Summary: Cholecystokinin A receptor, N-terminal

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Cholecystokinin A receptor Edit Wikipedia article

Cholecystokinin A receptor

PDB rendering based on 1d6g.

Available structures

PDB

Ortholog search: PDBe, RCSB

List of PDB id codes
1D6G, 1HZN

Identifiers

Symbols

CCKAR; CCK-A; CCK1-R; CCKRA

External IDs

OMIM: 118444 MGI: 99478 HomoloGene: 37337 IUPHAR: CCK₁ ChEMBL: 1901 GeneCards: CCKAR Gene

Gene Ontology
Molecular function	â¢ cholecystokinin receptor activity
Cellular component	â¢ lysosome â¢ endosome â¢ endoplasmic reticulum â¢ plasma membrane â¢ integral to plasma membrane â¢ terminal button
Biological process	â¢ temperature homeostasis â¢ gastric acid secretion â¢ neuron migration â¢ reduction of food intake in response to dietary excess â¢ phospholipase C-activating G-protein coupled receptor signaling pathway â¢ elevation of cytosolic calcium ion concentration â¢ axonogenesis â¢ response to nutrient â¢ digestion â¢ feeding behavior â¢ response to radiation â¢ response to heat â¢ insulin secretion â¢ pancreatic juice secretion â¢ forebrain development â¢ pancreas development â¢ organ regeneration â¢ actin cytoskeleton reorganization â¢ response to lipopolysaccharide â¢ cellular response to hormone stimulus â¢ response to starvation â¢ regulation of potassium ion transport â¢ response to glucocorticoid stimulus â¢ positive regulation of somatostatin secretion
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 4:
26.48 â 26.49 Mb

Chr 5:
53.7 â 53.71 Mb

PubMed search

[1]

[2]

Cholecystokinin A receptor, N-terminal domain

molecular complex of cholecystokinin-8 and n-terminus of the cholecystokinin a receptor by nmr spectroscopy

Identifiers

Symbol

CholecysA-Rec_N

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

The Cholecystokinin A receptor is a human protein, also known as CCKAR or CCK₁, with CCK₁ now being the IUPHAR-recommended name.

This gene encodes a G-protein coupled receptor that binds non-sulfated members of the cholecystokinin (CCK) family of peptide hormones. This receptor is a major physiologic mediator of pancreatic enzyme secretion and smooth muscle contraction of the gallbladder and stomach. In the central and peripheral nervous system this receptor regulates satiety and the release of beta-endorphin and dopamine.^[1]

The extracellular, N-terminal, domain of this protein adopts a tertiary structure consisting of a few helical turns and a disulfide-cross linked loop. It is required for interaction of the cholecystokinin A receptor with its corresponding hormonal ligand.^[2]

[edit] Selective Ligands

[edit] Agonists

Cholecystokinin
Gastrin
CCK-4
SR-146,131
A-71623 - modified tetrapeptide, potent and selective CCK_A agonist, IC₅₀ 3.7nM, 1200x selectivity over CCK_B, CAS# 130408-77-4

[edit] Antagonists

Proglumide
Lorglumide
Devazepide
Dexloxiglumide
Asperlicin
SR-27897
IQM-95333
JNJ-17156516

[edit] See also

[edit] References

^ "Entrez Gene: CCKAR cholecystokinin A receptor".
^ Pellegrini M, Mierke DF (November 1999). "Molecular complex of cholecystokinin-8 and N-terminus of the cholecystokinin A receptor by NMR spectroscopy". Biochemistry 38 (45): 14775â83. doi:10.1021/bi991272l. PMID 10555959.

[edit] External links

"Cholecystokinin Receptors: CCK₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

