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P49590

- SYHM_HUMAN

UniProt

P49590 - SYHM_HUMAN

Protein

Probable histidine--tRNA ligase, mitochondrial

Gene

HARS2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 1 (01 Feb 1996)
      Previous versions | rss
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    Functioni

    Catalytic activityi

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

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. histidine-tRNA ligase activity Source: UniProtKB
    3. poly(A) RNA binding Source: UniProtKB

    GO - Biological processi

    1. gene expression Source: Reactome
    2. histidyl-tRNA aminoacylation Source: InterPro
    3. translation Source: UniProtKB
    4. tRNA aminoacylation for protein translation Source: Reactome

    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: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:4817. HARS2.

    Subcellular locationi

    Mitochondrion matrix By similarity

    GO - Cellular componenti

    1. mitochondrial matrix Source: Reactome

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Perrault syndrome 2 (PRLTS2) [MIM:614926]: A 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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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.

    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 – 671Phosphoserine1 Publication
    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

    ArrayExpressiP49590.
    BgeeiP49590.
    CleanExiHS_HARS2.
    GenevestigatoriP49590.

    Organism-specific databases

    HPAiHPA035941.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    BioGridi117006. 5 interactions.
    DIPiDIP-59626N.
    IntActiP49590. 3 interactions.
    STRINGi9606.ENSP00000230771.

    Structurei

    3D structure databases

    ProteinModelPortaliP49590.
    SMRiP49590. Positions 56-505.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0124.
    HOGENOMiHOG000018075.
    HOVERGENiHBG002731.
    InParanoidiP49590.
    KOiK01892.
    OMAiRGDYLIR.
    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. Align

    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

    MPLLGLLPRR AWASLLSQLL RPPCASCTGA VRCQSQVAEA VLTSQLKAHQ    50
    EKPNFIIKTP KGTRDLSPQH MVVREKILDL VISCFKRHGA KGMDTPAFEL 100
    KETLTEKYGE DSGLMYDLKD QGGELLSLRY DLTVPFARYL AMNKVKKMKR 150
    YHVGKVWRRE SPTIVQGRYR EFCQCDFDIA GQFDPMIPDA ECLKIMCEIL 200
    SGLQLGDFLI KVNDRRIVDG MFAVCGVPES KFRAICSSID KLDKMAWKDV 250
    RHEMVVKKGL APEVADRIGD YVQCHGGVSL VEQMFQDPRL SQNKQALEGL 300
    GDLKLLFEYL TLFGIADKIS FDLSLARGLD YYTGVIYEAV LLQTPTQAGE 350
    EPLNVGSVAA GGRYDGLVGM FDPKGHKVPC VGLSIGVERI FYIVEQRMKT 400
    KGEKVRTTET QVFVATPQKN FLQERLKLIA ELWDSGIKAE MLYKNNPKLL 450
    TQLHYCESTG IPLVVIIGEQ ELKEGVIKIR SVASREEVAI KRENFVAEIQ 500
    KRLSES 506
    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:
    EMBL
    GenBank
    DDBJ
    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.
    NP_001265661.1. NM_001278732.1.
    NP_036340.1. NM_012208.3.
    UniGeneiHs.432560.

    Genome annotation databases

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

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS4238.1. [P49590-1 ]
    CCDS64267.1. [P49590-2 ]
    PIRi I38913.
    I38915.
    RefSeqi NP_001265660.1. NM_001278731.1.
    NP_001265661.1. NM_001278732.1.
    NP_036340.1. NM_012208.3.
    UniGenei Hs.432560.

    3D structure databases

    ProteinModelPortali P49590.
    SMRi P49590. Positions 56-505.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117006. 5 interactions.
    DIPi DIP-59626N.
    IntActi P49590. 3 interactions.
    STRINGi 9606.ENSP00000230771.

    PTM databases

    PhosphoSitei P49590.

    Proteomic databases

    MaxQBi P49590.
    PaxDbi P49590.
    PeptideAtlasi P49590.
    PRIDEi P49590.

    Protocols and materials databases

    DNASUi 23438.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000230771 ; ENSP00000230771 ; ENSG00000112855 . [P49590-1 ]
    ENST00000508522 ; ENSP00000423616 ; ENSG00000112855 . [P49590-2 ]
    GeneIDi 23438.
    KEGGi hsa:23438.
    UCSCi uc003lgx.3. human. [P49590-1 ]

    Organism-specific databases

    CTDi 23438.
    GeneCardsi GC05P140095.
    HGNCi HGNC:4817. HARS2.
    HPAi HPA035941.
    MIMi 600783. gene.
    614926. phenotype.
    neXtProti NX_P49590.
    Orphaneti 2855. Perrault syndrome.
    PharmGKBi PA29192.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0124.
    HOGENOMi HOG000018075.
    HOVERGENi HBG002731.
    InParanoidi P49590.
    KOi K01892.
    OMAi RGDYLIR.
    OrthoDBi EOG7WMCJC.
    PhylomeDBi P49590.
    TreeFami TF300652.

    Enzyme and pathway databases

    BRENDAi 6.1.1.21. 2681.
    Reactomei REACT_15302. Mitochondrial tRNA aminoacylation.

    Miscellaneous databases

    GeneWikii HARS2.
    GenomeRNAii 23438.
    NextBioi 35471063.
    PROi P49590.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49590.
    Bgeei P49590.
    CleanExi HS_HARS2.
    Genevestigatori P49590.

    Family and domain databases

    Gene3Di 3.40.50.800. 1 hit.
    InterProi IPR002314. aa-tRNA-synt_IIb_cons-dom.
    IPR006195. aa-tRNA-synth_II.
    IPR004154. Anticodon-bd.
    IPR015807. His-tRNA-ligase.
    IPR004516. HisRS/HisZ.
    [Graphical view ]
    PANTHERi PTHR11476. PTHR11476. 1 hit.
    Pfami PF03129. HGTP_anticodon. 1 hit.
    PF00587. tRNA-synt_2b. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001549. His-tRNA_synth. 1 hit.
    SUPFAMi SSF52954. SSF52954. 1 hit.
    TIGRFAMsi TIGR00442. hisS. 1 hit.
    PROSITEi PS50862. AA_TRNA_LIGASE_II. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. "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: October 1, 2014
    This is version 126 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