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avrg: GFI1 WT vs 36n/n vs KD

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Results for Smad3

Z-value: 7.71

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Transcription factors associated with Smad3

Gene Symbol Gene ID Gene Info
Smad3
ENSMUSG00000032402.13 SMAD family member 3

Activity-expression correlation:

GenePromoterPearson corr. coef.P-valuePlot
Smad3mm39_v1_chr9_-_63619251_636192760.866.5e-02Click!

Activity profile of Smad3 motif

Sorted Z-values of Smad3 motif

Top targets:  

Promoter Log-likelihood Transcript Gene Gene Info
chr13_+_23765546 27.78 ENSMUST00000102968.3
H4c4
H4 clustered histone 4
chr13_+_23940964 24.16 ENSMUST00000102965.4
H4c2
H4 clustered histone 2
chr13_+_23715220 23.60 ENSMUST00000102972.6
H4c8
H4 clustered histone 8
chr13_+_22220000 19.20 ENSMUST00000110455.4
H2bc12
H2B clustered histone 12
chr13_-_23735822 19.06 ENSMUST00000102971.2
H4c6
H4 clustered histone 6
chr13_+_22227359 18.84 ENSMUST00000110452.2
H2bc11
H2B clustered histone 11
chr3_-_96170627 18.50 ENSMUST00000171473.3
H4c14
H4 clustered histone 14
chr13_+_22017906 17.81 ENSMUST00000180288.2
H2bc24
H2B clustered histone 24
chr13_+_23718038 16.51 ENSMUST00000073261.3
H2ac10
H2A clustered histone 10
chr13_-_21934675 16.29 ENSMUST00000102983.2
H4c12
H4 clustered histone 12
chr13_+_23755551 13.26 ENSMUST00000079251.8
H2bc8
H2B clustered histone 8
chr13_-_22016364 12.70 ENSMUST00000102979.2
H4c18
H4 clustered histone 18
chr13_+_21971631 11.74 ENSMUST00000110473.3
ENSMUST00000102982.2
H2bc22
H2B clustered histone 22
chr13_-_21900313 10.35 ENSMUST00000091756.2
H2bc13
H2B clustered histone 13
chr13_-_22227114 9.07 ENSMUST00000091741.6
H2ac11
H2A clustered histone 11
chr13_-_22017677 8.98 ENSMUST00000081342.7
H2ac24
H2A clustered histone 24
chr13_-_23755374 8.56 ENSMUST00000102969.6
H2ac8
H2A clustered histone 8
chr13_-_21971388 6.20 ENSMUST00000091751.3
H2ac22
H2A clustered histone 22
chr13_+_23868175 6.12 ENSMUST00000018246.6
H2bc4
H2B clustered histone 4
chr11_-_94932158 5.48 ENSMUST00000038431.8
Pdk2
pyruvate dehydrogenase kinase, isoenzyme 2
chr18_+_31767369 4.96 ENSMUST00000235017.2
ENSMUST00000178164.8
ENSMUST00000025109.8
Sap130
Sin3A associated protein
chr13_-_22225527 4.72 ENSMUST00000102977.4
H4c9
H4 clustered histone 9
chr1_+_107456731 4.61 ENSMUST00000182198.8
Serpinb10
serine (or cysteine) peptidase inhibitor, clade B (ovalbumin), member 10
chr7_+_104506216 4.42 ENSMUST00000067695.8
Usp17la
ubiquitin specific peptidase 17-like A
chr13_-_23867924 4.31 ENSMUST00000171127.4
H2ac6
H2A clustered histone 6
chr13_-_42000958 4.12 ENSMUST00000072012.10
Adtrp
androgen dependent TFPI regulating protein
chr7_-_100613579 3.85 ENSMUST00000060174.6
P2ry6