[edit] Further reading

Varga G, BÃ¡lint A, Burghardt B, D'Amato M (2004). "Involvement of endogenous CCK and CCK1 receptors in colonic motor function.". Br. J. Pharmacol. 141 (8): 1275â84. doi:10.1038/sj.bjp.0705769. PMC 1574909. PMID 15100163.
Miller LJ, Holicky EL, Ulrich CD, Wieben ED (1995). "Abnormal processing of the human cholecystokinin receptor gene in association with gallstones and obesity.". Gastroenterology 109 (4): 1375â80. doi:10.1016/0016-5085(95)90601-0. PMID 7557108.
Huppi K, Siwarski D, Pisegna JR, Wank S (1995). "Chromosomal localization of the gastric and brain receptors for cholecystokinin (CCKAR and CCKBR) in human and mouse.". Genomics 25 (3): 727â9. doi:10.1016/0888-7543(95)80018-H. PMID 7759110.
de Weerth A, Pisegna JR, Huppi K, Wank SA (1993). "Molecular cloning, functional expression and chromosomal localization of the human cholecystokinin type A receptor.". Biochem. Biophys. Res. Commun. 194 (2): 811â8. doi:10.1006/bbrc.1993.1894. PMID 8343165.
Ulrich CD, Ferber I, Holicky E, et al. (1993). "Molecular cloning and functional expression of the human gallbladder cholecystokinin A receptor.". Biochem. Biophys. Res. Commun. 193 (1): 204â11. doi:10.1006/bbrc.1993.1610. PMID 8503909.
Kennedy K, Gigoux V, Escrieut C, et al. (1997). "Identification of two amino acids of the human cholecystokinin-A receptor that interact with the N-terminal moiety of cholecystokinin.". J. Biol. Chem. 272 (5): 2920â6. doi:10.1074/jbc.272.5.2920. PMID 9006937.
Inoue H, Iannotti CA, Welling CM, et al. (1997). "Human cholecystokinin type A receptor gene: cytogenetic localization, physical mapping, and identification of two missense variants in patients with obesity and non-insulin-dependent diabetes mellitus (NIDDM).". Genomics 42 (2): 331â5. doi:10.1006/geno.1997.4749. PMID 9192855.
Gigoux V, Escrieut C, Silvente-Poirot S, et al. (1998). "Met-195 of the cholecystokinin-A receptor interacts with the sulfated tyrosine of cholecystokinin and is crucial for receptor transition to high affinity state.". J. Biol. Chem. 273 (23): 14380â6. doi:10.1074/jbc.273.23.14380. PMID 9603948.
Funakoshi A, Fukamizu Y, Miyasaka K (2000). "Mechanism of cholecystokinin-A- receptor antagonist on human pancreatic exocrine secretion. Localization of CCK-A receptor in the human duodenum.". Digestion. 60 Suppl 1: 75â80. PMID 10026437.
Gigoux V, Escrieut C, Fehrentz JA, et al. (1999). "Arginine 336 and asparagine 333 of the human cholecystokinin-A receptor binding site interact with the penultimate aspartic acid and the C-terminal amide of cholecystokinin.". J. Biol. Chem. 274 (29): 20457â64. doi:10.1074/jbc.274.29.20457. PMID 10400673.
Gigoux V, Maigret B, Escrieut C, et al. (2000). "Arginine 197 of the cholecystokinin-A receptor binding site interacts with the sulfate of the peptide agonist cholecystokinin.". Protein Sci. 8 (11): 2347â54. doi:10.1110/ps.8.11.2347. PMC 2144185. PMID 10595537.
Funakoshi A, Miyasaka K, Matsumoto H, et al. (2000). "Gene structure of human cholecystokinin (CCK) type-A receptor: body fat content is related to CCK type-A receptor gene promoter polymorphism.". FEBS Lett. 466 (2â3): 264â6. doi:10.1016/S0014-5793(00)01080-2. PMID 10682840.
Tachikawa H, Harada S, Kawanishi Y, et al. (2000). "Novel polymorphisms of the human cholecystokinin A receptor gene: an association analysis with schizophrenia". Am. J. Med. Genet. 96 (2): 141â5. doi:10.1002/(SICI)1096-8628(20000403)96:2<141::AID-AJMG3>3.0.CO;2-R. PMID 10893485.
Giragossian C, Mierke DF (2001). "Intermolecular interactions between cholecystokinin-8 and the third extracellular loop of the cholecystokinin A receptor". Biochemistry 40 (13): 3804â9. doi:10.1021/bi002659n. PMID 11300760.
Schmitz F, Schrader H, Otte J, et al. (2002). "Identification of CCK-B/gastrin receptor splice variants in human peripheral blood mononuclear cells". Regul. Pept. 101 (1â3): 25â33. doi:10.1016/S0167-0115(01)00281-6. PMID 11495676.
Tachikawa H, Harada S, Kawanishi Y, et al. (2002). "Linked polymorphisms (-333G>T and -286A>G) in the promoter region of the CCK-A receptor gene may be associated with schizophrenia". Psychiatry Research 103 (2â3): 147â55. doi:10.1016/S0165-1781(01)00276-1. PMID 11549403.
Schmitz F, GÃ¶ke MN, Otte JM, et al. (2002). "Cellular expression of CCK-A and CCK-B/gastrin receptors in human gastric mucosa". Regul. Pept. 102 (2â3): 101â10. doi:10.1016/S0167-0115(01)00307-X. PMID 11730982.
Okubo T, Harada S, Higuchi S, Matsushita S (2003). "Investigation of quantitative trait loci in the CCKAR gene with susceptibility to alcoholism". Alcohol. Clin. Exp. Res. 26 (8 Suppl): 2Sâ5S. doi:10.1097/01.ALC.0000026826.96191.FB. PMID 12198366.
Takata Y, Takeda S, Kawanami T, et al. (2003). "Promoter analysis of human cholecystokinin type-A receptor gene". J. Gastroenterol. 37 (10): 815â20. doi:10.1007/s005350200135. PMID 12424565.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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PDB gallery

