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62  structures 532  species 0  interactions 4605  sequences 219  architectures

Family: SapB_1 (PF05184)

Summary: Saposin-like type B, region 1

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Saposin protein domain". More...

Saposin protein domain Edit Wikipedia article

Saposin A-type domain
Identifiers
SymbolSapA
PfamPF02199
InterProIPR003119
PROSITEPDOC51110
Saposin-like type B, region 1 (SapB1)
Saposin C 2qyp.png
Crystal structure of human saposin C dimer in an open conformation.[1]
Identifiers
SymbolSapB_1
PfamPF05184
InterProIPR007856
PROSITEPDOC50015
Saposin-like type B, region 2 (SapB2)
Identifiers
SymbolSapB_2
PfamPF03489
InterProIPR008138
PROSITEPDOC50015
CATH1qdmC03
SCOPe1nkl / SUPFAM
OPM superfamily76
OPM protein1sn6

The saposin domains refers to two evolutionally-conserved protein domains found in saposin and related proteins (SAPLIP). Saposins are small lysosomal proteins that serve as activators of various lysosomal lipid-degrading enzymes. They probably act by isolating the lipid substrate from the membrane surroundings, thus making it more accessible to the soluble degradative enzymes. All mammalian saposins are synthesized as a single precursor molecule (prosaposin) which contains four Saposin-B domains, yielding the active saposins after proteolytic cleavage, and two Saposin-A domains that are removed in the activation reaction.[2]

The Saposin-B domains also occur in other proteins, most of them playing a role in interacting with membranes.[2][3][4]

Classification

The saposin (SapB1-SapB2) domains are found in a wide range of proteins. Each half-domain encodes two alpha helices in the SapB domain for a total of four.[5]

The mamallian prosaposin (domain organization below) is a prototypic family member. It also includes the N- and C-terminal SapA domains, both of which are proteolyticly cleaved as the proprotein matures. Four connected pairs of SapB1-SapB2 domains are released, sequentially named Saposin-A through D. Some closely related proteins, such as PSAPL1 and SFTPB, share the architecture and the cleaving mechanism in whole or in part. While Prosaposin and PSAPL1 act in lysosomal lipid degradation, SFTPB is released into the pulmonary surfactant, playing a role in rearranging lipids.[6]

primary structure schematic of prosaposin.

However, proteins like GNLY and AOAH do not carry a SapA domain. While GNLY is essentially a SapB with N-terminal extensions specialized for lysing pathogen cell membranes,[7] the ADAH protein uses the uncleaved SapB domain for targeting the correct intracellular compartment.[8]

The plant-specific insert is an unusual variation on the SapB domains. It features a circular permutation compared to the usual topology: instead of featuring a SapB1-SapB2 unit, it is made up of a SapB2-linker-SapB1 unit seemingly derived by taking a half of each of two SapB units.[5]

Human proteins containing this domain

References

  1. ^ PDB: 2qyp​, Rossmann M, Schultz-Heienbrok R, Behlke J, Remmel N, Alings C, Sandhoff K, Saenger W, Maier T (May 2008). "Crystal structures of human saposins C andD: implications for lipid recognition and membrane interactions". Structure. 16 (5): 809–17. doi:10.1016/j.str.2008.02.016. PMID 18462685.
  2. ^ a b Munford RS, Sheppard PO, O'Hara PJ (August 1995). "Saposin-like proteins (SAPLIP) carry out diverse functions on a common backbone structure". Journal of Lipid Research. 36 (8): 1653–63. PMID 7595087.
  3. ^ Ponting CP (February 1994). "Acid sphingomyelinase possesses a domain homologous to its activator proteins: saposins B and D". Protein Science. 3 (2): 359–61. doi:10.1002/pro.5560030219. PMC 2142785. PMID 8003971.
  4. ^ Tschopp J, Hofmann K (March 1996). "Cytotoxic T cells: more weapons for new targets?". Trends in Microbiology. 4 (3): 91–4. doi:10.1016/0966-842X(96)81522-8. PMID 8868085.
  5. ^ a b Ponting CP, Russell RB (May 1995). "Swaposins: circular permutations within genes encoding saposin homologues". Trends in Biochemical Sciences. 20 (5): 179–80. doi:10.1016/S0968-0004(00)89003-9. PMID 7610480.
  6. ^ Hawgood S, Derrick M, Poulain F (Nov 1998). "Structure and properties of surfactant protein B". Biochimica et Biophysica Acta. 1408 (2–3): 150–60. doi:10.1016/S0925-4439(98)00064-7. PMID 9813296.
  7. ^ Anderson DH, Sawaya MR, Cascio D, Ernst W, Modlin R, Krensky A, Eisenberg D (2003). "Granulysin crystal structure and a structure-derived lytic mechanism". J. Mol. Biol. 325 (2): 355–365. CiteSeerX 10.1.1.327.5540. doi:10.1016/S0022-2836(02)01234-2. PMID 12488100.
  8. ^ Staab JF, Ginkel DL, Rosenberg GB, Munford RS (1994). "A saposin-like domain influences the intracellular localization, stability, and catalytic activity of human acyloxyacyl hydrolase". J. Biol. Chem. 269 (38): 23736–42. PMID 8089145.

