PROSITE documentation PDOC52103H-NOXA-type PAS domain profile
View entry in original PROSITE document format
View entry in raw text format (no links)
PURL: https://purl.expasy.org/prosite/documentation/PDOC52103
Nitric oxide (NO) is a gaseous signalling molecule that is involved in many important physiological processes, such as vasodilatation, neurotransmission, platelet aggregation, immunity, cell proliferation, and mitochondrial respiration. NO readily permeates target cell membranes, and after diffusing across the membrane, it binds and activates soluble guanylate cyclase (sGC), the primary NO acceptor. Upon NO binding, the global conformation of sGC switches from the inactive bent conformation to the activated extended conformation. sGC catalyzes the cyclization reaction of guanosine triphosphate (GTP) to generate inorganic pyrophosphate and the secondary messenger cyclic guanosine monophosphate (cGMP). cGMP then acts on downstream effectors, including cGMP-regulated protein kinases, phosphodiesterases, and ion channels, to regulate physiological processes in the cell.
sGCs are heme-containing dimeric proteins found throughout many domains of life. The best characterized sGCs are α/β-type, consisting of two heterodimeric subunits, denoted α and β. The α- and β-subunits have some sequence homology and are similarly organized into modular domains, including an N-terminal H-NOX domain (see <PDOC52090>), a H-NOX associated (H-NOXA) (or Heme NO Binding Associated, H-NOBA) Per/Arnt/Sim (PAS) domain, a coiled-coil (CC) domain, and a C-terminal catalytic domain (see <PDOC00425>). The H-NOXA-type PAS domain is also present at the N terminus of 2 other cyanobacterial signaling proteins: signal transduction histidine kinase (STHK) and 2-component hybrid sensor and regulator (2-CHSR). The H-NOXA-type PAS domains could be used for signal transduction purposes or perhaps even sensory purposes [1,2,3,4].
The H-NOXA-type PAS domain structure is comprised of a 6 or 7-stranded anti-parallel β-barrel flanked by several α-helices (see <PDB:4GJ4>). A hydrophobic patch near the N-terminus of the H-NOXA PAS domain mediates homo- and heterodimerization. The structure also reveals a small internal cavity that may serve to bind ligands or participate in signal transduction [2,3,4].
The profile we developed covers the entire H-NOXA-type PAS domain.
Last update:May 2026 / First entry.
-------------------------------------------------------------------------------
PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Iyer L.M. Anantharaman V. Aravind L. |
| Title | Ancient conserved domains shared by animal soluble guanylyl cyclases and bacterial signaling proteins. | |
| Source | BMC Genomics 4:5-5(2003). | |
| PubMed ID | 12590654 | |
| DOI | 10.1186/1471-2164-4-5 |
| 2 | Authors | Ma X. Sayed N. Baskaran P. Beuve A. van den Akker F. |
| Title | PAS-mediated dimerization of soluble guanylyl cyclase revealed by signal transduction histidine kinase domain crystal structure. | |
| Source | J. Biol. Chem. 283:1167-1178(2008). | |
| PubMed ID | 18006497 | |
| DOI | 10.1074/jbc.M706218200 |
| 3 | Authors | Purohit R. Weichsel A. Montfort W.R. |
| Title | Crystal structure of the Alpha subunit PAS domain from soluble guanylyl cyclase. | |
| Source | Protein. Sci. 22:1439-1444(2013). | |
| PubMed ID | 23934793 | |
| DOI | 10.1002/pro.2331 |
| 4 | Authors | Kang Y. Liu R. Wu J.X. Chen L. |
| Title | Structural insights into the mechanism of human soluble guanylate cyclase. | |
| Source | Nature 574:206-210(2019). | |
| PubMed ID | 31514202 | |
| DOI | 10.1038/s41586-019-1584-6 |
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.