SYDC_HUMAN
ID SYDC_HUMAN Reviewed; 501 AA.
AC P14868; A8K3J2; D3DP77; Q2TNI3; Q32Q69; Q53HV4; Q53YC5; Q68CR9; Q9BW52;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 2.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Aspartate--tRNA ligase, cytoplasmic {ECO:0000305};
DE EC=6.1.1.12 {ECO:0000250|UniProtKB:P15178};
DE AltName: Full=Aspartyl-tRNA synthetase;
DE Short=AspRS;
DE AltName: Full=Cell proliferation-inducing gene 40 protein;
GN Name=DARS1 {ECO:0000312|HGNC:HGNC:2678}; Synonyms=DARS; ORFNames=PIG40;
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=2674137; DOI=10.1016/s0021-9258(19)84749-x;
RA Jacobo-Molina A., Peterson R., Yang D.C.H.;
RT "cDNA sequence, predicted primary structure, and evolving amphiphilic helix
RT of human aspartyl-tRNA synthetase.";
RL J. Biol. Chem. 264:16608-16612(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kim J.W.;
RT "Identification of a cell proliferation-inducing gene.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Heart;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Adipose tissue;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Embryo;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [10]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [11]
RP INTERACTION WITH KARS1.
RX PubMed=18029264; DOI=10.1016/j.bbrc.2007.11.028;
RA Guzzo C.M., Yang D.C.H.;
RT "Lysyl-tRNA synthetase interacts with EF1alpha, aspartyl-tRNA synthetase
RT and p38 in vitro.";
RL Biochem. Biophys. Res. Commun. 365:718-723(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19131329; DOI=10.1074/jbc.m809636200;
RA Kaminska M., Havrylenko S., Decottignies P., Gillet S., Le Marechal P.,
RA Negrutskii B., Mirande M.;
RT "Dissection of the structural organization of the aminoacyl-tRNA synthetase
RT complex.";
RL J. Biol. Chem. 284:6053-6060(2009).
RN [14]
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=19289464; DOI=10.1074/jbc.m900480200;
RA Kaminska M., Havrylenko S., Decottignies P., Le Marechal P., Negrutskii B.,
RA Mirande M.;
RT "Dynamic Organization of Aminoacyl-tRNA Synthetase Complexes in the
RT Cytoplasm of Human Cells.";
RL J. Biol. Chem. 284:13746-13754(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-74 AND LYS-374, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP TISSUE SPECIFICITY, AND VARIANTS HBSL LEU-256; VAL-274; TYR-367; HIS-460;
RP LEU-464; CYS-487; CYS-494 AND GLY-494.
RX PubMed=23643384; DOI=10.1016/j.ajhg.2013.04.006;
RA Taft R.J., Vanderver A., Leventer R.J., Damiani S.A., Simons C.,
RA Grimmond S.M., Miller D., Schmidt J., Lockhart P.J., Pope K., Ru K.,
RA Crawford J., Rosser T., de Coo I.F., Juneja M., Verma I.C., Prabhakar P.,
RA Blaser S., Raiman J., Pouwels P.J., Bevova M.R., Abbink T.E.,
RA van der Knaap M.S., Wolf N.I.;
RT "Mutations in DARS cause hypomyelination with brain stem and spinal cord
RT involvement and leg spasticity.";
RL Am. J. Hum. Genet. 92:774-780(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-52 AND SER-249, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [20]
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 [21]
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 [22] {ECO:0007744|PDB:4J15}
RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS), AND SUBUNIT.
RX PubMed=23609930; DOI=10.1002/prot.24306;
RA Kim K.R., Park S.H., Kim H.S., Rhee K.H., Kim B.G., Kim D.G., Park M.S.,
RA Kim H.J., Kim S., Han B.W.;
RT "Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component
RT of multi-tRNA synthetase complex.";
RL Proteins 81:1840-1846(2013).
CC -!- FUNCTION: Catalyzes the specific attachment of an amino acid to its
CC cognate tRNA in a 2 step reaction: the amino acid (AA) is first
CC activated by ATP to form AA-AMP and then transferred to the acceptor
CC end of the tRNA. {ECO:0000250|UniProtKB:P15178}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-aspartate + tRNA(Asp) = AMP + diphosphate + L-
CC aspartyl-tRNA(Asp); Xref=Rhea:RHEA:19649, Rhea:RHEA-COMP:9660,
CC Rhea:RHEA-COMP:9678, ChEBI:CHEBI:29991, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:78442, ChEBI:CHEBI:78516,
CC ChEBI:CHEBI:456215; EC=6.1.1.12;
CC Evidence={ECO:0000250|UniProtKB:P15178};
CC -!- SUBUNIT: Homodimer (PubMed:23609930). Part of a multisubunit complex
CC that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile
CC (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase
CC for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38
CC and EEF1E1/p18 (PubMed:19131329, PubMed:19289464).
