The domain within your query sequence starts at position 352 and ends at position 393; the E-value for the PAC domain shown below is 1e-12.

SEAHESLMRTSSKREALEKTMRNKMDGEMRRLQDFNRDLRER

The domain was found using the schnipsel database

PAC

Motif C-terminal to PAS motifs (likely to contribute to PAS structural domain)

• SMART accession number: SM00086
• Description: PAC motif occurs C-terminal to a subset of all known PAS motifs. It is proposed to contribute to the PAS domain fold.
• Interpro abstract (IPR001610):

  PAC motifs occur C-terminal to a subset of all known PAS motifs (see IPR000014 ). It is proposed to contribute to the PAS domain fold [ (PUBMED:9301332) (PUBMED:7756254) (PUBMED:9382818) ].

There are 401760 PAC domains in 251051 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Pellequer JL, Wager-Smith KA, Kay SA, Getzoff ED
• Photoactive yellow protein: a structural prototype for the three-dimensional fold of the PAS domain superfamily.
• Proc Natl Acad Sci U S A. 1998; 95: 5884-90

PAS domains are found in diverse proteins throughout all three kingdoms of life, where they apparently function in sensing and signal transduction. Although a wealth of useful sequence and functional information has become recently available, these data have not been integrated into a three-dimensional (3D) framework. The very early evolutionary development and diverse functions of PAS domains have made sequence analysis and modeling of this protein superfamily challenging. Limited sequence similarities between the approximately 50-residue PAS repeats and one region of the bacterial blue-light photosensor photoactive yellow protein (PYP), for which ground-state and light-activated crystallographic structures have been determined to high resolution, originally were identified in sequence searches using consensus sequence probes from PAS-containing proteins. Here, we found that by changing a few residues particular to PYP function, the modified PYP sequence probe also could select PAS protein sequences. By mapping a typical approximately 150-residue PAS domain sequence onto the entire crystallographic structure of PYP, we show that the PAS sequence similarities and differences are consistent with a shared 3D fold (the PAS/PYP module) with obvious potential for a ligand-binding cavity. Thus, PYP appears to prototypically exhibit all the major structural and functional features characteristic of the PAS domain superfamily: the shared PAS/PYP modular domain fold of approximately 125-150 residues, a sensor function often linked to ligand or cofactor (chromophore) binding, and signal transduction capability governed by heterodimeric assembly (to the downstream partner of PYP). This 3D PAS/PYP module provides a structural model to guide experimental testing of hypotheses regarding ligand-binding, dimerization, and signal transduction.

• Rutila JE, Suri V, Le M, So WV, Rosbash M, Hall JC
• CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless.
• Cell. 1998; 93: 805-14

We report the identification, characterization, and cloning of another novel Drosophila clock gene, cycle (cyc). Homozygous cyc flies are completely arrhythmic. Heterozygous cyc/+ flies are rhythmic but have altered periods, indicating that the cyc locus has a dosage effect on period. The molecular circadian phenotype of homozygous cyc flies is like homozygous Clk flies presented in the accompanying paper: mutant flies have little or no transcription of the per and tim genes. Cloning of the gene indicates that it also encodes a bHLH-PAS transcription factor and is a Drosophila homolog of the human protein BMAL1. cyc is a nonsense mutation, consistent with its strong loss-of-function phenotype. We propose that the CYC:CLK heterodimer binds to per and tim E boxes and makes a major contribution to the circadian transcription of Drosophila clock genes.

