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UniProtKB - P12081 (SYHC_HUMAN)

Protein

Histidine--tRNA ligase, cytoplasmic

Gene

HARS

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

Functioni

Cytoplasmic histidine--tRNA ligase (Probable). Plays a role in axon guidance.Curated1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei157L-histidineCombined sources1 Publication1
Binding sitei173L-histidineCombined sources1 Publication1
Binding sitei177L-histidineCombined sources1 Publication1
Binding sitei326L-histidineCombined sources1 Publication1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • histidine-tRNA ligase activity Source: Reactome
  • identical protein binding Source: IntAct
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

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

Enzyme and pathway databases

BRENDAi6.1.1.21 2681
ReactomeiR-HSA-379716 Cytosolic tRNA aminoacylation

Names & Taxonomyi

Protein namesi
Recommended name:
Histidine--tRNA ligase, cytoplasmic (EC:6.1.1.21)
Alternative name(s):
Histidyl-tRNA synthetase
Short name:
HisRS
Gene namesi
Name:HARS
Synonyms:HRS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000170445.12
HGNCiHGNC:4816 HARS
MIMi142810 gene
neXtProtiNX_P12081

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

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Usher syndrome 3B (USH3B)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by progressive vision and hearing loss during early childhood. Some patients have the so-called 'Charles Bonnet syndrome,' involving decreased visual acuity and vivid visual hallucinations. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life.
See also OMIM:614504
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067918454Y → S in USH3B. 1 PublicationCorresponds to variant dbSNP:rs387906639EnsemblClinVar.1
Charcot-Marie-Tooth disease 2W (CMT2W)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant, axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2W patients manifest a peripheral neuropathy mainly affecting the lower limbs and resulting in gait difficulties and distal sensory impairment. Most patients also have upper limb involvement.
See also OMIM:616625
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075064132T → I in CMT2W; loss-of-function mutation. 1 PublicationCorresponds to variant dbSNP:rs143473232EnsemblClinVar.1
Natural variantiVAR_075065134P → H in CMT2W; loss-of-function mutation. 1 PublicationCorresponds to variant dbSNP:rs863225122EnsemblClinVar.1
Natural variantiVAR_069022137R → Q in CMT2W; has a neurotoxic effect in an animal model; results in loss of function. 1 PublicationCorresponds to variant dbSNP:rs191391414EnsemblClinVar.1
Natural variantiVAR_075066175D → E in CMT2W; hypomorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs863225123EnsemblClinVar.1
Natural variantiVAR_069024238V → A in CMT2W; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs536175170Ensembl.1
Natural variantiVAR_075067364D → Y in CMT2W; loss-of-function mutation. 1 PublicationCorresponds to variant dbSNP:rs863225124EnsemblClinVar.1
Natural variantiVAR_069026505P → S in CMT2W; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs747156884Ensembl.1

Keywords - Diseasei

Charcot-Marie-Tooth disease, Deafness, Disease mutation, Neurodegeneration, Neuropathy, Retinitis pigmentosa, Usher syndrome

Organism-specific databases

DisGeNETi3035
MalaCardsiHARS
MIMi614504 phenotype
616625 phenotype
OpenTargetsiENSG00000170445
Orphaneti231183 Usher syndrome type 3
PharmGKBiPA29191

Chemistry databases

ChEMBLiCHEMBL4002
DrugBankiDB00117 L-Histidine

Polymorphism and mutation databases

BioMutaiHARS
DMDMi135123

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001363322 – 509Histidine--tRNA ligase, cytoplasmicAdd BLAST508

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei66PhosphoserineBy similarity1
Modified residuei356PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP12081
MaxQBiP12081
PaxDbiP12081
PeptideAtlasiP12081
PRIDEiP12081
ProteomicsDBi12704
52824

PTM databases

iPTMnetiP12081
PhosphoSitePlusiP12081
SwissPalmiP12081

Expressioni

Tissue specificityi

Brain, heart, liver and kidney.

Gene expression databases

BgeeiENSG00000170445 Expressed in 222 organ(s), highest expression level in adenohypophysis
CleanExiHS_HARS
ExpressionAtlasiP12081 baseline and differential
GenevisibleiP12081 HS

Organism-specific databases

HPAiHPA036539

Interactioni

Subunit structurei

Homodimer.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-1057566,EBI-1057566

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi109285, 51 interactors
DIPiDIP-37596N
IntActiP12081, 4 interactors
MINTiP12081
STRINGi9606.ENSP00000425634

Chemistry databases

BindingDBiP12081

Structurei

Secondary structure

1509
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP12081
SMRiP12081
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12081

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 59WHEP-TRSAdd BLAST57

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni130 – 132L-histidine bindingCombined sources1 Publication3
Regioni330 – 331L-histidine bindingCombined sources1 Publication2

