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55  structures 3105  species 1  interaction 23723  sequences 5329  architectures

Family: PAS_3 (PF08447)

Summary: PAS fold

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PAS domain Edit Wikipedia article

PAS fold
FixL 1y28.png
Crystallographic structure of the PAS domain of the bacterial oxygen sensor protein fixL.[1] The protein is depicted as a rainbow colored cartoon (N-terminus = blue, C-terminus = red while the heme ligand is shown as sticks (carbon = white, nitrogen = blue, oxygen = red, iron = orange).
Identifiers
Symbol PAS
Pfam PF00989
InterPro IPR013767
SMART PAS
PROSITE PDOC50112
SCOP 2phy
SUPERFAMILY 2phy
CDD cd00130

A Per-Arnt-Sim (PAS) domain is a protein domain found in all kingdoms of life. [2] It is found in many signaling proteins, where it functions as a signaling sensor. [3][4]Generally, the PAS domain acts as a molecular velcro, whereby small molecules and other proteins via association with the PAS domain. [5][6][7]Due to this velcro capability, the PAS domain has been shown as the key structural motif involved in protein-protein interactions of the circadian clock.


Discovery

PAS domains are found in a large number of organisms from bacteria to mammals. The PAS domain was named after the three proteins in which it was first discovered[8]:

Per – period circadian protein

Arnt – aryl hydrocarbon receptor nuclear translocator protein

Sim – single-minded protein

Since the initial discovery the PAS domain, a a large quantity of PAS binding sites have been discovered in bacteria and eukaryotes, a subset of which are responsive to oxygen, light and voltage, which gives rise to PAS LOV proteins.[9]

Structure

Although the PAS domain exhibits a degree of sequence variability, the three-dimensional structure of the PAS domain core is broadly conserved. [10] This core consists of a five-stranded antiparallel β-sheet and several α-helices. Structural changes, as a result of signaling, predominantly originate within the β-sheet. These signals propagate via the α-helices of the core to the covalently-attached effector domain. [11] In 1998, the PAS domain core architecture was first characterized in the the structure of Halorhodospira halophila photoactive yellow protein (PYP). [10] In many proteins, a dimer of PAS domains is required, whereby one binds a ligand, and the other mediates interactions with other proteins. [7]

Examples of PAS in Organisms

The PAS domains that are known share less than 20% average pairwise sequence identity, meaning they are surprisingly dissimilar. [10] PAS domains are frequently found on proteins with other environmental sensing mechanisms. An example of PAS B domain of Hif1a and Hif2a are oxygen-sensing domains. [12] Many PAS domains are attached to photoreceptive cells. [12]

Bacteria

Often in the bacterial kingdom, PAS domains are positioned at the amino terminus of signaling proteins such as sensor histidine kinases, cyclic-di-GMP synthases and hydrolases, and methyl-accepting chemotaxis proteins. [10]

Neurospora

In the presence of light White Collar-1 (WC-1) and White Collar-2 (WC-2) dimerizes via mediation by the PAS domains, which activates translation of FRQ. [13]

Drosophila

In the presence of light, CLK and CYC attach via PAS, activating the translation of PER, which then associates to Tim via the PER PAS domain.


Genes in Drosophila Binding Domains
Per (per1,2) PAS
Tim PAS
Clk PAS, BHLH
Cyc PAS, BHLH

Arabidopsis

A PAS domain is found in the ZTL and NPH1 genes. These domains are very similar to the PAS domain found in the Neurospora circadian-associated protein WC-1. [14]

Mammals

The circadian clock that currently understood for mammals begins when light activates BMAL1 and CLK to bind via their PAS domains. That activator complex regulates the Per1/Per2/Per3 which also has PAS, which it uses to bind to cryptochromes 1 and 2 (CRY 1,2 family), which do not contain PAS domains.

Mammalian Genes Binding Domains
Per1, 2, 3 PAS
Cry1, 2 PAS
Bmal PAS, BHLH
Clk PAS, BHLH

Other Mammalian PAS roles

Within Mammals both PAS domains play other important role. PAS A is responsible for the protein-protein interactions with other PAS proteins, while PAS B has a more versatile role. It mediates interactions with chaperonins and other small molecules like dioxin, but PAS B domains in NPAS2, a homolog of the Drosophila clk gene, and the Hypoxia Inducible Factor (HIF) also help to mediate ligand binding . Furthermore, PAS containing the NPAS2 protein have been shown to be a substitute for the Clock gene in mutant mice who lack the Clock gene completely. [15]

