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O43612

- OREX_HUMAN

UniProt

O43612 - OREX_HUMAN

Protein

Orexin

Gene

HCRT

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

    Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested. Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity.

    GO - Biological processi

    1. eating behavior Source: Ensembl
    2. negative regulation of DNA replication Source: Ensembl
    3. negative regulation of potassium ion transport Source: Ensembl
    4. negative regulation of transmission of nerve impulse Source: Ensembl
    5. neuropeptide signaling pathway Source: UniProtKB-KW
    6. phospholipase C-activating G-protein coupled receptor signaling pathway Source: Ensembl
    7. positive regulation of calcium ion transport Source: Ensembl
    8. positive regulation of cytosolic calcium ion concentration Source: Ensembl
    9. positive regulation of transmission of nerve impulse Source: Ensembl
    10. protein kinase C-activating G-protein coupled receptor signaling pathway Source: Ensembl
    11. regulation of excitatory postsynaptic membrane potential Source: Ensembl
    12. regulation of neurotransmitter secretion Source: Ensembl
    13. synaptic transmission Source: ProtInc

    Keywords - Molecular functioni

    Neuropeptide

    Enzyme and pathway databases

    ReactomeiREACT_16973. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
    REACT_18283. G alpha (q) signalling events.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Orexin
    Alternative name(s):
    Hypocretin
    Short name:
    Hcrt
    Cleaved into the following 2 chains:
    Alternative name(s):
    Hypocretin-1
    Short name:
    Hcrt1
    Alternative name(s):
    Hypocretin-2
    Short name:
    Hcrt2
    Gene namesi
    Name:HCRT
    Synonyms:OX, PPORX, PPOX
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:4847. HCRT.

    Subcellular locationi

    Rough endoplasmic reticulum By similarity. Cytoplasmic vesicle By similarity. Cell junctionsynapse By similarity
    Note: Associated with perikaryal rough endoplasmic reticulum as well as cytoplasmic large granular vesicles at synapses.By similarity

    GO - Cellular componenti

    1. cell junction Source: UniProtKB-KW
    2. extracellular region Source: Reactome
    3. perinuclear region of cytoplasm Source: Ensembl
    4. rough endoplasmic reticulum Source: UniProtKB-SubCell
    5. secretory granule Source: Ensembl
    6. synaptic vesicle Source: ProtInc

    Keywords - Cellular componenti

    Cell junction, Cytoplasmic vesicle, Endoplasmic reticulum, Synapse

    Pathology & Biotechi

    Involvement in diseasei

    Narcolepsy 1 (NRCLP1) [MIM:161400]: Neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep, cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy is a sudden loss of muscle tone triggered by emotions, which is the most valuable clinical feature used to diagnose narcolepsy. Human narcolepsy is primarily a sporadically occurring disorder but familial clustering has been observed.
    Note: The disease is caused by mutations affecting the gene represented in this entry. Human narcolepsy is associated with a deficient orexin system. Orexins are absent and/or greatly diminished in the brain and cerebrospinal fluid (CSF) of most narcoleptic patients.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti16 – 161L → R in NRCLP1; early-onset; impaired trafficking and processing.
    VAR_011633

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi161400. phenotype.
    Orphaneti83465. Narcolepsy without cataplexy.
    2073. Narcolepsy-cataplexy.
    PharmGKBiPA29221.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3333By similarityAdd
    BLAST
    Peptidei34 – 6633Orexin-APRO_0000020261Add
    BLAST
    Peptidei70 – 9728Orexin-BPRO_0000020262Add
    BLAST
    Propeptidei98 – 13134PRO_0000020263Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei34 – 341Pyrrolidone carboxylic acidBy similarity
    Disulfide bondi39 ↔ 45
    Disulfide bondi40 ↔ 47
    Modified residuei66 – 661Leucine amideBy similarity
    Modified residuei97 – 971Methionine amideBy similarity

    Post-translational modificationi

    Specific enzymatic cleavages at paired basic residues yield the different active peptides.

