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P12081 (SYHC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histidine--tRNA ligase, cytoplasmic

EC=6.1.1.21
Alternative name(s):
Histidyl-tRNA synthetase
Short name=HisRS
Gene names
Name:HARS
Synonyms:HRS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length509 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

ATP + L-histidine + tRNA(His) = AMP + diphosphate + L-histidyl-tRNA(His). HAMAP-Rule MF_00127

Subcellular location

Cytoplasm HAMAP-Rule MF_00127.

Tissue specificity

Brain, heart, liver and kidney.

Involvement in disease

Usher syndrome 3B (USH3B) [MIM:614504]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

HARS mutations may be involved in peripheral neuropathy, a disease mainly characterized by distal motor and sensory dysfunction. Inherited peripheral neuropathies are clinically and genetically heterogeneous with variable age of onset and reduced penetrance associated with specific loci. HARS mutations may directly predispose patients to peripheral neuropathy or may modify a peripheral neuropathy phenotype by contributing to the genetic and environmental load in a given patient (Ref.11).

Sequence similarities

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

Contains 1 WHEP-TRS domain.

Sequence caution

The sequence CAA28956.1 differs from that shown. Reason: Frameshift at several positions.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P12081-1)

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: P12081-2)

The sequence of this isoform differs from the canonical sequence as follows:
     60-99: Missing.
Isoform 3 (identifier: P12081-3)

The sequence of this isoform differs from the canonical sequence as follows:
     60-99: Missing.
     155-174: Missing.
Isoform 4 (identifier: P12081-4)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.9
Chain2 – 509508Histidine--tRNA ligase, cytoplasmic HAMAP-Rule MF_00127
PRO_0000136332

Regions

Domain3 – 5957WHEP-TRS

Amino acid modifications

Modified residue21N-acetylalanine Ref.9

Natural variations

Alternative sequence60 – 9940Missing in isoform 2 and isoform 3.
VSP_045118
Alternative sequence155 – 17420Missing in isoform 3 and isoform 4.
VSP_046662
Natural variant51A → E. Ref.11
Corresponds to variant rs78741041 [ dbSNP | Ensembl ].
VAR_069021
Natural variant1371R → Q Found in a patient with peripheral neuropathy; unknown pathological significance; results in loss of function; has a neurotoxic effect in an animal model. Ref.11
Corresponds to variant rs191391414 [ dbSNP | Ensembl ].
VAR_069022
Natural variant2051G → D. Ref.11
Corresponds to variant rs147288996 [ dbSNP | Ensembl ].
VAR_069023
Natural variant2381V → A Found in a patient with peripheral neuropathy; unknown pathological role. Ref.11
VAR_069024
Natural variant3761K → R. Ref.11
Corresponds to variant rs139447495 [ dbSNP | Ensembl ].
VAR_069025
Natural variant3991A → V.
Corresponds to variant rs34732372 [ dbSNP | Ensembl ].
VAR_061908
Natural variant4541Y → S in USH3B. Ref.13
VAR_067918
Natural variant5051P → S Found in a patient with peripheral neuropathy; unknown pathological role. Ref.11
VAR_069026

Experimental info

Sequence conflict61A → P in CAA28956. Ref.2
Sequence conflict1261S → P in BAG58213. Ref.3
Sequence conflict1651R → G in CAA28956. Ref.2
Sequence conflict1811N → Q in CAA28956. Ref.2
Sequence conflict1861I → N in CAA28956. Ref.2
Sequence conflict1911C → S in CAA28956. Ref.2
Sequence conflict2061D → N in CAA28956. Ref.2
Sequence conflict2231I → V in CAA28956. Ref.2
Sequence conflict2271S → P in CAA28956. Ref.2
Sequence conflict2841L → V in CAA28956. Ref.2
Sequence conflict3471A → E in CAA28956. Ref.2
Sequence conflict373 – 3742KG → QR in CAA28956. Ref.2
Sequence conflict3751R → L in BAG58213. Ref.3
Sequence conflict4931D → E in CAA28956. Ref.2

Secondary structure

.............................................................................. 509
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1992. Version 2.
Checksum: 65D8BB71CE79B1FF

FASTA50957,411
        10         20         30         40         50         60 
MAERAALEEL VKLQGERVRG LKQQKASAEL IEEEVAKLLK LKAQLGPDES KQKFVLKTPK 