CC {ECO:0000269|PubMed:19131329, ECO:0000269|PubMed:19289464,
CC ECO:0000269|PubMed:23609930}.
CC -!- INTERACTION:
CC P14868; Q13155: AIMP2; NbExp=10; IntAct=EBI-358730, EBI-745226;
CC P14868; Q08050: FOXM1; NbExp=2; IntAct=EBI-358730, EBI-866480;
CC P14868; P62993: GRB2; NbExp=2; IntAct=EBI-358730, EBI-401755;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:19289464}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P14868-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P14868-2; Sequence=VSP_056192;
CC -!- TISSUE SPECIFICITY: Expression in the developing and adult brain shows
CC similar patterns. Highly expressed in the ventricular and
CC subventricular zones, including hippocampal subfields, the midlateral
CC temporal cortex and the frontal polar cortex. The cerebellum, cerebral
CC cortex, hippocampus, and lateral ventricle show preferential neuronal
CC expression. Expression in the peripheral neurons is evident in the
CC colon. {ECO:0000269|PubMed:23643384}.
CC -!- DISEASE: Hypomyelination with brainstem and spinal cord involvement and
CC leg spasticity (HBSL) [MIM:615281]: An autosomal recessive
CC leukoencephalopathy characterized by onset in the first year of life of
CC severe spasticity, mainly affecting the lower limbs and resulting in an
CC inability to achieve independent ambulation. Affected individuals show
CC delayed motor development and nystagmus; some may have mild
CC intellectual disability. Brain MRI shows hypomyelination and white
CC matter lesions in the cerebrum, brainstem, cerebellum, and spinal cord.
CC {ECO:0000269|PubMed:23643384}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC Type 2 subfamily. {ECO:0000305}.
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DR EMBL; J05032; AAA35567.1; -; mRNA.
DR EMBL; AY762100; AAX07827.1; -; mRNA.
DR EMBL; BT006710; AAP35356.1; -; mRNA.
DR EMBL; AK290607; BAF83296.1; -; mRNA.
DR EMBL; AK222476; BAD96196.1; -; mRNA.
DR EMBL; CR749809; CAH18669.1; -; mRNA.
DR EMBL; AC011999; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093391; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471058; EAX11617.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11620.1; -; Genomic_DNA.
DR EMBL; BC000629; AAH00629.1; -; mRNA.
DR EMBL; BC107749; AAI07750.1; -; mRNA.
DR CCDS; CCDS2180.1; -. [P14868-1]
DR PIR; A34393; SYHUDT.
DR RefSeq; NP_001280241.1; NM_001293312.1. [P14868-2]
DR RefSeq; NP_001340.2; NM_001349.3. [P14868-1]
DR PDB; 4J15; X-ray; 2.24 A; A/B=1-501.
DR PDB; 5Y6L; X-ray; 2.90 A; E=1-501.
DR PDB; 6IY6; X-ray; 3.60 A; A/B/G/H=21-501.
DR PDBsum; 4J15; -.
DR PDBsum; 5Y6L; -.
DR PDBsum; 6IY6; -.
DR AlphaFoldDB; P14868; -.
DR BMRB; P14868; -.
DR SMR; P14868; -.
DR BioGRID; 107984; 258.
DR CORUM; P14868; -.
DR IntAct; P14868; 57.
DR MINT; P14868; -.
DR STRING; 9606.ENSP00000264161; -.
DR DrugBank; DB00128; Aspartic acid.
DR DrugCentral; P14868; -.
DR GlyGen; P14868; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P14868; -.
DR MetOSite; P14868; -.
DR PhosphoSitePlus; P14868; -.
DR SwissPalm; P14868; -.
DR BioMuta; DARS; -.
DR DMDM; 20178330; -.
DR OGP; P14868; -.
DR REPRODUCTION-2DPAGE; IPI00216951; -.
DR EPD; P14868; -.
DR jPOST; P14868; -.
DR MassIVE; P14868; -.
DR MaxQB; P14868; -.