• Ponting CP, Aravind L
• PAS: a multifunctional domain family comes to light.
• Curr Biol. 1997; 7: 6747-6747

• Zelzer E, Wappner P, Shilo BZ
• The PAS domain confers target gene specificity of Drosophila bHLH/PAS proteins.
• Genes Dev. 1997; 11: 2079-89

Trachealess (Trh) and Single-minded (Sim) are highly similar Drosophila bHLH/PAS transcription factors. They activate nonoverlapping target genes and induce diverse cell fates. A single Drosophila gene encoding a bHLH/PAS protein homologous to the vertebrate ARNT protein was isolated and may serve as a partner for both Trh and Sim. We show that Trh and Sim complexes recognize similar DNA-binding sites in the embryo. To examine the basis for their distinct target gene specificity, the activity of Trh-Sim chimeric proteins was monitored in embryos. Replacement of the Trh PAS domain by the analogous region of Sim was sufficient to convert it into a functional Sim protein. The PAS domain thus mediates all the features conferring specificity and the distinct recognition of target genes. The normal expression pattern of additional proteins essential for the activity of the Trh or Sim complexes can be inferred from the induction pattern of target genes and binding-site reporters, triggered by ubiquitous expression of Trh or Sim. We postulate that the capacity of bHLH/PAS heterodimers to associate, through the PAS domain, with additional distinct proteins that bind target-gene DNA, is essential to confer specificity.

• Zhulin IB, Taylor BL, Dixon R
• PAS domain S-boxes in Archaea, Bacteria and sensors for oxygen and redox.
• Trends Biochem Sci. 1997; 22: 331-3

• Borgstahl GE, Williams DR, Getzoff ED
• 1.4 A structure of photoactive yellow protein, a cytosolic photoreceptor: unusual fold, active site, and chromophore.
• Biochemistry. 1995; 34: 6278-87

A photosensing protein directs light energy captured by its chromophore into a photocycle. The protein's structure must accommodate the photocycle and promote the resulting chemical or conformational changes that lead to signal transduction. The 1.4 A crystallographic structure of photoactive yellow protein, determined by multiple isomorphous replacement methods, provides the first view at atomic resolution of a protein with a photocycle. The alpha/beta fold, which differs from the original chain tracing, shows striking similarity to distinct parts of the signal transduction proteins profilin and the SH2 domain. In the dark state structure of photoactive yellow protein, the novel 4-hydroxycinnamyl chromophore, covalently attached to Cys69, is buried within the major hydrophobic core of the protein and is tethered at both ends by hydrogen bonds. In the active site, the yellow anionic form of the chromophore is stabilized by hydrogen bonds from the side chains of Tyr42 and buried Glu46 to the phenolic oxygen atom and by electrostatic complementarity with the positively charged guanidinium group of Arg52. Thr50 further interlocks Tyr42, Glu46, and Arg52 through a network of active site hydrogen bonds. Arg52, located in a concavity of the protein surface adjacent to the dominant patch of negative electrostatic potential, shields the chromophore from solvent and is positioned to form a gateway for the phototactic signal. Overall, the high-resolution structure of photoactive yellow protein supports a mechanism whereby electrostatic interactions create an active site poised for photon-induced rearrangements and efficient protein-mediated signal transduction.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
38.51	map02030	Bacterial chemotaxis - General
31.28	map02020	Two-component system - General
9.57	map04710	Circadian rhythm
7.66	map05211	Renal cell carcinoma
2.13	map04150	mTOR signaling pathway
1.70	map03010	Ribosome
1.28	map00230	Purine metabolism
0.64	map00632	Benzoate degradation via CoA ligation
0.64	map00720	Reductive carboxylate cycle (CO2 fixation)
0.64	map04914	Progesterone-mediated oocyte maturation
0.43	map00650	Butanoate metabolism
0.43	map00562	Inositol phosphate metabolism
0.43	map00020	Citrate cycle (TCA cycle)
0.43	map04540	Gap junction
0.43	map04730	Long-term depression
0.21	map00350	Tyrosine metabolism
0.21	map00260	Glycine, serine and threonine metabolism
0.21	map00970	Aminoacyl-tRNA biosynthesis
0.21	map00910	Nitrogen metabolism
0.21	map00620	Pyruvate metabolism
0.21	map00400	Phenylalanine, tyrosine and tryptophan biosynthesis
0.21	map02040	Flagellar assembly
0.21	map00340	Histidine metabolism
0.21	map04810	Regulation of actin cytoskeleton
0.21	map04020	Calcium signaling pathway
0.21	map00633	Trinitrotoluene degradation
0.21	map00190	Oxidative phosphorylation
0.21	map00860	Porphyrin and chlorophyll metabolism
0.21	map04510	Focal adhesion
0.21	map05060	Prion disease
0.21	map00640	Propanoate metabolism
0.21	map00540	Lipopolysaccharide biosynthesis
0.21	map03030	DNA replication

