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267  structures 8489  species 0  interactions 50817  sequences 493  architectures

Family: CPSase_L_D2 (PF02786)

Summary: Carbamoyl-phosphate synthase L chain, ATP binding domain

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Carbamoyl-phosphate synthase L chain, ATP binding domain Provide feedback

Carbamoyl-phosphate synthase catalyses the ATP-dependent synthesis of carbamyl-phosphate from glutamine or ammonia and bicarbonate. This important enzyme initiates both the urea cycle and the biosynthesis of arginine and/or pyrimidines [2]. The carbamoyl-phosphate synthase (CPS) enzyme in prokaryotes is a heterodimer of a small and large chain. The small chain promotes the hydrolysis of glutamine to ammonia, which is used by the large chain to synthesise carbamoyl phosphate. See PF00988. The small chain has a GATase domain in the carboxyl terminus. See PF00117. The ATP binding domain (this one) has an ATP-grasp fold.

Literature references

  1. Waldrop GL, Rayment I, Holden HM; , Biochemistry 1994;33:10249-10256.: Three-dimensional structure of the biotin carboxylase subunit. of acetyl-CoA carboxylase. PUBMED:7915138 EPMC:7915138

  2. Simmer JP, Kelly RE, Rinker AG Jr, Scully JL, Evans DR; , Biol Chem 1990;265:10395-10402.: Mammalian carbamyl phosphate synthetase (CPS). DNA sequence and evolution of the CPS domain of the Syrian hamster multifunctional protein CAD. PUBMED:1972379 EPMC:1972379

  3. Thoden JB, Raushel FM, Benning MM, Rayment I, Holden HM; , Acta Crystallogr D Biol Crystallogr 1999;55:8-24.: The structure of carbamoyl phosphate synthetase determined to 2.1 A resolution. PUBMED:10089390 EPMC:10089390


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR005479

Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, see below). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine ( EC ) or ammonia ( EC ), and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates [ PUBMED:10387030 , PUBMED:11212301 ]. CPSase has three active sites, one in the small subunit and two in the large subunit. The small subunit contains the glutamine binding site and catalyses the hydrolysis of glutamine to glutamate and ammonia. The large subunit has two homologous carboxy phosphate domains, both of which have ATP-binding sites; however, the N-terminal carboxy phosphate domain catalyses the phosphorylation of biocarbonate, while the C-terminal domain catalyses the phosphorylation of the carbamate intermediate [ PUBMED:8916922 ]. The carboxy phosphate domain found duplicated in the large subunit of CPSase is also present as a single copy in the biotin-dependent enzymes acetyl-CoA carboxylase ( EC ) (ACC), propionyl-CoA carboxylase ( EC ) (PCCase), pyruvate carboxylase ( EC ) (PC) and urea carboxylase ( EC ).

Most prokaryotes carry one form of CPSase that participates in both arginine and pyrimidine biosynthesis, however certain bacteria can have separate forms. The large subunit in bacterial CPSase has four structural domains: the carboxy phosphate domain 1, the oligomerisation domain, the carbamoyl phosphate domain 2 and the allosteric domain [ PUBMED:10089390 ]. CPSase heterodimers from Escherichia coli contain two molecular tunnels: an ammonia tunnel and a carbamate tunnel. These inter-domain tunnels connect the three distinct active sites, and function as conduits for the transport of unstable reaction intermediates (ammonia and carbamate) between successive active sites [ PUBMED:12379099 ]. The catalytic mechanism of CPSase involves the diffusion of carbamate through the interior of the enzyme from the site of synthesis within the N-terminal domain of the large subunit to the site of phosphorylation within the C-terminal domain.

Eukaryotes have two distinct forms of CPSase: a mitochondrial enzyme (CPSase I) that participates in both arginine biosynthesis and the urea cycle; and a cytosolic enzyme (CPSase II) involved in pyrimidine biosynthesis. CPSase II occurs as part of a multi-enzyme complex along with aspartate transcarbamoylase and dihydroorotase; this complex is referred to as the CAD protein [ PUBMED:7907330 ]. The hepatic expression of CPSase is transcriptionally regulated by glucocorticoids and/or cAMP [ PUBMED:17397987 ]. There is a third form of the enzyme, CPSase III, found in fish, which uses glutamine as a nitrogen source instead of ammonia [ PUBMED:17451989 ]. CPSase III is closely related to CPSase I, and is composed of a single polypeptide that may have arisen from gene fusion of the glutaminase and synthetase domains [ PUBMED:7932737 ].

