P07602 (SAP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proactivator polypeptide

Cleaved into the following 5 chains:

1. Saposin-A
   Alternative name(s):
   Protein A
2. Saposin-B-Val
3. Saposin-B
   Alternative name(s):
   Cerebroside sulfate activator
   Short name=CSAct
   Dispersin
   Sphingolipid activator protein 1
   Short name=SAP-1
   Sulfatide/GM1 activator
4. Saposin-C
   Alternative name(s):
   A1 activator
   Co-beta-glucosidase
   Glucosylceramidase activator
   Sphingolipid activator protein 2
   Short name=SAP-2
5. Saposin-D
   Alternative name(s):
   Component C
   Protein C

Gene names

Name:	PSAP
Synonyms:	GLBA, SAP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	524 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The lysosomal degradation of sphingolipids takes place by the sequential action of specific hydrolases. Some of these enzymes require specific low-molecular mass, non-enzymic proteins: the sphingolipids activator proteins (coproteins). Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate. Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases. Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).
Subunit structure	Saposin-B is a homodimer.
Subcellular location	Lysosome.
Post-translational modification	This precursor is proteolytically processed to 4 small peptides, which are similar to each other and are sphingolipid hydrolase activator proteins. N-linked glycans show a high degree of microheterogeneity. The one residue extended Saposin-B-Val is only found in 5% of the chains.
Involvement in disease	Combined saposin deficiency (CSAPD) [MIM:611721]: Due to absence of all saposins, leading to a fatal storage disorder with hepatosplenomegaly and severe neurological involvement. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.36 Ref.40 Leukodystrophy metachromatic due to saposin-B deficiency (MLD-SAPB) [MIM:249900]: An atypical form of metachromatic leukodystrophy. It is characterized by tissue accumulation of cerebroside-3-sulfate, demyelination, periventricular white matter abnormalities, peripheral neuropathy. Additional neurological features include dysarthria, ataxic gait, psychomotr regression, seizures, cognitive decline and spastic quadriparesis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.33 Ref.34 Ref.35 Ref.38 Ref.39 Gaucher disease, atypical, due to saposin C deficiency (AGD) [MIM:610539]: A disease characterized by marked glucosylceramide accumulation in the spleen without having a deficiency of glucosylceramide-beta glucosidase characteristic of classic Gaucher disease. Gaucher disease is a lysosomal storage disorder characterized by skeletal deterioration, hepatosplenomegaly, and organ dysfunction. There are several subtypes based on the presence and severity of neurological involvement. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.37 Ref.42 Krabbe disease, atypical, due to saposin A deficiency (AKRD) [MIM:611722]: A disorder of galactosylceramide metabolism. Clinical features include neurologic regression around age 3 months, loss of spontaneous movements, hyporeflexia, generalized brain atrophy, and diffuse white matter dysmyelination. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.41 Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis).
Miscellaneous	Saposin-B co-purifies with 1 molecule of phosphatidylethanolamine.
Sequence similarities	Contains 2 saposin A-type domains. Contains 4 saposin B-type domains.

Ontologies

Keywords
Biological process	Lipid metabolism Sphingolipid metabolism
Cellular component	Lysosome
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Gangliosidosis Gaucher disease Leukodystrophy Metachromatic leukodystrophy
Domain	Repeat Signal
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to organic substance Inferred from electronic annotation. Source: Compara epithelial cell differentiation involved in prostate gland development Inferred from electronic annotation. Source: Compara glycosphingolipid metabolic process Traceable author statement. Source: Reactome lipid transport Traceable author statement PubMed 1454804. Source: ProtInc phospholipid metabolic process Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome prostate gland growth Inferred from electronic annotation. Source: Compara regulation of MAPK cascade Inferred from electronic annotation. Source: Compara regulation of lipid metabolic process Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	Golgi apparatus Inferred from direct assay. Source: HPA extracellular space Inferred from direct assay PubMed 20551380. Source: BHF-UCL integral to membrane Traceable author statement PubMed 1454804. Source: ProtInc lysosomal lumen Traceable author statement. Source: Reactome lysosomal membrane Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara
Molecular_function	enzyme activator activity Traceable author statement Ref.13. Source: ProtInc lipid binding Traceable author statement PubMed 1454804. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform Sap-mu-0 (identifier: P07602-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Sap-mu-6 (identifier: P07602-2)

