PTH2_HUMAN
ID PTH2_HUMAN Reviewed; 179 AA.
AC Q9Y3E5; B3KUY4; Q9NTE5;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Peptidyl-tRNA hydrolase 2, mitochondrial;
DE Short=PTH 2;
DE EC=3.1.1.29 {ECO:0000269|PubMed:14660562};
DE AltName: Full=Bcl-2 inhibitor of transcription 1;
DE Flags: Precursor;
GN Name=PTRH2; Synonyms=BIT1, PTH2; ORFNames=CGI-147;
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 [LARGE SCALE MRNA].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 4-179.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP FUNCTION IN APOPTOSIS.
RX PubMed=15006356; DOI=10.1016/s0092-8674(04)00204-1;
RA Jan Y., Matter M., Pai J.-T., Chen Y.-L., Pilch J., Komatsu M., Ong E.,
RA Fukuda M., Ruoslahti E.;
RT "A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins
RT and Groucho/TLE corepressors.";
RL Cell 116:751-762(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
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=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP INVOLVEMENT IN IMNEPD1.
RX PubMed=25574476; DOI=10.1002/acn3.149;
RA Hu H., Matter M.L., Issa-Jahns L., Jijiwa M., Kraemer N., Musante L.,
RA de la Vega M., Ninnemann O., Schindler D., Damatova N., Eirich K.,
RA Sifringer M., Schroetter S., Eickholt B.J., van den Heuvel L., Casamina C.,
RA Stoltenburg-Didinger G., Ropers H.H., Wienker T.F., Huebner C.,
RA Kaindl A.M.;
RT "Mutations in PTRH2 cause novel infantile-onset multisystem disease with
RT intellectual disability, microcephaly, progressive ataxia, and muscle
RT weakness.";
RL Ann. Clin. Transl. Neurol. 1:1024-1035(2014).
RN [11]
RP INVOLVEMENT IN IMNEPD1, AND VARIANT IMNEPD1 PRO-85.
RX PubMed=25558065; DOI=10.1016/j.celrep.2014.12.015;
RA Alazami A.M., Patel N., Shamseldin H.E., Anazi S., Al-Dosari M.S.,
RA Alzahrani F., Hijazi H., Alshammari M., Aldahmesh M.A., Salih M.A.,
RA Faqeih E., Alhashem A., Bashiri F.A., Al-Owain M., Kentab A.Y., Sogaty S.,
RA Al Tala S., Temsah M.H., Tulbah M., Aljelaify R.F., Alshahwan S.A.,
RA Seidahmed M.Z., Alhadid A.A., Aldhalaan H., Alqallaf F., Kurdi W.,
RA Alfadhel M., Babay Z., Alsogheer M., Kaya N., Al-Hassnan Z.N.,
RA Abdel-Salam G.M., Al-Sannaa N., Al Mutairi F., El Khashab H.Y., Bohlega S.,
RA Jia X., Nguyen H.C., Hammami R., Adly N., Mohamed J.Y., Abdulwahab F.,
RA Ibrahim N., Naim E.A., Al-Younes B., Meyer B.F., Hashem M., Shaheen R.,
RA Xiong Y., Abouelhoda M., Aldeeri A.A., Monies D.M., Alkuraya F.S.;
RT "Accelerating novel candidate gene discovery in neurogenetic disorders via
RT whole-exome sequencing of prescreened multiplex consanguineous families.";
RL Cell Rep. 10:148-161(2015).
RN [12]
RP UBIQUITINATION AT LYS-47; LYS-76; LYS-81; LYS-95; LYS-106; LYS-115; LYS-171
RP AND LYS-177.
RX PubMed=25621951; DOI=10.1038/ncb3097;
RA Cunningham C.N., Baughman J.M., Phu L., Tea J.S., Yu C., Coons M.,
RA Kirkpatrick D.S., Bingol B., Corn J.E.;
RT "USP30 and parkin homeostatically regulate atypical ubiquitin chains on
RT mitochondria.";
RL Nat. Cell Biol. 17:160-169(2015).
RN [13]
RP IDENTIFICATION BY MASS 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 [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 63-179, AND CATALYTIC ACTIVITY.
RX PubMed=14660562; DOI=10.1074/jbc.m311449200;
RA De Pereda J.M., Waas W.F., Jan Y., Ruoslahti E., Schimmel P., Pascual J.;
RT "Crystal structure of a human peptidyl-tRNA hydrolase reveals a new fold
RT and suggests basis for a bifunctional activity.";
RL J. Biol. Chem. 279:8111-8115(2004).
