SYPM_HUMAN
ID SYPM_HUMAN Reviewed; 475 AA.
AC Q7L3T8; A8K0W4; Q9H6S5; Q9UFT1;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Probable proline--tRNA ligase, mitochondrial;
DE EC=6.1.1.15;
DE AltName: Full=Prolyl-tRNA synthetase;
DE Short=ProRS;
DE Flags: Precursor;
GN Name=PARS2;
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].
RC TISSUE=Amygdala;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
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=Muscle, and Uterus;
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 67-475.
RC TISSUE=Mammary cancer;
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 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 [7]
RP INVOLVEMENT IN DEE75, AND VARIANT DEE75 LEU-279.
RX PubMed=25629079; DOI=10.1002/mgg3.115;
RA Sofou K., Kollberg G., Holmstroem M., Davila M., Darin N., Gustafsson C.M.,
RA Holme E., Oldfors A., Tulinius M., Asin-Cayuela J.;
RT "Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the
RT mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in
RT patients with Alpers syndrome.";
RL Mol. Genet. Genomic Med. 3:59-68(2015).
RN [8]
RP INVOLVEMENT IN DEE75, AND VARIANTS DEE75 ILE-95 AND LYS-203.
RX PubMed=28077841; DOI=10.1038/jhg.2016.163;
RA Mizuguchi T., Nakashima M., Kato M., Yamada K., Okanishi T.,
RA Ekhilevitch N., Mandel H., Eran A., Toyono M., Sawaishi Y., Motoi H.,
RA Shiina M., Ogata K., Miyatake S., Miyake N., Saitsu H., Matsumoto N.;
RT "PARS2 and NARS2 mutations in infantile-onset neurodegenerative disorder.";
RL J. Hum. Genet. 62:525-529(2017).
RN [9]
RP ERRATUM OF PUBMED:28077841.
RX PubMed=28202951; DOI=10.1038/jhg.2017.13;
RA Mizuguchi T., Nakashima M., Kato M., Yamada K., Okanishi T.,
RA Ekhilevitch N., Mandel H., Eran A., Toyono M., Sawaishi Y., Motoi H.,
RA Shiina M., Ogata K., Miyatake S., Miyake N., Saitsu H., Matsumoto N.;
RL J. Hum. Genet. 62:587-587(2017).
RN [10]
RP INVOLVEMENT IN DEE75, AND VARIANTS DEE75 THR-80 AND ARG-364.
RX PubMed=29410512; DOI=10.1038/s10038-017-0401-z;
RA Ciara E., Rokicki D., Lazniewski M., Mierzewska H., Jurkiewicz E.,
RA Bekiesinska-Figatowska M., Piekutowska-Abramczuk D., Iwanicka-Pronicka K.,
RA Szymanska E., Stawinski P., Kosinska J., Pollak A., Pronicki M.,
RA Plewczynski D., Ploski R., Pronicka E.;
RT "Clinical and molecular characteristics of newly reported mitochondrial
RT disease entity caused by biallelic PARS2 mutations.";
RL J. Hum. Genet. 63:473-485(2018).
RN [11]
RP INVOLVEMENT IN DEE75, AND VARIANTS DEE75 ILE-95 AND GLY-202.
RX PubMed=29915213; DOI=10.1038/s10038-018-0478-z;
RA Yin X., Tang B., Mao X., Peng J., Zeng S., Wang Y., Jiang H., Li N.;
RT "The genotypic and phenotypic spectrum of PARS2-related infantile-onset
RT encephalopathy.";
RL J. Hum. Genet. 63:971-980(2018).
RN [12]
RP VARIANT DEE75 ILE-95.
