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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).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei158L-histidineBy similarity1
Binding sitei174L-histidineBy similarity1
Binding sitei178L-histidineBy similarity1
Binding sitei327L-histidineBy similarity1

GO - Molecular functioni

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

GO - Biological processi

  • histidyl-tRNA aminoacylation Source: WormBase
  • translation Source: UniProtKB
  • tRNA aminoacylation for protein translation Source: Reactome

Keywordsi

Molecular functionAminoacyl-tRNA synthetase, Ligase
Biological processProtein biosynthesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi6.1.1.21. 2681.
ReactomeiR-HSA-379726. 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
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000112855.14.
HGNCiHGNC:4817. HARS2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_069532200L → 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 PublicationCorresponds to variant dbSNP:rs397515410Ensembl.1
Natural variantiVAR_069533368V → 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 PublicationCorresponds to variant dbSNP:rs376177973Ensembl.1

Keywords - Diseasei

Deafness, Disease mutation

Organism-specific databases

DisGeNETi23438.
MalaCardsiHARS2.
MIMi614926. phenotype.
OpenTargetsiENSG00000112855.
Orphaneti2855. Perrault syndrome.
PharmGKBiPA29192.

Polymorphism and mutation databases

BioMutaiHARS2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 33MitochondrionSequence analysisAdd BLAST33
ChainiPRO_000013633634 – 506Probable histidine--tRNA ligase, mitochondrialAdd BLAST473

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei67PhosphoserineCombined sources1
Modified residuei444N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP49590.
MaxQBiP49590.
PaxDbiP49590.
PeptideAtlasiP49590.
PRIDEiP49590.

PTM databases

iPTMnetiP49590.
PhosphoSitePlusiP49590.

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

BgeeiENSG00000112855.
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

GO - Molecular functioni

  • protein homodimerization activity Source: WormBase

Protein-protein interaction databases

BioGridi117006. 43 interactors.
DIPiDIP-59626N.
IntActiP49590. 9 interactors.
STRINGi9606.ENSP00000230771.

Structurei

3D structure databases

ProteinModelPortaliP49590.
SMRiP49590.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni131 – 133L-histidine bindingBy similarity3
Regioni331 – 332L-histidine bindingBy similarity2

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1936. Eukaryota.
COG0124. LUCA.
GeneTreeiENSGT00390000005922.
HOGENOMiHOG000018075.
HOVERGENiHBG002731.
InParanoidiP49590.
KOiK01892.
OMAiARYVVMH.
OrthoDBiEOG091G05P3.
PhylomeDBiP49590.
TreeFamiTF300652.

Family and domain databases

CDDicd00859. HisRS_anticodon. 1 hit.
Gene3Di3.40.50.800. 1 hit.
InterProiView protein in InterPro
IPR006195. aa-tRNA-synth_II.
IPR004154. Anticodon-bd.
IPR036621. Anticodon-bd_dom_sf.
IPR015807. His-tRNA-ligase.
IPR004516. HisRS/HisZ.
IPR033656. HisRS_anticodon.
PANTHERiPTHR11476. PTHR11476. 1 hit.
PfamiView protein in Pfam
PF03129. HGTP_anticodon. 1 hit.
PIRSFiPIRSF001549. His-tRNA_synth. 1 hit.
SUPFAMiSSF52954. SSF52954. 1 hit.
TIGRFAMsiTIGR00442. hisS. 1 hit.
PROSITEiView protein in PROSITE
PS50862. AA_TRNA_LIGASE_II. 1 hit.

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_069532200L → 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 PublicationCorresponds to variant dbSNP:rs397515410Ensembl.1
Natural variantiVAR_069533368V → 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 PublicationCorresponds to variant dbSNP:rs376177973Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05513337 – 61Missing in isoform 2. 1 PublicationAdd BLAST25

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. [P49590-1]
ENST00000508522; ENSP00000423616; ENSG00000112855. [P49590-2]
GeneIDi23438.
KEGGihsa:23438.
UCSCiuc003lgx.5. human. [P49590-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSYHM_HUMAN
AccessioniPrimary (citable) accession number: P49590
Secondary accession number(s): B4DDY8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: October 25, 2017
This is version 155 of the entry and version 1 of the sequence. See 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