    Keywords - PTMi

    Amidation, Cleavage on pair of basic residues, Disulfide bond, Pyrrolidone carboxylic acid

    Proteomic databases

    MaxQBiO43612.
    PaxDbiO43612.
    PRIDEiO43612.

    Miscellaneous databases

    PMAP-CutDBO43612.

    Expressioni

    Tissue specificityi

    Abundantly expressed in subthalamic nucleus but undetectable in other brain regions tested (hypothalamus was not tested) and in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas.

    Gene expression databases

    BgeeiO43612.
    CleanExiHS_HCRT.
    HS_PPOX.
    GenevestigatoriO43612.

    Organism-specific databases

    HPAiCAB004758.

    Interactioni

    Protein-protein interaction databases

    BioGridi109310. 1 interaction.
    IntActiO43612. 1 interaction.
    STRINGi9606.ENSP00000293330.

    Structurei

    Secondary structure

    1
    131
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni40 – 423
    Beta strandi43 – 453
    Helixi47 – 548
    Helixi58 – 647
    Helixi76 – 8611
    Turni87 – 893
    Helixi91 – 955

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CQ0NMR-A71-97[»]
    1R02NMR-A34-66[»]
    1UVQX-ray1.80C1-12[»]
    1WSONMR-A34-66[»]
    ProteinModelPortaliO43612.
    SMRiO43612. Positions 34-66, 71-97.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO43612.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the orexin family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG70925.
    HOGENOMiHOG000230990.
    HOVERGENiHBG000256.
    InParanoidiO43612.
    KOiK05246.
    OMAiSECCRQP.
    OrthoDBiEOG7XSTHD.
    PhylomeDBiO43612.
    TreeFamiTF330756.

    Family and domain databases

    InterProiIPR001704. Orexin.
    [Graphical view]
    PANTHERiPTHR15173. PTHR15173. 1 hit.
    PfamiPF02072. Orexin. 1 hit.
    [Graphical view]
    PIRSFiPIRSF037824. Orexin. 1 hit.
    PRINTSiPR01091. OREXINPP.

    Sequencei

    Sequence statusi: Complete.

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

    O43612-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNLPSTKVSW AAVTLLLLLL LLPPALLSSG AAAQPLPDCC RQKTCSCRLY    50
    ELLHGAGNHA AGILTLGKRR SGPPGLQGRL QRLLQASGNH AAGILTMGRR 100
    AGAEPAPRPC LGRRCSAPAA ASVAPGGQSG I 131
    Length:131
    Mass (Da):13,363
    Last modified:June 1, 1998 - v1
    Checksum:i139D9C33E39E4EF1
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti16 – 161L → R in NRCLP1; early-onset; impaired trafficking and processing.
    VAR_011633

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF041240 mRNA. Translation: AAC39600.1.
    AF118885 Genomic DNA. Translation: AAD24459.1.
    CCDSiCCDS11421.1.
    RefSeqiNP_001515.1. NM_001524.1.
    UniGeneiHs.158348.

    Genome annotation databases

    EnsembliENST00000293330; ENSP00000293330; ENSG00000161610.
    GeneIDi3060.
    KEGGihsa:3060.
    UCSCiuc002hzc.1. human.

    Cross-referencesi

    Web resourcesi

    Protein Spotlight

    Qui dort dine - Issue 15 of October 2001

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF041240 mRNA. Translation: AAC39600.1 .
    AF118885 Genomic DNA. Translation: AAD24459.1 .
    CCDSi CCDS11421.1.
    RefSeqi NP_001515.1. NM_001524.1.
    UniGenei Hs.158348.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1CQ0 NMR - A 71-97 [» ]
    1R02 NMR - A 34-66 [» ]
    1UVQ X-ray 1.80 C 1-12 [» ]
    1WSO NMR - A 34-66 [» ]
    ProteinModelPortali O43612.
    SMRi O43612. Positions 34-66, 71-97.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109310. 1 interaction.
    IntActi O43612. 1 interaction.
    STRINGi 9606.ENSP00000293330.

