PREP_HUMAN
ID PREP_HUMAN Reviewed; 1037 AA.
AC Q5JRX3; B3KMJ6; B4E0J8; C9JSL2; E7ES23; O95204; Q2M2G6; Q4VBR1; Q5JRW7;
AC Q7L5Z7; Q9BSI6; Q9BVJ5; Q9UPP8;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2013, sequence version 3.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Presequence protease, mitochondrial {ECO:0000305|PubMed:16849325};
DE Short=hPreP {ECO:0000303|PubMed:16849325};
DE EC=3.4.24.- {ECO:0000269|PubMed:10360838, ECO:0000269|PubMed:16849325, ECO:0000269|PubMed:19196155, ECO:0000269|PubMed:24931469};
DE AltName: Full=Pitrilysin metalloproteinase 1 {ECO:0000303|PubMed:10360838};
DE Short=Metalloprotease 1 {ECO:0000303|PubMed:10360838};
DE Short=hMP1 {ECO:0000303|PubMed:10360838};
DE Flags: Precursor;
GN Name=PITRM1 {ECO:0000312|HGNC:HGNC:17663};
GN Synonyms=KIAA1104 {ECO:0000312|EMBL:BAA83056.2},
GN MP1 {ECO:0000303|PubMed:10360838}, PREP {ECO:0000303|PubMed:16849325};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND
RP VARIANTS SER-169; VAL-328; VAL-397; ILE-621 AND ARG-1037.
RX PubMed=10360838; DOI=10.1089/104454999315268;
RA Mzhavia N., Berman Y.L., Qian Y., Yan L., Devi L.A.;
RT "Cloning, expression, and characterization of human metalloprotease 1: a
RT novel member of the pitrilysin family of metalloendoproteases.";
RL DNA Cell Biol. 18:369-380(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANTS
RP VAL-328; VAL-397 AND ARG-1037.
RC TISSUE=Placenta, and Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ARG-8;
RP VAL-145; VAL-328; VAL-397; ILE-963 AND ARG-1037.
RC TISSUE=Brain, Lung, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 402-1037 (ISOFORM 1), AND VARIANT
RP ARG-1037.
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP ACTIVE SITE, DISULFIDE BOND, AND MUTAGENESIS OF GLU-107 AND CYS-119.
RX PubMed=16849325; DOI=10.1074/jbc.m602532200;
RA Falkevall A., Alikhani N., Bhushan S., Pavlov P.F., Busch K., Johnson K.A.,
RA Eneqvist T., Tjernberg L., Ankarcrona M., Glaser E.;
RT "Degradation of the amyloid beta-protein by the novel mitochondrial
RT peptidasome, PreP.";
RL J. Biol. Chem. 281:29096-29104(2006).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 1-MET--ARG-15.
RX PubMed=19196155; DOI=10.1021/bi8016125;
RA Chow K.M., Gakh O., Payne I.C., Juliano M.A., Juliano L., Isaya G.,
RA Hersh L.B.;
RT "Mammalian pitrilysin: substrate specificity and mitochondrial targeting.";
RL Biochemistry 48:2868-2877(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10] {ECO:0007744|PDB:4L3T, ECO:0007744|PDB:4NGE}
RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 33-1037 (ISOFORM 1) OF MUTANT
RP GLN-107 IN COMPLEX WITH AMYLOID-BETA PROTEIN 40 AND ZINC, FUNCTION,
RP CATALYTIC ACTIVITY, SUBUNIT, ACTIVE SITE, AND MUTAGENESIS OF GLU-107;
RP LEU-557 AND PRO-558.
RX PubMed=24931469; DOI=10.1016/j.str.2014.05.003;
RA King J.V., Liang W.G., Scherpelz K.P., Schilling A.B., Meredith S.C.,
RA Tang W.J.;
RT "Molecular basis of substrate recognition and degradation by human
RT presequence protease.";
RL Structure 22:996-1007(2014).
