Myometrial relaxation and contraction pathways (WP289)

Homo sapiens

This pathway illustrates signaling networks implicated in uterine muscle contraction at labor and quiescence throughout gestation (pregnancy). The muscle of the uterus, responsible for contractile activity is the myometrium. Genes in this pathway are either transcribed in myometrial muscle cells or act upon the myometrium to regulate contraction. The left half of this pathway illustrates pathways of myometrial relaxation that are active throughout normal gestation. These signaling events act to suppress coordinated contractions to prevent the early onset of labor at term, largely via activation of the adenylyl-cyclase thrhough G-protein coupled receptors. On the right side of this pathway are signaling componets involved in the activation of uterine contractions at labor, in particular, activation of calcium mobilization via Oxytocin mediated binding to the Oxytocin G-protein coupled receptor. Additional genes implicated in this pathway, based on microarray expression profiling of gestation, term and postpartum of term mice are also included (e.g., Guca2b, Rdc1, Edg2) have also been included. For a detailed description of this pathway see: Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


Nathan Salomonis , Alex Pico , Thomas Kelder , Kristina Hanspers , Martijn Van Iersel , Egon Willighagen , Martina Summer-Kutmon , Friederike Ehrhart , and Eric Weitz


last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.


Homo sapiens



Cell Type Ontology

smooth muscle cell

Pathway Ontology

signaling pathway


Label Type Compact URI Comment
ATP Metabolite cas:1927-31-7
Cyclic AMP Metabolite hmdb:HMDB0000058
ADP Metabolite cas:58-64-0
Cyclic GMP Metabolite hmdb:HMDB0001314
ADP Metabolite cas:58-64-0
ATP Metabolite cas:1927-31-7
Cyclic AMP Metabolite hmdb:HMDB0000058
RAMP1 GeneProduct ncbigene:10267
IGFBP6 GeneProduct ncbigene:3489
GNG13 GeneProduct ncbigene:51764
RGS11 GeneProduct ncbigene:8786
PRKCZ GeneProduct ncbigene:5590
ADCY5 GeneProduct ncbigene:111 There is no SwissProt entry for a full-length sequence in mouse. This EST is from the Affymetrix Murine6500 chip.
RYR1 GeneProduct ncbigene:6261
ATP2A3 GeneProduct ncbigene:489
ATF4 GeneProduct ncbigene:468
GUCY2E GeneProduct ncbigene:2985 PMID: 11854458
PRKAR2B GeneProduct ncbigene:5577
PRKCG GeneProduct ncbigene:5582
ADCY2 GeneProduct ncbigene:108 There is no SwissProt entry for a full-length sequence in mouse. This EST is from the Affymetrix Murine6500 chip.
PRKCE GeneProduct ncbigene:5581 This EST is listed on the Affymetrix Murine6500 chip. The SwissProt entry name is KPCE MOUSE.
IGFBP5 GeneProduct ncbigene:3488
GRK4 GeneProduct ncbigene:2868
GNB3 GeneProduct ncbigene:2784
GNG3 GeneProduct ncbigene:2785
PKIB GeneProduct ncbigene:5570
FOS GeneProduct ncbigene:2353 PMID: 10218980 PMID: 7628395 [
GRK5 GeneProduct ncbigene:2869
OXTR GeneProduct ncbigene:5021
MYLK2 GeneProduct ncbigene:85366 KML2 MOUSE
GNG12 GeneProduct ncbigene:55970
RGS2 GeneProduct ncbigene:5997
GNG2 GeneProduct ncbigene:54331
RGS6 GeneProduct ncbigene:9628
JUN GeneProduct ncbigene:3725 PMID: 10218980
ADCY3 GeneProduct ncbigene:109
GNG7 GeneProduct ncbigene:2788
PRKACB GeneProduct ncbigene:5567