    Proteomic databases

    MaxQBi O43612.
    PaxDbi O43612.
    PRIDEi O43612.

    Protocols and materials databases

    DNASUi 3060.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000293330 ; ENSP00000293330 ; ENSG00000161610 .
    GeneIDi 3060.
    KEGGi hsa:3060.
    UCSCi uc002hzc.1. human.

    Organism-specific databases

    CTDi 3060.
    GeneCardsi GC17M040337.
    HGNCi HGNC:4847. HCRT.
    HPAi CAB004758.
    MIMi 161400. phenotype.
    602358. gene.
    neXtProti NX_O43612.
    Orphaneti 83465. Narcolepsy without cataplexy.
    2073. Narcolepsy-cataplexy.
    PharmGKBi PA29221.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG70925.
    HOGENOMi HOG000230990.
    HOVERGENi HBG000256.
    InParanoidi O43612.
    KOi K05246.
    OMAi SECCRQP.
    OrthoDBi EOG7XSTHD.
    PhylomeDBi O43612.
    TreeFami TF330756.

    Enzyme and pathway databases

    Reactomei REACT_16973. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
    REACT_18283. G alpha (q) signalling events.

    Miscellaneous databases

    EvolutionaryTracei O43612.
    GenomeRNAii 3060.
    NextBioi 12107.
    PMAP-CutDB O43612.
    PROi O43612.
    SOURCEi Search...

    Gene expression databases

    Bgeei O43612.
    CleanExi HS_HCRT.
    HS_PPOX.
    Genevestigatori O43612.

    Family and domain databases

    InterProi IPR001704. Orexin.
    [Graphical view ]
    PANTHERi PTHR15173. PTHR15173. 1 hit.
    Pfami PF02072. Orexin. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF037824. Orexin. 1 hit.
    PRINTSi PR01091. OREXINPP.
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B."
      Lee J.-H., Bang E., Chae K.-J., Kim J.-Y., Lee D.W., Lee W.
      Eur. J. Biochem. 266:831-839(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 70-97.
    4. "Hypocretin/orexin, sleep and narcolepsy."
      Hungs M., Mignot E.
      Bioessays 23:397-408(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    5. "To eat or to sleep? Orexin in the regulation of feeding and wakefulness."
      Willie J.T., Chemelli R.M., Sinton C.M., Yanagisawa M.
      Annu. Rev. Neurosci. 24:429-458(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    6. "Solution structure of human orexin-A: regulator of appetite and wakefulness."
      Kim H.Y., Hong E., Kim J.I., Lee W.
      J. Biochem. Mol. Biol. 37:565-573(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 34-66, DISULFIDE BONDS.
    7. "Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy."
      Siebold C., Hansen B.E., Wyer J.R., Harlos K., Esnouf R.E., Svejgaard A., Bell J.I., Strominger J.L., Jones E.Y., Fugger L.
      Proc. Natl. Acad. Sci. U.S.A. 101:1999-2004(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-12 IN COMPLEX OF HLA-DQA1/HLA-DQB1 HETERODIMER (HLA-DQ0602).
    8. "Orexin-A is composed of a highly conserved C-terminal and a specific, hydrophilic N-terminal region, revealing the structural basis of specific recognition by the orexin-1 receptor."
      Takai T., Takaya T., Nakano M., Akutsu H., Nakagawa A., Aimoto S., Nagai K., Ikegami T.
      J. Pept. Sci. 12:443-454(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 35-66, DISULFIDE BONDS.
    9. Cited for: CHARACTERIZATION OF VARIANT NRCLP1 ARG-16.

    Entry informationi

    Entry nameiOREX_HUMAN
    AccessioniPrimary (citable) accession number: O43612
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: June 1, 1998
    Last modified: October 1, 2014
    This is version 127 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Protein Spotlight
      Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3