Further reading

External links

This article incorporates text from the public domain Pfam and InterPro: IPR008138

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Saposin-like type B, region 1 Provide feedback

Saposin B is a small non-enzymatic glycoprotein required for the breakdown of cerebroside sulphates (sulphatides) in lysosomes. Saposin B contains three intramolecular disulphide bridges, exists as a dimer and is remarkably heat, protease, and pH stable. The crystal structure of human saposin B reveals an unusual shell-like dimer consisting of a monolayer of alpha-helices enclosing a large hydrophobic cavity [1,2]. It is one of the most studied members of the saposin protein family and it is involved in the hydrolysis of glycolipids and glycerolipids. SapB is unique in the saposin family in that it facilitates degradation by interacting with the substrate, not the enzymes [3].

Literature references

  1. Ponting CP, Russell RB; , Trends Biochem Sci 1995;20:179-180.: Swaposins: circular permutations within genes encoding saposin homologues. PUBMED:7610480 EPMC:7610480

  2. Ahn VE, Faull KF, Whitelegge JP, Fluharty AL, Prive GG;, Proc Natl Acad Sci U S A. 2003;100:38-43.: Crystal structure of saposin B reveals a dimeric shell for lipid binding. PUBMED:12518053 EPMC:12518053

  3. Huta BP, Mehlenbacher MR, Nie Y, Lai X, Zubieta C, Bou-Abdallah F, Doyle RP;, ChemMedChem. 2016;11:277-282.: The Lysosomal Protein Saposin B Binds Chloroquine. PUBMED:26616259 EPMC:26616259


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR007856

Synonym(s):cerebroside sulphate activator, CSAct

Saposin B is a small non-enzymatic glycoprotein required for the breakdown of cerebroside sulphates (sulphatides) in lysosomes. Saposin B contains three intramolecular disulphide bridges, exists as a dimer and is remarkably heat, protease, and pH stable. The crystal structure of human saposin B reveals an unusual shell-like dimer consisting of a monolayer of alpha-helices enclosing a large hydrophobic cavity. Although the secondary structure of saposin B is similar to that of the known monomeric members of the saposin-like superfamily, the helices are repacked into a different tertiary arrangement to form the homodimer. A comparison of the two forms of the saposin B dimer suggests that extraction of target lipids from membranes involves a conformational change that facilitates access to the inner cavity [ PUBMED:12518053 ].

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 Saposin_like (CL0707), which has the following description:

This superfamily includes proteins with the common 3D fold from saposins, composed of five amphipathic alpha-helices.

The clan contains the following 3 members:

ARMET_N SapB_1 SapB_2

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
(428)
Full
(4605)
Representative proteomes UniProt
(8044)
RP15
(818)
RP35
(2133)
RP55
(3886)
RP75
(5161)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

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  Seed
(428)
Full
(4605)
Representative proteomes UniProt
(8044)
RP15
(818)
RP35
(2133)
RP55
(3886)
RP75
(5161)
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
(428)
Full
(4605)
Representative proteomes UniProt
(8044)
RP15
(818)
RP35
(2133)
RP55
(3886)
RP75
(5161)
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.

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: Manual
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 428
Number in full: 4605
Average length of the domain: 37.80 aa
Average identity of full alignment: 30 %
Average coverage of the sequence by the domain: 14.92 %

