Orexin receptor pathway (Homo sapiens)
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MAPK9
16
MAPK3
T202
Y204
5, 10
21
MAP2K2
S222
S216
Lysosome
Regulation of
Mesenchymal
Stem Cell
Differentiation
OR /
BOTH
Increased
Epinephrine
secretion
from adrenal
medullary cells
Orexin signaling pathway
Apoptosis pathway
Increased expression
In anoxia /
hypoglycemic
astrocytes
Genes transcriptionally regulated
by orexin A in GT1-7-OX1
(hypothalamic neurons derived
HCRTR1-expressed cell line)
Promotes
osteogenic
differentiation
& mineralization
mTORC1
Potential
regulation of
hypothalamic-
pituitary-
gonadal axis
Lysosome v-ATPase
Pathway
Map Legend
Increased
surface
expression
in striatum
Catecholamine
biosynthesis
in adrenal
medullary cells
In hypothalamic
neurons
Neuro-
protective
effect
Cortisol
secretion in
Adrenocortical
cells (H295R)
6
Orexin-A
effect is
Gs/Gq/Gi-
dependent
Orexin-B
effect is
Gq-dependent
Modulation of
Kappa opioid
receptor - Gai
signaling
Studied for Orexin A and not Orexin B
Studied for Orexin B and not Orexin A
Studied for both but predominenty Orexin A dependent
Studied for both but predominenty Orexin B dependent
Studied for both and induced by both
Studied with HCRTR1 modulation and not HCRTR2
Studied with HCRTR2 modulation and not HCRTR1
Studied for both but predominenty HCRTR1 dependent
Studied for both but predominenty HCRTR2 dependent
Studied for both and dependent on both
Not studied for both and receptor dependency unknown
Based on receptor expression HCRTR1 (predominent)
Based on receptor expression HCRTR2 (predominent)
Based on receptor expression (may be both)
In parvocellular
cells of PVN on
i.c.v injection
Secretion of
osteocalcin in
osteoblast-like
(ROB) cells
Adenylate
cyclase
6
In pre- and
differentiated
3T3-L1 adipocytes
NPFFR1
OPRK1
26
PIK3R1
HSD3B2
mRNA
mRNA
Modulation of
excitatory
transmission in
cerebral cortex
FMR1NB
JARID2
PDE11A
NSMAF
LAMA2
OPA1
CD24
IL4
CLEC4C
TOX
DDX52
BTF3
HCRTR1
MAPK8
T185
T183
MAPK14
T180
Y182
4, 10
MAPK1
Y187
T185
4, 5, 10
PPARG
SLC2A4
14
Glucose
metabolism
In differentiated
3T3-L1 adipocytes
AVP
CRH
3
HCRTR2
FOS
11
Potential activation
of HPA axis through
CRF and AVP neuron
stimulation
LIPE
PPARG
LPL
LIPE
LPL
In subcutaneous
HCRTR1 and R2
mRNA expressing
adipose tissue
explants
GCG
Reduced pro-glucagon
biosynthesis in
glucagon-producing
InR1-G9 cells
Glucose
CREB1
20
S133
PDPK1
S241
AKT1
S473
FOXO1
S256
PI3K
Catalytic
MAP2K1
S218
S222
GNAS
GNAI1
12, 22
12
GNAQ
PKA
STAR
STAR
Adreno-cortico
steroidogenesis
in H295R cells
BGLAP
CGA
LHB
19
19
Reduced
Glycerol release
in omental
adipose tissue
Secretion of LH &
FSH gonadotropins
in Primary anterior
pituatory cells
CGA
19
FSHB
HCRTR2
19
Increased HCRTR1
expression
counteracts
testosterone-
induced nuclear
transloaction of
Androgen Receptor
in LnCaP cells
HCRTR1
9, 19
Regulation of
expression of
HCRTR1/2 in
Primary anterior
pituatory cells
LH
FSH
MAPK7
T218
Y220
CYP11A1
CYP21A2
Cortisol
CYP11B1
CYP11B2
Triglyceride
Production
6
HCRTR2
19
6
6
cAMP
5, 6
6
6
6
ARRB1
HCRTR1
8
Y358
Y83
ARRB1
21
HCRTR1
21
ARRB2
HCRTR1
ARRB1
ARRB2
21
ARRB2
Cell death
in HCRTR1-
transfected
CHO-K1 cells
IP3
4, 5, 8
Ca2+
16
16
Release
from ER
DAG
16, 23
PIP2
PIP3
24
Ca2+
16
L-type
Calcium
channels
23
CNR1
2
TH
S40
Voltage-gated
Ca2+ and Na+
channels
CCK
Glycerol
CCK
Cholecystokinin
secretion in
STC-1 cells
GH1
Growth
Hormone
secretion in
somatotropes
16
Testosterone
9, 10
Testosterone
secretion in
testicular cells
Cytochrome C
9
Cytochrome C
CASP7
CASP3
Apoptosis in
OX1R+ HT29-D4,
SK-N-MC, C6 &
CHO cell lines
21
Sustained
HCRTR1-ARRB2
interaction
prolonged
MAPK1/3
activation
in HEK-293T
HCRTR1+ cells
PLCD1
PRKCE
PRKCZ
HIF1A
Increased
glucose
utilization in
hypothalamic
neurons
VHL
HIF1A
LDHA
PDK1
PDHB