RX PubMed=30237576; DOI=10.1038/s41436-018-0138-x;
RA Maddirevula S., Alzahrani F., Al-Owain M., Al Muhaizea M.A., Kayyali H.R.,
RA AlHashem A., Rahbeeni Z., Al-Otaibi M., Alzaidan H.I., Balobaid A.,
RA El Khashab H.Y., Bubshait D.K., Faden M., Yamani S.A., Dabbagh O.,
RA Al-Mureikhi M., Jasser A.A., Alsaif H.S., Alluhaydan I., Seidahmed M.Z.,
RA Alabbasi B.H., Almogarri I., Kurdi W., Akleh H., Qari A., Al Tala S.M.,
RA Alhomaidi S., Kentab A.Y., Salih M.A., Chedrawi A., Alameer S., Tabarki B.,
RA Shamseldin H.E., Patel N., Ibrahim N., Abdulwahab F., Samira M., Goljan E.,
RA Abouelhoda M., Meyer B.F., Hashem M., Shaheen R., AlShahwan S.,
RA Alfadhel M., Ben-Omran T., Al-Qattan M.M., Monies D., Alkuraya F.S.;
RT "Autozygome and high throughput confirmation of disease genes candidacy.";
RL Genet. Med. 21:736-742(2019).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-proline + tRNA(Pro) = AMP + diphosphate + L-prolyl-
CC tRNA(Pro); Xref=Rhea:RHEA:14305, Rhea:RHEA-COMP:9700, Rhea:RHEA-
CC COMP:9702, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:60039,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78532, ChEBI:CHEBI:456215;
CC EC=6.1.1.15;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 75 (DEE75)
CC [MIM:618437]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE75 is an autosomal recessive form characterized by
CC onset of severe refractory seizures in the first months of life.
CC {ECO:0000269|PubMed:25629079, ECO:0000269|PubMed:28077841,
CC ECO:0000269|PubMed:29410512, ECO:0000269|PubMed:29915213,
CC ECO:0000269|PubMed:30237576}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15178.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK025585; BAB15178.1; ALT_INIT; mRNA.
DR EMBL; AK289679; BAF82368.1; -; mRNA.
DR EMBL; AL139244; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06669.1; -; Genomic_DNA.
DR EMBL; BC007956; AAH07956.2; -; mRNA.
DR EMBL; BC011758; AAH11758.2; -; mRNA.
DR EMBL; AL117473; CAB55948.1; -; mRNA.
DR CCDS; CCDS597.1; -.
DR PIR; T17258; T17258.
DR RefSeq; NP_689481.2; NM_152268.3.
DR AlphaFoldDB; Q7L3T8; -.
DR SMR; Q7L3T8; -.
DR BioGRID; 117457; 42.
DR IntAct; Q7L3T8; 11.
DR MINT; Q7L3T8; -.
DR STRING; 9606.ENSP00000360327; -.
DR DrugBank; DB00172; Proline.
DR iPTMnet; Q7L3T8; -.
DR PhosphoSitePlus; Q7L3T8; -.
DR BioMuta; PARS2; -.
DR DMDM; 73919761; -.
DR EPD; Q7L3T8; -.
DR jPOST; Q7L3T8; -.
DR MassIVE; Q7L3T8; -.
DR MaxQB; Q7L3T8; -.
DR PaxDb; Q7L3T8; -.
DR PeptideAtlas; Q7L3T8; -.
DR PRIDE; Q7L3T8; -.
DR ProteomicsDB; 68772; -.
DR Antibodypedia; 33219; 62 antibodies from 19 providers.
DR DNASU; 25973; -.
DR Ensembl; ENST00000371279.4; ENSP00000360327.3; ENSG00000162396.6.
DR GeneID; 25973; -.
DR KEGG; hsa:25973; -.
DR MANE-Select; ENST00000371279.4; ENSP00000360327.3; NM_152268.4; NP_689481.2.
DR UCSC; uc001cxy.4; human.
DR CTD; 25973; -.
DR DisGeNET; 25973; -.
DR GeneCards; PARS2; -.
DR HGNC; HGNC:30563; PARS2.
DR HPA; ENSG00000162396; Low tissue specificity.
DR MalaCards; PARS2; -.
DR MIM; 612036; gene.
DR MIM; 618437; phenotype.
DR neXtProt; NX_Q7L3T8; -.
DR OpenTargets; ENSG00000162396; -.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA142671198; -.
DR VEuPathDB; HostDB:ENSG00000162396; -.
DR eggNOG; KOG2324; Eukaryota.
DR GeneTree; ENSGT00390000010922; -.
DR HOGENOM; CLU_016739_4_1_1; -.
DR InParanoid; Q7L3T8; -.
DR OMA; NCDYAAN; -.
DR OrthoDB; 409116at2759; -.
DR PhylomeDB; Q7L3T8; -.
DR TreeFam; TF105607; -.
DR PathwayCommons; Q7L3T8; -.
DR Reactome; R-HSA-379726; Mitochondrial tRNA aminoacylation.
DR SignaLink; Q7L3T8; -.
DR BioGRID-ORCS; 25973; 353 hits in 1091 CRISPR screens.
DR GenomeRNAi; 25973; -.
DR Pharos; Q7L3T8; Tbio.
DR PRO; PR:Q7L3T8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q7L3T8; protein.