The sequence of this isoform differs from the canonical sequence as follows:
     259-259: M → MDQ

Isoform Sap-mu-9 (identifier: P07602-3)

The sequence of this isoform differs from the canonical sequence as follows:
     260-260: Q → QDQQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 16

16

Ref.10 Ref.11

Propeptide

17 – 58

42

PRO_0000031616

Chain

60 – 142

83

Saposin-A

PRO_0000031617

Propeptide

144 – 194

51

PRO_0000031618

Chain

195 – 274

80

Saposin-B-Val

PRO_0000031619

Chain

195 – 273

79

Saposin-B

PRO_0000031620

Propeptide

276 – 309

34

PRO_0000031621

Chain

311 – 391

81

Saposin-C

PRO_0000031622

Propeptide

393 – 403

11

PRO_0000031623

Chain

405 – 486

82

Saposin-D

PRO_0000031624

Propeptide

488 – 524

37

PRO_0000031625

Regions

Domain

18 – 58

41

Saposin A-type 1

Domain

59 – 142

84

Saposin B-type 1

Domain

194 – 275

82

Saposin B-type 2

Domain

311 – 392

82

Saposin B-type 3

Domain

405 – 486

82

Saposin B-type 4

Domain

488 – 524

37

Saposin A-type 2

Sites

Site

215

1

Not glycosylated; in variant MLD-SAPB Ile-217

Amino acid modifications

Glycosylation

80

1

N-linked (GlcNAc...) Ref.8 Ref.28 Ref.29

Glycosylation

101

1

N-linked (GlcNAc...) Ref.8 Ref.28 Ref.29

Glycosylation

215

1

N-linked (GlcNAc...) (complex) Ref.28

CAR_000176

Glycosylation

332

1

N-linked (GlcNAc...) Ref.28 Ref.29

Glycosylation

426

1

N-linked (GlcNAc...) Ref.28 Ref.29

Disulfide bond

63 ↔ 138

Ref.23 Ref.25 Ref.26

Disulfide bond

66 ↔ 132

Ref.23 Ref.25 Ref.26

Disulfide bond

94 ↔ 106

Ref.23 Ref.25 Ref.26

Disulfide bond

198 ↔ 271

Ref.23 Ref.25 Ref.26

Disulfide bond

201 ↔ 265

Ref.23 Ref.25 Ref.26

Disulfide bond

230 ↔ 241

Ref.23 Ref.25 Ref.26

Disulfide bond

315 ↔ 388

Ref.23 Ref.25 Ref.26

Disulfide bond

318 ↔ 382

Ref.23 Ref.25 Ref.26

Disulfide bond

346 ↔ 357

Ref.23 Ref.25 Ref.26

Disulfide bond

409 ↔ 482

Ref.23 Ref.25 Ref.26

Disulfide bond

412 ↔ 476

Ref.23 Ref.25 Ref.26

Disulfide bond

440 ↔ 451

Ref.23 Ref.25 Ref.26

Natural variations

Alternative sequence

259

1

M → MDQ in isoform Sap-mu-6.

VSP_006014

Alternative sequence

260

1

Q → QDQQ in isoform Sap-mu-9.

VSP_006015

Natural variant

70

1

Missing in AKRD. Ref.41

VAR_042440

Natural variant

215

1

N → H in MLD-SAPB; reduces the intracellular activity of the protein significantly. Ref.39

VAR_031823

Natural variant

215

1

N → K in MLD-SAPB. Ref.38

VAR_031899

Natural variant

217

1

T → I in MLD-SAPB; juvenile; affects glycosylation at N-215. Ref.33 Ref.34

VAR_006943

Natural variant

241

1

C → S in MLD-SAPB; severe. Ref.35
Corresponds to variant rs1130793 [ dbSNP | Ensembl ].

