Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Probable histidine--tRNA ligase, mitochondrial

Gene

HARS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

ATP + L-histidine + tRNA(His) = AMP + diphosphate + L-histidyl-tRNA(His).

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • histidine-tRNA ligase activity Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • protein homodimerization activity Source: WormBase

GO - Biological processi

  • gene expression Source: Reactome
  • histidyl-tRNA aminoacylation Source: WormBase
  • translation Source: UniProtKB
  • tRNA aminoacylation for protein translation Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Aminoacyl-tRNA synthetase, Ligase

Keywords - Biological processi

Protein biosynthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi6.1.1.21. 2681.
ReactomeiREACT_15302. Mitochondrial tRNA aminoacylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Probable histidine--tRNA ligase, mitochondrial (EC:6.1.1.21)
Alternative name(s):
Histidine--tRNA ligase-like
Histidyl-tRNA synthetase
Short name:
HisRS
Gene namesi
Name:HARS2
Synonyms:HARSL, HARSR, HO3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:4817. HARS2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: WormBase
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Perrault syndrome 2 (PRLTS2)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile.

See also OMIM:614926
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti200 – 2001L → V in PRLTS2; the mutant protein is expressed, can dimerize and localizes to the mitochondria; has significantly decreased enzymatic activity compared to wild-type. 1 Publication
VAR_069532
Natural varianti368 – 3681V → L in PRLTS2; the mutant protein is expressed, can dimerize and localizes to the mitochondria; has significantly decreased enzymatic activity compared to wild-type. 1 Publication
VAR_069533

Keywords - Diseasei

Deafness, Disease mutation

Organism-specific databases

MIMi614926. phenotype.
Orphaneti2855. Perrault syndrome.
PharmGKBiPA29192.

Polymorphism and mutation databases

BioMutaiHARS2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3333MitochondrionSequence AnalysisAdd
BLAST
Chaini34 – 506473Probable histidine--tRNA ligase, mitochondrialPRO_0000136336Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei67 – 671Phosphoserine2 Publications
Modified residuei444 – 4441N6-acetyllysine1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP49590.
PaxDbiP49590.
PeptideAtlasiP49590.
PRIDEiP49590.

PTM databases

PhosphoSiteiP49590.

Expressioni

Tissue specificityi

A high level expression is seen in the heart, kidney and skeletal muscle while a lower level expression is seen in the brain and liver.

Gene expression databases

BgeeiP49590.
CleanExiHS_HARS2.
ExpressionAtlasiP49590. baseline and differential.
GenevisibleiP49590. HS.

Organism-specific databases

HPAiHPA035941.

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
AGTRAPQ6RW133EBI-3909030,EBI-741181

Protein-protein interaction databases

BioGridi117006. 13 interactions.
DIPiDIP-59626N.
IntActiP49590. 4 interactions.
STRINGi9606.ENSP00000230771.

Structurei

3D structure databases

ProteinModelPortaliP49590.
SMRiP49590. Positions 55-505.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0124.
GeneTreeiENSGT00390000005922.
HOGENOMiHOG000018075.
HOVERGENiHBG002731.
InParanoidiP49590.
KOiK01892.
OMAiLHYCENM.
OrthoDBiEOG7WMCJC.
PhylomeDBiP49590.
TreeFamiTF300652.