CC -!- FUNCTION: The natural substrate for this enzyme may be peptidyl-tRNAs
CC which drop off the ribosome during protein synthesis. {ECO:0000250}.
CC -!- FUNCTION: Promotes caspase-independent apoptosis by regulating the
CC function of two transcriptional regulators, AES and TLE1.
CC {ECO:0000269|PubMed:15006356}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acyl-L-alpha-aminoacyl-tRNA + H2O = a tRNA + an N-acyl-L-
CC amino acid + H(+); Xref=Rhea:RHEA:54448, Rhea:RHEA-COMP:10123,
CC Rhea:RHEA-COMP:13883, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:59874, ChEBI:CHEBI:78442, ChEBI:CHEBI:138191;
CC EC=3.1.1.29; Evidence={ECO:0000269|PubMed:14660562};
CC -!- SUBUNIT: Monomer.
CC -!- INTERACTION:
CC Q9Y3E5; Q05397: PTK2; NbExp=2; IntAct=EBI-1056751, EBI-702142;
CC Q9Y3E5; Q08117: TLE5; NbExp=7; IntAct=EBI-1056751, EBI-717810;
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- PTM: Ubiquitinated by PRKN during mitophagy, leading to its degradation
CC and enhancement of mitophagy. Deubiquitinated by USP30.
CC {ECO:0000269|PubMed:25621951}.
CC -!- DISEASE: Neurologic, endocrine, and pancreatic disease, multisystem,
CC infantile-onset 1 (IMNEPD1) [MIM:616263]: A progressive multisystem
CC disease characterized by a variety of neurologic, endocrine, and, in
CC some patients, pancreatic features. Variable clinical symptoms include
CC global developmental delay, hypotonia, hearing loss, ataxia,
CC hyporeflexia, facial dysmorphism, hypothyroidism, and pancreatic
CC insufficiency. {ECO:0000269|PubMed:25558065,
CC ECO:0000269|PubMed:25574476}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PTH2 family. {ECO:0000305}.
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DR EMBL; AF151905; AAD34142.1; -; mRNA.
DR EMBL; AK098219; BAG53596.1; -; mRNA.
DR EMBL; CH471109; EAW94394.1; -; Genomic_DNA.
DR EMBL; BC006807; AAH06807.1; -; mRNA.
DR EMBL; AL137322; CAB70696.1; -; mRNA.
DR CCDS; CCDS11618.1; -.
DR PIR; T46479; T46479.
DR RefSeq; NP_001015509.1; NM_001015509.2.
DR RefSeq; NP_057161.1; NM_016077.4.
DR RefSeq; XP_011523189.1; XM_011524887.1.
DR PDB; 1Q7S; X-ray; 2.00 A; A/B=63-179.
DR PDBsum; 1Q7S; -.
DR AlphaFoldDB; Q9Y3E5; -.
DR SMR; Q9Y3E5; -.
DR BioGRID; 119659; 236.
DR IntAct; Q9Y3E5; 45.
DR MINT; Q9Y3E5; -.
DR STRING; 9606.ENSP00000464327; -.
DR MoonDB; Q9Y3E5; Curated.
DR MoonProt; Q9Y3E5; -.
DR GlyGen; Q9Y3E5; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y3E5; -.
DR MetOSite; Q9Y3E5; -.
DR PhosphoSitePlus; Q9Y3E5; -.
DR SwissPalm; Q9Y3E5; -.
DR BioMuta; PTRH2; -.
DR DMDM; 6686183; -.
DR EPD; Q9Y3E5; -.
DR jPOST; Q9Y3E5; -.
DR MassIVE; Q9Y3E5; -.
DR MaxQB; Q9Y3E5; -.
DR PaxDb; Q9Y3E5; -.
DR PeptideAtlas; Q9Y3E5; -.
DR PRIDE; Q9Y3E5; -.
DR ProteomicsDB; 86030; -.
DR TopDownProteomics; Q9Y3E5; -.
DR Antibodypedia; 2479; 381 antibodies from 36 providers.
DR DNASU; 51651; -.
DR Ensembl; ENST00000393038.3; ENSP00000376758.2; ENSG00000141378.15.
DR Ensembl; ENST00000470557.2; ENSP00000464327.1; ENSG00000141378.15.
DR GeneID; 51651; -.
DR KEGG; hsa:51651; -.
DR MANE-Select; ENST00000393038.3; ENSP00000376758.2; NM_016077.5; NP_057161.1.
DR UCSC; uc002ixt.4; human.
DR CTD; 51651; -.
DR DisGeNET; 51651; -.
