SYSM_HUMAN
ID SYSM_HUMAN Reviewed; 518 AA.
AC Q9NP81; A6NHW7; B4DE10; Q9BVP3;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Serine--tRNA ligase, mitochondrial;
DE EC=6.1.1.11;
DE AltName: Full=SerRSmt;
DE AltName: Full=Seryl-tRNA synthetase;
DE Short=SerRS;
DE AltName: Full=Seryl-tRNA(Ser/Sec) synthetase;
DE Flags: Precursor;
GN Name=SARS2; Synonyms=SARSM;
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 1).
RX PubMed=10764807; DOI=10.1074/jbc.m908473199;
RA Yokogawa T., Shimada N., Takeuchi N., Benkowski L., Suzuki T., Omori A.,
RA Ueda T., Nishikawa K., Spremulli L.L., Watanabe K.;
RT "Characterization and tRNA recognition of mammalian mitochondrial seryl-
RT tRNA synthetase.";
RL J. Biol. Chem. 275:19913-19920(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Eye;
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 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 [6]
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 [7]
RP VARIANT HUPRAS GLY-390.
RX PubMed=21255763; DOI=10.1016/j.ajhg.2010.12.010;
RA Belostotsky R., Ben-Shalom E., Rinat C., Becker-Cohen R., Feinstein S.,
RA Zeligson S., Segel R., Elpeleg O., Nassar S., Frishberg Y.;
RT "Mutations in the mitochondrial seryl-tRNA synthetase cause hyperuricemia,
RT pulmonary hypertension, renal failure in infancy and alkalosis, HUPRA
RT syndrome.";
RL Am. J. Hum. Genet. 88:193-200(2011).
CC -!- FUNCTION: Catalyzes the attachment of serine to tRNA(Ser). Is also
CC probably able to aminoacylate tRNA(Sec) with serine, to form the
CC misacylated tRNA L-seryl-tRNA(Sec), which will be further converted
CC into selenocysteinyl-tRNA(Sec). {ECO:0000250|UniProtKB:Q9N0F3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-serine + tRNA(Ser) = AMP + diphosphate + H(+) + L-
CC seryl-tRNA(Ser); Xref=Rhea:RHEA:12292, Rhea:RHEA-COMP:9669,
CC Rhea:RHEA-COMP:9703, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:33384, ChEBI:CHEBI:78442,
CC ChEBI:CHEBI:78533, ChEBI:CHEBI:456215; EC=6.1.1.11;
CC Evidence={ECO:0000250|UniProtKB:Q9N0F3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-serine + tRNA(Sec) = AMP + diphosphate + H(+) + L-
CC seryl-tRNA(Sec); Xref=Rhea:RHEA:42580, Rhea:RHEA-COMP:9742,
CC Rhea:RHEA-COMP:10128, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:33384, ChEBI:CHEBI:78442,
CC ChEBI:CHEBI:78533, ChEBI:CHEBI:456215; EC=6.1.1.11;
CC Evidence={ECO:0000250|UniProtKB:Q9N0F3};
CC -!- PATHWAY: Aminoacyl-tRNA biosynthesis; selenocysteinyl-tRNA(Sec)
CC biosynthesis; L-seryl-tRNA(Sec) from L-serine and tRNA(Sec): step 1/1.
CC -!- SUBUNIT: Homodimer. The tRNA molecule probably binds across the dimer.
CC {ECO:0000250|UniProtKB:Q9N0F3}.
CC -!- INTERACTION:
CC Q9NP81; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-1049768, EBI-741158;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q9N0F3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NP81-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NP81-2; Sequence=VSP_043020;
CC -!- DOMAIN: Consists of two distinct domains, a catalytic core and a N-
CC terminal extension that is involved in tRNA binding.
CC {ECO:0000250|UniProtKB:Q9N0F3}.
CC -!- DISEASE: Hyperuricemia, pulmonary hypertension, renal failure, and
CC alkalosis syndrome (HUPRAS) [MIM:613845]: A multisystem disorder
CC characterized by onset in infancy of progressive renal failure leading
CC to electrolyte imbalances, metabolic alkalosis, pulmonary hypertension,
CC hypotonia, and delayed development. Affected individuals are born
CC prematurely. {ECO:0000269|PubMed:21255763}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC Type-1 seryl-tRNA synthetase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH01020.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB029948; BAA99557.1; -; mRNA.
