UniProt functional annotation for P10809



	UniProt functional annotation for P10809

UniProt code: P10809.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:1346131, PubMed:11422376). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back- to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). {ECO:0000269|PubMed:11422376, ECO:0000269|PubMed:1346131, ECO:0000305|PubMed:25918392}.

Catalytic activity: Reaction=ATP + H(2)O + a folded polypeptide = ADP + phosphate + an unfolded polypeptide.; EC=5.6.1.7; Evidence={ECO:0000305};

Subunit: Homoheptamer arranged in a ring structure (PubMed:1346131, PubMed:11422376, PubMed:25918392). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. Interacts with 2 heptameric Hsp10 rings to form the symmetrical football complex (PubMed:25918392). Interacts with HRAS (By similarity). Interacts with ATAD3A (PubMed:22664726). Interacts with ETFBKMT and METTL21B (PubMed:23349634). Interacts with MFHAS1 (PubMed:24286120). {ECO:0000250|UniProtKB:P63038, ECO:0000269|PubMed:11422376, ECO:0000269|PubMed:1346131, ECO:0000269|PubMed:22664726, ECO:0000269|PubMed:23349634, ECO:0000269|PubMed:24286120, ECO:0000269|PubMed:25918392}.

Subunit: (Microbial infection) Interacts with hepatits B virus/HBV protein X. {ECO:0000269|PubMed:15120623}.

Subunit: (Microbial infection) Interacts with HTLV-1 protein p40tax. {ECO:0000269|PubMed:1731090}.

Subcellular location: Mitochondrion matrix.

Disease: Spastic paraplegia 13, autosomal dominant (SPG13) [MIM:605280]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269|PubMed:11898127}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Leukodystrophy, hypomyelinating, 4 (HLD4) [MIM:612233]: A severe autosomal recessive hypomyelinating leukodystrophy. Clinically characterized by infantile-onset rotary nystagmus, progressive spastic paraplegia, neurologic regression, motor impairment, profound mental retardation. Death usually occurs within the first two decades of life. {ECO:0000269|PubMed:18571143}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the chaperonin (HSP60) family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix (PubMed:1346131, PubMed:11422376). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back- to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein (Probable). {ECO:0000269\|PubMed:11422376, ECO:0000269\|PubMed:1346131, ECO:0000305\|PubMed:25918392}.


Catalytic activity:		Reaction=ATP + H(2)O + a folded polypeptide = ADP + phosphate + an unfolded polypeptide.; EC=5.6.1.7; Evidence={ECO:0000305};
Subunit:		Homoheptamer arranged in a ring structure (PubMed:1346131, PubMed:11422376, PubMed:25918392). The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. Interacts with 2 heptameric Hsp10 rings to form the symmetrical football complex (PubMed:25918392). Interacts with HRAS (By similarity). Interacts with ATAD3A (PubMed:22664726). Interacts with ETFBKMT and METTL21B (PubMed:23349634). Interacts with MFHAS1 (PubMed:24286120). {ECO:0000250\|UniProtKB:P63038, ECO:0000269\|PubMed:11422376, ECO:0000269\|PubMed:1346131, ECO:0000269\|PubMed:22664726, ECO:0000269\|PubMed:23349634, ECO:0000269\|PubMed:24286120, ECO:0000269\|PubMed:25918392}.
Subunit:		(Microbial infection) Interacts with hepatits B virus/HBV protein X. {ECO:0000269\|PubMed:15120623}.
Subunit:		(Microbial infection) Interacts with HTLV-1 protein p40tax. {ECO:0000269\|PubMed:1731090}.
Subcellular location:		Mitochondrion matrix.
Disease:		Spastic paraplegia 13, autosomal dominant (SPG13) [MIM:605280]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269\|PubMed:11898127}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Leukodystrophy, hypomyelinating, 4 (HLD4) [MIM:612233]: A severe autosomal recessive hypomyelinating leukodystrophy. Clinically characterized by infantile-onset rotary nystagmus, progressive spastic paraplegia, neurologic regression, motor impairment, profound mental retardation. Death usually occurs within the first two decades of life. {ECO:0000269\|PubMed:18571143}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the chaperonin (HSP60) family. {ECO:0000305}.