DR GeneCards; PTRH2; -.
DR GeneReviews; PTRH2; -.
DR HGNC; HGNC:24265; PTRH2.
DR HPA; ENSG00000141378; Low tissue specificity.
DR MalaCards; PTRH2; -.
DR MIM; 608625; gene.
DR MIM; 616263; phenotype.
DR neXtProt; NX_Q9Y3E5; -.
DR OpenTargets; ENSG00000141378; -.
DR Orphanet; 456312; Infantile multisystem neurologic-endocrine-pancreatic disease.
DR PharmGKB; PA143485586; -.
DR VEuPathDB; HostDB:ENSG00000141378; -.
DR eggNOG; KOG3282; Eukaryota.
DR GeneTree; ENSGT00390000015991; -.
DR HOGENOM; CLU_073661_1_1_1; -.
DR InParanoid; Q9Y3E5; -.
DR OMA; GHAAVEC; -.
DR OrthoDB; 1564104at2759; -.
DR PhylomeDB; Q9Y3E5; -.
DR TreeFam; TF324583; -.
DR BRENDA; 3.1.1.29; 2681.
DR PathwayCommons; Q9Y3E5; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; Q9Y3E5; -.
DR SIGNOR; Q9Y3E5; -.
DR BioGRID-ORCS; 51651; 32 hits in 1023 CRISPR screens.
DR ChiTaRS; PTRH2; human.
DR EvolutionaryTrace; Q9Y3E5; -.
DR GenomeRNAi; 51651; -.
DR Pharos; Q9Y3E5; Tbio.
DR PRO; PR:Q9Y3E5; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9Y3E5; protein.
DR Bgee; ENSG00000141378; Expressed in cervix squamous epithelium and 203 other tissues.
DR ExpressionAtlas; Q9Y3E5; baseline and differential.
DR Genevisible; Q9Y3E5; HS.
DR GO; GO:0005829; C:cytosol; IMP:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0004045; F:aminoacyl-tRNA hydrolase activity; IMP:CAFA.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:2000210; P:positive regulation of anoikis; IMP:UniProtKB.
DR CDD; cd02430; PTH2; 1.
DR Gene3D; 3.40.1490.10; -; 1.
DR InterPro; IPR023476; Pep_tRNA_hydro_II_dom_sf.
DR InterPro; IPR002833; PTH2.
DR PANTHER; PTHR12649; PTHR12649; 1.
DR Pfam; PF01981; PTH2; 1.
DR SUPFAM; SSF102462; SSF102462; 1.
DR TIGRFAMs; TIGR00283; arch_pth2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Disease variant; Hydrolase; Isopeptide bond;
KW Mitochondrion; Reference proteome; Transit peptide; Ubl conjugation.
FT TRANSIT 1..62
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 63..179
FT /note="Peptidyl-tRNA hydrolase 2, mitochondrial"
FT /id="PRO_0000029862"
FT CROSSLNK 47
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 76
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 81
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 95
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 106
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 115
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 171
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT CROSSLNK 177
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25621951"
FT VARIANT 85
FT /note="Q -> P (in IMNEPD1; dbSNP:rs730882234)"
FT /evidence="ECO:0000269|PubMed:25558065"
FT /id="VAR_073386"
FT STRAND 65..72
FT /evidence="ECO:0007829|PDB:1Q7S"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:1Q7S"
FT HELIX 79..100
FT /evidence="ECO:0007829|PDB:1Q7S"
FT HELIX 102..110
FT /evidence="ECO:0007829|PDB:1Q7S"
FT STRAND 115..122
FT /evidence="ECO:0007829|PDB:1Q7S"
FT HELIX 123..135
FT /evidence="ECO:0007829|PDB:1Q7S"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:1Q7S"
FT STRAND 147..151
FT /evidence="ECO:0007829|PDB:1Q7S"
FT STRAND 153..165
FT /evidence="ECO:0007829|PDB:1Q7S"
FT HELIX 166..173
FT /evidence="ECO:0007829|PDB:1Q7S"
SQ SEQUENCE 179 AA; 19194 MW; 11A0BA9ECF6B5E46 CRC64;
MPSKSLVMEY LAHPSTLGLA VGVACGMCLG WSLRVCFGML PKSKTSKTHT DTESEASILG
DSGEYKMILV VRNDLKMGKG KVAAQCSHAA VSAYKQIQRR NPEMLKQWEY CGQPKVVVKA
PDEETLIALL AHAKMLGLTV SLIQDAGRTQ IAPGSQTVLG IGPGPADLID KVTGHLKLY
