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PR01797

Identifier
SAPOSIN  [View Relations]  [View Alignment]  
Accession
PR01797
No. of Motifs
13
Creation Date
18-NOV-2002  (UPDATE 02-APR-2003)
Title
Saposin signature
Database References

PFAM; PF02199 SAPA
INTERPRO; IPR003119 SapA
Literature References
1. DEWJI, N., WENGER, D., FUJINAYASHI, S., DONOVIEL, M., ESCH, F., HILL, F.
AND O'BRIEN, J.S.
Molecular cloning of the sphingolipid activator protein-1 (SAP-1), the 
sulfatide sulfatase activator.
BIOCHEM.BIOPHYS.RES.COMMUN. 134 989-994 (1986).
 
2. RORMAN, E.G. AND GRABOWSKI, G.A.
Molecular cloning of a human co-beta-glucosidase cDNA: evidence that four 
sphingolipid hydrolase activator proteins are encoded by single genes in 
humans and rats.
GENOMICS 5 486-492 (1989).
 
3. HOLTSCHMIDT, H., SANDHOFF, K., KWON, H.Y., HARZER, K., NAKANO, T. AND 
SUZUKI, K.
Sulfatide activator protein. Alternative splicing that generates three mRNAs
and a newly found mutation responsible for a clinical disease.
J.BIOL.CHEM. 266 7556-7560 (1991).
 
4. HERBST, R., OTT, C., JACOBS, T., MARTI, T., MARCIANO-CABRAL, F. AND 
LIEPPE, M. 
Pore-forming peptides of the pathogenic protozoan Naegleria fowleri.
J.BIOL.CHEM. 277 22353-22360 (2002).

Documentation
Sphingolipids are bioactive compounds found in lower and higher eukaryotes.
They are involved in the regulation of various cellular functions, such as
growth, differentiation and apoptosis, and are believed to be essential in
a healthy diet [1]. Sphigolipids are degraded in the lysosome, and the 
products from their hydrolysis are used in other biosynthetic and regulatory 
pathways in the host [1].
 
There are a number of lysosomal enzymes involved in the breakdown of 
sphinogolipids, and these act in sequence to degrade the moieties [2].
These enzymes require co-proteins called sphingolipid activator proteins,
(SAPs or saposins), to stabilise and activate them as necessary [2]. SAPs
are non-enzymic and usually have a low molecular weight. They are conserved 
across a wide range of eukaryotes and contain specific saposin domains that 
aid in the activation of hydrolase enzymes [3]. There have been four human 
saposins described so far, sharing significant similarity with each other 
and with other euakaryotic SAP proteins [3].
 
Mutations in SAP genes have been linked to a number of conditions. A defect
in the saposin B region leads to metachromatic leucodystrophy (MLD), while
a single nucleotide polymorphism in the SAP-C region may give rise to
Gaucher disease [3]. More recently, an opportunistic protozoan parasite
protein has shown similarity both to the higher and lower eukaryotic 
saposins [4]. The pore-forming protein isolated from virulent Naegleria 
fowleri trophoziotes has been dubbed Naegleriapore A. It also shares 
structural similarity with cytolytic bacterial peptides, although this
similarity does not extend to the sequence level [4].
 