VAR_006944

Natural variant

349

1

L → P in AGD. Ref.42

VAR_042441

Natural variant

388

1

C → F in AGD. Ref.37

VAR_006945

Experimental info

Mutagenesis

240

1

I → C: Strongly decreases stimulation of cerebroside sulfate hydrolysis. Ref.31

Sequence conflict

369

1

L → P in CAG33027. Ref.4

Secondary structure

1

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524

Helix Strand Turn

Details...

Helix

61 – 78

18

Helix

82 – 94

13

Beta strand

97 – 99

3

Helix

101 – 125

25

Helix

128 – 134

7

Helix

196 – 214

19

Helix

218 – 229

12

Helix

230 – 233

4

Helix

237 – 256

20

Helix

261 – 267

7

Helix

314 – 330

17

Helix

335 – 345

11

Helix

346 – 348

3

Helix

351 – 373

23

Helix

378 – 384

7

Turn

386 – 388

3

Helix

409 – 422

14

Helix

429 – 439

11

Helix

440 – 442

3

Helix

445 – 447

3

Helix

448 – 466

19

Helix

472 – 478

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform Sap-mu-0 [UniParc]. Last modified August 1, 1990. Version 2. Checksum: 71977F7A8C9E1533	FASTA	524	58,113
	10 20 30 40 50 60 MYALFLLASL LGAALAGPVL GLKECTRGSA VWCQNVKTAS DCGAVKHCLQ TVWNKPTVKS 70 80 90 100 110 120 LPCDICKDVV TAAGDMLKDN ATEEEILVYL EKTCDWLPKP NMSASCKEIV DSYLPVILDI 130 140 150 160 170 180 IKGEMSRPGE VCSALNLCES LQKHLAELNH QKQLESNKIP ELDMTEVVAP FMANIPLLLY 190 200 210 220 230 240 PQDGPRSKPQ PKDNGDVCQD CIQMVTDIQT AVRTNSTFVQ ALVEHVKEEC DRLGPGMADI 250 260 270 280 290 300 CKNYISQYSE IAIQMMMHMQ PKEICALVGF CDEVKEMPMQ TLVPAKVASK NVIPALELVE 310 320 330 340 350 360 PIKKHEVPAK SDVYCEVCEF LVKEVTKLID NNKTEKEILD AFDKMCSKLP KSLSEECQEV 370 380 390 400 410 420 VDTYGSSILS ILLEEVSPEL VCSMLHLCSG TRLPALTVHV TQPKDGGFCE VCKKLVGYLD 430 440 450 460 470 480 RNLEKNSTKQ EILAALEKGC SFLPDPYQKQ CDQFVAEYEP VLIEILVEVM DPSFVCLKIG 490 500 510 520 ACPSAHKPLL GTEKCIWGPS YWCQNTETAA QCNAVEHCKR HVWN
	Isoform Sap-mu-6 [UniParc]. Checksum: 2A6E54624BA9D814	FASTA	526	58,356
	10 20 30 40 50 60 MYALFLLASL LGAALAGPVL GLKECTRGSA VWCQNVKTAS DCGAVKHCLQ TVWNKPTVKS 70 80 90 100 110 120 LPCDICKDVV TAAGDMLKDN ATEEEILVYL EKTCDWLPKP NMSASCKEIV DSYLPVILDI 130 140 150 160 170 180 IKGEMSRPGE VCSALNLCES LQKHLAELNH QKQLESNKIP ELDMTEVVAP FMANIPLLLY 190 200 210 220 230 240 PQDGPRSKPQ PKDNGDVCQD CIQMVTDIQT AVRTNSTFVQ ALVEHVKEEC DRLGPGMADI 250 260 270 280 290 300 CKNYISQYSE IAIQMMMHMD QQPKEICALV GFCDEVKEMP MQTLVPAKVA SKNVIPALEL 310 320 330 340 350 360 VEPIKKHEVP AKSDVYCEVC EFLVKEVTKL IDNNKTEKEI LDAFDKMCSK LPKSLSEECQ 370 380 390 400 410 420 EVVDTYGSSI LSILLEEVSP ELVCSMLHLC SGTRLPALTV HVTQPKDGGF CEVCKKLVGY 430 440 450 460 470 480 LDRNLEKNST KQEILAALEK GCSFLPDPYQ KQCDQFVAEY EPVLIEILVE VMDPSFVCLK 490 500 510 520 IGACPSAHKP LLGTEKCIWG PSYWCQNTET AAQCNAVEHC KRHVWN
	Isoform Sap-mu-9 [UniParc]. Checksum: 293FBB7472D82BD0	FASTA	527	58,484
	10 20 30 40 50 60 MYALFLLASL LGAALAGPVL GLKECTRGSA VWCQNVKTAS DCGAVKHCLQ TVWNKPTVKS 70 80 90 100 110 120 LPCDICKDVV TAAGDMLKDN ATEEEILVYL EKTCDWLPKP NMSASCKEIV DSYLPVILDI 130 140 150 160 170 180 IKGEMSRPGE VCSALNLCES LQKHLAELNH QKQLESNKIP ELDMTEVVAP FMANIPLLLY 190 200 210 220 230 240 PQDGPRSKPQ PKDNGDVCQD CIQMVTDIQT AVRTNSTFVQ ALVEHVKEEC DRLGPGMADI 250 260 270 280 290 300 CKNYISQYSE IAIQMMMHMQ DQQPKEICAL VGFCDEVKEM PMQTLVPAKV ASKNVIPALE 310 320 330 340 350 360 LVEPIKKHEV PAKSDVYCEV CEFLVKEVTK LIDNNKTEKE ILDAFDKMCS KLPKSLSEEC 370 380 390 400 410 420 QEVVDTYGSS ILSILLEEVS PELVCSMLHL CSGTRLPALT VHVTQPKDGG