This entry represents the ATP-binding domain found in the large subunit of carbamoyl phosphate synthase, as well as in other proteins, including acetyl-CoA carboxylases and pyruvate carboxylases.

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 ATP-grasp (CL0179), which has the following description:

The ATP-grasp domain is found in a wide variety of carboxylate-amine/thiol ligases [1]. It is composed of two subdomains, with ATP being bound in the cleft between the two.

The clan contains the following 26 members:

ATP-grasp ATP-grasp_2 ATP-grasp_3 ATP-grasp_4 ATP-grasp_5 ATP-grasp_6 ATPgrasp_ST ATPgrasp_Ter ATPgrasp_TupA ATPgrasp_YheCD CP_ATPgrasp_1 CP_ATPgrasp_2 CPSase_L_D2 D123 Dala_Dala_lig_C DUF1297 GARS_A GSH-S_ATP GSP_synth Ins134_P3_kin PPDK_N R2K_2 R2K_3 RimK Synapsin_C TTL

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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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
(16)
Full
(50817)
Representative proteomes UniProt
(215843)
RP15
(6773)
RP35
(23377)
RP55
(48791)
RP75
(80624)
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PP/heatmap 1            

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

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(16)
Full
(50817)
Representative proteomes UniProt
(215843)
RP15
(6773)
RP35
(23377)
RP55
(48791)
RP75
(80624)
Alignment:
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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
(16)
Full
(50817)
Representative proteomes UniProt
(215843)
RP15
(6773)
RP35
(23377)
RP55
(48791)
RP75
(80624)
Raw Stockholm Download   Download   Download   Download   Download   Download    
Gzipped 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.

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 View help on the curation process

Seed source: Prosite
Previous IDs: CPSase;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Griffiths-Jones SR
Number in seed: 16
Number in full: 50817
Average length of the domain: 201.40 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 27.10 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 19.8 19.8
Trusted cut-off 19.8 19.8
Noise cut-off 19.7 19.7
Model length: 211
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Selections

