STUB1 (
STIP1 homology and
U-
Box containing protein
1) is a human gene that codes for the protein CHIP (
C terminus of
HSC70-
Interacting
Protein).
Function
The CHIP protein encoded by this gene binds to and inhibits the
ATPase
ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...
activity of the
chaperone proteins
In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assi ...
HSC70
Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the ''HSPA8'' gene on chromosome 11. As a member of the heat shock protein 70 family and a chaperon ...
and
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 ...
and blocks the forward reaction of the HSC70-HSP70 substrate-binding cycle.
In addition, CHIP possesses
E3 ubiquitin ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin ...
activity and promotes
ubiquitylation
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fou ...
,
mainly of chaperone-bound misfolded proteins.
CHIP enhances HSP70 induction during acute stress and also mediates its turnover during the stress recovery process. Hence CHIP appears to maintain protein homeostasis by controlling chaperone levels during stress and recovery.
Mutations in STUB1 cause spinocerebellar
ataxia
Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
type 16.
Interactions
STUB1 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:
*
C-Raf
RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme that in humans is encoded by the ''RAF1'' gene. The c-Raf protein is part of the ERK1/2 pathway as a MAP kinase ( ...
,
*
DNAJB1
DnaJ homolog subfamily B member 1 is a protein that in humans is encoded by the ''DNAJB1'' gene.
Interactions
DNAJB1 has been shown to interact with:
* HSPA4, and
* STUB1
STUB1 (STIP1 homology and U-Box containing protein 1) is a human gene t ...
,
*
HSPA1A
Heat shock 70 kDa protein 1, also termed Hsp72, is a protein that in humans is encoded by the ''HSPA1A'' gene. As a member of the heat shock protein 70 family and a chaperone protein, it facilitates the proper folding of newly translated and misfo ...
,
[
* ]HSPA4
Heat shock 70 kDa protein 4 is a protein that in humans is encoded by the ''HSPA4'' gene.
The protein encoded by this gene was originally suggested to be a member of the heat shock protein 70 family. However it is now known that human HSPA4 is a ...
,[
* ]HSPA8
Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the ''HSPA8'' gene on chromosome 11. As a member of the heat shock protein 70 family and a chaperon ...
,[
* ]Parkin (ligase)
Parkin is a 465-amino acid residue E3 ubiquitin ligase, a protein that in humans and mice is encoded by the ''PARK2'' gene. Parkin plays a critical role in ubiquitination – the process whereby molecules are covalently labelled with ubiquitin (Ub ...
,RUNX2
Runt-related transcription factor 2 (RUNX2) also known as core-binding factor subunit alpha-1 (CBF-alpha-1) is a protein that in humans is encoded by the ''RUNX2'' gene. RUNX2 is a key transcription factor associated with osteoblast differentia ...
.
References
Further reading
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External links
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{{PDB Gallery, geneid=10273