CREBL1 GeneProduct ncbigene:1388
ACTA2 GeneProduct ncbigene:59
RAMP2 GeneProduct ncbigene:10266
ADMR GeneProduct ncbigene:11318
CALCA GeneProduct ncbigene:796 CRF HUMAN PMID: 11854458
ADCY8 GeneProduct ncbigene:114
ADCY1 GeneProduct ncbigene:107 CYA1 HUMAN
ARRB2 GeneProduct ncbigene:409
ATF1 GeneProduct ncbigene:466
NOS1 GeneProduct ncbigene:4842 PMID: 11854458
GRK5 GeneProduct ncbigene:2869
RGS17 GeneProduct ncbigene:26575
PRKCH GeneProduct ncbigene:5583
RYR2 GeneProduct ncbigene:6262
RGS18 GeneProduct ncbigene:64407
YWHAB GeneProduct ncbigene:7529
IL6 GeneProduct ncbigene:3569
GRK6 GeneProduct ncbigene:2870
RCP9 GeneProduct ncbigene:27297
LGR7 GeneProduct ncbigene:59350 PMID: 11809971
CNN1 GeneProduct ncbigene:1264
YWHAH GeneProduct ncbigene:7533
CAMK2G GeneProduct ncbigene:818
RGS7 GeneProduct ncbigene:6000
MYL4 GeneProduct ncbigene:4635
RGS1 GeneProduct ncbigene:5996
PRKCB1 GeneProduct ncbigene:5579
MYLK2 GeneProduct ncbigene:85366 KML2 MOUSE
EDG2 GeneProduct ncbigene:1902
RAMP3 GeneProduct ncbigene:10268
CAMK2D GeneProduct ncbigene:817
PRKCQ GeneProduct ncbigene:5588
NOS3 GeneProduct ncbigene:4846 PMID: 11854458
CALD1 GeneProduct ncbigene:800
GSTO1 GeneProduct ncbigene:9446
CRH GeneProduct ncbigene:1392 CRF HUMAN PMID: 11854458
PRKCA GeneProduct ncbigene:5578
YWHAZ GeneProduct ncbigene:7534 PMID: 9861170 PMID: 1317796
GRK4 GeneProduct ncbigene:2868
CNN2 GeneProduct ncbigene:1265
PRKAR2A GeneProduct ncbigene:5576
ARRB2 GeneProduct ncbigene:409
GNB2 GeneProduct ncbigene:2783
GNG11 GeneProduct ncbigene:2791
OXTR GeneProduct ncbigene:5021 Sladek SM, Westerhausen-Larson A, Roberts JM. PMID: 10377025
IGFBP4 GeneProduct ncbigene:3487
RYR3 GeneProduct ncbigene:6263
RGS10 GeneProduct ncbigene:6001
DGKZ GeneProduct ncbigene:8525
RGS5 GeneProduct ncbigene:8490
ATP2A2 GeneProduct ncbigene:488
IGFBP2 GeneProduct ncbigene:3485
RGS20 GeneProduct ncbigene:8601
GNAQ GeneProduct ncbigene:2776
GNB5 GeneProduct ncbigene:10681
YWHAE GeneProduct ncbigene:7531
OXT GeneProduct ncbigene:5020 MGI:97453
PRKAR1A GeneProduct ncbigene:5573 KAP0 HUMAN
RGS9 GeneProduct ncbigene:8787
SFN GeneProduct ncbigene:2810
ADCY7 GeneProduct ncbigene:113
ATF5 GeneProduct ncbigene:22809
PLCG2 GeneProduct ncbigene:5336
IL1B GeneProduct ncbigene:3553
GNG5 GeneProduct ncbigene:2787
ADM GeneProduct ncbigene:133
RGS16 GeneProduct ncbigene:6004
ITPR3 GeneProduct ncbigene:3710
PRKD1 GeneProduct ncbigene:5587 KPCM HUMAN
ACTG1 GeneProduct ncbigene:71
GNG8 GeneProduct ncbigene:94235
LGR8 GeneProduct ncbigene:122042 PMID: 11809971 LGR8 MOUSE
GNB4 GeneProduct ncbigene:59345
PRKAR1B GeneProduct ncbigene:5575
RGS19 GeneProduct ncbigene:10287
ACTB GeneProduct ncbigene:60
CORIN GeneProduct ncbigene:10699 MGI:97367
GABPB2 GeneProduct ncbigene:2553
PRKCD GeneProduct ncbigene:5580
SP1 GeneProduct ncbigene:6667
GABPA GeneProduct ncbigene:2551
ADCY6 GeneProduct ncbigene:112
GUCA2A GeneProduct ncbigene:2980
ITPR1 GeneProduct ncbigene:3708
CAMK2B GeneProduct ncbigene:816
CRHR1 GeneProduct ncbigene:1394
RLN1 GeneProduct ncbigene:6013
PDE4D GeneProduct ncbigene:5144
GRK6 GeneProduct ncbigene:2870
ETS2 GeneProduct ncbigene:2114
ATF3 GeneProduct ncbigene:467
ADCY4 GeneProduct ncbigene:196883 There is no SwissProt entry for a full-length sequence in mouse. This EST is from the Affymetrix Murine6500 chip.