PAS also directly interacts with BHLH. It is typically located on the C-Terminus of the BHLH protein. PAS domains containing BHLH proteins form a BHLH-Pas protein, typically found and encoded in HIF and the Clock gene. [16]

References

  1. ^ PDB: 1y28​; Dunham CM, Dioum EM, Tuckerman JR, Gonzalez G, Scott WG, Gilles-Gonzalez MA (July 2003). "A distal arginine in oxygen-sensing heme-PAS domains is essential to ligand binding, signal transduction, and structure". Biochemistry. 42 (25): 7701–8. doi:10.1021/bi0343370. PMID 12820879. 
  2. ^ Henry, Jonathan T.; Crosson, Sean (1 January 2011). "Ligand-binding PAS domains in a genomic, cellular, and structural context". Annual Review of Microbiology. pp. 261–286. doi:10.1146/annurev-micro-121809-151631. 
  3. ^ Ponting CP, Aravind L (November 1997). "PAS: a multi-functional domain family comes to light". Curr. Biol. 7 (11): R674–7. doi:10.1016/S0960-9822(06)00352-6. PMID 9382818. 
  4. ^ Hefti MH, Françoijs KJ, de Vries SC, Dixon R, Vervoort J (March 2004). "The PAS fold. A redefinition of the PAS domain based upon structural prediction". Eur. J. Biochem. 271 (6): 1198–208. doi:10.1111/j.1432-1033.2004.04023.x. PMID 15009198. 
  5. ^ Liu, Yu C.; Machuca, Mayra A.; Beckham, Simone A.; Gunzburg, Menachem J.; Roujeinikova, Anna (1 October 2015). "Structural basis for amino-acid recognition and transmembrane signalling by tandem Per-Arnt-Sim (tandem PAS) chemoreceptor sensory domains". Acta Crystallographica. Section D, Biological Crystallography. pp. 2127–2136. doi:10.1107/S139900471501384X. 
  6. ^ Möglich, Andreas; Ayers, Rebecca A.; Moffat, Keith (14 October 2009). "Structure and signaling mechanism of Per-ARNT-Sim domains". Structure (London, England: 1993). pp. 1282–1294. doi:10.1016/j.str.2009.08.011. 
  7. ^ a b Hennig, Sven; Strauss, Holger M.; Vanselow, Katja; Yildiz, Özkan; Schulze, Sabrina; Arens, Julia; Kramer, Achim; Wolf, Eva (28 April 2009). "Structural and Functional Analyses of PAS Domain Interactions of the Clock Proteins Drosophila PERIOD and Mouse PERIOD2". PLOS Biology. pp. e1000094. doi:10.1371/journal.pbio.1000094. 
  8. ^ Nambu JR, Lewis JO, Wharton KA Jr, Crews ST (December 1990). "The Drosophila single-minded gene encodes a helix-loop-helix protein that acts as a master regulator of CNS midline development". Cell. 67 (6): 1157–67. doi:10.1016/0092-8674(91)90292-7. PMID 1760843. 
  9. ^ Rosato, Ezio; Tauber, Eran; Kyriacou, Charalambos P. (1 January 2006). "Molecular genetics of the fruit-fly circadian clock". European Journal of Human Genetics. pp. 729–738. doi:10.1038/sj.ejhg.5201547. 
  10. ^ a b c d Henry, Jonathan T.; Crosson, Sean (1 January 2011). "Ligand-Binding PAS Domains in a Genomic, Cellular, and Structural Context". Annual Review of Microbiology. pp. 261–286. doi:10.1146/annurev-micro-121809-151631. 
  11. ^ "Structure and Signaling Mechanism of Per-ARNT-Sim Domains" (PDF). 
  12. ^ a b McIntosh, Brian; Hogenesch, John; Bradfield, Christopher. "Mammalian Per-Arnt-Sim Proteins in Environmental Adaptation | Annual Review of Physiology". Annual Review of Physiology. doi:10.1146/annurev-physiol-021909-135922#_i21. 
  13. ^ Harmer, Stacey L.; Panda, Satchidananda; Kay, Steve A. (28 November 2003). "Molecular Bases of Circadian Rhythms". Annual Review of Cell and Developmental Biology. pp. 215–253. doi:10.1146/annurev.cellbio.17.1.215. 
  14. ^ Somers, David; Schultz, Thomas; Kay, Steve; Milnamow, Maureen. "ZEITLUPE Encodes a Novel Clock-Associated PAS Protein from Arabidopsis". ScienceDirect. Cell. doi:10.1016/S0092-8674(00)80841-7. 
  15. ^ Debruyne JP, Noton E, Lambert CM, Maywood ES, Weaver DR, Reppert SM (May 2006). "A clock shock: mouse CLOCK is not required for circadian oscillator function". Neuron. 50 (3): 465–77. doi:10.1016/j.neuron.2006.03.041. PMID 16675400. 
  16. ^ Jones, Susan (1 January 2004). "An overview of the basic helix-loop-helix proteins". Genome Biology. p. 226. doi:10.1186/gb-2004-5-6-226. 