pyrimidinergic receptor P2Y, G-protein coupled, 6
chr5_+_72360631 3.70 ENSMUST00000169617.3
Atp10d
ATPase, class V, type 10D
chrX_+_72454702 3.68 ENSMUST00000033740.12
Zfp92
zinc finger protein 92
chr10_+_79690452 3.44 ENSMUST00000165704.8
Ptbp1
polypyrimidine tract binding protein 1
chr2_+_29759495 3.18 ENSMUST00000047521.7
ENSMUST00000134152.2
Cercam
cerebral endothelial cell adhesion molecule
chr2_-_90301592 3.00 ENSMUST00000111493.8
Ptprj
protein tyrosine phosphatase, receptor type, J
chr15_-_103161237 2.99 ENSMUST00000154510.8
Nfe2
nuclear factor, erythroid derived 2
chr1_-_21149392 2.80 ENSMUST00000037998.6
Tram2
translocating chain-associating membrane protein 2
chr13_-_23015518 2.78 ENSMUST00000226294.2
ENSMUST00000226180.2
Vmn1r210
vomeronasal 1 receptor 210
chr4_+_150366028 2.72 ENSMUST00000105682.9
Rere
arginine glutamic acid dipeptide (RE) repeats
chr16_-_44978546 2.61 ENSMUST00000114600.2
Slc35a5
solute carrier family 35, member A5
chr18_+_31768126 2.57 ENSMUST00000234846.2
ENSMUST00000234772.2
Sap130
Sin3A associated protein
chr7_+_24920840 2.56 ENSMUST00000055604.6
Zfp526
zinc finger protein 526
chr10_+_79690492 2.06 ENSMUST00000171599.8
ENSMUST00000095457.11
Ptbp1
polypyrimidine tract binding protein 1
chr13_+_23191826 1.92 ENSMUST00000228758.2
ENSMUST00000228031.2
ENSMUST00000227573.2
Vmn1r213
vomeronasal 1 receptor 213
chr15_+_81820954 1.90 ENSMUST00000038757.8
ENSMUST00000230633.2
Csdc2
cold shock domain containing C2, RNA binding
chr2_-_148250024 1.87 ENSMUST00000099270.5
Thbd
thrombomodulin
chr3_+_107008867 1.80 ENSMUST00000038695.6
Kcna2
potassium voltage-gated channel, shaker-related subfamily, member 2
chr17_-_10538253 1.66 ENSMUST00000233828.2
ENSMUST00000233645.2
ENSMUST00000042296.9
Qk
quaking, KH domain containing RNA binding
chr4_+_150171822 1.62 ENSMUST00000094451.4
Gpr157
G protein-coupled receptor 157
chr19_-_47907628 1.61 ENSMUST00000237029.2
Itprip
inositol 1,4,5-triphosphate receptor interacting protein
chr13_+_23398297 1.56 ENSMUST00000236177.2
Vmn1r221
vomeronasal 1 receptor 221
chr11_+_70323452 1.46 ENSMUST00000084954.13
ENSMUST00000108568.10
ENSMUST00000079056.9
ENSMUST00000102564.11
ENSMUST00000124943.8
ENSMUST00000150076.8
ENSMUST00000102563.2
Arrb2
arrestin, beta 2
chr13_+_22268610 1.41 ENSMUST00000228243.2
ENSMUST00000226680.2
Vmn1r188
vomeronasal 1 receptor 188
chr8_-_85549452 1.15 ENSMUST00000065539.6
Dand5
DAN domain family member 5, BMP antagonist
chr10_+_33780993 1.08 ENSMUST00000169670.8
Rsph4a
radial spoke head 4 homolog A (Chlamydomonas)
chr6_+_136785230 1.06 ENSMUST00000074556.7
ENSMUST00000203982.2
H2aj
H2J.A histone
chr1_-_74076279 1.03 ENSMUST00000187281.7
Tns1
tensin 1
chr5_-_53864874 0.99 ENSMUST00000031093.5
Cckar
cholecystokinin A receptor
chr2_-_132787790 0.95 ENSMUST00000038280.5
Fermt1