Sequence similaritiesi

Belongs to the class-II aminoacyl-tRNA synthetase family.Curated

Phylogenomic databases

eggNOGiKOG1936 Eukaryota
COG0124 LUCA
GeneTreeiENSGT00390000005922
HOGENOMiHOG000018075
HOVERGENiHBG002731
InParanoidiP12081
KOiK01892
OMAiCDFDFIG
OrthoDBiEOG091G05P3
PhylomeDBiP12081
TreeFamiTF300652

Family and domain databases

CDDicd00859 HisRS_anticodon, 1 hit
Gene3Di3.40.50.800, 1 hit
HAMAPiMF_00127 His_tRNA_synth, 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
IPR009068 S15_NS1_RNA-bd
IPR000738 WHEP-TRS_dom
PANTHERiPTHR11476 PTHR11476, 1 hit
PfamiView protein in Pfam
PF03129 HGTP_anticodon, 1 hit
PF00458 WHEP-TRS, 1 hit
PIRSFiPIRSF001549 His-tRNA_synth, 1 hit
SMARTiView protein in SMART
SM00991 WHEP-TRS, 1 hit
SUPFAMiSSF47060 SSF47060, 1 hit
TIGRFAMsiTIGR00442 hisS, 1 hit
PROSITEiView protein in PROSITE
PS50862 AA_TRNA_LIGASE_II, 1 hit
PS00762 WHEP_TRS_1, 1 hit
PS51185 WHEP_TRS_2, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 7 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: P12081-1) [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
MAERAALEEL VKLQGERVRG LKQQKASAEL IEEEVAKLLK LKAQLGPDES 
        60         70         80         90        100
KQKFVLKTPK GTRDYSPRQM AVREKVFDVI IRCFKRHGAE VIDTPVFELK 
       110        120        130        140        150
ETLMGKYGED SKLIYDLKDQ GGELLSLRYD LTVPFARYLA MNKLTNIKRY 
       160        170        180        190        200
HIAKVYRRDN PAMTRGRYRE FYQCDFDIAG NFDPMIPDAE CLKIMCEILS 
       210        220        230        240        250
SLQIGDFLVK VNDRRILDGM FAICGVSDSK FRTICSSVDK LDKVSWEEVK 
       260        270        280        290        300
NEMVGEKGLA PEVADRIGDY VQQHGGVSLV EQLLQDPKLS QNKQALEGLG 
       310        320        330        340        350
DLKLLFEYLT LFGIDDKISF DLSLARGLDY YTGVIYEAVL LQTPAQAGEE 
       360        370        380        390        400
PLGVGSVAAG GRYDGLVGMF DPKGRKVPCV GLSIGVERIF SIVEQRLEAL 
       410        420        430        440        450
EEKIRTTETQ VLVASAQKKL LEERLKLVSE LWDAGIKAEL LYKKNPKLLN 
       460        470        480        490        500
QLQYCEEAGI PLVAIIGEQE LKDGVIKLRS VTSREEVDVR REDLVEEIKR 

RTGQPLCIC
Length:509
Mass (Da):57,411
Last modified:May 1, 1992 - v2
Checksum:i65D8BB71CE79B1FF
GO
Isoform 2 (identifier: P12081-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     60-99: Missing.

Show »
Length:469
Mass (Da):52,720
Checksum:iB02783AB9FED1E1D
GO
Isoform 3 (identifier: P12081-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     60-99: Missing.
     155-174: Missing.

Show »
Length:449
Mass (Da):50,156
Checksum:i9B97F9CC4FE63BB9
GO
Isoform 4 (identifier: P12081-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     155-174: Missing.

Show »
Length:489
Mass (Da):54,847
Checksum:iE0C0825FF411F391
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4E1C5B4E1C5_HUMAN
Histidine--tRNA ligase, cytoplasmic
HARS
395Annotation score:
B4DDD8B4DDD8_HUMAN
Histidine--tRNA ligase, cytoplasmic
HARS
435Annotation score:
E7ETE2E7ETE2_HUMAN
Histidine--tRNA ligase, cytoplasmic
HARS
288Annotation score:
B3KWE1B3KWE1_HUMAN
Histidine--tRNA ligase, cytoplasmic
HARS hCG_1782886
440Annotation score:
D6RF05D6RF05_HUMAN
Histidine--tRNA ligase, cytoplasmic
HARS
60Annotation score:
A0A2R8YCI2A0A2R8YCI2_HUMAN
Histidine--tRNA ligase, cytoplasmic
HARS
84Annotation score:
A0A2R8YFR1A0A2R8YFR1_HUMAN
Histidine--tRNA ligase, cytoplasmic
HARS
52Annotation score:

