Q9NP81 (SYSM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine--tRNA ligase, mitochondrial
EC=6.1.1.11

Alternative name(s):
SerRSmt
Seryl-tRNA synthetase
Short name=SerRS
Seryl-tRNA(Ser/Sec) synthetase

Gene names

Name:	SARS2
Synonyms:	SARSM

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	518 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the attachment of serine to tRNA(Ser). Is also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) By similarity.
Catalytic activity	ATP + L-serine + tRNA(Ser) = AMP + diphosphate + L-seryl-tRNA(Ser). ATP + L-serine + tRNA(Sec) = AMP + diphosphate + L-seryl-tRNA(Sec).
Pathway	Aminoacyl-tRNA biosynthesis; selenocysteinyl-tRNA(Sec) biosynthesis; L-seryl-tRNA(Sec) from L-serine and tRNA(Sec): step 1/1.
Subunit structure	Homodimer. The tRNA molecule binds across the dimer By similarity.
Subcellular location	Mitochondrion matrix By similarity.
Domain	Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding By similarity.
Involvement in disease	Hyperuricemia pulmonary hypertension renal failure and alkalosis (HUPRA) [MIM:613845]: A multisystem disorder characterized by onset in infancy of progressive renal failure leading to electrolyte imbalances, metabolic alkalosis, pulmonary hypertension, hypotonia, and delayed development. Affected individuals are born prematurely. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.
Sequence caution	The sequence AAH01020.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Aminoacyl-tRNA synthetase Ligase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	selenocysteinyl-tRNA(Sec) biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway seryl-tRNA aminoacylation Inferred from sequence or structural similarity Ref.1. Source: UniProtKB
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from sequence or structural similarity Ref.1. Source: UniProtKB serine-tRNA ligase activity Inferred from sequence or structural similarity Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NP81-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9NP81-2)

The sequence of this isoform differs from the canonical sequence as follows:
     132-155: DPKYQGLRARGREIRKELVHLYPR → VRLDPGAGSIFGPTFLPFPGQLSLLV

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 34	34	Mitochondrion By similarity
	Chain	35 – 518	484	Serine--tRNA ligase, mitochondrial		PRO_0000035822
Regions
	Nucleotide binding	330 – 332	3	ATP By similarity
	Nucleotide binding	418 – 421	4	ATP By similarity
	Region	299 – 301	3	Serine binding By similarity
Sites
	Binding site	345	1	ATP; via amide nitrogen and carbonyl oxygen By similarity
	Binding site	352	1	Serine By similarity
	Binding site	453	1	Serine By similarity
Amino acid modifications
	Modified residue	110	1	N6-acetyllysine Ref.5
Natural variations
	Alternative sequence	132 – 155	24	DPKYQ…HLYPR → VRLDPGAGSIFGPTFLPFPG QLSLLV in isoform 2.		VSP_043020
	Natural variant	35	1	T → A. Corresponds to variant rs34264048 [ dbSNP | Ensembl ].		VAR_052645
	Natural variant	83	1	S → L. Corresponds to variant rs34050897 [ dbSNP | Ensembl ].		VAR_052646
	Natural variant	390	1	D → G in HUPRA. Ref.7		VAR_065820