PLCD1 GeneProduct ncbigene:5333
RGS4 GeneProduct ncbigene:5999
RGS14 GeneProduct ncbigene:10636
SLC8A1 GeneProduct ncbigene:6546
GUCA2B GeneProduct ncbigene:2981
ARRB1 GeneProduct ncbigene:408
GJA1 GeneProduct ncbigene:2697
ARRB1 GeneProduct ncbigene:408
YWHAG GeneProduct ncbigene:7532
CACNB3 GeneProduct ncbigene:784
CMKOR1 GeneProduct ncbigene:57007 PMID: 10614663
IGFBP1 GeneProduct ncbigene:3484
PKIG GeneProduct ncbigene:11142
PDE4B GeneProduct ncbigene:5142
GNGT1 GeneProduct ncbigene:2792
PKIA GeneProduct ncbigene:5569
YWHAQ GeneProduct ncbigene:10971
CREB3 GeneProduct ncbigene:10488
ACTC GeneProduct ncbigene:70
IGFBP3 GeneProduct ncbigene:3486 Relaxin is a member of the Insulin Growth Factor family of proteins. IGFBP-3 binds IGFII preferentially. (SwissProt).
PLCG1 GeneProduct ncbigene:5335
GNAS GeneProduct ncbigene:2778
MAFF GeneProduct ncbigene:23764 OMIM: Inoue et al. (1994) demonstrated that the US-2 element in the promoter of the human oxytocin receptor gene (OXTR; 167055) binds specifically nuclear proteins from human myometrium at parturition. Using the US-2 element in a yeast 1-hybrid system to screen a human myometrium cDNA library, Kimura et al. (1999) isolated a full-length cDNA encoding the homolog of chicken MafF. Human MAFF encodes a deduced 164-amino acid protein with a predicted molecular mass of 17.8 kD. Like other small MAF proteins (e.g., MAFG, 602020), it contains an extended leucine zipper structure and lacks an N-terminal transactivating domain. Northern blot analysis showed a strong 2.6-kb signal in mRNA from term myometrium and from kidney, but not from nonpregnant myometrium. The MAFF protein is also preferentially expressed in term myometrium. The authors concluded that MAFF plays a role in OXTR gene upregulation at term.
PRKACA GeneProduct ncbigene:5566
CALM3 GeneProduct ncbigene:808
ATF2 GeneProduct ncbigene:1386
GNG4 GeneProduct ncbigene:2786
CALM2 GeneProduct ncbigene:805
ADCY9 GeneProduct ncbigene:115
CALM1 GeneProduct ncbigene:801
ACTA1 GeneProduct ncbigene:58
GNB1 GeneProduct ncbigene:2782
MYL2 GeneProduct ncbigene:4633
RGS3 GeneProduct ncbigene:5998
ITPR2 GeneProduct ncbigene:3709
PLCB3 GeneProduct ncbigene:5331
CAMK2A GeneProduct ncbigene:815
NFKB1 GeneProduct ncbigene:4790 Localization of regulatory protein binding sites in the proximal region of human myometrial connexin 43 gene. Echetebu CO, Ali M, Izban MG, MacKay L, Garfield RE. PMID: 10421804
CREB1 GeneProduct ncbigene:1385
GUCY1A3 GeneProduct ncbigene:2982 PMID: 11854458


  1. Is up-regulation of phosphodiesterase 4 activity by PGE2 involved in the desensitization of beta-mimetics in late pregnancy human myometrium? Méhats C, Tanguy G, Dallot E, Cabrol D, Ferré F, Leroy MJ. J Clin Endocrinol Metab. 2001 Nov;86(11):5358–65. PubMed Europe PMC Scholia
  2. Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells. Aggelidou E, Hillhouse EW, Grammatopoulos DK. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3300–5. PubMed Europe PMC Scholia
  3. Identifying genetic networks underlying myometrial transition to labor. Salomonis N, Cotte N, Zambon AC, Pollard KS, Vranizan K, Doniger SW, et al. Genome Biol. 2005;6(2):R12. PubMed Europe PMC Scholia