copies ranges from a few molecules per cell up to 20 million. Not all genes coding proteins are expressed in most cells and their number depends on, for example, cell type and external stimuli. For instance, of
10192-440: The physical and chemical properties, folding, stability, activity, and ultimately, the function of the proteins. Some proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors . Proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes . Once formed, proteins only exist for a certain period and are then degraded and recycled by
10304-424: The process of cell signaling and signal transduction . Some proteins, such as insulin , are extracellular proteins that transmit a signal from the cell in which they were synthesized to other cells in distant tissues . Others are membrane proteins that act as receptors whose main function is to bind a signaling molecule and induce a biochemical response in the cell. Many receptors have a binding site exposed on
10416-534: The protein or proteins of interest based on properties such as molecular weight, net charge and binding affinity. The level of purification can be monitored using various types of gel electrophoresis if the desired protein's molecular weight and isoelectric point are known, by spectroscopy if the protein has distinguishable spectroscopic features, or by enzyme assays if the protein has enzymatic activity. Additionally, proteins can be isolated according to their charge using electrofocusing . For natural proteins,
10528-427: The proteins in the cytoskeleton , which form a system of scaffolding that maintains cell shape. Other proteins are important in cell signaling, immune responses , cell adhesion , and the cell cycle . In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized . Digestion breaks the proteins down for metabolic use. Proteins have been studied and recognized since
10640-582: The same molecule, they can oligomerize to form fibrils; this process occurs often in structural proteins that consist of globular monomers that self-associate to form rigid fibers. Protein–protein interactions also regulate enzymatic activity, control progression through the cell cycle , and allow the assembly of large protein complexes that carry out many closely related reactions with a common biological function. Proteins can also bind to, or even be integrated into, cell membranes. The ability of binding partners to induce conformational changes in proteins allows
10752-581: The sample, allowing scientists to obtain more information and analyze larger structures. Computational protein structure prediction of small protein structural domains has also helped researchers to approach atomic-level resolution of protein structures. As of April 2024 , the Protein Data Bank contains 181,018 X-ray, 19,809 EM and 12,697 NMR protein structures. Proteins are primarily classified by sequence and structure, although other classifications are commonly used. Especially for enzymes
10864-430: The sequencing of complex proteins. In 1999, Roger Kornberg succeeded in sequencing the highly complex structure of RNA polymerase using high intensity X-rays from synchrotrons . Since then, cryo-electron microscopy (cryo-EM) of large macromolecular assemblies has been developed. Cryo-EM uses protein samples that are frozen rather than crystals, and beams of electrons rather than X-rays. It causes less damage to
10976-459: The single-nucleotide polymorphisms that confer hypoxia adaptation with the Himalayan wolf. The adaptation of the Ethiopian wolf to living in high elevations may occur at other single-nucleotide polymorphism locations. This indicates that the Ethiopian wolf's adaptation has not been inherited by descent from a common ancestor shared with the Himalayan wolf. In China, the Himalayan wolf lives on
11088-531: The smaller Tibetan gazelle over the larger white-lipped deer , and the plains-dwelling Tibetan gazelle over the cliff-dwelling blue sheep . Supplementary diet includes the small Himalayan marmot , big-eared pika and woolly hare . Himalayan wolves avoid livestock where wild prey is available, but habitat encroachment and the depletion of wild prey populations is expected to lead to conflict with herders. To protect them, securing healthy wild prey populations through setting aside wildlife habitat reserves and refuges
11200-405: The substrate, and an even smaller fraction—three to four residues on average—that are directly involved in catalysis. The region of the enzyme that binds the substrate and contains the catalytic residues is known as the active site . Dirigent proteins are members of a class of proteins that dictate the stereochemistry of a compound synthesized by other enzymes. Many proteins are involved in
11312-716: The surrounding amino acids may determine the exact binding specificity). Many such motifs has been collected in the Eukaryotic Linear Motif (ELM) database. Topology of a protein describes the entanglement of the backbone and the arrangement of contacts within the folded chain. Two theoretical frameworks of knot theory and Circuit topology have been applied to characterise protein topology. Being able to describe protein topology opens up new pathways for protein engineering and pharmaceutical development, and adds to our understanding of protein misfolding diseases such as neuromuscular disorders and cancer. Proteins are
