Q9H300 · PARL_HUMAN
- ProteinPresenilin-associated rhomboid-like protein, mitochondrial
- GenePARL
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids379 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptotic signals (By similarity).
Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088).
Promotes cleavage of serine/threonine-protein phosphatase PGAM5 in damaged mitochondria in response to loss of mitochondrial membrane potential (PubMed:22915595).
Mediates differential cleavage of PINK1 and PGAM5 depending on the health status of mitochondria, disassociating from PINK1 and associating with PGAM5 in response to mitochondrial membrane potential loss (PubMed:22915595).
Required for processing of CLPB into a form with higher protein disaggregase activity by removing an autoinhibitory N-terminal peptide (PubMed:28288130, PubMed:32573439).
Promotes processing of DIABLO/SMAC in the mitochondrion which is required for DIABLO apoptotic activity (PubMed:28288130).
Also required for cleavage of STARD7 and TTC19 (PubMed:28288130).
Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain (PubMed:14732705, PubMed:17116872).
Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088).
Promotes cleavage of serine/threonine-protein phosphatase PGAM5 in damaged mitochondria in response to loss of mitochondrial membrane potential (PubMed:22915595).
Mediates differential cleavage of PINK1 and PGAM5 depending on the health status of mitochondria, disassociating from PINK1 and associating with PGAM5 in response to mitochondrial membrane potential loss (PubMed:22915595).
Required for processing of CLPB into a form with higher protein disaggregase activity by removing an autoinhibitory N-terminal peptide (PubMed:28288130, PubMed:32573439).
Promotes processing of DIABLO/SMAC in the mitochondrion which is required for DIABLO apoptotic activity (PubMed:28288130).
Also required for cleavage of STARD7 and TTC19 (PubMed:28288130).
Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain (PubMed:14732705, PubMed:17116872).
Catalytic activity
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 277 | Nucleophile | ||||
Sequence: S | ||||||
Active site | 335 | |||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrion | |
Cellular Component | nucleus | |
Molecular Function | endopeptidase activity | |
Molecular Function | serine-type endopeptidase activity | |
Biological Process | membrane protein proteolysis | |
Biological Process | mitochondrial fusion | |
Biological Process | negative regulation of intrinsic apoptotic signaling pathway | |
Biological Process | negative regulation of release of cytochrome c from mitochondria | |
Biological Process | protein processing | |
Biological Process | proteolysis | |
Biological Process | regulation of mitochondrion organization | |
Biological Process | regulation of mitophagy | |
Biological Process | regulation of protein targeting to mitochondrion | |
Biological Process | regulation of proteolysis | |
Biological Process | regulation of reactive oxygen species metabolic process | |
Biological Process | signal peptide processing |
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended namePresenilin-associated rhomboid-like protein, mitochondrial
- EC number
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9H300
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Multi-pass membrane protein
P-beta
Note: Translocated into the nucleus by an unknown mechanism (PubMed:17116872).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 53-101 | Mitochondrial matrix | ||||
Sequence: FRKAPRKVEPRRSDPGTSGEAYKRSALIPPVEETVFYPSPYPIRSLIKP | ||||||
Transmembrane | 102-121 | Helical | ||||
Sequence: LFFTVGFTGCAFGSAAIWQY | ||||||
Topological domain | 122-167 | Mitochondrial intermembrane | ||||
Sequence: ESLKSRVQSYFDGIKADWLDSIRPQKEGDFRKEINKWWNNLSDGQR | ||||||
Transmembrane | 168-187 | Helical | ||||
Sequence: TVTGIIAANVLVFCLWRVPS | ||||||
Topological domain | 188-207 | Mitochondrial matrix | ||||
Sequence: LQRTMIRYFTSNPASKVLCS | ||||||
Transmembrane | 208-230 | Helical | ||||
Sequence: PMLLSTFSHFSLFHMAANMYVLW | ||||||
Topological domain | 231-244 | Mitochondrial intermembrane | ||||
Sequence: SFSSSIVNILGQEQ | ||||||
Transmembrane | 245-262 | Helical | ||||