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: C6516A9527B34EB7	FASTA	518	58,283
	10 20 30 40 50 60 MAASMARRLW PLLTRRGFRP RGGCISNDSP RRSFTTEKRN RNLLYEYARE GYSALPQLDI 70 80 90 100 110 120 ERFCACPEEA AHALELRKGE LRSADLPAII STWQELRQLQ EQIRSLEEEK AAVTEAVRAL 130 140 150 160 170 180 LANQDSGEVQ QDPKYQGLRA RGREIRKELV HLYPREAQLE EQFYLQALKL PNQTHPDVPV 190 200 210 220 230 240 GDESQARVLH MVGDKPVFSF QPRGHLEIGE KLDIIRQKRL SHVSGHRSYY LRGAGALLQH 250 260 270 280 290 300 GLVNFTFNKL LRRGFTPMTV PDLLRGAVFE GCGMTPNANP SQIYNIDPAR FKDLNLAGTA 310 320 330 340 350 360 EVGLAGYFMD HTVAFRDLPV RMVCSSTCYR AETNTGQEPR GLYRVHHFTK VEMFGVTGPG 370 380 390 400 410 420 LEQSSQLLEE FLSLQMEILT ELGLHFRVLD MPTQELGLPA YRKFDIEAWM PGRGRFGEVT 430 440 450 460 470 480 SASNCTDFQS RRLHIMFQTE AGELQFAHTV NATACAVPRL LIALLESNQQ KDGSVLVPPA 490 500 510 LQSYLGTDRI TAPTHVPLQY IGPNQPRKPG LPGQPAVS
	Isoform 2 [UniParc]. Checksum: 1CB28DA9FBFEED8D	FASTA	520	58,030
	10 20 30 40 50 60 MAASMARRLW PLLTRRGFRP RGGCISNDSP RRSFTTEKRN RNLLYEYARE GYSALPQLDI 70 80 90 100 110 120 ERFCACPEEA AHALELRKGE LRSADLPAII STWQELRQLQ EQIRSLEEEK AAVTEAVRAL 130 140 150 160 170 180 LANQDSGEVQ QVRLDPGAGS IFGPTFLPFP GQLSLLVEAQ LEEQFYLQAL KLPNQTHPDV 190 200 210 220 230 240 PVGDESQARV LHMVGDKPVF SFQPRGHLEI GEKLDIIRQK RLSHVSGHRS YYLRGAGALL 250 260 270 280 290 300 QHGLVNFTFN KLLRRGFTPM TVPDLLRGAV FEGCGMTPNA NPSQIYNIDP ARFKDLNLAG 310 320 330 340 350 360 TAEVGLAGYF MDHTVAFRDL PVRMVCSSTC YRAETNTGQE PRGLYRVHHF TKVEMFGVTG 370 380 390 400 410 420 PGLEQSSQLL EEFLSLQMEI LTELGLHFRV LDMPTQELGL PAYRKFDIEA WMPGRGRFGE 430 440 450 460 470 480 VTSASNCTDF QSRRLHIMFQ TEAGELQFAH TVNATACAVP RLLIALLESN QQKDGSVLVP 490 500 510 520 PALQSYLGTD RITAPTHVPL QYIGPNQPRK PGLPGQPAVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization and tRNA recognition of mammalian mitochondrial seryl-tRNA synthetase." Yokogawa T., Shimada N., Takeuchi N., Benkowski L., Suzuki T., Omori A., Ueda T., Nishikawa K., Spremulli L.L., Watanabe K. J. Biol. Chem. 275:19913-19920(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Eye.
[5]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-110, MASS SPECTROMETRY.
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"Mutations in the mitochondrial seryl-tRNA synthetase cause hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis, HUPRA syndrome." Belostotsky R., Ben-Shalom E., Rinat C., Becker-Cohen R., Feinstein S., Zeligson S., Segel R., Elpeleg O., Nassar S., Frishberg Y. Am. J. Hum. Genet. 88:193-200(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HUPRA GLY-390.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB029948 mRNA. Translation: BAA99557.1. AK000457 mRNA. Translation: BAA91176.1. AK293414 mRNA. Translation: BAG56921.1. AC011455 Genomic DNA. No translation available. BC001020 mRNA. Translation: AAH01020.2. Different initiation. BC042912 mRNA. Translation: AAH42912.1.
IPI	IPI00328361. IPI00927163.
RefSeq	NP_001139373.1. NM_001145901.1. NP_060297.1. NM_017827.3.
UniGene	Hs.709416.
3D structure databases
ProteinModelPortal	Q9NP81.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NP81. 5 interactions.
PTM databases
PhosphoSite	Q9NP81.
Polymorphism databases
DMDM	23822219.
Proteomic databases
PRIDE	Q9NP81.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000221431; ENSP00000221431; ENSG00000104835. ENST00000600042; ENSP00000472847; ENSG00000104835.
GeneID	54938.
KEGG	hsa:54938.
UCSC	uc002ojz.2. human.
Organism-specific databases
CTD	54938.
GeneCards	GC19M039405.
HGNC	HGNC:17697. SARS2.
MIM	612804. gene. 613845. phenotype.
neXtProt	NX_Q9NP81.
PharmGKB	PA134899753.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HOG000035937.
HOVERGEN	HBG023869.
InParanoid	Q9NP81.
KO	K01875.
Enzyme and pathway databases
BRENDA	6.1.1.11. 2681.
Reactome	REACT_71. Gene Expression.
UniPathway	UPA00906; UER00895.
Gene expression databases
ArrayExpress	Q9NP81.
Bgee	Q9NP81.
CleanEx	HS_SARS2.
Genevestigator	Q9NP81.
GermOnline	ENSG00000104835. Homo sapiens.
Family and domain databases
Gene3D	1.10.287.40. 1 hit.
InterPro	IPR002314. aa-tRNA-synt_IIb_cons-dom. IPR006195. aa-tRNA-synth_II. IPR002317. Ser-tRNA-ligase_type_1. IPR015866. Ser-tRNA-synth_1_N. IPR010978. tRNA-bd_arm. [Graphical view]
PANTHER	PTHR11778. PTHR11778. 1 hit.
Pfam	PF00587. tRNA-synt_2b. 1 hit. [Graphical view]
PIRSF	PIRSF001529. Ser-tRNA-synth_IIa. 1 hit.
PRINTS	PR00981. TRNASYNTHSER.
SUPFAM	SSF46589. tRNA_binding_arm. 1 hit.
TIGRFAMs	TIGR00414. serS. 1 hit.
PROSITE	PS50862. AA_TRNA_LIGASE_II. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SARS2. human.
GenomeRNAi	54938.
NextBio	58062.
SOURCE	Search...

Entry information

Entry name

SYSM_HUMAN

Accession

Primary (citable) accession number: Q9NP81
Secondary accession number(s): A6NHW7, B4DE10, Q9BVP3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2002
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.