Sequence cautioni

The sequence CAA28956 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6A → P in CAA28956 (PubMed:3554142).Curated1
Sequence conflicti126S → P in BAG58213 (PubMed:14702039).Curated1
Sequence conflicti165R → G in CAA28956 (PubMed:3554142).Curated1
Sequence conflicti181N → Q in CAA28956 (PubMed:3554142).Curated1
Sequence conflicti186I → N in CAA28956 (PubMed:3554142).Curated1
Sequence conflicti191C → S in CAA28956 (PubMed:3554142).Curated1
Sequence conflicti206D → N in CAA28956 (PubMed:3554142).Curated1
Sequence conflicti223I → V in CAA28956 (PubMed:3554142).Curated1
Sequence conflicti227S → P in CAA28956 (PubMed:3554142).Curated1
Sequence conflicti284L → V in CAA28956 (PubMed:3554142).Curated1
Sequence conflicti347A → E in CAA28956 (PubMed:3554142).Curated1
Sequence conflicti373 – 374KG → QR in CAA28956 (PubMed:3554142).Curated2
Sequence conflicti375R → L in BAG58213 (PubMed:14702039).Curated1
Sequence conflicti493D → E in CAA28956 (PubMed:3554142).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0690215A → E1 PublicationCorresponds to variant dbSNP:rs78741041EnsemblClinVar.1
Natural variantiVAR_075064132T → I in CMT2W; loss-of-function mutation. 1 PublicationCorresponds to variant dbSNP:rs143473232EnsemblClinVar.1
Natural variantiVAR_075065134P → H in CMT2W; loss-of-function mutation. 1 PublicationCorresponds to variant dbSNP:rs863225122EnsemblClinVar.1
Natural variantiVAR_069022137R → Q in CMT2W; has a neurotoxic effect in an animal model; results in loss of function. 1 PublicationCorresponds to variant dbSNP:rs191391414EnsemblClinVar.1
Natural variantiVAR_075066175D → E in CMT2W; hypomorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs863225123EnsemblClinVar.1
Natural variantiVAR_069023205G → D1 PublicationCorresponds to variant dbSNP:rs147288996EnsemblClinVar.1
Natural variantiVAR_069024238V → A in CMT2W; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs536175170Ensembl.1
Natural variantiVAR_075067364D → Y in CMT2W; loss-of-function mutation. 1 PublicationCorresponds to variant dbSNP:rs863225124EnsemblClinVar.1
Natural variantiVAR_069025376K → R1 PublicationCorresponds to variant dbSNP:rs139447495EnsemblClinVar.1
Natural variantiVAR_061908399A → V. Corresponds to variant dbSNP:rs34732372EnsemblClinVar.1
Natural variantiVAR_067918454Y → S in USH3B. 1 PublicationCorresponds to variant dbSNP:rs387906639EnsemblClinVar.1
Natural variantiVAR_069026505P → S in CMT2W; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs747156884Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04511860 – 99Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_046662155 – 174Missing in isoform 3 and isoform 4. 2 PublicationsAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z11518 mRNA Translation: CAA77607.1
X05345 mRNA Translation: CAA28956.1 Frameshift.
AK295219 mRNA Translation: BAG58213.1
AK302295 mRNA Translation: BAG63635.1
AK225776 mRNA No translation available.
AC116353 Genomic DNA No translation available.
BC011807 mRNA Translation: AAH11807.1
BC080514 mRNA Translation: AAH80514.1
M96646 Genomic DNA Translation: AAA58668.1
U18936 Genomic DNA Translation: AAA73973.1
CCDSiCCDS4237.1 [P12081-1]
CCDS58976.1 [P12081-2]
CCDS58977.1 [P12081-3]
CCDS58978.1 [P12081-4]
PIRiI37559 SYHUHT
RefSeqiNP_001244969.1, NM_001258040.2 [P12081-2]
NP_001244970.1, NM_001258041.2 [P12081-4]
NP_001244971.1, NM_001258042.2 [P12081-3]
NP_002100.2, NM_002109.5 [P12081-1]
UniGeneiHs.528050

Genome annotation databases

EnsembliENST00000307633; ENSP00000304668; ENSG00000170445 [P12081-3]
ENST00000438307; ENSP00000411511; ENSG00000170445 [P12081-2]
ENST00000457527; ENSP00000387893; ENSG00000170445 [P12081-4]
ENST00000504156; ENSP00000425634; ENSG00000170445 [P12081-1]
ENST00000644191; ENSP00000495156; ENSG00000170445 [P12081-1]
GeneIDi3035
KEGGihsa:3035
UCSCiuc003lgv.6 human [P12081-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSYHC_HUMAN
AccessioniPrimary (citable) accession number: P12081
Secondary accession number(s): B4DHQ1
, B4DY73, D6REN6, J3KNE5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: May 1, 1992
Last modified: September 12, 2018
This is version 197 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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