FCEVCKKLVG 430 440 450 460 470 480 YLDRNLEKNS TKQEILAALE KGCSFLPDPY QKQCDQFVAE YEPVLIEILV EVMDPSFVCL 490 500 510 520 KIGACPSAHK PLLGTEKCIW GPSYWCQNTE TAAQCNAVEH CKRHVWN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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." Rorman E.G., Grabowski G.A. Genomics 5:486-492(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Structure of full-length cDNA coding for sulfatide activator, a Co-beta-glucosidase and two other homologous proteins: two alternate forms of the sulfatide activator." Nakano T., Sandhoff K., Stuemper J., Christomanou H., Suzuki K. J. Biochem. 105:152-154(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SAP-MU-0). Tissue: Brain, Eye and Skin.
[8]	"Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same genetic locus." O'Brien J.S., Kretz K.A., Dewji N., Wenger D.A., Esch F., Fluharty A.L. Science 241:1098-1101(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-524.
[9]	"Structure and evolution of the human prosaposin chromosomal gene." Rorman E.G., Scheinker V., Grabowski G.A. Genomics 13:312-318(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 14-524.
[10]	"Isolation, characterization, and proteolysis of human prosaposin, the precursor of saposins (sphingolipid activator proteins)." Hiraiwa M., O'Brien J.S., Kishimoto Y., Galdzicka M., Fluharty A.L., Ginns E.I., Martin B.M. Arch. Biochem. Biophys. 304:110-116(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-24; 165-172; 180-189 AND 298-302.
[11]	"Isolation and characterization of prosaposin from human milk." Kondoh K., Hineno T., Sano A., Kakimoto Y. Biochem. Biophys. Res. Commun. 181:286-292(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-26. Tissue: Milk.
[12]	"The organization of the gene for the human cerebroside sulfate activator protein." Holtschmidt H., Sandhoff K., Fuerst W., Kwon H.Y., Schnabel D., Suzuki K. FEBS Lett. 280:267-270(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 59-125 AND 304-513. Tissue: Brain.
[13]	"Saposin A: second cerebrosidase activator protein." Morimoto S., Martin B.M., Yamamoto Y., Kretz K.A., O'Brien J.S., Kishimoto Y. Proc. Natl. Acad. Sci. U.S.A. 86:3389-3393(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 60-142.
[14]	"Storage of saposins A and D in infantile neuronal ceroid-lipofuscinosis." Tyynela J., Palmer D.N., Baumann M., Haltia M. FEBS Lett. 330:8-12(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 62-84 AND 410-431.
[15]	"Nucleotide sequence of cloned cDNA for human sphingolipid activator protein 1 precursor." Dewji N.N., Wenger D.A., O'Brien J.S. Proc. Natl. Acad. Sci. U.S.A. 84:8652-8656(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 164-524.
[16]	"Molecular cloning of the sphingolipid activator protein-1 (SAP-1), the sulfatide sulfatase activator." Dewji N.N., Wenger D.A., Fujibayashi S., Donoviel M., Esch F., Hill F., O'Brien J.S. Biochem. Biophys. Res. Commun. 134:989-994(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 195-263.
[17]	"Complete amino-acid sequence of the naturally occurring A2 activator protein for enzymic sphingomyelin degradation: identity to the sulfatide activator protein (SAP-1)." Kleinschmidt T., Christomanou H., Braunitzer G. Biol. Chem. Hoppe-Seyler 369:1361-1365(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 195-274.
