Hop, occasionally written HOP, is an abbreviation for

Hsp70 The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an importa ...

Hsp90 Hsp90 (heat shock protein 90) is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, ...

Organizing Protein. It functions as a co-chaperone which reversibly links together the protein chaperones Hsp70 and Hsp90. Hop belongs to the large group of

co-chaperone Co-chaperones are proteins that assist chaperone (protein), chaperones in protein folding and other functions. Co-chaperones are the non-client binding molecules that assist in protein folding mediated by Hsp70 and Hsp90. They are particularly esse ...

s, which regulate and assist the major chaperones (mainly

heat shock protein Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including expo ...

s). It is one of the best studied co-chaperones of the Hsp70/Hsp90-complex. It was first discovered in

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...

and homologues were identified in human, mouse, rat, insects, plants, parasites, and virus. The family of these proteins is referred to as STI1 (stress inducible protein) and can be divided into yeast, plant, and animal STI1 (Hop).

Synonyms

Gene

The gene for human Hop is located on

chromosome 11 Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...

q13.1 and consists of 14

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

Structure

STI proteins are characterized by some structural features: All homologues have nine tetratricopeptide repeat (TPR) motifs, that are clustered into domains of three TPRs. The TPR motif is a very common structural feature used by many proteins and provides the ability of directing protein-protein interactions.

Crystallographic Crystallography is the experimental science of determining the arrangement of atoms in crystalline solids. Crystallography is a fundamental subject in the fields of materials science and solid-state physics (condensed matter physics). The word ...

structural information is available for the

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

TPR1 and the central TPR2A domains in complex with Hsp90 resp. Hsp70

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

s. The Hsp70-Hsp90 Organizing Protein (Hop, STIP1 in humans) is the co-chaperone responsible for the transfer of client proteins between Hsp70 and Hsp90. Hop is evolutionarily conserved in Eukaryotes and is found in both the nucleus and cytoplasm. ''Drosophila'' Hop is a monomeric protein that consists of three tetratricopeptide repeat domain regions (TPR1, TPR2A, TPR2B), one aspartic acid-proline repeat domain (DP). The TPR domains interact with the c-terminals of Hsp90 and Hsp70, with TPR1 and TPR2B binding to Hsp70 and TPR2A binding preferentially to Hsp90. The intermediate structures of heat shock machinery are difficult to characterize completely because of the transient and fast paced nature of chaperone function.

Function

The main function of Hop is to link

and

together. But recent investigations indicate that it also modulates the chaperone activities of the linked proteins and possibly interacts with other chaperones and proteins. Apart from its role in the Hsp70/Hsp90 "chaperone machine" it seems to participate in other protein complexes too (for example in the

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

complex EcR/USP and in the

Hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...

B virus

reverse transcriptase A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, ...

complex, which enables the viral replication). It acts as a receptor for

prion Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It ...

proteins too. Hop is located in diverse cellular regions and also moves between the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

and the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

. In ''Drosophila''

RNA interference RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by o ...

pathways, Hop has been shown to be an integral part of the pre-RISC complex for siRNAs. In the ''Drosophila''

Piwi-interacting RNA Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules expressed in animal cells. piRNAs form RNA-protein complexes through interactions with piwi-subfamily Argonaute proteins. These piRNA complexes are mostly involved ...

pathway, the RNA interference pathway responsible for the repression of transposable elements (transposons), Hop has been shown to interact with Piwi, and in the absence of Hop, transposons are derepressed, leading to severe genomic instability and infertility.

Interactions

Human Hop (STIP1) has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with

PRNP Major prion protein (PrP), is encoded in the human by the ''PRNP'' gene also known as CD230 (cluster of differentiation 230). Expression of the protein is most predominant in the nervous system but occurs in many other tissues throughout the bod ...

and

Heat shock protein 90kDa alpha (cytosolic), member A1 Heat shock protein HSP 90-alpha is a protein that in humans is encoded by the ''HSP90AA1'' gene. Function The gene, HSP90AA1, encodes the human stress-inducible 90-kDa heat shock protein alpha (Hsp90A). Complemented by the constitutively expr ...

Synonyms

Gene

Structure

Function

Interactions

References

Further reading