DR EMBL; AK000457; BAA91176.1; -; mRNA.
DR EMBL; AK293414; BAG56921.1; -; mRNA.
DR EMBL; AC011455; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001020; AAH01020.2; ALT_INIT; mRNA.
DR EMBL; BC042912; AAH42912.1; -; mRNA.
DR CCDS; CCDS33017.1; -. [Q9NP81-1]
DR CCDS; CCDS54265.1; -. [Q9NP81-2]
DR RefSeq; NP_001139373.1; NM_001145901.1. [Q9NP81-2]
DR RefSeq; NP_060297.1; NM_017827.3. [Q9NP81-1]
DR AlphaFoldDB; Q9NP81; -.
DR SMR; Q9NP81; -.
DR BioGRID; 120278; 76.
DR IntAct; Q9NP81; 30.
DR MINT; Q9NP81; -.
DR STRING; 9606.ENSP00000472847; -.
DR GlyGen; Q9NP81; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NP81; -.
DR PhosphoSitePlus; Q9NP81; -.
DR BioMuta; SARS2; -.
DR DMDM; 23822219; -.
DR EPD; Q9NP81; -.
DR jPOST; Q9NP81; -.
DR MassIVE; Q9NP81; -.
DR MaxQB; Q9NP81; -.
DR PaxDb; Q9NP81; -.
DR PeptideAtlas; Q9NP81; -.
DR PRIDE; Q9NP81; -.
DR Antibodypedia; 30224; 134 antibodies from 26 providers.
DR DNASU; 54938; -.
DR Ensembl; ENST00000221431.11; ENSP00000221431.6; ENSG00000104835.15. [Q9NP81-1]
DR Ensembl; ENST00000600042.5; ENSP00000472847.1; ENSG00000104835.15. [Q9NP81-2]
DR Ensembl; ENST00000634687.3; ENSP00000489539.1; ENSG00000283104.3. [Q9NP81-1]
DR Ensembl; ENST00000635245.1; ENSP00000489453.1; ENSG00000283104.3. [Q9NP81-2]
DR GeneID; 54938; -.
DR KEGG; hsa:54938; -.
DR MANE-Select; ENST00000221431.11; ENSP00000221431.6; NM_017827.4; NP_060297.1.
DR UCSC; uc002oka.3; human. [Q9NP81-1]
DR CTD; 54938; -.
DR DisGeNET; 54938; -.
DR GeneCards; SARS2; -.
DR HGNC; HGNC:17697; SARS2.
DR HPA; ENSG00000104835; Low tissue specificity.
DR MalaCards; SARS2; -.
DR MIM; 612804; gene.
DR MIM; 613845; phenotype.
DR neXtProt; NX_Q9NP81; -.
DR OpenTargets; ENSG00000104835; -.
DR Orphanet; 363694; Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome.
DR PharmGKB; PA134899753; -.
DR VEuPathDB; HostDB:ENSG00000104835; -.
DR eggNOG; KOG2509; Eukaryota.
DR GeneTree; ENSGT00940000153792; -.
DR HOGENOM; CLU_023797_4_1_1; -.
DR InParanoid; Q9NP81; -.
DR OrthoDB; 726296at2759; -.
DR PhylomeDB; Q9NP81; -.
DR BRENDA; 6.1.1.11; 2681.
DR PathwayCommons; Q9NP81; -.
DR Reactome; R-HSA-379726; Mitochondrial tRNA aminoacylation.
DR SignaLink; Q9NP81; -.
DR UniPathway; UPA00906; UER00895.
DR BioGRID-ORCS; 54938; 443 hits in 1073 CRISPR screens.
DR ChiTaRS; SARS2; human.
DR GeneWiki; SARS2; -.
DR GenomeRNAi; 54938; -.
DR Pharos; Q9NP81; Tbio.