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 25.2 25.2
Trusted cut-off 25.2 25.2
Noise cut-off 25.1 25.1
Model length: 38
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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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 SapB_1 domain has been found. There are 62 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
A0A0K1H345 View 3D Structure Click here
A0A0R0E9Y9 View 3D Structure Click here
A0A0R0EKV9 View 3D Structure Click here
A0A0R0ELQ9 View 3D Structure Click here
A0A0R0F2S3 View 3D Structure Click here
A0A0R0FFL6 View 3D Structure Click here
A0A0R0GA69 View 3D Structure Click here
A0A0R0H5M6 View 3D Structure Click here
A0A0R0KLL5 View 3D Structure Click here
A0A1D6FAT4 View 3D Structure Click here
A0A1D6FKF4 View 3D Structure Click here
A0A1D6FQR4 View 3D Structure Click here
A0A1D6IFM3 View 3D Structure Click here
A0A1D6KTR8 View 3D Structure Click here
A0A1D6M2V9 View 3D Structure Click here
A0A1D6MKR9 View 3D Structure Click here
A0A1D6MKR9 View 3D Structure Click here
A0A1D6PSA9 View 3D Structure Click here
A0A1D6PSA9 View 3D Structure Click here
A0A1R3PT38 View 3D Structure Click here
A0A2R8PV52 View 3D Structure Click here
A0A2R8Q3N6 View 3D Structure Click here
A0A2R8Q3P8 View 3D Structure Click here
B0G0Z4 View 3D Structure Click here
B4FVJ2 View 3D Structure Click here
B4FVJ2 View 3D Structure Click here
B9GBH9 View 3D Structure Click here
B9GBH9 View 3D Structure Click here
C0P3K6 View 3D Structure Click here
C0P7L5 View 3D Structure Click here
C0PNI3 View 3D Structure Click here
C0PNI3 View 3D Structure Click here
E7FCT1 View 3D Structure Click here
E7FCT1 View 3D Structure Click here
E7FCT1 View 3D Structure Click here
I1J7N2 View 3D Structure Click here
I1J7N2 View 3D Structure Click here
I1KNG0 View 3D Structure Click here
I1KZU7 View 3D Structure Click here
I1L1Y7 View 3D Structure Click here
I1L729 View 3D Structure Click here
I1L730 View 3D Structure Click here
I1L730 View 3D Structure Click here
I1LAZ3 View 3D Structure Click here
I1LYD2 View 3D Structure Click here
I1MHN2 View 3D Structure Click here
I1MS12 View 3D Structure Click here
I1NBM7 View 3D Structure Click here
I1NEU4 View 3D Structure Click here
K7KGI6 View 3D Structure Click here
K7KKE5 View 3D Structure Click here
K7MTS2 View 3D Structure Click here
K7MTS2 View 3D Structure Click here
K7V6R3 View 3D Structure Click here
M0R3X1 View 3D Structure Click here
O65390 View 3D Structure Click here
P07602 View 3D Structure Click here
P07602 View 3D Structure Click here
P07602 View 3D Structure Click here
P07602 View 3D Structure Click here
P07988 View 3D Structure Click here
P10960 View 3D Structure Click here
P10960 View 3D Structure Click here
P10960 View 3D Structure Click here
P22355 View 3D Structure Click here
P42211 View 3D Structure Click here
P50405 View 3D Structure Click here
Q0IV51 View 3D Structure Click here
Q0JKM8 View 3D Structure Click here
Q18276 View 3D Structure Click here
Q23498 View 3D Structure Click here
Q42456 View 3D Structure Click here
Q54C16 View 3D Structure Click here
Q54C60 View 3D Structure Click here
Q54D30 View 3D Structure Click here
Q54F52 View 3D Structure Click here
Q54IR3 View 3D Structure Click here
Q54LG1 View 3D Structure Click here
Q54LG3 View 3D Structure Click here
Q54LG3 View 3D Structure Click here
Q54LG3 View 3D Structure Click here
Q54PT7 View 3D Structure Click here
Q54PT7 View 3D Structure Click here
Q54Q68 View 3D Structure Click here
Q54Q68 View 3D Structure Click here
Q54Q68 View 3D Structure Click here
Q54SX7 View 3D Structure Click here
Q54SX7 View 3D Structure Click here
Q54WE0 View 3D Structure Click here
Q54WE0 View 3D Structure Click here
Q54WE4 View 3D Structure Click here
Q54WE4 View 3D Structure Click here
Q55C09 View 3D Structure Click here
Q55EI1 View 3D Structure Click here
Q55EI1 View 3D Structure Click here
Q5VQH7 View 3D Structure Click here
Q5VQH7 View 3D Structure Click here
Q61207 View 3D Structure Click here
Q61207 View 3D Structure Click here
Q61207 View 3D Structure Click here
Q6NUJ1 View 3D Structure Click here
Q75K05 View 3D Structure Click here
Q86KA8 View 3D Structure Click here
Q8C1C1 View 3D Structure Click here
Q8VYL3 View 3D Structure Click here
Q9LGZ3 View 3D Structure Click here
Q9LZW6 View 3D Structure Click here
Q9LZW6 View 3D Structure Click here
Q9SCT5 View 3D Structure Click here
Q9SCT5 View 3D Structure Click here
Q9XEC4 View 3D Structure Click here
Q9Y125 View 3D Structure Click here
Q9Y125 View 3D Structure Click here
Q9Y125 View 3D Structure Click here
Q9Y125 View 3D Structure Click here
Q9Y125 View 3D Structure Click here
Q9Y125 View 3D Structure Click here