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PAC domain which could be assigned to a KEGG orthologous group, and not all proteins containing PAC domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of PAC domains in PDB

PDB code	Title
1byw	STRUCTURE OF THE N-TERMINAL DOMAIN OF THE HUMAN-ERG POTASSIUM CHANNEL
1dp6	OXYGEN-BINDING COMPLEX OF FIXL HEME DOMAIN
1dp8	CRYSTAL STRUCTURE OF THE NITRIC OXIDE BOUND FIXL HEME DOMAIN
1dp9	CRYSTAL STRUCTURE OF IMIDAZOLE-BOUND FIXL HEME DOMAIN
1drm	CRYSTAL STRUCTURE OF THE LIGAND FREE BJFIXL HEME DOMAIN
1dwy	Bovine prion protein fragment 121-230
1dwz	Bovine prion protein fragment 121-230
1dx0	BOVINE PRION PROTEIN RESIDUES 23-230
1dx1	BOVINE PRION PROTEIN RESIDUES 23-230
1g28	STRUCTURE OF A FLAVIN-BINDING DOMAIN, LOV2, FROM THE CHIMERIC PHYTOCHROME/PHOTOTROPIN PHOTORECEPTOR PHY3
1jnu	Photoexcited structure of the plant photoreceptor domain, phy3 LOV2
1lsv	Crystal structure of the CO-bound BjFixL heme domain
1lsw	Crystal structure of the ferrous BjFixL heme domain
1lsx	Crystal structure of the methylimidazole-bound BjFixL heme domain
1lt0	Crystal structure of the CN-bound BjFixL heme domain
1n9l	Crystal structure of the Phot-LOV1 domain from Chlamydomonas reinhardtii in the dark state.
1n9n	Crystal structure of the Phot-LOV1 domain from Chlamydomonas reinhardtii in illuminated state. Data set of a single crystal.
1n9o	Crystal structure of the Phot-LOV1 domain from Chlamydomonas reinhardtii in illuminated state. Composite data set.
1p97	NMR structure of the C-terminal PAS domain of HIF2a
1s66	Crystal structure of heme domain of direct oxygen sensor from E. coli
1s67	Crystal structure of heme domain of direct oxygen sensor from E. coli
1v9y	Crystal Structure of the heme PAS sensor domain of Ec DOS (ferric form)
1v9z	Crystal Structure of the heme PAS sensor domain of Ec DOS (Ferrous Form)
1vb6	Crystal Structure of the heme PAS sensor domain of Ec DOS (oxygen-bound form)
1wa9	Crystal Structure of the PAS repeat region of the Drosophila clock protein PERIOD
1x0o	human ARNT C-terminal PAS domain
1xj2	CO-bound structure of bjFixLH
1xj3	bjFixLH in unliganded ferrous form
1xj4	CO-bound structure of BjFixLH
1xj6	Structure of bjFixLH in the unliganded ferrous form
1y28	Crystal structure of the R220A metBJFIXL HEME domain
2a24	HADDOCK Structure of HIF-2a/ARNT PAS-B Heterodimer
2b02	Crystal Structure of ARNT PAS-B Domain
2cmn	A Proximal Arginine Residue in the Switching Mechanism of the FixL Oxygen Sensor
2gj3	Crystal structure of the FAD-containing PAS domain of the protein NifL from Azotobacter vinelandii.
2hv1	HADDOCK structure of ARNT PAS-B Homodimer
2k7s	Human ARNT C-Terminal PAS Domain, 3 Residue IB slip
2kdk	Structure of human circadian clock protein BMAL2 C-terminal PAS domain
2l0w	Solution NMR structure of the N-terminal PAS domain of HERG potassium channel
2l1m	Solution structure of the eag domain of the hERG (Kv11.1) K+ channel
2l4r	NMR solution structure of the N-terminal PAS domain of hERG
2mwg	2MWG
2owh	Structure of an early-microsecond photolyzed state of CO-bjFixLH
2owj	Structure of an early-microsecond photolyzed state of CO-bjFixLH, dark state
2pd7	2.0 Angstrom Crystal Structure of the Fungal Blue-Light Photoreceptor Vivid
