Integral membrane Acyl-coA desaturase superfamily
Families in this clan are integral membrane di-iron-containing enzymes that share the same fold consisting of four transmembrane helices (TM1-TM4) that anchor them to the endoplasmic reticulum (ER) membrane, capped by a cytosolic domain containing a unique 9-10 histidine-coordinating dimetal (di-iron) catalytic centre. This fold is found in fatty acid hydroxylases and fatty acid desaturases, which hydroxylate or desaturate lipid-based substrates in a NADH and oxygen-dependent reaction [1,2,3]. The structure of mouse stearoyl-CoA desaturase (SDC) revealed that TM2 and TM4 are longer than TM1 and TM3 and protrude into the cytosolic domain, providing three of the nine histidine residues that coordinate the two metal ions, while the other histidine residues are provided by the soluble domain in this enzyme .
This clan contains 3 families and the total number of domains in the clan is 51009. The clan was built by S;0000-0002-0520-0736 Chuguransky.
- Zhu G, Koszelak-Rosenblum M, Connelly SM, Dumont ME, Malkowski MG;, J Biol Chem. 2015;290:29820-29833.: The Crystal Structure of an Integral Membrane Fatty Acid alpha-Hydroxylase. PUBMED:26515067 EPMC:26515067
- Wang H, Klein MG, Zou H, Lane W, Snell G, Levin I, Li K, Sang BC;, Nat Struct Mol Biol. 2015;22:581-585.: Crystal structure of human stearoyl-coenzyme A desaturase in complex with substrate. PUBMED:26098317 EPMC:26098317
- Bai Y, McCoy JG, Levin EJ, Sobrado P, Rajashankar KR, Fox BG, Zhou M;, Nature. 2015;524:252-256.: X-ray structure of a mammalian stearoyl-CoA desaturase. PUBMED:26098370 EPMC:26098370
- Shen J, Wu G, Tsai AL, Zhou M;, J Mol Biol. 2020;432:5152-5161.: Structure and Mechanism of a Unique Diiron Center in Mammalian Stearoyl-CoA Desaturase. PUBMED:32470559 EPMC:32470559
This clan contains the following 3 member families:FA_desaturase FA_hydroxylase Lipid_desat
Below is a listing of the unique domain organisations or architectures from this clan. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by
clicking on the graphic. You can also choose to see all sequences which
have a given architecture by clicking on the
in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
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The table below shows the number of occurrences of each domain throughout the sequence database. More...
In brackets beside each number is the percentage of the total number of sequence hits for the clan that are represented by this domain. The rightmost column provides a link to the alignments tab for each domain. Finally, the last row in the table provides a link to the HTML representation of the alignment for the seed alignments for all members of this clan.
Please note: the clan alignment can be extremely large and the resulting HTML file is often too large to be rendered by web-browsers. Please consider downloading the alignment (by right-clicking the link) rather than viewing it in your browser.
|Pfam family||Num. domains||Alignment|
|FA_desaturase (PF00487)||28403 (55.7%)||View|
|FA_hydroxylase (PF04116)||21479 (42.1%)||View|
|Lipid_desat (PF10520)||1127 (2.2%)||View|
|Total: 3||Total: 51009||Clan alignment|
Please note: Clan alignments can be very large and can cause problems for some browsers. Read the note above before viewing.
This diagram shows the relationships between members of this clan. More...
Relationships between families in a clan are determined using HHsearch. Families are deemed to be closely related if their E-value is less than 10-3 and these relationships are shown with a solid line. Less closely related family pairs, with an E-value of between 10-3 and 10-1, are shown with a dashed line.
The E-value for each pair of closely or partially related families is shown next to the line linking the families. You can see the information regarding a Pfam family by clicking on the family box.
This tree shows the occurrence of the domains in this clan across different species. More...
For all of the domain matches in a full alignment we count the number of domains 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.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- 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
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the MSD group, to allow us to map Pfam domains onto UniProt three-dimensional structures. The table below shows the mapping between the Pfam families in this clan, the corresponding UniProt entries, and the region of the three-dimensional structures that are available for that sequence.
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