RN [11]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-1037, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP VARIANT SCAR30 GLN-183, INVOLVEMENT IN SCAR30, CHARACTERIZATION OF VARIANT
RP SCAR30 GLN-183, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26697887; DOI=10.15252/emmm.201505894;
RA Brunetti D., Torsvik J., Dallabona C., Teixeira P., Sztromwasser P.,
RA Fernandez-Vizarra E., Cerutti R., Reyes A., Preziuso C., D'Amati G.,
RA Baruffini E., Goffrini P., Viscomi C., Ferrero I., Boman H., Telstad W.,
RA Johansson S., Glaser E., Knappskog P.M., Zeviani M., Bindoff L.A.;
RT "Defective PITRM1 mitochondrial peptidase is associated with Abeta
RT amyloidotic neurodegeneration.";
RL EMBO Mol. Med. 8:176-190(2016).
RN [13]
RP VARIANT SCAR30 MET-931, CHARACTERIZATION OF VARIANT SCAR30 MET-931, AND
RP FUNCTION.
RX PubMed=29764912; DOI=10.1136/jmedgenet-2018-105330;
RA Langer Y., Aran A., Gulsuner S., Abu Libdeh B., Renbaum P., Brunetti D.,
RA Teixeira P.F., Walsh T., Zeligson S., Ruotolo R., Beeri R., Dweikat I.,
RA Shahrour M., Weinberg-Shukron A., Zahdeh F., Baruffini E., Glaser E.,
RA King M.C., Levy-Lahad E., Zeviani M., Segel R.;
RT "Mitochondrial PITRM1 peptidase loss-of-function in childhood cerebellar
RT atrophy.";
RL J. Med. Genet. 55:599-606(2018).
RN [14]
RP VARIANT SCAR30 GLN-183, CHARACTERIZATION OF VARIANT SCAR30 GLN-183,
RP MUTAGENESIS OF GLU-107; 182-TRP--LYS-199; ARG-183; GLU-185 AND LYS-199, AND
RP FUNCTION.
RX PubMed=29383861; DOI=10.1002/pro.3380;
RA Smith-Carpenter J.E., Alper B.J.;
RT "Functional requirement for human pitrilysin metallopeptidase 1 arginine
RT 183, mutated in amyloidogenic neuropathy.";
RL Protein Sci. 27:861-873(2018).
CC -!- FUNCTION: Metalloendopeptidase of the mitochondrial matrix that
CC functions in peptide cleavage and degradation rather than in protein
CC processing (PubMed:10360838, PubMed:16849325, PubMed:19196155,
CC PubMed:24931469). Has an ATP-independent activity (PubMed:16849325).
CC Specifically cleaves peptides in the range of 5 to 65 residues
CC (PubMed:19196155). Shows a preference for cleavage after small polar
CC residues and before basic residues, but without any positional
CC preference (PubMed:10360838, PubMed:19196155, PubMed:24931469).
CC Degrades the transit peptides of mitochondrial proteins after their
CC cleavage (PubMed:19196155). Also degrades other unstructured peptides
CC (PubMed:19196155). It is also able to degrade amyloid-beta protein 40,
CC one of the peptides produced by APP processing, when it accumulates in
CC mitochondrion (PubMed:16849325, PubMed:24931469, PubMed:26697887). It
CC is a highly efficient protease, at least toward amyloid-beta protein 40
CC (PubMed:24931469, PubMed:29764912, PubMed:29383861). Cleaves that
CC peptide at a specific position and is probably not processive,
CC releasing digested peptides intermediates that can be further cleaved
CC subsequently (PubMed:24931469). It is also able to degrade amyloid-beta
CC protein 42 (PubMed:29764912). {ECO:0000269|PubMed:10360838,
CC ECO:0000269|PubMed:16849325, ECO:0000269|PubMed:19196155,
CC ECO:0000269|PubMed:24931469, ECO:0000269|PubMed:26697887,
CC ECO:0000269|PubMed:29383861, ECO:0000269|PubMed:29764912}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:24931469};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:24931469};
CC -!- ACTIVITY REGULATION: Mainly exists in a closed and catalytically
CC competent conformation but a closed-to-open switch allows substrate
CC entry into the catalytic chamber (PubMed:24931469). Substrate binding
CC induces closure and dimerization (PubMed:24931469). A disulfide bond
CC may lock the enzyme in a closed conformation preventing substrate entry
CC into the catalytic chamber, participating in redox regulation of the
CC enzyme (Probable). Inhibited by metal-chelating agents
CC (PubMed:10360838). Inhibited by nickel and zinc excess, and slightly
CC activated by manganese (PubMed:19196155). {ECO:0000269|PubMed:10360838,
CC ECO:0000269|PubMed:19196155, ECO:0000269|PubMed:24931469,
CC ECO:0000305|PubMed:16849325, ECO:0000305|PubMed:24931469}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.07 uM for leumorphin ARG-ARG-GLN-PHE-LYS-VAL-VAL-THR-ARG-SER-GLN
CC peptide (at pH 7.5) {ECO:0000269|PubMed:19196155};
CC KM=0.5 uM for TYR-GLY-GLY-LEU-ARG-ARG-GLY-GLN peptide (at pH 7.5)
CC {ECO:0000269|PubMed:19196155};
CC pH dependence:
CC Optimum pH is 7.7. {ECO:0000269|PubMed:10360838};
CC -!- SUBUNIT: Monomer and homodimer; homodimerization is induced by binding
CC of the substrate. {ECO:0000269|PubMed:24931469}.