2pd8	1.8 Angstrom Crystal Structure of the Cys71Ser mutant of Vivid
2pdr	1.7 Angstrom Crystal Structure of the Photo-excited Blue-light Photoreceptor Vivid
2pdt	2.3 Angstrom Structure of Phosphodiesterase treated Vivid
2pr5	Structural Basis for Light-dependent Signaling in the Dimeric LOV Photosensor YtvA (Dark Structure)
2pr6	Structural Basis for Light-dependent Signaling in the Dimeric LOV Photosensor YtvA (Light Structure)
2v0u	n- and c-terminal helices of oat lov2 (404-546) are involved in light-induced signal transduction (cryo dark structure of lov2 (404-546))
2v0w	N- and C-terminal helices of oat LOV2 (404-546) are involved in light- induced signal transduction (cryo-trapped light structure of LOV2 ( 404-546))
2v1a	N- and C-terminal helices of oat LOV2 (404-546) are involved in light-induced signal transduction (room temperature (293K) dark structure of LOV2 (404-546))
2v1b	N- and C-terminal helices of oat LOV2 (404-546) are involved in light-induced signal transduction (room temperature (293K) light structure of LOV2 (404-546))
2vlg	KinA PAS-A domain, homodimer
2vv6	BJFIXLH IN FERRIC FORM
2vv7	BJFIXLH IN UNLIGANDED FERROUS FORM
2vv8	Molecular mechanism of signal transduction in bjFixL
2wkp	Structure of a photoactivatable Rac1 containing Lov2 Wildtype
2wkq	Structure of a photoactivatable Rac1 containing the Lov2 C450A Mutant
2wkr	Structure of a photoactivatable Rac1 containing the Lov2 C450M Mutant
2z6c	Crystal structure of LOV1 domain of phototropin1 from Arabidopsis thaliana
2z6d	Crystal structure of LOV1 domain of phototropin2 from Arabidopsis thaliana
3d72	1.65 Angstrom crystal structure of the Cys71Val variant in the fungal photoreceptor VVD
3ewk	Structure of the redox sensor domain of Methylococcus capsulatus (Bath) MmoS
3f1n	Crystal structure of a high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains, with internally bound ethylene glycol.
3f1o	Crystal structure of the high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains, with an internally-bound artificial ligand
3f1p	Crystal structure of a high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains
3gdi	Mammalian Clock Protein mPER2 - Crystal Struture of a PAS Domain Fragment
3gec	Crystal structure of a tandem PAS domain fragment of Drosophila PERIOD
3h7w	Crystal structure of the high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains with the artificial ligand THS017
3h82	Crystal structure of the high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains with the artificial ligand THS020
3h9w	Crystal Structure of the N-terminal domain of Diguanylate cyclase with PAS/PAC sensor (Maqu_2914) from Marinobacter aquaeolei, Northeast Structural Genomics Consortium Target MqR66C
3hji	1.8 Angstrom Crystal Structure of the I74V:I85V Variant of Vivid (VVD).
3hjk	2.0 Angstrom Structure of the Ile74Val Variant of Vivid (VVD).
3is2	2.3 Angstrom Crystal Structure of a Cys71 Sulfenic Acid form of Vivid
3k3c	The N-terminal PAS domain crystal structure of Rv1364c from Mycobacterium tuberculosis at 1.62
3k3d	The N-terminal PAS domain crystal structure of RV1364C from Mycobacterium Tuberculosis at 2.3 angstrom
3kx0	Crystal Structure of the PAS domain of Rv1364c