1d6g: MOLECULAR COMPLEX OF CHOLECYSTOKININ-8 AND N-TERMINUS OF THE CHOLECYSTOKININ A RECEPTOR BY NMR SPECTROSCOPY

Cell surface receptor: G protein-coupled receptors

Class A:
Rhodopsin like

Neurotransmitter

Adrenergic	Î±1 (A B D) Î±2 (A B C) Î²1 Î²2 Î²3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic
glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F:
Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

Neuropeptide receptors

G protein-coupled receptor

Hormone receptors

Hypothalamic	CRH Â· FSH Â· LHRH Â· TRH Â· Somatostatin

Pituitary	Vasopressin (1A, 1B, 2) Â· Oxytocin Â· LHCG Â· TSH

Other	Atrial natriuretic factor (NPR3) Â· Calcitonin Â· Cholecystokinin (A, B) Â· VIP

Opioid receptors

Delta Â· Kappa Â· Mu Â· Nociceptin

Other neuropeptide receptors

Angiotensin Â· Bradykinin (B1, B2) / Tachykinin (TACR1) Â· Calcitonin gene-related peptide Â· Galanin Â· GPCR neuropeptide (B/W, FF, S, Y) Â· Neurotensin

Type I cytokine receptor

GH Â· Prolactin

Enzyme-linked receptor

Atrial natriuretic factor (NPR1, NPR2)

Other

Sigma (1, 2)

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

Neuropeptidergics

Cholecystokinin

CCK_A	Agonists: Cholecystokinin CCK-4 Antagonists: Asperlicin Proglumide Lorglumide Devazepide Dexloxiglumide

CCK_B	Agonists: Cholecystokinin CCK-4 Gastrin Antagonists: Proglumide CI-988

CRH

CRF₁	Agonists: Corticotropin releasing hormone Antagonists: Antalarmin CP-154,526 Pexacerfont

CRF₂	Agonists: Corticotropin releasing hormone

Galanin

GAL₁	Agonists: Galanin Galanin-like peptide Galmic Galnon

GAL₂	Agonists: Galanin Galanin-like peptide Galmic Galnon

GAL₃	Agonists: Galanin Galmic Galnon

Ghrelin

GnRH

MCH

MCH₁	Agonists: Melanin concentrating hormone Antagonists: ATC-0175 GW-803,430 NGD-4715 SNAP-7941 SNAP-94847

MCH₂	Agonists: Melanin concentrating hormone

Melanocortin

MC₁	Agonists: alpha-MSH Afamelanotide BMS-470,539 Bremelanotide Melanotan II Antagonists: Agouti signalling peptide

MC₂	Agonists: ACTH Cosyntropin Tetracosactide

MC₃	Agonists: alpha-MSH Bremelanotide Melanotan II

MC₄	Agonists: alpha-MSH Bremelanotide Melanotan II PF-00446687 THIQ Antagonists: Agouti-related peptide

MC₅	Agonists: alpha-MSH Melanotan II

Neuropeptide S

Agonists: Neuropeptide S
Antagonists: SHA-68

Neuropeptide Y

Y₁	Agonists: Neuropeptide Y Peptide YY Antagonists: BIBP-3226

Y₂	Agonists: Neuropeptide Y Peptide YY Antagonists: BIIE-0246

Y₄	Agonists: Neuropeptide Y Pancreatic polypeptide Peptide YY Antagonists: UR-AK49

Y₅	Agonists: Neuropeptide Y Peptide YY Antagonists: Lu AA-33810

Neurotensin

NTS₁	Agonists: Neurotensin Neuromedin N Antagonists: SR-48692 SR-142,948

NTS₂	Agonists: Neurotensin Antagonists: Levocabastine SR-142,948

Orexin

OX₁	Agonists: Orexin-A Antagonists: Almorexant SB-334,867 SB-408,124 SB-649,868 Suvorexant