CC -!- INTERACTION:
CC Q5JRX3-1; PRO_0000000093 [P05067]: APP; NbExp=3; IntAct=EBI-16109799, EBI-2431589;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:26697887}.
CC Mitochondrion matrix {ECO:0000269|PubMed:16849325,
CC ECO:0000269|PubMed:19196155}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5JRX3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5JRX3-2; Sequence=VSP_020597;
CC Name=3;
CC IsoId=Q5JRX3-3; Sequence=VSP_046494, VSP_046495;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in
CC muscle and heart compared to brain, pancreas, liver, lung and placenta.
CC {ECO:0000269|PubMed:10360838}.
CC -!- PTM: A disulfide bond locks the enzyme in the closed conformation
CC preventing substrate entry into the catalytic chamber.
CC {ECO:0000305|PubMed:16849325, ECO:0000305|PubMed:24931469}.
CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 30 (SCAR30)
CC [MIM:619405]: A form of spinocerebellar ataxia, a clinically and
CC genetically heterogeneous group of cerebellar disorders due to
CC degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCAR30 is a progressive disease
CC characterized by childhood-onset global developmental delay with
CC variably impaired intellectual development, motor dysfunction, and
CC cerebellar ataxia. Affected individuals may also have psychiatric
CC abnormalities. {ECO:0000269|PubMed:26697887,
CC ECO:0000269|PubMed:29383861, ECO:0000269|PubMed:29764912}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the peptidase M16 family. PreP subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH01150.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAI39997.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF061243; AAC67244.1; -; mRNA.
DR EMBL; AK002061; BAG51008.1; -; mRNA.
DR EMBL; AK303406; BAG64460.1; -; mRNA.
DR EMBL; AL451164; CAI40001.1; -; Genomic_DNA.
DR EMBL; AL451164; CAI39997.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC001150; AAH01150.1; ALT_INIT; mRNA.
DR EMBL; BC005025; AAH05025.1; -; mRNA.
DR EMBL; BC095422; AAH95422.1; -; mRNA.
DR EMBL; BC111987; AAI11988.1; -; mRNA.
DR EMBL; BC113369; AAI13370.1; -; mRNA.
DR EMBL; AB029027; BAA83056.2; -; mRNA.
DR CCDS; CCDS55699.1; -. [Q5JRX3-2]
DR CCDS; CCDS55700.1; -. [Q5JRX3-3]
DR CCDS; CCDS59208.1; -. [Q5JRX3-1]
DR RefSeq; NP_001229236.1; NM_001242307.1. [Q5JRX3-2]
DR RefSeq; NP_001229238.1; NM_001242309.1. [Q5JRX3-3]
DR RefSeq; NP_055704.2; NM_014889.3. [Q5JRX3-1]
DR PDB; 4L3T; X-ray; 2.03 A; A/B=33-1037.
DR PDB; 4NGE; X-ray; 2.70 A; A/D=33-1037.
DR PDB; 4RPU; X-ray; 2.27 A; A/B=33-1037.
DR PDB; 6XOS; EM; 3.70 A; A=33-1037.
DR PDB; 6XOT; EM; 3.90 A; A=33-1037.
DR PDB; 6XOU; EM; 4.00 A; A=33-1037.
DR PDB; 6XOV; EM; 3.30 A; A=33-1037.
