PITRM1
entrez
10531
canonical
uniprot
Q5JRX3
canonical
ensembl
ENSG00000107959
resolver
ensp
ENSP00000224949
resolver
ensp
ENSP00000370377
resolver
ensp
ENSP00000370382
resolver
ensp
ENSP00000391526
resolver
ensp
ENSP00000401201
resolver
ensp
ENSP00000503187
resolver
ensp
ENSP00000503630
resolver
enst
ENST00000380994
resolver
enst
ENST00000678436
resolver
genesymbol
PITRM1
resolver
genesymbol_syn
KIAA1104
resolver
genesymbol_syn
MP1
resolver
genesymbol_syn
PREP
resolver
hgnc
HGNC:17663
resolver
uniprot
A0A0A0MRX9
resolver
uniprot
A0A7I2V397
resolver
uniprot
B3KMJ6
resolver
uniprot
B4E0J8
resolver
uniprot
C9JSL2
resolver
uniprot
E7ES23
resolver
uniprot
O95204
resolver
uniprot
Q2M2G6
resolver
uniprot
Q4VBR1
resolver
uniprot
Q5JRW7
resolver
uniprot
Q7L5Z7
resolver
uniprot
Q9BSI6
resolver
uniprot
Q9BVJ5
resolver
uniprot
Q9UPP8
resolver
uniprot_entry
A0A0A0MRX9_HUMAN
resolver
uniprot_entry
A0A7I2V397_HUMAN
resolver
uniprot_entry
PREP_HUMAN
resolver
uniprot_sec
B3KMJ6
resolver
uniprot_sec
B4E0J8
resolver
uniprot_sec
C9JSL2
resolver
uniprot_sec
E7ES23
resolver
uniprot_sec
O95204
resolver
uniprot_sec
Q2M2G6
resolver
uniprot_sec
Q4VBR1
resolver
uniprot_sec
Q5JRW7
resolver
uniprot_sec
Q7L5Z7
resolver
uniprot_sec
Q9BSI6
resolver
uniprot_sec
Q9BVJ5
resolver
uniprot_sec
Q9UPP8
resolver
activity_regulation
ACTIVITY REGULATION: Mainly exists in a closed and catalytically competent conformation but a closed-to-open switch allows substrate entry into the catalytic chamber (PubMed:24931469). Substrate binding induces closure and dimerization (PubMed:24931469). A disulfide bond may lock the enzyme in a closed conformation preventing substrate entry into the catalytic chamber, participating in redox regulation of the enzyme (Probable). Inhibited by metal-chelating agents (PubMed:10360838). Inhibited by nickel and zinc excess, and slightly activated by manganese (PubMed:19196155). {ECO:0000269|PubMed:10360838, ECO:0000269|PubMed:19196155, ECO:0000269|PubMed:24931469, ECO:0000305|PubMed:16849325, ECO:0000305|PubMed:24931469}.
uniprot
proteins
amino_acid_sequence
MWRCGGRQGLCVLRRLSGGHAHHRAWRWNSNRACERALQYKLGDKIHGFTVNQVTSVPELFLTAVKLTHDDTGARYLHLAREDTNNLFSVQFRTTPMDSTGVPHILEHTVLCGSQKYPCRDPFFKMLNRSLSTFMNAFTASDYTLYPFSTQNPKDFQNLLSVYLDATFFPCLRELDFWQEGWRLEHENPSDPQTPLVFKGVVFNEMKGAFTDNERIFSQHLQNRLLPDHTYSVVSGGDPLCIPELTWEQLKQFHATHYHPSNARFFTYGNFPLEQHLKQIHEEALSKFQKIEPSTVVPAQTPWDKPREFQITCGPDSFATDPSKQTTISVSFLLPDITDTFEAFTLSLLSSLLTSGPNSPFYKALIESGLGTDFSPDVGYNGYTREAYFSVGLQGIAEKDIETVRSLIDRTIDEVVEKGFEDDRIEALLHKIEIQMKHQSTSFGLMLTSYIASCWNHDGDPVELLKLGNQLAKFRQCLQENPKFLQEKVKQYFKNNQHKLTLSMRPDDKYHEKQAQVEATKLKQKVEALSPGDRQQIYEKGLELRSQQSKPQDASCLPALKVSDIEPTIPVTELDVVLTAGDIPVQYCAQPTNGMVYFRAFSSLNTLPEELRPYVPLFCSVLTKLGCGLLDYREQAQQIELKTGGMSASPHVLPDDSHMDTYEQGVLFSSLCLDRNLPDMMQLWSEIFNNPCFEEEEHFKVLVKMTAQELANGIPDSGHLYASIRAGRTLTPAGDLQETFSGMDQVRLMKRIAEMTDIKPILRKLPRIKKHLLNGDNMRCSVNATPQQMPQTEKAVEDFLRSIGRSKKERRPVRPHTVEKPVPSSSGGDAHVPHGSQVIRKLVMEPTFKPWQMKTHFLMPFPVNYVGECIRTVPYTDPDHASLKILARLMTAKFLHTEIREKGGAYGGGAKLSHNGIFTLYSYRDPNTIETLQSFGKAVDWAKSGKFTQQDIDEAKLSVFSTVDAPVAPSDKGMDHFLYGLSDEMKQAHREQLFAVSHDKLLAVSDRYLGTGKSTHGLAILGPENPKIAKDPSWIIQ
uniprot
proteins
disease_involvement
DISEASE: Spinocerebellar ataxia, autosomal recessive, 30 (SCAR30) [MIM:619405]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR30 is a progressive disease characterized by childhood-onset global developmental delay with variably impaired intellectual development, motor dysfunction, and cerebellar ataxia. Affected individuals may also have psychiatric abnormalities. {ECO:0000269|PubMed:26697887, ECO:0000269|PubMed:29383861, ECO:0000269|PubMed:29764912}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.4.24.-
uniprot
proteins
function