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PAS fold Provide feedback

The PAS fold corresponds to the structural domain that has previously been defined as PAS and PAC motifs [4]. The PAS fold appears in archaea, eubacteria and eukarya.

Literature references

  1. Zhulin IB, Taylor BL, Dixon R; , Trends Biochem Sci 1997;22:331-333.: PAS domain S-boxes in archaea, bacteria and sensors for oxygen and redox. PUBMED:9301332 EPMC:9301332

  2. Borgstahl GE, Williams DR, Getzoff ED; , Biochemistry 1995;34:6278-6287.: 1.4 A structure of photoactive yellow protein, a cytosolic photoreceptor: unusual fold, active site, and chromophore. PUBMED:7756254 EPMC:7756254

  3. Ponting CP, Aravind L; , Curr Biol 1997;7:674-677.: PAS: a multifunctional domain family comes to light. PUBMED:9382818 EPMC:9382818

  4. Hefti MH, Francoijs KJ, de Vries SC, Dixon R, Vervoort J; , Eur J Biochem 2004;271:1198-1208.: The PAS fold: a redefination of the PAS domain based upon structural prediction. PUBMED:15009198 EPMC:15009198


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013655

The PAS fold corresponds to the structural domain that has previously been defined as PAS and PAC motifs [PUBMED:15009198]. The PAS fold appears in archaea, eubacteria and eukarya. The PAS domain contains a sensory box, or S-box domain that occupies the central portion of the PAS domain but is more widely distributed. It is often tandemly repeated. Known prosthetic groups bound in the S-box domain include haem in the oxygen sensor FixL [PUBMED:16681374], FAD in the redox potential sensor NifL [PUBMED:16417511], and a 4-hydroxycinnamyl chromophore in photoactive yellow protein [PUBMED:14979724]. Proteins containing the domain often contain other regulatory domains such as response regulator or sensor histidine kinase domains. Other S-box proteins include phytochromes and the aryl hydrocarbon receptor nuclear translocator.

This domain has been found in the gene product of the madA gene of the filamentous zygomycete fungus Phycomyces blakesleeanus. It has been shown that MadA encodes a blue-light photoreceptor for phototropism and other light responses. The gene is involved in the phototropic responses associated with sporangiophore growth; they exhibit phototropism by bending toward near-UV and blue wavelengths and away from far-UV wavelengths in a manner that is physiologically similar to plant phototropic responses [PUBMED:16537433].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan PAS_Fold (CL0183), which has the following description:

This clan contains PAS domains that are found in a wide variety of bacterial signaling proteins.

The clan contains the following 13 members:

CpxA_peri MEKHLA PAS PAS_10 PAS_11 PAS_2 PAS_3 PAS_4 PAS_5 PAS_6 PAS_7 PAS_8 PAS_9

Alignments

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  Seed
(119)
Full
(23723)
Representative proteomes UniProt
(64544)
NCBI
(200496)
Meta
(1773)
RP15
(4178)
RP35
(13109)
RP55
(23583)
RP75
(37534)
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  Seed
(119)
Full
(23723)
Representative proteomes UniProt
(64544)
NCBI
(200496)
Meta
(1773)
RP15
(4178)
RP35
(13109)
RP55
(23583)
RP75
(37534)
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  Seed
(119)
Full
(23723)
Representative proteomes UniProt
(64544)
NCBI
(200496)
Meta
(1773)
RP15
(4178)
RP35
(13109)
RP55
(23583)
RP75
(37534)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_64 (Release 18.0)
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 119
Number in full: 23723
Average length of the domain: 86.90 aa
Average identity of full alignment: 18 %
Average coverage of the sequence by the domain: 13.76 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.6 25.6
Trusted cut-off 25.6 25.6
Noise cut-off 25.5 25.5
Model length: 89
Family (HMM) version: 11
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

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Interactions

There is 1 interaction for this family. More...

PAS_3

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PAS_3 domain has been found. There are 55 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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