DR PDB; 6XOW; EM; 4.60 A; A=33-1037.
DR PDBsum; 4L3T; -.
DR PDBsum; 4NGE; -.
DR PDBsum; 4RPU; -.
DR PDBsum; 6XOS; -.
DR PDBsum; 6XOT; -.
DR PDBsum; 6XOU; -.
DR PDBsum; 6XOV; -.
DR PDBsum; 6XOW; -.
DR AlphaFoldDB; Q5JRX3; -.
DR SASBDB; Q5JRX3; -.
DR SMR; Q5JRX3; -.
DR BioGRID; 115786; 162.
DR DIP; DIP-52900N; -.
DR IntAct; Q5JRX3; 28.
DR MINT; Q5JRX3; -.
DR STRING; 9606.ENSP00000370377; -.
DR BindingDB; Q5JRX3; -.
DR ChEMBL; CHEMBL3124731; -.
DR MEROPS; M16.009; -.
DR GlyGen; Q5JRX3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5JRX3; -.
DR MetOSite; Q5JRX3; -.
DR PhosphoSitePlus; Q5JRX3; -.
DR SwissPalm; Q5JRX3; -.
DR BioMuta; PITRM1; -.
DR DMDM; 485956568; -.
DR EPD; Q5JRX3; -.
DR jPOST; Q5JRX3; -.
DR MassIVE; Q5JRX3; -.
DR MaxQB; Q5JRX3; -.
DR PaxDb; Q5JRX3; -.
DR PeptideAtlas; Q5JRX3; -.
DR PRIDE; Q5JRX3; -.
DR ProteomicsDB; 11495; -.
DR ProteomicsDB; 17899; -.
DR ProteomicsDB; 63119; -. [Q5JRX3-1]
DR ProteomicsDB; 63120; -. [Q5JRX3-2]
DR Antibodypedia; 1721; 191 antibodies from 30 providers.
DR DNASU; 10531; -.
DR Ensembl; ENST00000224949.9; ENSP00000224949.4; ENSG00000107959.17. [Q5JRX3-1]
DR Ensembl; ENST00000380989.6; ENSP00000370377.2; ENSG00000107959.17. [Q5JRX3-2]
DR Ensembl; ENST00000451104.6; ENSP00000401201.2; ENSG00000107959.17. [Q5JRX3-3]
DR GeneID; 10531; -.
DR KEGG; hsa:10531; -.
DR MANE-Select; ENST00000224949.9; ENSP00000224949.4; NM_014889.4; NP_055704.2.
DR UCSC; uc001igt.3; human. [Q5JRX3-1]
DR CTD; 10531; -.
DR DisGeNET; 10531; -.
DR GeneCards; PITRM1; -.
DR HGNC; HGNC:17663; PITRM1.
DR HPA; ENSG00000107959; Low tissue specificity.
DR MIM; 618211; gene.
DR MIM; 619405; phenotype.
DR neXtProt; NX_Q5JRX3; -.
DR OpenTargets; ENSG00000107959; -.
DR PharmGKB; PA134902269; -.
DR VEuPathDB; HostDB:ENSG00000107959; -.
DR eggNOG; KOG2019; Eukaryota.
DR GeneTree; ENSGT00390000018381; -.
DR HOGENOM; CLU_009165_0_0_1; -.
DR InParanoid; Q5JRX3; -.
DR OMA; MTYPDKT; -.
DR OrthoDB; 107079at2759; -.
DR TreeFam; TF300333; -.
DR BRENDA; 3.4.24.56; 2681.
DR PathwayCommons; Q5JRX3; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR SignaLink; Q5JRX3; -.
DR SIGNOR; Q5JRX3; -.
DR BioGRID-ORCS; 10531; 198 hits in 1094 CRISPR screens.
DR ChiTaRS; PITRM1; human.
DR GeneWiki; PITRM1; -.
DR GenomeRNAi; 10531; -.
DR Pharos; Q5JRX3; Tchem.
DR PRO; PR:Q5JRX3; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q5JRX3; protein.
DR Bgee; ENSG00000107959; Expressed in apex of heart and 194 other tissues.
DR ExpressionAtlas; Q5JRX3; baseline and differential.