Sequence: FMAVYLSAGVISNFVSYV | ||||||
Topological domain | 263-272 | Mitochondrial matrix | ||||
Sequence: GKVATGRYGP | ||||||
Transmembrane | 273-289 | Helical | ||||
Sequence: SLGASGAIMTVLAAVCT | ||||||
Topological domain | 290-295 | Mitochondrial intermembrane | ||||
Sequence: KIPEGR | ||||||
Transmembrane | 296-318 | Helical | ||||
Sequence: LAIIFLPMFTFTAGNALKAIIAM | ||||||
Topological domain | 319-332 | Mitochondrial matrix | ||||
Sequence: DTAGMILGWKFFDH | ||||||
Transmembrane | 333-354 | Helical | ||||
Sequence: AAHLGGALFGIWYVTYGHELIW | ||||||
Topological domain | 355-379 | Mitochondrial intermembrane | ||||
Sequence: KNREPLVKIWHEIRTNGPKKGGGSK |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 65 | Strongly reduces the beta cleavage; when associated with D-69 and D-70. | ||||
Sequence: S → D | ||||||
Mutagenesis | 69 | Strongly reduces the beta cleavage; when associated with D-65 and D-70. | ||||
Sequence: T → D | ||||||
Mutagenesis | 70 | Strongly reduces the beta cleavage; when associated with D-65 and D-69. | ||||
Sequence: S → D | ||||||
Mutagenesis | 76 | Abolishes the beta cleavage. | ||||
Sequence: R → E | ||||||
Mutagenesis | 76 | Abolishes the beta cleavage. | ||||
Sequence: R → G | ||||||
Mutagenesis | 77 | Abolishes the beta cleavage. | ||||
Sequence: S → E | ||||||
Mutagenesis | 78 | Abolishes the beta cleavage. | ||||
Sequence: A → E | ||||||
Mutagenesis | 79 | Abolishes the beta cleavage. | ||||
Sequence: L → E | ||||||
Natural variant | VAR_029801 | 137 | in dbSNP:rs4912470 | |||
Sequence: A → G | ||||||
Natural variant | VAR_021578 | 262 | in dbSNP:rs3732581 | |||
Sequence: V → L | ||||||
Mutagenesis | 277 | Loss of cleavage of CLPB, DIABLO, STARD7 and TTC19. | ||||
Sequence: S → A | ||||||
Mutagenesis | 277 | Loss of PGAM5 cleavage. | ||||
Sequence: S → G | ||||||
Mutagenesis | 335 | Loss of PGAM5 cleavage. | ||||
Sequence: H → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 400 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-52 | Mitochondrion | ||||
Sequence: MAWRGWAQRGWGCGQAWGASVGGRSCEELTAVLTPPQLLGRRFNFFIQQKCG | ||||||
Peptide | PRO_0000027387 | 53-77 | P-beta | |||
Sequence: FRKAPRKVEPRRSDPGTSGEAYKRS | ||||||
Chain | PRO_0000027386 | 53-379 | Presenilin-associated rhomboid-like protein, mitochondrial | |||
Sequence: FRKAPRKVEPRRSDPGTSGEAYKRSALIPPVEETVFYPSPYPIRSLIKPLFFTVGFTGCAFGSAAIWQYESLKSRVQSYFDGIKADWLDSIRPQKEGDFRKEINKWWNNLSDGQRTVTGIIAANVLVFCLWRVPSLQRTMIRYFTSNPASKVLCSPMLLSTFSHFSLFHMAANMYVLWSFSSSIVNILGQEQFMAVYLSAGVISNFVSYVGKVATGRYGPSLGASGAIMTVLAAVCTKIPEGRLAIIFLPMFTFTAGNALKAIIAMDTAGMILGWKFFDHAAHLGGALFGIWYVTYGHELIWKNREPLVKIWHEIRTNGPKKGGGSK | ||||||
Modified residue | 65 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 69 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 70 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
P-beta is proteolytically processed (beta-cleavage) in a PARL-dependent manner. The cleavage is inhibited when residues Ser-65, Thr-69 and Ser-70 are all phosphorylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Structure
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
Q9H300-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length379
- Mass (Da)42,190
- Last updated2007-04-03 v2
- Checksum2B07EF04C7130B0B
Q9H300-2
- Name2
- Differences from canonical
- 203-253: KVLCSPMLLSTFSHFSLFHMAANMYVLWSFSSSIVNILGQEQFMAVYLSAG → S
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F8WCQ4 | F8WCQ4_HUMAN | PARL | 173 | ||
C9JNP8 | C9JNP8_HUMAN | PARL | 295 | ||
A0A1W2PP66 | A0A1W2PP66_HUMAN | PARL | 188 | ||
A0A1W2PS40 | A0A1W2PS40_HUMAN | PARL | 177 | ||
H7C1V6 | H7C1V6_HUMAN | PARL | 63 | ||
H7C122 | H7C122_HUMAN | PARL | 171 | ||
H7C0U0 | H7C0U0_HUMAN | PARL | 159 | ||
H7C045 | H7C045_HUMAN | PARL | 112 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_013310 | 203-253 | in isoform 2 | |||
Sequence: KVLCSPMLLSTFSHFSLFHMAANMYVLWSFSSSIVNILGQEQFMAVYLSAG → S |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF197937 EMBL· GenBank· DDBJ | AAG28519.1 EMBL· GenBank· DDBJ | mRNA | ||
BC003653 EMBL· GenBank· DDBJ | AAH03653.1 EMBL· GenBank· DDBJ | mRNA | ||
BC014058 EMBL· GenBank· DDBJ | AAH14058.1 EMBL· GenBank· DDBJ | mRNA | ||
AF116692 EMBL· GenBank· DDBJ | AAF71112.1 EMBL· GenBank· DDBJ | mRNA |