DR PRO; PR:Q9NP81; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9NP81; protein.
DR Bgee; ENSG00000104835; Expressed in apex of heart and 93 other tissues.
DR ExpressionAtlas; Q9NP81; baseline and differential.
DR Genevisible; Q9NP81; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0004828; F:serine-tRNA ligase activity; ISS:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IBA:GO_Central.
DR GO; GO:0070158; P:mitochondrial seryl-tRNA aminoacylation; IBA:GO_Central.
DR GO; GO:0097056; P:selenocysteinyl-tRNA(Sec) biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006434; P:seryl-tRNA aminoacylation; ISS:UniProtKB.
DR CDD; cd00770; SerRS_core; 1.
DR Gene3D; 1.10.287.40; -; 1.
DR Gene3D; 3.30.930.10; -; 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; IPR002317; Ser-tRNA-ligase_type_1.
DR InterPro; IPR042103; SerRS_1_N_sf.
DR InterPro; IPR033729; SerRS_core.
DR InterPro; IPR010978; tRNA-bd_arm.
DR PANTHER; PTHR11778; PTHR11778; 1.
DR Pfam; PF00587; tRNA-synt_2b; 1.
DR PIRSF; PIRSF001529; Ser-tRNA-synth_IIa; 1.
DR PRINTS; PR00981; TRNASYNTHSER.
DR SUPFAM; SSF46589; SSF46589; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00414; serS; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding;
KW Ligase; Mitochondrion; Nucleotide-binding; Protein biosynthesis;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..34
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:Q9N0F3"
FT CHAIN 35..518
FT /note="Serine--tRNA ligase, mitochondrial"
FT /id="PRO_0000035822"
FT REGION 498..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 299..301
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000250|UniProtKB:Q9N0F3"
FT BINDING 330..332
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9N0F3"
FT BINDING 345
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9N0F3"
FT BINDING 352
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000250|UniProtKB:Q9N0F3"
FT BINDING 418..421
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9N0F3"
FT BINDING 453
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000250|UniProtKB:Q9N0F3"
FT MOD_RES 110
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JJL8"
FT MOD_RES 195
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JJL8"
FT VAR_SEQ 132..155
FT /note="DPKYQGLRARGREIRKELVHLYPR -> VRLDPGAGSIFGPTFLPFPGQLSL
FT LV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043020"
FT VARIANT 35
FT /note="T -> A (in dbSNP:rs34264048)"
FT /id="VAR_052645"
FT VARIANT 83
FT /note="S -> L (in dbSNP:rs34050897)"
FT /id="VAR_052646"
FT VARIANT 390
FT /note="D -> G (in HUPRAS; dbSNP:rs727502784)"
FT /evidence="ECO:0000269|PubMed:21255763"
FT /id="VAR_065820"
SQ SEQUENCE 518 AA; 58283 MW; C6516A9527B34EB7 CRC64;
MAASMARRLW PLLTRRGFRP RGGCISNDSP RRSFTTEKRN RNLLYEYARE GYSALPQLDI
ERFCACPEEA AHALELRKGE LRSADLPAII STWQELRQLQ EQIRSLEEEK AAVTEAVRAL
LANQDSGEVQ QDPKYQGLRA RGREIRKELV HLYPREAQLE EQFYLQALKL PNQTHPDVPV
GDESQARVLH MVGDKPVFSF QPRGHLEIGE KLDIIRQKRL SHVSGHRSYY LRGAGALLQH
GLVNFTFNKL LRRGFTPMTV PDLLRGAVFE GCGMTPNANP SQIYNIDPAR FKDLNLAGTA
EVGLAGYFMD HTVAFRDLPV RMVCSSTCYR AETNTGQEPR GLYRVHHFTK VEMFGVTGPG
LEQSSQLLEE FLSLQMEILT ELGLHFRVLD MPTQELGLPA YRKFDIEAWM PGRGRFGEVT
SASNCTDFQS RRLHIMFQTE AGELQFAHTV NATACAVPRL LIALLESNQQ KDGSVLVPPA
LQSYLGTDRI TAPTHVPLQY IGPNQPRKPG LPGQPAVS