SAPOSINA is a 13-element fingerprint that provides a signature for the
saposin family. The fingerprint was derived from an initial alignment of
6 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length - motifs 1-2 encode the first propeptide; motifs
3-4 span the saposin A domain; motif 5 encodes the second propeptide; motifs
6-7 span the saposin B domain; motifs 8-9 span the saposin C domain; motifs
10-12 span the saposin D domain; and motif 13 encodes the third propeptide.
Two iterations on SPTR40_20f were required to reach convergence, at which
point a true set comprising 7 sequences was identified. Several partial 
matches were also found, all of which are related saposins, surfactant 
proteins and Naegleriapore A pore-forming proteins that fail to match 7 or 
more motifs.
Summary Information
   7 codes involving 13 elements
0 codes involving 12 elements
0 codes involving 11 elements
0 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 codes involving 7 elements
1 codes involving 6 elements
1 codes involving 5 elements
0 codes involving 4 elements
4 codes involving 3 elements
4 codes involving 2 elements
Composite Feature Index
137777777777777
120000000000000
110000000000000
100000000000000
90000000000000
80000000000000
70000000000000
61100000110110
51010000110100
40000000000000
32000000220240
22000011020110
12345678910111213
True Positives
Q8UVZ4        Q9DG82        SAP_BOVIN     SAP_CHICK     
SAP_HUMAN SAP_MOUSE SAP_RAT
True Positive Partials
Codes involving 6 elements
O15997
Codes involving 5 elements
Q9Y125
Codes involving 3 elements
P79333 PSPB_RABIT Q9BKM2 SAP_CAVPO
Codes involving 2 elements
PSPB_MOUSE PSPB_RAT Q9BKM1 SAP_PIG
Sequence Titles
Q8UVZ4      LYSOSOMAL COFACTOR/NEUROTROPHIC FACTOR PROSAPOSIN - Brachydanio rerio (Zebrafish) (Zebra danio). 
Q9DG82 PROSAPOSIN - Brachydanio rerio (Zebrafish) (Zebra danio).
SAP_BOVIN Proactivator polypeptide precursor [Contains: Saposin A (Protein A); Saposin B (Sphingolipid activator protein 1) (SAP-1) (Cerebroside sulfate activator) (CSAct) (Dispersin) (Sulfatide/GM1 activator); Saposin C (Co-beta-glucosidase) (A1 activator) (Glucosylceramidase activator) (Sphingolipid activator protein 2) (SAP-2); Saposin D (Protein C) (Component C)] - Bos taurus (Bovine).
SAP_CHICK Proactivator polypeptide precursor [Contains: Saposin A; Saposin B; Saposin C; Saposin D] - Gallus gallus (Chicken).
SAP_HUMAN Proactivator polypeptide precursor [Contains: Saposin A (Protein A); Saposin B (Sphingolipid activator protein 1) (SAP-1) (Cerebroside sulfate activator) (CSAct) (Dispersin) (Sulfatide/GM1 activator); Saposin C (Co-beta-glucosidase) (A1 activator) (Glucosylceramidase activator) (Sphingolipid activator protein 2) (SAP-2); Saposin D (Protein C) (Component C)] - Homo sapiens (Human).
SAP_MOUSE Sulfated glycoprotein 1 precursor (SGP-1) (Prosaposin) - Mus musculus (Mouse).
SAP_RAT Sulfated glycoprotein 1 precursor (SGP-1) (Prosaposin) - Rattus norvegicus (Rat).

O15997 BMP109 - Bombyx mori (Silk moth).

Q9Y125 SAP-R PROTEIN - Drosophila melanogaster (Fruit fly).

P79333 SURFACTANT PROTEIN B (SP-B) - Oryctolagus cuniculus (Rabbit).
PSPB_RABIT Pulmonary surfactant-associated protein B precursor (SP-B) (6 kDa protein) (Pulmonary surfactant-associated proteolipid SPL(Phe)) - Oryctolagus cuniculus (Rabbit).
Q9BKM2 NAEGLERIAPORE A PORE-FORMING PEPTIDE - Naegleria fowleri.
SAP_CAVPO Saposin C (CO-beta-glucosidase) (Glucosylceramidase activator) (Sphingolipid activator protein 2) (SAP-2) - Cavia porcellus (Guinea pig).

PSPB_MOUSE Pulmonary surfactant-associated protein B precursor (SP-B) (Pulmonary surfactant-associated proteolipid SPL(Phe)) - Mus musculus (Mouse).
PSPB_RAT Pulmonary surfactant-associated protein B precursor (SP-B) (Pulmonary surfactant-associated proteolipid SPL(Phe)) - Rattus norvegicus (Rat).
Q9BKM1 NAEGLERIAPORE B PORE-FORMING PEPTIDE - Naegleria fowleri.
SAP_PIG Saposin B (Cerebroside sulfate activator) (CS-ACT) (NON-specific activator) (Sphingolipid activator protein 1) (SAP-1) - Sus scrofa (Pig).
Scan History
SPTR40_20f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=25
Element Seqn Id St Int Rpt
PVLGLKECTRGSAVWCQNVKTASDC SAP_HUMAN 18 18 -
PVLGLRECTRGSAVWCQNVKTAADC SAP_BOVIN 18 18 -
PLLGTEQCARGPPYWCQNVKTASLC Q8UVZ4 16 16 -
PLLGTEQCARGPPYWCQNVKTASLC Q9DG82 16 16 -
PVQDPKICSGGSAVVCRDVKTAVDC SAP_RAT 18 18 -
PVLWQKDCAKGPEVWCQSLRTASQC SAP_CHICK 19 19 -