Family and domain databases

Gene3Di3.40.50.800. 1 hit.
InterProiIPR002314. aa-tRNA-synt_IIb_cons-dom.
IPR006195. aa-tRNA-synth_II.
IPR004154. Anticodon-bd.
IPR015807. His-tRNA-ligase.
IPR004516. HisRS/HisZ.
[Graphical view]
PANTHERiPTHR11476. PTHR11476. 1 hit.
PfamiPF03129. HGTP_anticodon. 1 hit.
PF00587. tRNA-synt_2b. 1 hit.
[Graphical view]
PIRSFiPIRSF001549. His-tRNA_synth. 1 hit.
SUPFAMiSSF52954. SSF52954. 1 hit.
TIGRFAMsiTIGR00442. hisS. 1 hit.
PROSITEiPS50862. AA_TRNA_LIGASE_II. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49590-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPLLGLLPRR AWASLLSQLL RPPCASCTGA VRCQSQVAEA VLTSQLKAHQ
60 70 80 90 100
EKPNFIIKTP KGTRDLSPQH MVVREKILDL VISCFKRHGA KGMDTPAFEL
110 120 130 140 150
KETLTEKYGE DSGLMYDLKD QGGELLSLRY DLTVPFARYL AMNKVKKMKR
160 170 180 190 200
YHVGKVWRRE SPTIVQGRYR EFCQCDFDIA GQFDPMIPDA ECLKIMCEIL
210 220 230 240 250
SGLQLGDFLI KVNDRRIVDG MFAVCGVPES KFRAICSSID KLDKMAWKDV
260 270 280 290 300
RHEMVVKKGL APEVADRIGD YVQCHGGVSL VEQMFQDPRL SQNKQALEGL
310 320 330 340 350
GDLKLLFEYL TLFGIADKIS FDLSLARGLD YYTGVIYEAV LLQTPTQAGE
360 370 380 390 400
EPLNVGSVAA GGRYDGLVGM FDPKGHKVPC VGLSIGVERI FYIVEQRMKT
410 420 430 440 450
KGEKVRTTET QVFVATPQKN FLQERLKLIA ELWDSGIKAE MLYKNNPKLL
460 470 480 490 500
TQLHYCESTG IPLVVIIGEQ ELKEGVIKIR SVASREEVAI KRENFVAEIQ

KRLSES
Length:506
Mass (Da):56,888
Last modified:February 1, 1996 - v1
Checksum:iE1CE879837AE26E7
GO
Isoform 2 (identifier: P49590-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     37-61: Missing.

Show »
Length:481
Mass (Da):54,115
Checksum:i26B2276C1B73911C
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti200 – 2001L → V in PRLTS2; the mutant protein is expressed, can dimerize and localizes to the mitochondria; has significantly decreased enzymatic activity compared to wild-type. 1 Publication
VAR_069532
Natural varianti368 – 3681V → L in PRLTS2; the mutant protein is expressed, can dimerize and localizes to the mitochondria; has significantly decreased enzymatic activity compared to wild-type. 1 Publication
VAR_069533

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei37 – 6125Missing in isoform 2. 1 PublicationVSP_055133Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U18936 Genomic DNA. Translation: AAA73972.1.
U18937 mRNA. Translation: AAA73974.1.
AK293390 mRNA. Translation: BAG56899.1.
AC116353 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW62019.1.
BC007680 mRNA. Translation: AAH07680.1.
BC014982 mRNA. Translation: AAH14982.1.
CCDSiCCDS4238.1. [P49590-1]
CCDS64267.1. [P49590-2]
PIRiI38913.
I38915.
RefSeqiNP_001265660.1. NM_001278731.1. [P49590-2]
NP_001265661.1. NM_001278732.1.
NP_036340.1. NM_012208.3. [P49590-1]
UniGeneiHs.432560.

Genome annotation databases

EnsembliENST00000230771; ENSP00000230771; ENSG00000112855.
ENST00000508522; ENSP00000423616; ENSG00000112855. [P49590-2]
GeneIDi23438.
KEGGihsa:23438.
UCSCiuc003lgx.3. human. [P49590-1]
uc011czr.2. human.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U18936 Genomic DNA. Translation: AAA73972.1.
U18937 mRNA. Translation: AAA73974.1.
AK293390 mRNA. Translation: BAG56899.1.
AC116353 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW62019.1.
BC007680 mRNA. Translation: AAH07680.1.
BC014982 mRNA. Translation: AAH14982.1.
CCDSiCCDS4238.1. [P49590-1]
CCDS64267.1. [P49590-2]
PIRiI38913.
I38915.
RefSeqiNP_001265660.1. NM_001278731.1. [P49590-2]
NP_001265661.1. NM_001278732.1.
NP_036340.1. NM_012208.3. [P49590-1]
UniGeneiHs.432560.