DR Genevisible; Q5JRX3; HS.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0008047; F:enzyme activator activity; TAS:ProtInc.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008237; F:metallopeptidase activity; EXP:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:0006626; P:protein targeting to mitochondrion; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR InterPro; IPR011249; Metalloenz_LuxS/M16.
DR InterPro; IPR011765; Pept_M16_N.
DR InterPro; IPR007863; Peptidase_M16_C.
DR InterPro; IPR013578; Peptidase_M16C_assoc.
DR Pfam; PF08367; M16C_assoc; 1.
DR Pfam; PF00675; Peptidase_M16; 1.
DR Pfam; PF05193; Peptidase_M16_C; 2.
DR SMART; SM01264; M16C_associated; 1.
DR SUPFAM; SSF63411; SSF63411; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Disease variant;
KW Disulfide bond; Hydrolase; Metal-binding; Metalloprotease; Mitochondrion;
KW Neurodegeneration; Protease; Reference proteome; Transit peptide; Zinc.
FT TRANSIT 1..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 29..1037
FT /note="Presequence protease, mitochondrial"
FT /id="PRO_0000249931"
FT REGION 804..834
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 107
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:16849325,
FT ECO:0000269|PubMed:24931469"
FT BINDING 104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:24931469,
FT ECO:0007744|PDB:4L3T, ECO:0007744|PDB:4NGE"
FT BINDING 108
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:24931469,
FT ECO:0007744|PDB:4L3T, ECO:0007744|PDB:4NGE"
FT BINDING 205
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:24931469,
FT ECO:0007744|PDB:4L3T, ECO:0007744|PDB:4NGE"
FT MOD_RES 759
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT MOD_RES 770
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT MOD_RES 770
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT MOD_RES 849
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT MOD_RES 884
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT MOD_RES 946
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8K411"
FT DISULFID 119..556
FT /evidence="ECO:0000305|PubMed:16849325"
FT VAR_SEQ 1..53
FT /note="MWRCGGRQGLCVLRRLSGGHAHHRAWRWNSNRACERALQYKLGDKIHGFTVN
FT Q -> MRNVALRRAAGPVCAEAAERR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046494"
FT VAR_SEQ 624..689
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046495"
FT VAR_SEQ 664
FT /note="Q -> QV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10360838"
FT /id="VSP_020597"
FT VARIANT 8
FT /note="Q -> R (in dbSNP:rs11818724)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_027517"
FT VARIANT 145
FT /note="L -> V (in dbSNP:rs9423502)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_027518"
FT VARIANT 169
FT /note="F -> S (in dbSNP:rs3814596)"
FT /evidence="ECO:0000269|PubMed:10360838"
FT /id="VAR_027519"
FT VARIANT 183
FT /note="R -> Q (in SCAR30; decreased function in degradation
FT of amyloid-beta protein 40; decreased metalloendopeptidase
FT activity towards different substrates including an amyloid-
FT beta peptide derivative; decreased protein levels in
FT patient tissues; no effect on mitochondrial localization)"
FT /evidence="ECO:0000269|PubMed:26697887,
FT ECO:0000269|PubMed:29383861"
FT /id="VAR_085987"
FT VARIANT 328
FT /note="I -> V (in dbSNP:rs4242746)"
FT /evidence="ECO:0000269|PubMed:10360838,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_027520"
FT VARIANT 397
FT /note="A -> V (in dbSNP:rs3182535)"
FT /evidence="ECO:0000269|PubMed:10360838,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_027521"
FT VARIANT 516
FT /note="Q -> H (in dbSNP:rs3765101)"
FT /id="VAR_027522"
FT VARIANT 554
FT /note="A -> D (in dbSNP:rs12248937)"
FT /id="VAR_057059"
FT VARIANT 621
FT /note="V -> I (in dbSNP:rs2388556)"
FT /evidence="ECO:0000269|PubMed:10360838"
FT /id="VAR_027523"
FT VARIANT 805
FT /note="R -> Q (in dbSNP:rs34837384)"
FT /id="VAR_057060"
FT VARIANT 931
FT /note="T -> M (in SCAR30; strongly decreased
FT metalloendopeptidase activity towards amyloid-beta protein
FT 40 and amyloid-beta protein 42)"
FT /evidence="ECO:0000269|PubMed:29764912"
FT /id="VAR_085988"
FT VARIANT 952
FT /note="I -> M (in dbSNP:rs2279219)"
FT /id="VAR_027524"
FT VARIANT 963
FT /note="V -> I (in dbSNP:rs17849904)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_027525"
FT VARIANT 969
FT /note="P -> L (in dbSNP:rs2279218)"
FT /id="VAR_027526"
FT VARIANT 1037
FT /note="Q -> R (in dbSNP:rs6901)"
FT /evidence="ECO:0000269|PubMed:10360838,
FT ECO:0000269|PubMed:10470851, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0007744|PubMed:25944712"
FT /id="VAR_027527"
FT MUTAGEN 1..15
FT /note="Missing: Loss of localization to the mitochondrion."