        70         80         90        100        110        120 
GTRDYSPRQM AVREKVFDVI IRCFKRHGAE VIDTPVFELK ETLMGKYGED SKLIYDLKDQ 

       130        140        150        160        170        180 
GGELLSLRYD LTVPFARYLA MNKLTNIKRY HIAKVYRRDN PAMTRGRYRE FYQCDFDIAG 

       190        200        210        220        230        240 
NFDPMIPDAE CLKIMCEILS SLQIGDFLVK VNDRRILDGM FAICGVSDSK FRTICSSVDK 

       250        260        270        280        290        300 
LDKVSWEEVK NEMVGEKGLA PEVADRIGDY VQQHGGVSLV EQLLQDPKLS QNKQALEGLG 

       310        320        330        340        350        360 
DLKLLFEYLT LFGIDDKISF DLSLARGLDY YTGVIYEAVL LQTPAQAGEE PLGVGSVAAG 

       370        380        390        400        410        420 
GRYDGLVGMF DPKGRKVPCV GLSIGVERIF SIVEQRLEAL EEKIRTTETQ VLVASAQKKL 

       430        440        450        460        470        480 
LEERLKLVSE LWDAGIKAEL LYKKNPKLLN QLQYCEEAGI PLVAIIGEQE LKDGVIKLRS 

       490        500 
VTSREEVDVR REDLVEEIKR RTGQPLCIC 

« Hide

Isoform 2 [UniParc].

Checksum: B02783AB9FED1E1D
Show »

FASTA46952,720
Isoform 3 [UniParc].

Checksum: 9B97F9CC4FE63BB9
Show »

FASTA44950,156
Isoform 4 [UniParc].

Checksum: E0C0825FF411F391
Show »

FASTA48954,847

References

« Hide 'large scale' references
[1]"Human histidyl-tRNA synthetase: recognition of amino acid signature regions in class 2a aminoacyl-tRNA synthetases."
Raben N., Borriello F., Amin J., Horwitz R., Fraser D., Plotz P.
Nucleic Acids Res. 20:1075-1081(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Isolation, structure and expression of mammalian genes for histidyl-tRNA synthetase."
Tsui F.W.L., Siminovitch L.
Nucleic Acids Res. 15:3349-3367(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"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. expand/collapse author list , 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 2 AND 3).
Tissue: Caudate nucleus and Testis.
[4]"Homo sapiens protein coding cDNA."
Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Brain.
[5]"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. expand/collapse author list , 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].
[6]"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: Lung and Uterus.
[7]"Transcriptional analyses of the gene region that encodes human histidyl-tRNA synthetase: identification of a novel bidirectional regulatory element."
Tsui H.W., Mok S., de Souza L., Martin A., Tsui F.W.L.
Gene 131:201-208(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-30.
[8]"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] OF 1-30.
[9]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[10]"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].
[11]"A loss-of-function variant in the human histidyl-tRNA synthetase (HARS) gene is neurotoxic in vivo."
NISC comparative sequencing program
Vester A., Velez-Ruiz G., McLaughlin H.M., Lupski J.R., Talbot K., Vance J.M., Zuchner S., Roda R.H., Fischbeck K.H., Biesecker L.G., Nicholson G., Beg A.A., Antonellis A.
Hum. Mutat. 34:191-199(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN PERIPHERAL NEUROPATHY, VARIANTS GLU-5; GLN-137; ASP-205; ALA-238; ARG-376 AND SER-505, CHARACTERIZATION OF VARIANT GLN-137.
[12]"Solution structures of the WHEP-TRS domain of human histidyl-tRNA synthetase."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 1-60.
[13]"Genetic mapping and exome sequencing identify variants associated with five novel diseases."
Puffenberger E.G., Jinks R.N., Sougnez C., Cibulskis K., Willert R.A., Achilly N.P., Cassidy R.P., Fiorentini C.J., Heiken K.F., Lawrence J.J., Mahoney M.H., Miller C.J., Nair D.T., Politi K.A., Worcester K.N., Setton R.A., Dipiazza R., Sherman E.A. expand/collapse author list , Eastman J.T., Francklyn C., Robey-Bond S., Rider N.L., Gabriel S., Morton D.H., Strauss K.A.
PLoS ONE 7:E28936-E28936(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT USH3B SER-454.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS4237.1. [P12081-1]
CCDS58976.1. [P12081-2]
CCDS58977.1. [P12081-3]
CCDS58978.1. [P12081-4]
PIRSYHUHT. I37559.
RefSeqNP_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]
UniGeneHs.528050.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1X59NMR-A1-60[»]
2LW7NMR-A2-509[»]
4G84X-ray2.40A/B54-506[»]
4G85X-ray3.11A/B1-506[»]
ProteinModelPortalP12081.
SMRP12081. Positions 1-508.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109285. 29 interactions.
DIPDIP-37596N.
IntActP12081. 2 interactions.
MINTMINT-3007818.
STRING9606.ENSP00000304668.