11424-400: The tRNA molecules with the correct amino acids. The growing polypeptide is often termed the nascent chain . Proteins are always biosynthesized from N-terminus to C-terminus . The size of a synthesized protein can be measured by the number of amino acids it contains and by its total molecular mass , which is normally reported in units of daltons (synonymous with atomic mass units ), or
11536-472: The tertiary structure of the protein, which defines the binding site pocket, and by the chemical properties of the surrounding amino acids' side chains. Protein binding can be extraordinarily tight and specific; for example, the ribonuclease inhibitor protein binds to human angiogenin with a sub-femtomolar dissociation constant (<10 M) but does not bind at all to its amphibian homolog onconase (> 1 M). Extremely minor chemical changes such as
11648-472: Was insulin , by Frederick Sanger , in 1949. Sanger correctly determined the amino acid sequence of insulin, thus conclusively demonstrating that proteins consisted of linear polymers of amino acids rather than branched chains, colloids , or cyclols . He won the Nobel Prize for this achievement in 1958. Christian Anfinsen 's studies of the oxidative folding process of ribonuclease A, for which he won
11760-434: Was closely related to white in arctic wolves from North America. This result suggests a common origin for dominant yellow in dogs and white in wolves but without recent gene flow, because this clade was found to be basal to the golden jackal and genetically distinct from all other canids. The most recent common ancestor of the golden jackal and the wolf lineage dates back to 2 million YBP. The study proposes that 35,000 YBP there
11872-414: Was due to prehistoric interbreeding with the wolves of Tibet. In 2020, a genomic analysis indicates that the wolves of the Himalayas and the Tibetan plateau are closely related. These wolves have an admixed history which includes gray wolves, dogs, and a ghost population of an unknown wolf-like canid. This ghost population is deeply-diverged from modern Holarctic wolves and dogs, has contributed 39% to
11984-585: Was evidence of hybridization with the grey wolf at Sachyat-Ertash in the Issyk-Kul region of Kyrgyzstan , and of introgression from either the grey wolf or the dog into the Himalayan wolf in Nepal. A genomic study on China's wolves included museum specimens of wolves from southern China that were collected between 1963 and 1988. The wolves in the study formed three clades: north Asian wolves that included those from northern China and eastern Russia, wolves from
12096-551: Was genetic introgression into the Late Pleistocene grey wolf from a ghost population of an extinct canid which had diverged from the grey wolf lineage over 2 million YBP. This colour diversity could be found 35,000 YBP in wolves and 9,500 YBP in dogs. A closely related haplotype exists among those wolves of Tibet which possess yellow shading in their coats. The study explains the colour relationships between modern dogs and wolves, white wolves from North America, yellow dogs, and yellowish wolves from Tibet. The study concludes that during
12208-581: Was not fully appreciated until 1926, when James B. Sumner showed that the enzyme urease was in fact a protein. Linus Pauling is credited with the successful prediction of regular protein secondary structures based on hydrogen bonding , an idea first put forth by William Astbury in 1933. Later work by Walter Kauzmann on denaturation , based partly on previous studies by Kaj Linderstrøm-Lang , contributed an understanding of protein folding and structure mediated by hydrophobic interactions . The first protein to have its amino acid chain sequenced
12320-653: Was proposed as a distinct wolf species through the Nomenclature Specialist on the CITES Animals Committee. The proposal was based on one study that relied on only a limited number of museum and zoo samples that may not have been representative of the wild population. The committee recommended against this proposal, but suggested that the name be entered into the CITES species database as a synonym for Canis lupus . The committee stated that
12432-624: Was sighted in the alpine meadows above the treeline northeast of Nanda Devi National Park in Uttarakhand . In 2013, a wolf was photographed by a camera trap installed at an elevation around 3,500 m (11,500 ft) near the Sunderdhunga Glacier in Uttarakhand's Bageshwar district . In Nepal, it was recorded in Api Nampa Conservation Area , Upper Dolpa , Humla , Manaslu , Upper Mustang , and
12544-583: Was the scientific name proposed by John Edward Gray in 1863, who described a skin of a wolf that was shot in Chinese Tartary . This specimen was classified as a wolf subspecies Canis lupus chanco by St. George Jackson Mivart in 1880. In the 19th and 20th centuries, several zoological specimens were described: In 1938, Glover Morrill Allen classified these specimens as synonyms for C. l. chanco . In 1941, Reginald Pocock corroborated this assessment after reviewing wolf skins and skulls in
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