Motif 2 width=21
Element Seqn Id St Int Rpt
HCLQTVWNKPTVKSLPCDICK SAP_HUMAN 47 4 -
HCLQTVWSKPTVKSLPCDICK SAP_BOVIN 47 4 -
HCQQNVWNKPQMKTVPCDLCK Q8UVZ4 45 4 -
HCQQNVWNKPQMKTVPCDLCK Q9DG82 45 4 -
HCQQMVWSKPTAKSLPCDICK SAP_RAT 47 4 -
HCQQNVWSKPAVNSIPCDLCK SAP_CHICK 48 4 -

Motif 3 width=18
Element Seqn Id St Int Rpt
LKDNATEEEILVYLEKTC SAP_HUMAN 77 9 -
LKDNATEQEILMYLERTC SAP_BOVIN 77 9 -
LKDNVTESELLGYLEKAC Q8UVZ4 75 9 -
LKDNVTESELLGYLEKAC Q9DG82 75 9 -
LKDNATEEEILHYLEKTC SAP_RAT 77 9 -
LKDNGTEDEIRSYLEKRC SAP_CHICK 78 9 -

Motif 4 width=19
Element Seqn Id St Int Rpt
PGEVCSALNLCESLQKHLA SAP_HUMAN 128 33 -
PGEVCSALNLCESLQKHLA SAP_BOVIN 128 33 -
PGVVCGALGLCVSQQAALA Q8UVZ4 126 33 -
PGVVCGALGLCVSQQAALA Q9DG82 126 33 -
PGEVCSALNLCQSLQEYLA SAP_RAT 128 33 -
PEVVCSALSLCQSLQKHLA SAP_CHICK 129 33 -

Motif 5 width=26
Element Seqn Id St Int Rpt
SNKIPELDMTEVVAPFMANIPLLLYP SAP_HUMAN 156 9 -
SNQIPELDMAEVVAPFMANIPFLLYP SAP_BOVIN 156 9 -
SNEIPQVDLNQRVSPFLLNIPQLLYP Q8UVZ4 150 5 -
SNEIPQVDLNQRVSPFLLNIPQLLYP Q9DG82 150 5 -
SNKIPEVDLARVVAPFMSNIPLLLYP SAP_RAT 155 8 -
SNKIPELDFSELTSPFMANVPLLLYP SAP_CHICK 157 9 -

Motif 6 width=22
Element Seqn Id St Int Rpt
VCQDCIQMVTDIQTAVRTNSTF SAP_HUMAN 197 15 -
VCQDCIQLVTDVQEALRTNSTF SAP_BOVIN 198 16 -
VCQDCVTFISDTQDEARVNSSF Q8UVZ4 188 12 -
VCQDCVTFISDTQDEARVNSSF Q9DG82 188 12 -
VCQDCMKLVTDIQTAVRTNSSF SAP_RAT 196 15 -
VCQDCIRLVTDVQEAVRTNATF SAP_CHICK 196 13 -

Motif 7 width=22
Element Seqn Id St Int Rpt
LGPGMADICKNYISQYSEIAIQ SAP_HUMAN 233 14 -
LGPGMSDMCKNYINQYSEVAIQ SAP_BOVIN 234 14 -
LGPGMSDMCKEYISQYGPLVFQ Q8UVZ4 224 14 -
LGPGMSDMCKEYISQYGPLVFQ Q9DG82 224 14 -
LGPGVSDICKNYVDQYSEVAVQ SAP_RAT 232 14 -
LGPGMSDMCKSYISEYSDLAIQ SAP_CHICK 232 14 -