FT /evidence="ECO:0000269|PubMed:19196155"
FT MUTAGEN 107
FT /note="E->Q: Loss of metalloendopeptidase activity. Loss of
FT activity towards an amyloid-beta peptide derivative."
FT /evidence="ECO:0000269|PubMed:16849325,
FT ECO:0000269|PubMed:24931469, ECO:0000269|PubMed:29383861"
FT MUTAGEN 119
FT /note="C->S: No loss of metalloendopeptidase activity under
FT oxidizing conditions."
FT /evidence="ECO:0000269|PubMed:16849325"
FT MUTAGEN 182..199
FT /note="Missing: Loss of metalloendopeptidase activity
FT towards an amyloid-beta peptide derivative."
FT /evidence="ECO:0000269|PubMed:29383861"
FT MUTAGEN 183
FT /note="R->A,K,N: Decreased metalloendopeptidase activity
FT towards an amyloid-beta peptide derivative."
FT /evidence="ECO:0000269|PubMed:29383861"
FT MUTAGEN 183
FT /note="R->D,E: Loss of metalloendopeptidase activity
FT towards an amyloid-beta peptide derivative."
FT /evidence="ECO:0000269|PubMed:29383861"
FT MUTAGEN 185
FT /note="E->A: Loss of metalloendopeptidase activity towards
FT an amyloid-beta peptide derivative."
FT /evidence="ECO:0000269|PubMed:29383861"
FT MUTAGEN 185
FT /note="E->D,Q: No effect on metalloendopeptidase activity
FT towards an amyloid-beta peptide derivative."
FT /evidence="ECO:0000269|PubMed:29383861"
FT MUTAGEN 185
FT /note="E->R,K,N: Decreased metalloendopeptidase activity
FT towards an amyloid-beta peptide derivative."
FT /evidence="ECO:0000269|PubMed:29383861"
FT MUTAGEN 199
FT /note="K->A,D,E,Q: Decreased metalloendopeptidase activity
FT towards an amyloid-beta peptide derivative."
FT /evidence="ECO:0000269|PubMed:29383861"
FT MUTAGEN 199
FT /note="K->N,R: No effect on metalloendopeptidase activity
FT towards an amyloid-beta peptide derivative."
FT /evidence="ECO:0000269|PubMed:29383861"
FT MUTAGEN 557
FT /note="L->E: Decreased metalloendopeptidase activity
FT without effect on protein stability."
FT /evidence="ECO:0000269|PubMed:24931469"
FT MUTAGEN 558
FT /note="P->G: Decreased metalloendopeptidase activity
FT without effect on protein stability."