FUNCTION: Metalloendopeptidase of the mitochondrial matrix that functions in peptide cleavage and degradation rather than in protein processing (PubMed:10360838, PubMed:16849325, PubMed:19196155, PubMed:24931469). Has an ATP-independent activity (PubMed:16849325). Specifically cleaves peptides in the range of 5 to 65 residues (PubMed:19196155). Shows a preference for cleavage after small polar residues and before basic residues, but without any positional preference (PubMed:10360838, PubMed:19196155, PubMed:24931469). Degrades the transit peptides of mitochondrial proteins after their cleavage (PubMed:19196155). Also degrades other unstructured peptides (PubMed:19196155). It is also able to degrade amyloid-beta protein 40, one of the peptides produced by APP processing, when it accumulates in mitochondrion (PubMed:16849325, PubMed:24931469, PubMed:26697887). It is a highly efficient protease, at least toward amyloid-beta protein 40 (PubMed:24931469, PubMed:29383861, PubMed:29764912). Cleaves that peptide at a specific position and is probably not processive, releasing digested peptides intermediates that can be further cleaved subsequently (PubMed:24931469). It is also able to degrade amyloid-beta protein 42 (PubMed:29764912). {ECO:0000269|PubMed:10360838, ECO:0000269|PubMed:16849325, ECO:0000269|PubMed:19196155, ECO:0000269|PubMed:24931469, ECO:0000269|PubMed:26697887, ECO:0000269|PubMed:29383861, ECO:0000269|PubMed:29764912}.
uniprot
proteins
mass_dalton
117413
uniprot
proteins
mutagenesis
MUTAGEN 1..15; /note="Missing: Loss of localization to the mitochondrion."; /evidence="ECO:0000269|PubMed:19196155"; MUTAGEN 107; /note="E->Q: Loss of metalloendopeptidase activity. Loss of activity towards an amyloid-beta peptide derivative."; /evidence="ECO:0000269|PubMed:16849325, ECO:0000269|PubMed:24931469, ECO:0000269|PubMed:29383861"; MUTAGEN 119; /note="C->S: No loss of metalloendopeptidase activity under oxidizing conditions."; /evidence="ECO:0000269|PubMed:16849325"; MUTAGEN 182..199; /note="Missing: Loss of metalloendopeptidase activity towards an amyloid-beta peptide derivative."; /evidence="ECO:0000269|PubMed:29383861"; MUTAGEN 183; /note="R->A,K,N: Decreased metalloendopeptidase activity towards an amyloid-beta peptide derivative."; /evidence="ECO:0000269|PubMed:29383861"; MUTAGEN 183; /note="R->D,E: Loss of metalloendopeptidase activity towards an amyloid-beta peptide derivative."; /evidence="ECO:0000269|PubMed:29383861"; MUTAGEN 185; /note="E->A: Loss of metalloendopeptidase activity towards an amyloid-beta peptide derivative."; /evidence="ECO:0000269|PubMed:29383861"; MUTAGEN 185; /note="E->D,Q: No effect on metalloendopeptidase activity towards an amyloid-beta peptide derivative."; /evidence="ECO:0000269|PubMed:29383861"; MUTAGEN 185; /note="E->R,K,N: Decreased metalloendopeptidase activity towards an amyloid-beta peptide derivative."; /evidence="ECO:0000269|PubMed:29383861"; MUTAGEN 199; /note="K->A,D,E,Q: Decreased metalloendopeptidase activity towards an amyloid-beta peptide derivative."; /evidence="ECO:0000269|PubMed:29383861"; MUTAGEN 199; /note="K->N,R: No effect on metalloendopeptidase activity towards an amyloid-beta peptide derivative."; /evidence="ECO:0000269|PubMed:29383861"; MUTAGEN 557; /note="L->E: Decreased metalloendopeptidase activity without effect on protein stability."; /evidence="ECO:0000269|PubMed:24931469"; MUTAGEN 558; /note="P->G: Decreased metalloendopeptidase activity without effect on protein stability."; /evidence="ECO:0000269|PubMed:24931469
uniprot
proteins
post_translational_modification
PTM: A disulfide bond locks the enzyme in the closed conformation preventing substrate entry into the catalytic chamber. {ECO:0000305|PubMed:16849325, ECO:0000305|PubMed:24931469}.
uniprot
proteins
protein_family
Peptidase M16 family
uniprot
proteins
protein_family
PreP subfamily
uniprot
proteins
pubmed
10360838
uniprot
proteins
pubmed
10470851
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16849325
uniprot
proteins
pubmed
19196155
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21621546
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24931469
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26697887
uniprot
proteins
pubmed
29383861
uniprot
proteins
pubmed
29764912
uniprot
proteins
sequence_length
1037
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:16849325, ECO:0000269|PubMed:19196155, ECO:0000269|PubMed:21621546, ECO:0000305|PubMed:26697887}.
uniprot
proteins