Motif 8 width=21
Element Seqn Id St Int Rpt
CEVCEFLVKEVTKLIDNNKTE SAP_HUMAN 315 60 -
CEVCEFVVKEVAKLIDNNRTE SAP_BOVIN 316 60 -
CAICEYVMKEIENMIQDQTSE Q8UVZ4 312 66 -
CAICEYVMKEIENMIQDQTSE Q9DG82 314 68 -
CQVCQLVMRKLSELIINNATE SAP_RAT 314 60 -
CEICETMVKEVTGLLESNKTE SAP_CHICK 311 57 -

Motif 9 width=19
Element Seqn Id St Int Rpt
YGSSILSILLEEVSPELVC SAP_HUMAN 364 28 -
YGRSILSILLDEASPELVC SAP_BOVIN 365 28 -
YGQAIIDLLVQEADPKTVC Q8UVZ4 361 28 -
YGQAIIDLLVQEADPKTVC Q9DG82 363 28 -
FGPSLLDVLMHEVNPNFLC SAP_RAT 363 28 -
YGQALIDMLLEATNPEAVC SAP_CHICK 360 28 -

Motif 10 width=23
Element Seqn Id St Int Rpt
GGFCEVCKKLVGYLDRNLEKNST SAP_HUMAN 406 23 -
GGFCEVCKKLVGYLDRNLEKNST SAP_BOVIN 407 23 -
GGFCDVCKMAVRYVDGILEQNAT Q8UVZ4 402 22 -
GGFCDVCKMAVRYVDGILEQNAT Q9DG82 404 22 -
GGFCEVCKKLVIYLEHNLEKNST SAP_RAT 436 54 -
GGFCDICKMIVAYADKELEKNAT SAP_CHICK 400 21 -

Motif 11 width=23
Element Seqn Id St Int Rpt
KGCSFLPDPYQKQCDQFVAEYEP SAP_HUMAN 438 9 -
KGCSFLPDQYRKQCDQFVTEYEP SAP_BOVIN 439 9 -
KVCSFLPDAVKDECNQLIEQYEP Q8UVZ4 434 9 -
KVCSFLPYAVKDECNQLIEQYEP Q9DG82 436 9 -
KGCSFLPDPYQKQCDEFVAEYEP SAP_RAT 468 9 -
KVCHFLPESVSDQCVQFVEQYEP SAP_CHICK 432 9 -

Motif 12 width=24
Element Seqn Id St Int Rpt
PVLIEILVEVMDPSFVCLKIGACP SAP_HUMAN 460 -1 -
PVLIEILVEVMDPSFVCLKIGACP SAP_BOVIN 461 -1 -
PLLVQLLLQTLDPDFVCMKLGACP Q8UVZ4 456 -1 -
PLLVQLLLQTLDPDFVCMKLGACP Q9DG82 458 -1 -
PLLLEILVEVMDPSFVCSKIGVCP SAP_RAT 490 -1 -
PVVVQLLAEMMDPTFVCTKLGVCG SAP_CHICK 454 -1 -

Motif 13 width=22
Element Seqn Id St Int Rpt
LLGTEKCIWGPSYWCQNTETAA SAP_HUMAN 489 5 -
LLGAEKCVWGPSYWCQNMESAA SAP_BOVIN 490 5 -
LLGLNQCSWGPAYWCKNVQTAA Q8UVZ4 485 5 -
LLGLNQCSWGPAYWCKNVQTAA Q9DG82 487 5 -
LLGTEKCVWGPGYWCQNSETAA SAP_RAT 519 5 -
LLGEDACVWGPGYWCKNMETAA SAP_CHICK 483 5 -
Final Motifs
Motif 1  width=25
Element Seqn Id St Int Rpt
PVLGLKECTRGSAVWCQNVKTASDC SAP_HUMAN 18 18 -
PVLGLRECTRGSAVWCQNVKTAADC SAP_BOVIN 18 18 -
PLLGTEQCARGPPYWCQNVKTASLC Q8UVZ4 16 16 -
PLLGTEQCARGPPYWCQNVKTASLC Q9DG82 16 16 -
PVQDPKICSGGSAVVCRDVKTAVDC SAP_RAT 18 18 -
PVLWQKDCAKGPEVWCQSLRTASQC SAP_CHICK 19 19 -
PVQDPKTCSGGSAVLCRDVKTAVDC SAP_MOUSE 18 18 -