fermitin family member 1
chr17_-_71575584 0.81 ENSMUST00000233148.2
Emilin2
elastin microfibril interfacer 2
chr10_-_12424623 0.69 ENSMUST00000219003.2
Utrn
utrophin
chr13_-_42001102 0.68 ENSMUST00000121404.8
Adtrp
androgen dependent TFPI regulating protein
chr3_-_27764522 0.62 ENSMUST00000195008.6
Fndc3b
fibronectin type III domain containing 3B
chr14_-_50020788 0.60 ENSMUST00000118129.2
ENSMUST00000036972.14
Armh4
armadillo-like helical domain containing 4
chr1_+_172168764 0.60 ENSMUST00000056136.4
Kcnj10
potassium inwardly-rectifying channel, subfamily J, member 10
chr7_-_104019046 0.59 ENSMUST00000106831.3
Trim30b
tripartite motif-containing 30B
chr7_-_127187767 0.59 ENSMUST00000072155.5
Ccdc189
coiled-coil domain containing 189
chr14_+_20398230 0.54 ENSMUST00000224930.2
ENSMUST00000224110.2
ENSMUST00000225942.2
ENSMUST00000051915.7
ENSMUST00000090499.13
ENSMUST00000224721.2
ENSMUST00000090503.12
ENSMUST00000225991.2
ENSMUST00000037698.13
Fam149b
family with sequence similarity 149, member B
chr18_+_60659257 0.53 ENSMUST00000223984.2
ENSMUST00000025505.7
ENSMUST00000223590.2
Dctn4
dynactin 4
chr8_-_13727575 0.48 ENSMUST00000117551.4
Rasa3
RAS p21 protein activator 3
chr14_+_31750946 0.45 ENSMUST00000022460.11
Galnt15
polypeptide N-acetylgalactosaminyltransferase 15
chr9_-_66500404 0.43 ENSMUST00000127569.8
Usp3
ubiquitin specific peptidase 3
chr9_-_66500274 0.39 ENSMUST00000174387.2
Usp3
ubiquitin specific peptidase 3
chr1_+_180720666 0.37 ENSMUST00000085797.6
Lefty2
left-right determination factor 2
chr9_-_66500312 0.36 ENSMUST00000098613.9
Usp3
ubiquitin specific peptidase 3
chr13_-_96572460 0.34 ENSMUST00000181761.2
Ankdd1b
ankyrin repeat and death domain containing 1B
chr3_-_79645101 0.28 ENSMUST00000078527.13
Rxfp1
relaxin/insulin-like family peptide receptor 1
chr4_-_129015493 0.28 ENSMUST00000135763.2
ENSMUST00000149763.3
ENSMUST00000164649.8
Hpca
hippocalcin
chr5_+_34700709 0.26 ENSMUST00000101316.10
Sh3bp2
SH3-domain binding protein 2
chr15_-_81581457 0.24 ENSMUST00000072910.6
Chadl
chondroadherin-like
chr3_+_107008343 0.22 ENSMUST00000197470.5
Kcna2
potassium voltage-gated channel, shaker-related subfamily, member 2
chr6_+_21985902 0.22 ENSMUST00000115383.9
Cped1
cadherin-like and PC-esterase domain containing 1
chr4_-_60455331 0.21 ENSMUST00000135953.2
Mup1
major urinary protein 1
chr4_-_118792037 0.20 ENSMUST00000081960.5
Olfr1328
olfactory receptor 1328
chr11_-_82070629 0.20 ENSMUST00000108189.9
ENSMUST00000021043.5
Ccl1
chemokine (C-C motif) ligand 1
chrX_+_152615221 0.17 ENSMUST00000148708.2
ENSMUST00000123264.2
ENSMUST00000049999.9
Spin2c
spindlin family, member 2C
chr17_+_56935118 0.15 ENSMUST00000112979.4
Catsperd
cation channel sperm associated auxiliary subunit delta
chr7_+_26006594 0.15 ENSMUST00000098657.5