OX₂	Agonists: Orexin-A Antagonists: Almorexant SB-649,868 Suvorexant TCS-OX2-29

Oxytocin

Tachykinin

NK₁	Agonists: Substance P Antagonists: Aprepitant Befetupitant Casopitant CI-1021 CP-96,345 CP-99,994 CP-122,721 Dapitant Ezlopitant FK-888 Fosaprepitant GR-203,040 GW-597,599 HSP-117 L-733,060 L-741,671 L-743,310 L-758,298 Lanepitant LY-306,740 Maropitant Netupitant NKP-608 Nolpitantium Orvepitant RP-67,580 SDZ NKT 343 Vestipitant Vofopitant

NK₂	Agonists: Neurokinin A Antagonists: GR-159,897 Ibodutant Saredutant

NK₃	Agonists: Neurokinin B Antagonists: Osanetant Talnetant

Vasopressin

V_1A	Agonists: Desmopressin Felypressin Ornipressin Terlipressin Vasopressin Antagonists: Conivaptan Demeclocycline Relcovaptan

V_1B	Agonists: Felypressin Ornipressin Terlipressin Vasopressin Antagonists: Demeclocycline Nelivaptan

V₂	Agonists: Desmopressin Ornipressin Vasopressin Antagonists: Conivaptan Demeclocycline Lixivaptan Mozavaptan Satavaptan Tolvaptan

This article incorporates text from the public domain Pfam and InterPro IPR015276

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Cholecystokinin A receptor, N-terminal Provide feedback

Members of this family are found in the extracellular region of the cholecystokinin A receptor, where they adopt a tertiary structure consisting of a few helical turns and a disulphide-crosslinked loop. They are required for interaction of the cholecystokinin A receptor with it's corresponding hormonal ligand [1].

Literature references

Pellegrini M, Mierke DF; , Biochemistry. 1999;38:14775-14783.: Molecular complex of cholecystokinin-8 and N-terminus of the cholecystokinin A receptor by NMR spectroscopy. PUBMED:10555959 EPMC:10555959

External database links

PANDIT:	PF09193
Pseudofam:	PF09193
SCOP:	1d6g
SYSTERS:	CholecysA-Rec_N

This tab holds annotation information from the InterPro database.

InterPro entry IPR015276

This entry represents the extracellular N-terminal domain of the cholecystokinin A receptor. This domain adopts a tertiary structure consisting of a few helical turns and a disulphide-cross linked loop. It is required for interaction of the cholecystokinin A receptor with its corresponding hormonal ligand [PUBMED:10555959].

Domain organisation

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

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
Pfam viewer: an HTML-based viewer that uses DAS to retrieve alignment fragments on request

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

Selex
Stockholm
FASTA
MSF

You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (5)	Full (39)	Representative proteomes				NCBI (37)	Meta (0)
	Seed (5)	Full (39)	RP15 (1)	RP35 (1)	RP55 (3)	RP75 (20)	NCBI (37)	Meta (0)
Jalview	View	View	View	View	View	View	View
HTML	View	View	View	View	View	View
PP/heatmap	₁	View	View	View	View	View
Pfam viewer	View	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (5)	Full (39)	Representative proteomes				NCBI (37)	Meta (0)
	Seed (5)	Full (39)	RP15 (1)	RP35 (1)	RP55 (3)	RP75 (20)	NCBI (37)	Meta (0)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (5)	Full (39)	Representative proteomes				NCBI (37)	Meta (0)
	Seed (5)	Full (39)	RP15 (1)	RP35 (1)	RP55 (3)	RP75 (20)	NCBI (37)	Meta (0)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

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.

Note: You can also download the data file for the tree.

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

Seed source:

pdb_1d6g

Previous IDs:

none

Type:

Domain

Author:

Sammut SJ

Number in seed:

5

Number in full:

39

Average length of the domain:

47.20 aa

Average identity of full alignment:

73 %

Average coverage of the sequence by the domain:

11.41 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.3	20.3
Trusted cut-off	20.7	24.7
Noise cut-off	20.1	17.5

Model length:

47

Family (HMM) version:

5

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

Loading sunburst data...

Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

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 CholecysA-Rec_N domain has been found. There are 1 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.

Loading structure mapping...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: CholecysA-Rec_N (PF09193)

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