DR PaxDb; P14868; -.
DR PeptideAtlas; P14868; -.
DR PRIDE; P14868; -.
DR ProteomicsDB; 53092; -. [P14868-1]
DR ProteomicsDB; 66028; -.
DR ABCD; P14868; 1 sequenced antibody.
DR Antibodypedia; 18737; 211 antibodies from 31 providers.
DR DNASU; 1615; -.
DR Ensembl; ENST00000264161.9; ENSP00000264161.4; ENSG00000115866.11. [P14868-1]
DR GeneID; 1615; -.
DR KEGG; hsa:1615; -.
DR MANE-Select; ENST00000264161.9; ENSP00000264161.4; NM_001349.4; NP_001340.2.
DR UCSC; uc002tux.2; human. [P14868-1]
DR CTD; 1615; -.
DR DisGeNET; 1615; -.
DR GeneCards; DARS1; -.
DR HGNC; HGNC:2678; DARS1.
DR HPA; ENSG00000115866; Low tissue specificity.
DR MalaCards; DARS1; -.
DR MIM; 603084; gene.
DR MIM; 615281; phenotype.
DR neXtProt; NX_P14868; -.
DR OpenTargets; ENSG00000115866; -.
DR Orphanet; 363412; Hypomyelination with brain stem and spinal cord involvement and leg spasticity.
DR PharmGKB; PA27146; -.
DR VEuPathDB; HostDB:ENSG00000115866; -.
DR eggNOG; KOG0556; Eukaryota.
DR GeneTree; ENSGT01030000234618; -.
DR HOGENOM; CLU_004553_2_1_1; -.
DR InParanoid; P14868; -.
DR OMA; WVHEIRD; -.
DR PhylomeDB; P14868; -.
DR TreeFam; TF105676; -.
DR BRENDA; 6.1.1.12; 2681.
DR PathwayCommons; P14868; -.
DR Reactome; R-HSA-2408522; Selenoamino acid metabolism.
DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation.
DR SignaLink; P14868; -.
DR BioGRID-ORCS; 1615; 795 hits in 1060 CRISPR screens.
DR ChiTaRS; DARS; human.
DR GeneWiki; DARS_(gene); -.
DR GenomeRNAi; 1615; -.
DR Pharos; P14868; Tbio.
DR PRO; PR:P14868; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P14868; protein.
DR Bgee; ENSG00000115866; Expressed in oocyte and 213 other tissues.
DR ExpressionAtlas; P14868; baseline and differential.
DR Genevisible; P14868; HS.
DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0004046; F:aminoacylase activity; TAS:ProtInc.
DR GO; GO:0004815; F:aspartate-tRNA ligase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0006422; P:aspartyl-tRNA aminoacylation; IBA:GO_Central.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR GO; GO:0006412; P:translation; TAS:ProtInc.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR HAMAP; MF_02075; Asp_tRNA_synth_type2; 1.
DR InterPro; IPR004364; Aa-tRNA-synt_II.
DR InterPro; IPR006195; aa-tRNA-synth_II.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR004523; Asp-tRNA_synthase_2.
DR InterPro; IPR002312; Asp/Asn-tRNA-synth_IIb.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR004365; NA-bd_OB_tRNA.
DR PANTHER; PTHR43450; PTHR43450; 1.
DR Pfam; PF00152; tRNA-synt_2; 1.
DR Pfam; PF01336; tRNA_anti-codon; 1.
DR PRINTS; PR01042; TRNASYNTHASP.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00458; aspS_nondisc; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase;
KW ATP-binding; Cytoplasm; Disease variant; Ligase; Nucleotide-binding;
KW Phosphoprotein; Protein biosynthesis; Reference proteome.