Motif 2 width=21
Element Seqn Id St Int Rpt
HCLQTVWNKPTVKSLPCDICK SAP_HUMAN 47 4 -
HCLQTVWSKPTVKSLPCDICK SAP_BOVIN 47 4 -
HCQQNVWNKPQMKTVPCDLCK Q8UVZ4 45 4 -
HCQQNVWNKPQMKTVPCDLCK Q9DG82 45 4 -
HCQQMVWSKPTAKSLPCDICK SAP_RAT 47 4 -
HCQQNVWSKPAVNSIPCDLCK SAP_CHICK 48 4 -
HCQQMVWSKPTAKSLPCDICK SAP_MOUSE 47 4 -

Motif 3 width=18
Element Seqn Id St Int Rpt
LKDNATEEEILVYLEKTC SAP_HUMAN 77 9 -
LKDNATEQEILMYLERTC SAP_BOVIN 77 9 -
LKDNVTESELLGYLEKAC Q8UVZ4 75 9 -
LKDNVTESELLGYLEKAC Q9DG82 75 9 -
LKDNATEEEILHYLEKTC SAP_RAT 77 9 -
LKDNGTEDEIRSYLEKRC SAP_CHICK 78 9 -
LKDNATQEEILHYLEKTC SAP_MOUSE 77 9 -

Motif 4 width=19
Element Seqn Id St Int Rpt
PGEVCSALNLCESLQKHLA SAP_HUMAN 128 33 -
PGEVCSALNLCESLQKHLA SAP_BOVIN 128 33 -
PGVVCGALGLCVSQQAALA Q8UVZ4 126 33 -
PGVVCGALGLCVSQQAALA Q9DG82 126 33 -
PGEVCSALNLCQSLQEYLA SAP_RAT 128 33 -
PEVVCSALSLCQSLQKHLA SAP_CHICK 129 33 -
PGEVCSALNLCQSLQEYLA SAP_MOUSE 128 33 -

Motif 5 width=26
Element Seqn Id St Int Rpt
SNKIPELDMTEVVAPFMANIPLLLYP SAP_HUMAN 156 9 -
SNQIPELDMAEVVAPFMANIPFLLYP SAP_BOVIN 156 9 -
SNEIPQVDLNQRVSPFLLNIPQLLYP Q8UVZ4 150 5 -
SNEIPQVDLNQRVSPFLLNIPQLLYP Q9DG82 150 5 -
SNKIPEVDLARVVAPFMSNIPLLLYP SAP_RAT 155 8 -
SNKIPELDFSELTSPFMANVPLLLYP SAP_CHICK 157 9 -
SNKIPEVDMARVVAPFMSNIPLLLYP SAP_MOUSE 155 8 -

Motif 6 width=22
Element Seqn Id St Int Rpt
VCQDCIQMVTDIQTAVRTNSTF SAP_HUMAN 197 15 -
VCQDCIQLVTDVQEALRTNSTF SAP_BOVIN 198 16 -
VCQDCVTFISDTQDEARVNSSF Q8UVZ4 188 12 -
VCQDCVTFISDTQDEARVNSSF Q9DG82 188 12 -
VCQDCMKLVTDIQTAVRTNSSF SAP_RAT 196 15 -
VCQDCIRLVTDVQEAVRTNATF SAP_CHICK 196 13 -
VCQDCMKLVSDVQTAVKTNSSF SAP_MOUSE 196 15 -

Motif 7 width=22
Element Seqn Id St Int Rpt
LGPGMADICKNYISQYSEIAIQ SAP_HUMAN 233 14 -
LGPGMSDMCKNYINQYSEVAIQ SAP_BOVIN 234 14 -
LGPGMSDMCKEYISQYGPLVFQ Q8UVZ4 224 14 -
LGPGMSDMCKEYISQYGPLVFQ Q9DG82 224 14 -
LGPGVSDICKNYVDQYSEVAVQ SAP_RAT 232 14 -
LGPGMSDMCKSYISEYSDLAIQ SAP_CHICK 232 14 -
LGPGVSDICKNYVDQYSEVCVQ SAP_MOUSE 232 14 -