3D structure databases

ProteinModelPortaliP49590.
SMRiP49590. Positions 55-505.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117006. 13 interactions.
DIPiDIP-59626N.
IntActiP49590. 4 interactions.
STRINGi9606.ENSP00000230771.

PTM databases

PhosphoSiteiP49590.

Polymorphism and mutation databases

BioMutaiHARS2.

Proteomic databases

MaxQBiP49590.
PaxDbiP49590.
PeptideAtlasiP49590.
PRIDEiP49590.

Protocols and materials databases

DNASUi23438.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000230771; ENSP00000230771; ENSG00000112855.
ENST00000508522; ENSP00000423616; ENSG00000112855. [P49590-2]
GeneIDi23438.
KEGGihsa:23438.
UCSCiuc003lgx.3. human. [P49590-1]
uc011czr.2. human.

Organism-specific databases

CTDi23438.
GeneCardsiGC05P140110.
HGNCiHGNC:4817. HARS2.
HPAiHPA035941.
MIMi600783. gene.
614926. phenotype.
neXtProtiNX_P49590.
Orphaneti2855. Perrault syndrome.
PharmGKBiPA29192.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0124.
GeneTreeiENSGT00390000005922.
HOGENOMiHOG000018075.
HOVERGENiHBG002731.
InParanoidiP49590.
KOiK01892.
OMAiLHYCENM.
OrthoDBiEOG7WMCJC.
PhylomeDBiP49590.
TreeFamiTF300652.

Enzyme and pathway databases

BRENDAi6.1.1.21. 2681.
ReactomeiREACT_15302. Mitochondrial tRNA aminoacylation.

Miscellaneous databases

GeneWikiiHARS2.
GenomeRNAii23438.
NextBioi35471063.
PROiP49590.
SOURCEiSearch...

Gene expression databases

BgeeiP49590.
CleanExiHS_HARS2.
ExpressionAtlasiP49590. baseline and differential.
GenevisibleiP49590. HS.

Family and domain databases

Gene3Di3.40.50.800. 1 hit.
InterProiIPR002314. aa-tRNA-synt_IIb_cons-dom.
IPR006195. aa-tRNA-synth_II.
IPR004154. Anticodon-bd.
IPR015807. His-tRNA-ligase.
IPR004516. HisRS/HisZ.
[Graphical view]
PANTHERiPTHR11476. PTHR11476. 1 hit.
PfamiPF03129. HGTP_anticodon. 1 hit.
PF00587. tRNA-synt_2b. 1 hit.
[Graphical view]
PIRSFiPIRSF001549. His-tRNA_synth. 1 hit.
SUPFAMiSSF52954. SSF52954. 1 hit.
TIGRFAMsiTIGR00442. hisS. 1 hit.
PROSITEiPS50862. AA_TRNA_LIGASE_II. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A novel gene oriented in a head-to-head configuration with the human histidyl-tRNA synthetase (HRS) gene encodes an mRNA that predicts a polypeptide homologous to HRS."
    O'Hanlon T.P., Raben N., Miller F.W.
    Biochem. Biophys. Res. Commun. 210:556-566(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / 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] (ISOFORM 2).
    Tissue: Urinary bladder.
  3. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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 Skin.
  6. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
    Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
    Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. "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-444, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  11. "Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome."
    Pierce S.B., Chisholm K.M., Lynch E.D., Lee M.K., Walsh T., Opitz J.M., Li W., Klevit R.E., King M.C.
    Proc. Natl. Acad. Sci. U.S.A. 108:6543-6548(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PRLTS2 VAL-200 AND LEU-368, CHARACTERIZATION OF VARIANTS PRLTS2 VAL-200 AND LEU-368, SUBUNIT.

Entry informationi

Entry nameiSYHM_HUMAN
AccessioniPrimary (citable) accession number: P49590
Secondary accession number(s): B4DDY8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: July 22, 2015
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Aminoacyl-tRNA synthetases
    List of aminoacyl-tRNA synthetase entries
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.