DR Bgee; ENSG00000162396; Expressed in secondary oocyte and 139 other tissues.
DR Genevisible; Q7L3T8; HS.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:UniProt.
DR GO; GO:0004827; F:proline-tRNA ligase activity; IBA:GO_Central.
DR GO; GO:0006433; P:prolyl-tRNA aminoacylation; IBA:GO_Central.
DR CDD; cd00779; ProRS_core_prok; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR Gene3D; 3.40.50.800; -; 1.
DR InterPro; IPR002314; aa-tRNA-synt_IIb.
DR InterPro; IPR006195; aa-tRNA-synth_II.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR004154; Anticodon-bd.
DR InterPro; IPR036621; Anticodon-bd_dom_sf.
DR InterPro; IPR002316; Pro-tRNA-ligase_IIa.
DR InterPro; IPR033730; ProRS_core_prok.
DR Pfam; PF03129; HGTP_anticodon; 1.
DR Pfam; PF00587; tRNA-synt_2b; 1.
DR PRINTS; PR01046; TRNASYNTHPRO.
DR SUPFAM; SSF55681; SSF55681; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
PE 1: Evidence at protein level;
KW Aminoacyl-tRNA synthetase; ATP-binding; Disease variant; Epilepsy; Ligase;
KW Mitochondrion; Nucleotide-binding; Protein biosynthesis;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..29
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 30..475
FT /note="Probable proline--tRNA ligase, mitochondrial"
FT /id="PRO_0000035818"
FT VARIANT 28
FT /note="R -> S (in dbSNP:rs11577368)"
FT /id="VAR_052644"
FT VARIANT 80
FT /note="I -> T (in DEE75; unknown pathological significance;
FT dbSNP:rs1246773873)"
FT /evidence="ECO:0000269|PubMed:29410512"
FT /id="VAR_082617"
FT VARIANT 95
FT /note="V -> I (in DEE75; unknown pathological significance;
FT dbSNP:rs147227819)"
FT /evidence="ECO:0000269|PubMed:28077841,
FT ECO:0000269|PubMed:29915213, ECO:0000269|PubMed:30237576"
FT /id="VAR_082149"
FT VARIANT 202
FT /note="R -> G (in DEE75; unknown pathological significance;
FT dbSNP:rs141760650)"
FT /evidence="ECO:0000269|PubMed:29915213"
FT /id="VAR_082618"
FT VARIANT 203
FT /note="E -> K (in DEE75; unknown pathological significance;
FT dbSNP:rs1557762729)"
FT /evidence="ECO:0000269|PubMed:28077841"
FT /id="VAR_082619"
FT VARIANT 235
FT /note="N -> S (in dbSNP:rs2270004)"
FT /id="VAR_034527"
FT VARIANT 279
FT /note="S -> L (in DEE75; unknown pathological significance;
FT dbSNP:rs730882153)"
FT /evidence="ECO:0000269|PubMed:25629079"
FT /id="VAR_082620"
FT VARIANT 364
FT /note="P -> R (in DEE75; unknown pathological significance;
FT dbSNP:rs35201073)"
FT /evidence="ECO:0000269|PubMed:29410512"
FT /id="VAR_082621"
SQ SEQUENCE 475 AA; 53263 MW; E3B1B07CB6225BA2 CRC64;
MEGLLTRCRA LPALATCSRQ LSGYVPCRFH HCAPRRGRRL LLSRVFQPQN LREDRVLSLQ
DKSDDLTCKS QRLMLQVGLI YPASPGCYHL LPYTVRAMEK LVRVIDQEMQ AIGGQKVNMP
SLSPAELWQA TNRWDLMGKE LLRLRDRHGK EYCLGPTHEE AITALIASQK KLSYKQLPFL
LYQVTRKFRD EPRPRFGLLR GREFYMKDMY TFDSSPEAAQ QTYSLVCDAY CSLFNKLGLP
FVKVQADVGT IGGTVSHEFQ LPVDIGEDRL AICPRCSFSA NMETLDLSQM NCPACQGPLT
KTKGIEVGHT FYLGTKYSSI FNAQFTNVCG KPTLAEMGCY GLGVTRILAA AIEVLSTEDC
VRWPSLLAPY QACLIPPKKG SKEQAASELI GQLYDHITEA VPQLHGEVLL DDRTHLTIGN
RLKDANKFGY PFVIIAGKRA LEDPAHFEVW CQNTGEVAFL TKDGVMDLLT PVQTV