Activation
of PDH and
Suppresion
of lactate
production
in adipocytes
GCG
PTPN11
8
PRKCA
T638
IP1
IP2
GRIN1
GRIN2A
GRIN2B
GRIA1
GRIA2
In cortical
neurons
GRIA1
PRKCD
T505
PRKCB
T641
PRKD1
S916
PRKD3
S744
S748
HCRTR2
ARRB1
ARRB2
5
5
HCRTR2
ARRB2
5
ARRB1
5
5
PIK3R2
SLC2A4
SLC2A4
Increased
Glucose/
stimulated
insulin
secretion in
INS-1 cells
14
ADIPOQ
Adiponectin
secretion in
adipocytes
Increased
glucose
uptake in
adipocytes
PLD1
BMP7
BMPR1A
BMP7
BMPR1A
SMAD1
S463
SMAD5
S465
PRDM16
DYNLT1
DYNLT3
Regulation
of receptor
internalization
HCRTR1
Regulation of
expression of
HCRTR1/2 in
leuteal cells
Progesterone
Decreased
Progesterone
secretion by
luteal cells
Receptor internalization and recycling
Epinephrine
PRKAA1
23
T172
Increased
Neuropeptide Y
production and
regulation of
feeding
behavior
CAMKK2
23
NPY
23
INS
Reduced
glucagon
secretion in
glucagon-
producing
InR1-G9 cells
18
Pro-survival /
anti-apoptotic
functions in
INS-1 cells &
BGC-823 gastric
cancer cells
18
HCRTR1
15
Regulation of
expression of
HCRTR1 in
INS-1 cells
Inhibition of
osteoblastogenesis
and augmentation
of bone formation
GHRL
LEP
MTOR
S2481
Hepatocyte
proliferation
RPS6
S235
S236
S240
S244
RPS6KB1
T389
EIF4B
S422
RPS6KA1
S380
MTOR
RRAGC
GTP
DAGLA
CASP9
7
Pro-survival /
anti-apoptotic
functions in
SGC-7901 cells
EIF4EBP1
27
T46
T37
Cortisol
secretion
in H295R
cells
27
NFE2L2
25
HMOX1
Angiogenesis
25
NFE2L2
HMOX1
25
25
CASP3
18
Proliferation /
anti-apoptotic
functions in
H295R cells
SLC2A1
SLC2A1
Increased
glucose
uptake in
Hep3B &
HepG2 cells
Activation
of PDH and
Mitochondrial
glucose
oxidation in
Hep3B/G2 cells
2-AG
MAPK3
Y204
T202
MAPK1
T185
Y187
STAT3
S727
POMC
Repression
of satiety
POMC
Reduced
alpha-MSH
release in
ARC primary
neurons
NRF2 pathway
GNA11
22
SLC2A1
PDHB
RUNX1
GJA3
RARA
GLIS1
HOMER1
LDLR
DOK7
NPAS4
NOCT
CLDN4
SERP1
KCNK3
LUZP1
NR4A1
OPN3
PDP1
SFPQ
PER2
YARS2
TRIM9
KLF4
CDKN1A
HSPA5
CCN2
MANF
NR4A3
DUSP4
TRA2A
OSBPL3
TENT5A
EGR3
EGR1
FOSL2
EGR2
ARC
HBEGF
MAFF
HMGA2
JUNB
NOG
PAPPA
GADD45B
CXXC5
TNC
SKIL
DCLK1
ID3
FOS
LRRC8C
IRF5
ID1
SPP1
HES1
MYC
BHLH40
SRF
FOSB
GLIS2
HMGA1
ID4
KLF10
RUNX2
ZFP28
ZMYM3
HAGHL
DBP
RUNX1T1
Sleep deprivation
SGK1
SGK1
Genes
regulated
by SGK1
Regulation of
lipogenesis
and lipolysis
LEP
14
LEP
14, 17
Regulation
of leptin
secretion in
adipocytes
LEP
VEGFA
FLT4
NOS3
PDP1
In hypothalamic
neurons
In hypothalamic
neurons
PRKCA
MAPK1
MAPK3
Glutamic
acid
uptake
Regulation of
neuron survival
following
hypoxic
injury
SLC1A2
SLC1A2
SLC1A2
Glutamic acid
In anoxia /
hypoglycemic
astrocytes
TFAM
COX7A1
UCP1
COX8BP
DIO2
PPARG
CEBPA
Mitochondrial
biogenesis
and brown fat
adipogenesis
CY
PM
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
PM
CY
CY
EC
CY
PM
CY
EC
CY
EC
Glucose
CY
EC
CY
EC
CY
EC
CY
EC
CY
EC
CY
PM
CY
PM
CY
PM
CY
PM
CY
PM
CY
PM
CY
PM
CY
EC
SRC
family
8
HCRT
HCRT
HCRT
HCRT
RUNX2
SP7
ALPP
BGLAP
CALCA
PPOX
COX2
Gastroprotection
Incorporation
of glucose
to NEFA in
adipocytes
Triglyceride
production
2-AG
Decreased expression
Metabolite
Protein
Protein
Protein function activation
Regulation of gene expression
Protein-protein interaction
Protein activity inhibition
Leads to through known
or unknown mechanisms
(Multiple colored edges
are used to delineate
the interconnectivity
across crossing edges)
Protein
Protein family/specific
subunits or isozymes
not reported in studies
Protein phosphosite & residue
CY
PM
Protein transport
NU
EC
Plasma membrane
Cytoplasm
Nucleus
Extracellular
Receptor
Orexin A
Protein
Receptor
hypersensitization
NU
CY
MT
CY
GNRH1
26
NPVF
26
IL6
CXCL8
MMP3
MMP13
VCAM1
ICAM1
13
13
SELE
13
TNF
TNF
1, 13
IL1B
IL9
IL4
IL10
NOX4
CXCL2
Anti-inflammatory
response of orexin
in Intracerebral
hemorrhage
Protein
Xnnn
Mitochondria
MT
Protein cleavage
PA
2
AA
PLA2G4A
2
2
24
Orexin B