Chemistry

BindingDBP12081.
ChEMBLCHEMBL4002.
DrugBankDB00117. L-Histidine.

PTM databases

PhosphoSiteP12081.

Polymorphism databases

DMDM135123.

Proteomic databases

MaxQBP12081.
PaxDbP12081.
PeptideAtlasP12081.
PRIDEP12081.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000307633; ENSP00000304668; ENSG00000170445. [P12081-3]
ENST00000438307; ENSP00000411511; ENSG00000170445. [P12081-2]
ENST00000457527; ENSP00000387893; ENSG00000170445. [P12081-4]
ENST00000504156; ENSP00000425634; ENSG00000170445. [P12081-1]
GeneID3035.
KEGGhsa:3035.
UCSCuc003lgu.3. human. [P12081-1]
uc011czm.3. human.

Organism-specific databases

CTD3035.
GeneCardsGC05M140034.
HGNCHGNC:4816. HARS.
HPAHPA036539.
MIM142810. gene.
614504. phenotype.
neXtProtNX_P12081.
Orphanet231183. Usher syndrome type 3.
PharmGKBPA29191.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0124.
HOGENOMHOG000018075.
HOVERGENHBG002731.
InParanoidP12081.
KOK01892.
OMAIFSITKA.
PhylomeDBP12081.
TreeFamTF300652.

Enzyme and pathway databases

BRENDA6.1.1.21. 2681.
ReactomeREACT_71. Gene Expression.

Gene expression databases

ArrayExpressP12081.
BgeeP12081.
CleanExHS_HARS.
GenevestigatorP12081.

Family and domain databases

Gene3D1.10.287.10. 1 hit.
3.40.50.800. 1 hit.
HAMAPMF_00127. His_tRNA_synth.
InterProIPR002314. aa-tRNA-synt_IIb_cons-dom.
IPR006195. aa-tRNA-synth_II.
IPR004154. Anticodon-bd.
IPR015807. His-tRNA-ligase.
IPR004516. HisRS/HisZ.
IPR009068. S15_NS1_RNA-bd.
IPR000738. WHEP-TRS.
[Graphical view]
PANTHERPTHR11476. PTHR11476. 1 hit.
PfamPF03129. HGTP_anticodon. 1 hit.
PF00587. tRNA-synt_2b. 1 hit.
PF00458. WHEP-TRS. 1 hit.
[Graphical view]
PIRSFPIRSF001549. His-tRNA_synth. 1 hit.
SMARTSM00991. WHEP-TRS. 1 hit.
[Graphical view]
SUPFAMSSF47060. SSF47060. 1 hit.
SSF52954. SSF52954. 1 hit.
TIGRFAMsTIGR00442. hisS. 1 hit.
PROSITEPS50862. AA_TRNA_LIGASE_II. 1 hit.
PS00762. WHEP_TRS_1. 1 hit.
PS51185. WHEP_TRS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHARS. human.
EvolutionaryTraceP12081.
GeneWikiHARS.
GenomeRNAi3035.
NextBio12014.
PROP12081.
SOURCESearch...

Entry information

Entry nameSYHC_HUMAN
AccessionPrimary (citable) accession number: P12081
Secondary accession number(s): B4DHQ1 expand/collapse secondary AC list , B4DY73, D6REN6, J3KNE5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: May 1, 1992
Last modified: July 9, 2014
This is version 156 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Aminoacyl-tRNA synthetases

List of aminoacyl-tRNA synthetase entries