[18]	"The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein." Furst W., Schubert J., Machleidt W., Meyer H.E., Sandhoff K. Eur. J. Biochem. 192:709-714(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 195-274. Tissue: Kidney.
[19]	"Complete amino-acid sequence and carbohydrate content of the naturally occurring glucosylceramide activator protein (A1 activator) absent from a new human Gaucher disease variant." Kleinschmidt T., Christomanou H., Braunitzer G. Biol. Chem. Hoppe-Seyler 368:1571-1578(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 311-390.
[20]	"Saposin D: a sphingomyelinase activator." Morimoto S., Martin B.M., Kishimoto Y., O'Brien J.S. Biochem. Biophys. Res. Commun. 156:403-410(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 405-484.
[21]	"The precursor of sulfatide activator protein is processed to three different proteins." Furst W., Machleidt W., Sandhoff K. Biol. Chem. Hoppe-Seyler 369:317-328(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 407-484.
[22]	"Preparation of the cerebroside sulfate activator (CSAct or saposin B) from human urine." Fluharty A.L., Lombardo C., Louis A., Stevens R.L., Whitelegge J.P., Waring A.J., To T., Fluharty C.B., Faull K.F. Mol. Genet. Metab. 68:391-403(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE (SAPOSIN-B), STRUCTURE OF CARBOHYDRATES. Tissue: Urine.
[23]	"Structural analysis of saposin C and B. Complete localization of disulfide bridges." Vaccaro A.M., Salvioli R., Barca A., Tatti M., Ciaffoni F., Maras B., Siciliano R., Zappacosta F., Amoresano A., Pucci P. J. Biol. Chem. 270:9953-9960(1995) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS IN SAPOSINS-B AND C, MASS SPECTROMETRY.
[24]	"Structure of the asparagine-linked sugar chains of porcine kidney and human urine cerebroside sulfate activator protein." Faull K.F., Johnson J., Kim M.J., To T., Whitelegge J.P., Stevens R.L., Fluharty C.B., Fluharty A.L. J. Mass Spectrom. 35:1416-1424(2000) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE OF CARBOHYDRATE ON ASN-215.
[25]	"Structural and membrane-binding properties of saposin D." Tatti M., Salvioli R., Ciaffoni F., Pucci P., Andolfo A., Amoresano A., Vaccaro A.M. Eur. J. Biochem. 263:486-494(1999) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS IN SAPOSIN-D.
[26]	"Expression, purification, crystallization, and preliminary X-ray analysis of recombinant human saposin B." Ahn V.E., Faull K.F., Whitelegge J.P., Higginson J., Fluharty A.L., Prive G.G. Protein Expr. Purif. 27:186-193(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS IN SAPOSIN-B.
[27]	"Cerebroside sulfate activator protein (Saposin B): chromatographic and electrospray mass spectrometric properties." Faull K.F., Whitelegge J.P., Higginson J., To T., Johnson J., Krutchinsky A.N., Standing K.G., Waring A.J., Stevens R.L., Fluharty C.B., Fluharty A.L. J. Mass Spectrom. 34:1040-1054(1999) [PubMed] [Europe PMC] [Abstract] Cited for: MASS SPECTROMETRY. Tissue: Urine.
[28]	"Cotranslational and posttranslational N-glycosylation of polypeptides by distinct mammalian OST isoforms." Ruiz-Canada C., Kelleher D.J., Gilmore R. Cell 136:272-283(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-80; ASN-101; ASN-215; ASN-332 AND ASN-426.
[29]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-80; ASN-101; ASN-332 AND ASN-426, MASS SPECTROMETRY. Tissue: Liver.