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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 CPSase_L_D2 domain has been found. There are 267 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0R0EBC0 View 3D Structure Click here
A0A0R0EBC0 View 3D Structure Click here
A0A0R0HXH4 View 3D Structure Click here
A0A0R0K6S7 View 3D Structure Click here
A0A0R4IFJ4 View 3D Structure Click here
A0A0R4IH35 View 3D Structure Click here
A0A1D6EDR6 View 3D Structure Click here
A0A1D6GRS0 View 3D Structure Click here
A0A1D6J3D9 View 3D Structure Click here
A0A1D6MPT8 View 3D Structure Click here
A0A1D6NJW9 View 3D Structure Click here
A0A1D6NJW9 View 3D Structure Click here
A0A1D8PDC6 View 3D Structure Click here
A0A1D8PLY4 View 3D Structure Click here
A0A1D8PRR7 View 3D Structure Click here
A0A1D8PTD1 View 3D Structure Click here
A0A1D8PTD1 View 3D Structure Click here
A0A2R8PV58 View 3D Structure Click here
A0A2R8Q0M3 View 3D Structure Click here
A0A2R8Q0M3 View 3D Structure Click here
A1Z784 View 3D Structure Click here
A4HRC6 View 3D Structure Click here
A4HWV8 View 3D Structure Click here
A4HWV8 View 3D Structure Click here
A4I7A2 View 3D Structure Click here
A4I7C0 View 3D Structure Click here
B2RQC6 View 3D Structure Click here
B2RQC6 View 3D Structure Click here
B6SKB7 View 3D Structure Click here
B9EXM2 View 3D Structure Click here
B9EXM2 View 3D Structure Click here
B9FK36 View 3D Structure Click here
D4A8A0 View 3D Structure Click here
D4A8A0 View 3D Structure Click here
E9PSQ0 View 3D Structure Click here
E9Q4Z2 View 3D Structure Click here
F1QH12 View 3D Structure Click here
F1QM37 View 3D Structure Click here
F1QYZ6 View 3D Structure Click here
F4I1L3 View 3D Structure Click here
H2L0M0 View 3D Structure Click here
I1JF82 View 3D Structure Click here
I1KA18 View 3D Structure Click here
I6YEU0 View 3D Structure Click here
K7M387 View 3D Structure Click here
K7M387 View 3D Structure Click here
K7M9L4 View 3D Structure Click here
K7M9L4 View 3D Structure Click here
K7V2Z8 View 3D Structure Click here
K7V2Z8 View 3D Structure Click here
O00763 View 3D Structure Click here
O04983 View 3D Structure Click here
O17732 View 3D Structure Click here
O23960 View 3D Structure Click here
O45430 View 3D Structure Click here
O81273 View 3D Structure Click here
O94313 View 3D Structure Click here
O94313 View 3D Structure Click here
P00968 View 3D Structure Click here
P00968 View 3D Structure Click here
P03965 View 3D Structure Click here
P03965 View 3D Structure Click here
P05165 View 3D Structure Click here
P05990 View 3D Structure Click here
P05990 View 3D Structure Click here
P07259 View 3D Structure Click here
P07259 View 3D Structure Click here
P07756 View 3D Structure Click here
P07756 View 3D Structure Click here
P11154 View 3D Structure Click here
P11497 View 3D Structure Click here
P11498 View 3D Structure Click here
P14882 View 3D Structure Click here
P20054 View 3D Structure Click here
P20054 View 3D Structure Click here
P24182 View 3D Structure Click here
P27708 View 3D Structure Click here
P27708 View 3D Structure Click here
P31327 View 3D Structure Click here
P31327 View 3D Structure Click here
P32327 View 3D Structure Click here
P32528 View 3D Structure Click here
P32874 View 3D Structure Click here
P52873 View 3D Structure Click here
P71538 View 3D Structure Click here
P78820 View 3D Structure Click here
P96890 View 3D Structure Click here
P9WPK3 View 3D Structure Click here
P9WPK3 View 3D Structure Click here
P9WPQ3 View 3D Structure Click here
Q00955 View 3D Structure Click here
Q05920 View 3D Structure Click here
Q09794 View 3D Structure Click here
Q09794 View 3D Structure Click here
Q0E9E2 View 3D Structure Click here
Q13085 View 3D Structure Click here
Q18990 View 3D Structure Click here
Q18990 View 3D Structure Click here
Q19842 View 3D Structure Click here
Q2FXX1 View 3D Structure Click here
Q2FY43 View 3D Structure Click here
Q2FZ72 View 3D Structure Click here
Q2FZ72 View 3D Structure Click here
Q2G2C1 View 3D Structure Click here
Q2QMG2 View 3D Structure Click here
Q38970 View 3D Structure Click here
Q42523 View 3D Structure Click here
Q42601 View 3D Structure Click here
Q42601 View 3D Structure Click here
Q42777 View 3D Structure Click here
Q4CS16 View 3D Structure Click here
Q4CSV9 View 3D Structure Click here
Q4CSV9 View 3D Structure Click here
Q4CT14 View 3D Structure Click here
Q4D6X8 View 3D Structure Click here
Q54J08 View 3D Structure Click here
Q54KE6 View 3D Structure Click here
Q553S7 View 3D Structure Click here
Q58626 View 3D Structure Click here
Q58773 View 3D Structure Click here
Q58776 View 3D Structure Click here
Q5A8A6 View 3D Structure Click here
Q5A8A6 View 3D Structure Click here
Q5I0C3 View 3D Structure Click here
Q5SWU9 View 3D Structure Click here
Q8C196 View 3D Structure Click here
Q8C196 View 3D Structure Click here
Q8IEN3 View 3D Structure Click here
Q8IEN3 View 3D Structure Click here
Q8S6N5 View 3D Structure Click here
Q91ZA3 View 3D Structure Click here
Q96RQ3 View 3D Structure Click here
Q99MR8 View 3D Structure Click here
Q9UUE1 View 3D Structure Click here
Q9V9T5 View 3D Structure Click here
Q9XUC3 View 3D Structure Click here
U3JAV8 View 3D Structure Click here
U3JAV8 View 3D Structure Click here