Motif 8 width=21
Element Seqn Id St Int Rpt
CEVCEFLVKEVTKLIDNNKTE SAP_HUMAN 315 60 -
CEVCEFVVKEVAKLIDNNRTE SAP_BOVIN 316 60 -
CAICEYVMKEIENMIQDQTSE Q8UVZ4 312 66 -
CAICEYVMKEIENMIQDQTSE Q9DG82 314 68 -
CQVCQLVMRKLSELIINNATE SAP_RAT 314 60 -
CEICETMVKEVTGLLESNKTE SAP_CHICK 311 57 -
CQTCQFVMNKFSELIVNNATE SAP_MOUSE 317 63 -

Motif 9 width=19
Element Seqn Id St Int Rpt
YGSSILSILLEEVSPELVC SAP_HUMAN 364 28 -
YGRSILSILLDEASPELVC SAP_BOVIN 365 28 -
YGQAIIDLLVQEADPKTVC Q8UVZ4 361 28 -
YGQAIIDLLVQEADPKTVC Q9DG82 363 28 -
FGPSLLDVLMHEVNPNFLC SAP_RAT 363 28 -
YGQALIDMLLEATNPEAVC SAP_CHICK 360 28 -
FGPSLLDIFIHEVNPSSLC SAP_MOUSE 366 28 -

Motif 10 width=23
Element Seqn Id St Int Rpt
GGFCEVCKKLVGYLDRNLEKNST SAP_HUMAN 406 23 -
GGFCEVCKKLVGYLDRNLEKNST SAP_BOVIN 407 23 -
GGFCDVCKMAVRYVDGILEQNAT Q8UVZ4 402 22 -
GGFCDVCKMAVRYVDGILEQNAT Q9DG82 404 22 -
GGFCEVCKKLVIYLEHNLEKNST SAP_RAT 436 54 -
GGFCDICKMIVAYADKELEKNAT SAP_CHICK 400 21 -
GGFCEVCKKLVLYLEHNLEKNST SAP_MOUSE 439 54 -

Motif 11 width=23
Element Seqn Id St Int Rpt
KGCSFLPDPYQKQCDQFVAEYEP SAP_HUMAN 438 9 -
KGCSFLPDQYRKQCDQFVTEYEP SAP_BOVIN 439 9 -
KVCSFLPDAVKDECNQLIEQYEP Q8UVZ4 434 9 -
KVCSFLPYAVKDECNQLIEQYEP Q9DG82 436 9 -
KGCSFLPDPYQKQCDEFVAEYEP SAP_RAT 468 9 -
KVCHFLPESVSDQCVQFVEQYEP SAP_CHICK 432 9 -
KGCSFLPDPYQKQCDDFVAEYEP SAP_MOUSE 471 9 -

Motif 12 width=24
Element Seqn Id St Int Rpt
PVLIEILVEVMDPSFVCLKIGACP SAP_HUMAN 460 -1 -
PVLIEILVEVMDPSFVCLKIGACP SAP_BOVIN 461 -1 -
PLLVQLLLQTLDPDFVCMKLGACP Q8UVZ4 456 -1 -
PLLVQLLLQTLDPDFVCMKLGACP Q9DG82 458 -1 -
PLLLEILVEVMDPSFVCSKIGVCP SAP_RAT 490 -1 -
PVVVQLLAEMMDPTFVCTKLGVCG SAP_CHICK 454 -1 -
PLLLEILVEVMDPGFVCSKIGVCP SAP_MOUSE 493 -1 -

Motif 13 width=22
Element Seqn Id St Int Rpt
LLGTEKCIWGPSYWCQNTETAA SAP_HUMAN 489 5 -
LLGAEKCVWGPSYWCQNMESAA SAP_BOVIN 490 5 -
LLGLNQCSWGPAYWCKNVQTAA Q8UVZ4 485 5 -
LLGLNQCSWGPAYWCKNVQTAA Q9DG82 487 5 -
LLGTEKCVWGPGYWCQNSETAA SAP_RAT 519 5 -
LLGEDACVWGPGYWCKNMETAA SAP_CHICK 483 5 -
LLGTEKCVWGPSYWCQNMETAA SAP_MOUSE 522 5 -