3lyx	Crystal structure of the PAS domain of the protein CPS_1291 from Colwellia psychrerythraea. Northeast Structural Genomics Consortium target id CsR222B
3mr0	Crystal Structure of Sensory Box Histidine Kinase/Response Regulator from Burkholderia thailandensis E264
3nja	The crystal structure of the PAS domain of a GGDEF family protein from Chromobacterium violaceum ATCC 12472.
3p7n	Crystal structure of light activated transcription factor El222 from Erythrobacter litoralis
3rh8	Crystal Structure of the Light-state Dimer of Fungal Blue-Light Photoreceptor Vivid
3rty	Structure of an Enclosed Dimer Formed by The Drosophila Period Protein
3sw1	Structure of a full-length bacterial LOV protein
3t50	X-ray structure of the LOV domain from the LOV-HK sensory protein from Brucella abortus (dark state).
3ue6	The dark structure of the blue-light photoreceptor Aureochrome1 LOV
3ulf	The light state structure of the blue-light photoreceptor Aureochrome1 LOV
4dj2	Unwinding the Differences of the Mammalian PERIOD Clock Proteins from Crystal Structure to Cellular Function
4dj3	Unwinding the Differences of the Mammalian PERIOD Clock Proteins from Crystal Structure to Cellular Function
4eep	Crystal structure of LOV2 domain of Arabidopsis thaliana phototropin 2
4eer	Crystal structure of LOV2 domain of Arabidopsis thaliana phototropin 2 C426A mutant
4ees	Crystal structure of iLOV
4eet	Crystal structure of iLOV
4eeu	Crystal structure of phiLOV2.1
4eq1	Crystal Structure of the ARNT PAS-B homodimer
4f3l	Crystal Structure of the Heterodimeric CLOCK:BMAL1 Transcriptional Activator Complex
4gcz	Structure of a blue-light photoreceptor
4ghi	Crystal structure of the high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains in complex with a benzoxadiazole antagonist
4gs9	Crystal structure of the high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains in complex with an inactive benzoxadiazole antagonist
4gw9	Structure of a bacteriophytochrome and light-stimulated protomer swapping with a gene repressor
4h6j	Identification of Cys 255 in HIF-1 as a novel site for development of covalent inhibitors of HIF-1 /ARNT PasB domain protein-protein interaction.
4hhd	2.75 Angstrom resolution crystal structure of the A. thaliana LOV2 domain with an extended N-terminal A' helix (cryo dark structure)
4hoi	Crystal structure of PAS domain from the mouse EAG1 potassium channel
4hp4	Crystal structure of PAS domain from the fruit-fly ELK potassium channel
4hp9	Crystal structure of the N-terminal truncated PAS domain from the hERG potassium channel
4hqa	Crystal structure of PAS domain from the human ERG (hERG) potassium channel
4i5s	Structure and function of sensor histidine kinase
4kuk	4KUK
4kuo	4KUO
4llo	Structure of the eag domain-CNBHD complex of the mouse EAG1 channel
4lpz	4LPZ
4nxb	4NXB
4nxe	4NXE
4nxf	4NXF
4nxg	4NXG
4pky	4PKY
4r38	4R38
4r3a	4R3A
4wf0	4WF0
4wn5	4WN5
4xt2	4XT2
4yx2	4YX2
4zp4	4ZP4
4zph	4ZPH
4zpk	4ZPK
4zpr	4ZPR
4zqd	4ZQD
5a8b	5A8B
5djt	5DJT
5dju	5DJU
5dkk	5DKK
5dkl	5DKL
5efw	5EFW
5hwt	5HWT
5hwv	5HWV
5hww	5HWW
5j3w	5J3W
5j4e	5J4E
5j7e	5J7E
5k7l	5K7L
5kiz	5KIZ
5sy5	5SY5
5sy7	5SY7
5t0t	5T0T
5tbm	5TBM

Links (links to other resources describing this domain)

• INTERPRO: IPR001610