Cyp2a4
cytochrome P450, family 2, subfamily a, polypeptide 4
chrX_-_143471176 0.14 ENSMUST00000040184.4
Trpc5
transient receptor potential cation channel, subfamily C, member 5
chr5_+_105848598 0.14 ENSMUST00000120847.8
Lrrc8d
leucine rich repeat containing 8D
chr5_+_136067350 0.13 ENSMUST00000062606.8
Upk3b
uroplakin 3B
chr9_+_108867633 0.11 ENSMUST00000112059.10
ENSMUST00000026737.12
Shisa5
shisa family member 5
chrX_-_7054952 0.11 ENSMUST00000004428.14
Clcn5
chloride channel, voltage-sensitive 5
chr9_-_106533279 0.10 ENSMUST00000023959.13
ENSMUST00000201681.2
Grm2
glutamate receptor, metabotropic 2
chr12_-_76842263 0.07 ENSMUST00000082431.6
Gpx2
glutathione peroxidase 2
chr11_+_69047815 0.07 ENSMUST00000036424.3
Alox12b
arachidonate 12-lipoxygenase, 12R type
chr3_+_107538638 0.07 ENSMUST00000106703.2
Gm10961
predicted gene 10961
chr11_+_87457544 0.07 ENSMUST00000060360.7
Septin4
septin 4
chr2_+_3115250 0.06 ENSMUST00000072955.12
Fam171a1
family with sequence similarity 171, member A1
chr10_-_120815232 0.06 ENSMUST00000119944.8
ENSMUST00000119093.2
Lemd3
LEM domain containing 3
chr7_-_30335277 0.06 ENSMUST00000108147.3
Etv2
ets variant 2
chr13_-_22289994 0.05 ENSMUST00000227357.2
ENSMUST00000228428.2
Vmn1r189
vomeronasal 1 receptor 189
chr7_-_32026670 0.05 ENSMUST00000183195.2
Scgb2b12
secretoglobin, family 2B, member 12
chr7_-_34914675 0.05 ENSMUST00000118444.3
ENSMUST00000122409.8
Lrp3
low density lipoprotein receptor-related protein 3
chr11_-_102338473 0.05 ENSMUST00000049057.5
Fam171a2
family with sequence similarity 171, member A2
chr7_-_32529087 0.04 ENSMUST00000182975.2
Scgb2b15
secretoglobin, family 2B, member 15
chr5_-_72661546 0.03 ENSMUST00000005352.10
Corin
corin, serine peptidase
chr4_-_88562696 0.03 ENSMUST00000105149.3
Ifna13
interferon alpha 13
chr1_-_130839178 0.03 ENSMUST00000027673.11
Il20
interleukin 20
chr7_+_103065903 0.03 ENSMUST00000079348.4
Usp17lc
ubiquitin specific peptidase 17-like C
chr7_-_81104423 0.03 ENSMUST00000178892.3
ENSMUST00000098331.10
Cpeb1
cytoplasmic polyadenylation element binding protein 1
chr14_+_64331130 0.03 ENSMUST00000224112.2
ENSMUST00000165710.2
ENSMUST00000170709.2
Prss51
protease, serine 51
chr8_+_124532781 0.02 ENSMUST00000117702.2
Rab4a
RAB4A, member RAS oncogene family
chr7_-_31405182 0.02 ENSMUST00000178258.3
Scgb2b7
secretoglobin, family 2B, member 7
chr1_-_92408341 0.02 ENSMUST00000086837.2
Olfr1416
olfactory receptor 1416
chr19_+_55886708 0.02 ENSMUST00000148666.3
Tcf7l2
transcription factor 7 like 2, T cell specific, HMG box
chr7_-_32979763 0.01 ENSMUST00000179688.3
Scgb2b19
secretoglobin, family 2B, member 19
chr7_+_123061535 0.01 ENSMUST00000098056.6
Aqp8
aquaporin 8
chr7_-_102901712 0.01 ENSMUST00000073394.3
Usp17ld
ubiquitin specific peptidase 17-like D