FT /evidence="ECO:0000269|PubMed:24931469"
FT CONFLICT 121
FT /note="D -> N (in Ref. 1; AAC67244)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="T -> V (in Ref. 3; CAI40001)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="D -> N (in Ref. 3; CAI40001)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="D -> E (in Ref. 1; AAC67244)"
FT /evidence="ECO:0000305"
FT CONFLICT 418..420
FT /note="KGF -> TRI (in Ref. 1; AAC67244)"
FT /evidence="ECO:0000305"
FT CONFLICT 883..884
FT /note="LK -> FE (in Ref. 4; AAH95422)"
FT /evidence="ECO:0000305"
FT HELIX 33..37
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 62..69
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 84..93
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 102..109
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:4NGE"
FT HELIX 122..127
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:6XOV"
FT STRAND 141..151
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 156..168
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 174..180
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 183..188
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:4RPU"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 201..209
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 213..225
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 247..250
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 253..257
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 263..271
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 273..277
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 280..283
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 307..313
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:6XOV"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:4RPU"
FT STRAND 326..336
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 340..354
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 360..362
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 366..369
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 370..374
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 383..396
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 401..418
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 422..430
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 433..437
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 443..456
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 461..465
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 468..480
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 484..487
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 490..494
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 499..506
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 508..512
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 515..520
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 523..527
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 531..539
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 542..549
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 562..564
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 575..579
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 580..582
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 583..589
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 593..603
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 609..614
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 615..621
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 622..624
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 632..641
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 643..654
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 661..673
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 674..676
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 677..689
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 696..699
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 706..712
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 713..717
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 718..727
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 728..730
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 732..741
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 743..749
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 752..754
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 759..762
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 766..772
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 773..775
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 778..784
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 786..788
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 789..793
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 796..802
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 813..815
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 817..821
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 839..844
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 855..858
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 862..871
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 878..883
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 886..893
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 895..899
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 900..903
FT /evidence="ECO:0007829|PDB:4RPU"
FT STRAND 906..912
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 916..926
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 929..936
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 939..942
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 949..955
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 958..963
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 969..971
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 974..979
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 983..994
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 1002..1008
FT /evidence="ECO:0007829|PDB:4L3T"
FT TURN 1011..1013
FT /evidence="ECO:0007829|PDB:4RPU"
FT STRAND 1016..1023
FT /evidence="ECO:0007829|PDB:4L3T"
FT HELIX 1026..1029
FT /evidence="ECO:0007829|PDB:4L3T"
FT STRAND 1034..1036
FT /evidence="ECO:0007829|PDB:4L3T"
SQ SEQUENCE 1037 AA; 117413 MW; F488389F0E219718 CRC64;
MWRCGGRQGL CVLRRLSGGH AHHRAWRWNS NRACERALQY KLGDKIHGFT VNQVTSVPEL
FLTAVKLTHD DTGARYLHLA REDTNNLFSV QFRTTPMDST GVPHILEHTV LCGSQKYPCR
DPFFKMLNRS LSTFMNAFTA SDYTLYPFST QNPKDFQNLL SVYLDATFFP CLRELDFWQE
GWRLEHENPS DPQTPLVFKG VVFNEMKGAF TDNERIFSQH LQNRLLPDHT YSVVSGGDPL
CIPELTWEQL KQFHATHYHP SNARFFTYGN FPLEQHLKQI HEEALSKFQK IEPSTVVPAQ
TPWDKPREFQ ITCGPDSFAT DPSKQTTISV SFLLPDITDT FEAFTLSLLS SLLTSGPNSP
FYKALIESGL GTDFSPDVGY NGYTREAYFS VGLQGIAEKD IETVRSLIDR TIDEVVEKGF
EDDRIEALLH KIEIQMKHQS TSFGLMLTSY IASCWNHDGD PVELLKLGNQ LAKFRQCLQE
NPKFLQEKVK QYFKNNQHKL TLSMRPDDKY HEKQAQVEAT KLKQKVEALS PGDRQQIYEK
GLELRSQQSK PQDASCLPAL KVSDIEPTIP VTELDVVLTA GDIPVQYCAQ PTNGMVYFRA
FSSLNTLPEE LRPYVPLFCS VLTKLGCGLL DYREQAQQIE LKTGGMSASP HVLPDDSHMD
TYEQGVLFSS LCLDRNLPDM MQLWSEIFNN PCFEEEEHFK VLVKMTAQEL ANGIPDSGHL
YASIRAGRTL TPAGDLQETF SGMDQVRLMK RIAEMTDIKP ILRKLPRIKK HLLNGDNMRC
SVNATPQQMP QTEKAVEDFL RSIGRSKKER RPVRPHTVEK PVPSSSGGDA HVPHGSQVIR
KLVMEPTFKP WQMKTHFLMP FPVNYVGECI RTVPYTDPDH ASLKILARLM TAKFLHTEIR
EKGGAYGGGA KLSHNGIFTL YSYRDPNTIE TLQSFGKAVD WAKSGKFTQQ DIDEAKLSVF
STVDAPVAPS DKGMDHFLYG LSDEMKQAHR EQLFAVSHDK LLAVSDRYLG TGKSTHGLAI
LGPENPKIAK DPSWIIQ