FT CHAIN 1..501
FT /note="Aspartate--tRNA ligase, cytoplasmic"
FT /id="PRO_0000111010"
FT REGION 251..254
FT /note="Aspartate"
FT /evidence="ECO:0000250"
FT REGION 411..415
FT /note="Binding site for the 3'-end of tRNA"
FT /evidence="ECO:0000255"
FT BINDING 229
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250"
FT BINDING 273..275
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 273
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250"
FT BINDING 281..283
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 424
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 427
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250"
FT BINDING 431
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250"
FT BINDING 472..475
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 52
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 74
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 374
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 500
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_056192"
FT VARIANT 256
FT /note="M -> L (in HBSL; dbSNP:rs886037635)"
FT /evidence="ECO:0000269|PubMed:23643384"
FT /id="VAR_070038"
FT VARIANT 274
FT /note="A -> V (in HBSL; dbSNP:rs369152939)"
FT /evidence="ECO:0000269|PubMed:23643384"
FT /id="VAR_070039"
FT VARIANT 367
FT /note="D -> Y (in HBSL; dbSNP:rs370064817)"
FT /evidence="ECO:0000269|PubMed:23643384"
FT /id="VAR_070040"
FT VARIANT 426
FT /note="L -> F (in dbSNP:rs1803165)"
FT /id="VAR_027611"
FT VARIANT 460
FT /note="R -> H (in HBSL; dbSNP:rs587776985)"
FT /evidence="ECO:0000269|PubMed:23643384"
FT /id="VAR_070041"
FT VARIANT 464
FT /note="P -> L (in HBSL; dbSNP:rs148806569)"
FT /evidence="ECO:0000269|PubMed:23643384"
FT /id="VAR_070042"
FT VARIANT 487
FT /note="R -> C (in HBSL; dbSNP:rs587776984)"
FT /evidence="ECO:0000269|PubMed:23643384"
FT /id="VAR_070043"
FT VARIANT 494
FT /note="R -> C (in HBSL; dbSNP:rs147077598)"
FT /evidence="ECO:0000269|PubMed:23643384"
FT /id="VAR_070044"
FT VARIANT 494
FT /note="R -> G (in HBSL; dbSNP:rs147077598)"
FT /evidence="ECO:0000269|PubMed:23643384"
FT /id="VAR_070045"
FT CONFLICT 5..7
FT /note="SAS -> TQ (in Ref. 1; AAA35567)"
FT /evidence="ECO:0000305"
FT CONFLICT 31
FT /note="I -> T (in Ref. 9; AAI07750)"
FT /evidence="ECO:0000305"
FT CONFLICT 38
FT /note="Q -> H (in Ref. 5; BAD96196)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="A -> Q (in Ref. 1; AAA35567)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="Q -> H (in Ref. 2; AAX07827)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="N -> K (in Ref. 1; AAA35567)"
FT /evidence="ECO:0000305"
FT CONFLICT 447
FT /note="I -> N (in Ref. 1; AAA35567)"
FT /evidence="ECO:0000305"
FT HELIX 26..28
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 59..72
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 75..82
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 85..93
FT /evidence="ECO:0007829|PDB:4J15"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 99..107
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 113..122
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 134..146
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 156..160
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 176..181
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 183..186
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 190..212
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 250..259
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 264..271
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 286..294
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 300..320
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 322..331
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:5Y6L"
FT STRAND 344..347
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 348..357
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 370..384
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 387..392
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 396..398
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 407..409
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 412..420
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 423..431
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 435..444
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 450..452
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 453..457
FT /evidence="ECO:0007829|PDB:4J15"
FT TURN 458..461
FT /evidence="ECO:0007829|PDB:4J15"
FT STRAND 466..472
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 473..481
FT /evidence="ECO:0007829|PDB:4J15"
FT HELIX 486..489
FT /evidence="ECO:0007829|PDB:4J15"
SQ SEQUENCE 501 AA; 57136 MW; B181572DF0AF5F94 CRC64;
MPSASASRKS QEKPREIMDA AEDYAKERYG ISSMIQSQEK PDRVLVRVRD LTIQKADEVV
WVRARVHTSR AKGKQCFLVL RQQQFNVQAL VAVGDHASKQ MVKFAANINK ESIVDVEGVV
RKVNQKIGSC TQQDVELHVQ KIYVISLAEP RLPLQLDDAV RPEAEGEEEG RATVNQDTRL
DNRVIDLRTS TSQAVFRLQS GICHLFRETL INKGFVEIQT PKIISAASEG GANVFTVSYF
KNNAYLAQSP QLYKQMCICA DFEKVFSIGP VFRAEDSNTH RHLTEFVGLD IEMAFNYHYH
EVMEEIADTM VQIFKGLQER FQTEIQTVNK QFPCEPFKFL EPTLRLEYCE ALAMLREAGV
EMGDEDDLST PNEKLLGHLV KEKYDTDFYI LDKYPLAVRP FYTMPDPRNP KQSNSYDMFM
RGEEILSGAQ RIHDPQLLTE RALHHGIDLE KIKAYIDSFR FGAPPHAGGG IGLERVTMLF
LGLHNVRQTS MFPRDPKRLT P