Network of associatons between targets according to the STRING database.

First level regulatory network of Smad3

PNG image of the network

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Gene Ontology Analysis

Gene overrepresentation in biological process category:

Log-likelihood per target  Total log-likelihood Term Description
1.4 5.5 GO:0010510 regulation of acetyl-CoA biosynthetic process from pyruvate(GO:0010510)
0.7 2.7 GO:0021691 cerebellar Purkinje cell layer maturation(GO:0021691)
0.4 3.8 GO:0030321 transepithelial chloride transport(GO:0030321)
0.3 2.0 GO:0021633 optic nerve structural organization(GO:0021633)
0.3 1.0 GO:0048817 negative regulation of hair follicle maturation(GO:0048817)
0.3 1.2 GO:1900108 sequestering of BMP in extracellular matrix(GO:0035582) negative regulation of nodal signaling pathway(GO:1900108)
0.3 2.8 GO:0045048 protein insertion into ER membrane(GO:0045048)
0.2 5.5 GO:0075522 IRES-dependent viral translational initiation(GO:0075522)
0.2 3.0 GO:0034242 negative regulation of syncytium formation by plasma membrane fusion(GO:0034242)
0.2 3.0 GO:0010572 positive regulation of platelet activation(GO:0010572)
0.2 1.0 GO:0090274 reduction of food intake in response to dietary excess(GO:0002023) positive regulation of somatostatin secretion(GO:0090274)
0.2 1.5 GO:0042699 follicle-stimulating hormone signaling pathway(GO:0042699)
0.1 0.6 GO:0051933 amino acid neurotransmitter reuptake(GO:0051933) glutamate reuptake(GO:0051935)
0.1 0.7 GO:0007527 adult somatic muscle development(GO:0007527)
0.1 1.7 GO:0061158 3'-UTR-mediated mRNA destabilization(GO:0061158)
0.1 0.3 GO:0031283 negative regulation of cGMP metabolic process(GO:0030824) negative regulation of cGMP biosynthetic process(GO:0030827) negative regulation of guanylate cyclase activity(GO:0031283)
0.1 1.6 GO:0060019 radial glial cell differentiation(GO:0060019)
0.0 0.1 GO:1902630 regulation of membrane hyperpolarization(GO:1902630)
0.0 1.2 GO:0016578 histone deubiquitination(GO:0016578)
0.0 0.2 GO:1903054 negative regulation of extracellular matrix organization(GO:1903054)
0.0 5.9 GO:0019236 response to pheromone(GO:0019236)
0.0 0.6 GO:0060510 Type II pneumocyte differentiation(GO:0060510)
0.0 3.5 GO:0016579 protein deubiquitination(GO:0016579)
0.0 0.3 GO:0007567 parturition(GO:0007567)
0.0 0.1 GO:0009609 response to symbiont(GO:0009608) response to symbiotic bacterium(GO:0009609)
0.0 0.2 GO:0071394 cellular response to testosterone stimulus(GO:0071394)
0.0 1.9 GO:0043488 regulation of mRNA stability(GO:0043488)
0.0 0.5 GO:0007097 nuclear migration(GO:0007097) establishment of nucleus localization(GO:0040023)
0.0 1.1 GO:0035082 axoneme assembly(GO:0035082)
0.0 0.1 GO:0051122 hepoxilin metabolic process(GO:0051121) hepoxilin biosynthetic process(GO:0051122)
0.0 0.1 GO:0044821 meiotic telomere tethering at nuclear periphery(GO:0044821) meiotic attachment of telomere to nuclear envelope(GO:0070197) chromosome attachment to the nuclear envelope(GO:0097240)
0.0 0.1 GO:0060796 regulation of transcription involved in primary germ layer cell fate commitment(GO:0060796)

Gene overrepresentation in cellular component category:

Log-likelihood per target  Total log-likelihood Term Description
1.8 5.5 GO:0005967 mitochondrial pyruvate dehydrogenase complex(GO:0005967)
0.3 7.5 GO:0070822 Sin3-type complex(GO:0070822)
0.1 1.9 GO:0070938 contractile ring(GO:0070938)
0.1 2.0 GO:0044224 juxtaparanode region of axon(GO:0044224)
0.1 1.9 GO:0016327 apicolateral plasma membrane(GO:0016327)
0.0 3.0 GO:0001772 immunological synapse(GO:0001772)
0.0 0.5 GO:0005869 dynactin complex(GO:0005869)
0.0 1.6 GO:0060170 ciliary membrane(GO:0060170)
0.0 0.6 GO:0097449 astrocyte projection(GO:0097449)
0.0 0.5 GO:0031235 intrinsic component of the cytoplasmic side of the plasma membrane(GO:0031235)
0.0 0.3 GO:0044327 dendritic spine head(GO:0044327)
0.0 1.7 GO:0000118 histone deacetylase complex(GO:0000118)
0.0 4.9 GO:0044306 neuron projection terminus(GO:0044306)
0.0 3.0 GO:0032993 protein-DNA complex(GO:0032993)
0.0 1.0 GO:0031941 filamentous actin(GO:0031941)
0.0 0.1 GO:0036128 CatSper complex(GO:0036128)

Gene overrepresentation in molecular function category:

