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O43612

- OREX_HUMAN

UniProt

O43612 - OREX_HUMAN

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Protein

Orexin

Gene

HCRT

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

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
Complete GO annotation...

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. endoplasmic reticulum Source: UniProtKB-KW
  3. extracellular region Source: Reactome
  4. perinuclear region of cytoplasm Source: Ensembl
  5. secretory granule Source: Ensembl
  6. synaptic vesicle Source: ProtInc
Complete GO annotation...

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 – 423Combined sources
Beta strandi43 – 453Combined sources
Helixi47 – 548Combined sources
Helixi58 – 647Combined sources
Helixi76 – 8611Combined sources
Turni87 – 893Combined sources
Helixi91 – 955Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00390000014272.
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

        10         20         30         40         50
MNLPSTKVSW AAVTLLLLLL LLPPALLSSG AAAQPLPDCC RQKTCSCRLY
60 70 80 90 100
ELLHGAGNHA AGILTLGKRR SGPPGLQGRL QRLLQASGNH AAGILTMGRR
110 120 130
AGAEPAPRPC LGRRCSAPAA ASVAPGGQSG I
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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.
GeneTreei ENSGT00390000014272.
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: November 26, 2014
This is version 129 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