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52  structures 411  species 5  interactions 3383  sequences 175  architectures

Family: SapB_2 (PF03489)

Summary: Saposin-like type B, region 2

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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 2 Provide feedback

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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


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR008138

Saposins are small lysosomal proteins that serve as activators of various lysosomal lipid-degrading enzymes [PUBMED:7595087]. 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. The Saposin-B domains also occur in other proteins, many of them active in the lysis of membranes [PUBMED:8003971, PUBMED:8868085].

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

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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
(521)
Full
(3383)
Representative proteomes UniProt
(5795)
NCBI
(8716)
Meta
(8)
RP15
(908)
RP35
(1784)
RP55
(2604)
RP75
(2935)
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  Seed
(521)
Full
(3383)
Representative proteomes UniProt
(5795)
NCBI
(8716)
Meta
(8)
RP15
(908)
RP35
(1784)
RP55
(2604)
RP75
(2935)
Alignment:
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  Seed
(521)
Full
(3383)
Representative proteomes UniProt
(5795)
NCBI
(8716)
Meta
(8)
RP15
(908)
RP35
(1784)
RP55
(2604)
RP75
(2935)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

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Curation and family details

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Curation View help on the curation process

Seed source: Manual
Previous IDs: Surfactant_B;
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD
Number in seed: 521
Number in full: 3383
Average length of the domain: 33.70 aa
Average identity of full alignment: 30 %
Average coverage of the sequence by the domain: 13.88 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 20.7 20.7
Noise cut-off 20.6 20.6
Model length: 34
Family (HMM) version: 17
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Species distribution

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Interactions

There are 5 interactions for this family. More...

SapB_1 SapB_1 Asp SapB_2 Asp

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_2 domain has been found. There are 52 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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