Log-likelihood per target  Total log-likelihood Term Description
1.4 5.5 GO:0004740 pyruvate dehydrogenase (acetyl-transferring) kinase activity(GO:0004740)
1.0 3.8 GO:0015065 uridine nucleotide receptor activity(GO:0015065) G-protein coupled pyrimidinergic nucleotide receptor activity(GO:0071553)
0.5 1.5 GO:0031826 type 2A serotonin receptor binding(GO:0031826)
0.4 5.5 GO:0001069 regulatory region RNA binding(GO:0001069)
0.4 1.2 GO:0016015 morphogen activity(GO:0016015)
0.2 3.0 GO:0070097 delta-catenin binding(GO:0070097)
0.1 2.0 GO:0015271 outward rectifier potassium channel activity(GO:0015271)
0.1 2.6 GO:0005351 sugar:proton symporter activity(GO:0005351)
0.1 0.6 GO:0015272 ATP-activated inward rectifier potassium channel activity(GO:0015272)
0.1 0.2 GO:0005009 insulin-activated receptor activity(GO:0005009)
0.1 2.7 GO:0001106 RNA polymerase II transcription corepressor activity(GO:0001106)
0.0 2.7 GO:0050699 WW domain binding(GO:0050699)
0.0 6.0 GO:0005550 pheromone binding(GO:0005550)
0.0 4.7 GO:0004843 thiol-dependent ubiquitin-specific protease activity(GO:0004843)
0.0 0.5 GO:0015278 calcium-release channel activity(GO:0015278) ligand-gated calcium channel activity(GO:0099604)
0.0 0.5 GO:0004653 polypeptide N-acetylgalactosaminyltransferase activity(GO:0004653)
0.0 0.7 GO:0017166 vinculin binding(GO:0017166)
0.0 0.1 GO:0004052 arachidonate 12-lipoxygenase activity(GO:0004052)
0.0 0.1 GO:0070679 inositol 1,4,5 trisphosphate binding(GO:0070679)
0.0 0.1 GO:0001640 adenylate cyclase inhibiting G-protein coupled glutamate receptor activity(GO:0001640)
0.0 0.1 GO:0005225 volume-sensitive anion channel activity(GO:0005225)

Gene overrepresentation in curated gene sets: canonical pathways category:

Log-likelihood per target  Total log-likelihood Term Description
0.0 1.5 PID NFKAPPAB ATYPICAL PATHWAY Atypical NF-kappaB pathway
0.0 1.9 PID FRA PATHWAY Validated transcriptional targets of AP1 family members Fra1 and Fra2
0.0 3.0 PID VEGFR1 2 PATHWAY Signaling events mediated by VEGFR1 and VEGFR2
0.0 4.2 NABA ECM REGULATORS Genes encoding enzymes and their regulators involved in the remodeling of the extracellular matrix
0.0 1.0 PID ILK PATHWAY Integrin-linked kinase signaling

Gene overrepresentation in curated gene sets: REACTOME pathways category:

Log-likelihood per target  Total log-likelihood Term Description
0.4 5.5 REACTOME REGULATION OF PYRUVATE DEHYDROGENASE PDH COMPLEX Genes involved in Regulation of pyruvate dehydrogenase (PDH) complex
0.2 3.8 REACTOME P2Y RECEPTORS Genes involved in P2Y receptors
0.1 1.9 REACTOME COMMON PATHWAY Genes involved in Common Pathway
0.1 3.7 REACTOME ION TRANSPORT BY P TYPE ATPASES Genes involved in Ion transport by P-type ATPases
0.0 1.5 REACTOME ACTIVATED NOTCH1 TRANSMITS SIGNAL TO THE NUCLEUS Genes involved in Activated NOTCH1 Transmits Signal to the Nucleus
0.0 5.5 REACTOME MRNA SPLICING Genes involved in mRNA Splicing
0.0 2.0 REACTOME VOLTAGE GATED POTASSIUM CHANNELS Genes involved in Voltage gated Potassium channels
0.0 3.0 REACTOME FACTORS INVOLVED IN MEGAKARYOCYTE DEVELOPMENT AND PLATELET PRODUCTION Genes involved in Factors involved in megakaryocyte development and platelet production
0.0 0.4 REACTOME SIGNALING BY NODAL Genes involved in Signaling by NODAL
0.0 0.6 REACTOME INHIBITION OF VOLTAGE GATED CA2 CHANNELS VIA GBETA GAMMA SUBUNITS Genes involved in Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits
0.0 0.1 REACTOME ROLE OF SECOND MESSENGERS IN NETRIN1 SIGNALING Genes involved in Role of second messengers in netrin-1 signaling