[30]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[31]	"Crystal structure of saposin B reveals a dimeric shell for lipid binding." Ahn V.E., Faull K.F., Whitelegge J.P., Fluharty A.L., Prive G.G. Proc. Natl. Acad. Sci. U.S.A. 100:38-43(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 195-273, MUTAGENESIS OF ILE-240.
[32]	"Molecular genetics of metachromatic leukodystrophy." Gieselmann V., Zlotogora J., Harris A., Wenger D.A., Morris C.P. Hum. Mutat. 4:233-242(1994) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON MLD-SAPB VARIANTS.
[33]	"Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy." Rafi M.A., Zhang X.-L., Degala G., Wenger D.A. Biochem. Biophys. Res. Commun. 166:1017-1023(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MLD-SAPB ILE-217.
[34]	"Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect." Kretz K.A., Carson G.S., Morimoto S., Kishimoto Y., Fluharty A.L., O'Brien J.S. Proc. Natl. Acad. Sci. U.S.A. 87:2541-2544(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MLD-SAPB ILE-217.
[35]	"Sulfatide activator protein. Alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease." Holtschmidt H., Sandhoff K., Kwon H.Y., Harzer K., Nakano T., Suzuki K. J. Biol. Chem. 266:7556-7560(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MLD-SAPB SER-241, NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
[36]	"Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene." Schnabel D., Schroder M., Furst W., Klein A., Hurwitz R., Zenk T., Weber J., Harzer K., Paton B.C., Poulos A., Suzuki K., Sandhoff K. J. Biol. Chem. 267:3312-3315(1992) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CSAPD.
[37]	"Mutation in the sphingolipid activator protein 2 in a patient with a variant of Gaucher disease." Schnabel D., Schroeder M., Sandhoff K. FEBS Lett. 284:57-59(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT AGD PHE-388.
[38]	"An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity." Regis S., Filocamo M., Corsolini F., Caroli F., Keulemans J.L.M., van Diggelen O.P., Gatti R. Eur. J. Hum. Genet. 7:125-130(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MLD-SAPB LYS-215.
[39]	"A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD)." Wrobe D., Henseler M., Huettler S., Pascual Pascual S.I., Chabas A., Sandhoff K. J. Inherit. Metab. Dis. 23:63-76(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MLD-SAPB HIS-215, CHARACTERIZATION OF VARIANT MLD-SAPB HIS-215.
[40]	"A novel mutation in the coding region of the prosaposin gene leads to a complete deficiency of prosaposin and saposins, and is associated with a complex sphingolipidosis dominated by lactosylceramide accumulation." Hulkova H., Cervenkova M., Ledvinova J., Tochackova M., Hrebicek M., Poupetova H., Befekadu A., Berna L., Paton B.C., Harzer K., Boor A., Smid F., Elleder M. Hum. Mol. Genet. 10:927-940(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CSAPD.
[41]	"A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans." Spiegel R., Bach G., Sury V., Mengistu G., Meidan B., Shalev S., Shneor Y., Mandel H., Zeigler M. Mol. Genet. Metab. 84:160-166(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT AKRD VAL-70 DEL.
[42]	"Non-neuronopathic Gaucher disease due to saposin C deficiency." Tylki-Szymanska A., Czartoryska B., Vanier M.T., Poorthuis B.J., Groener J.A., Lugowska A., Millat G., Vaccaro A.M., Jurkiewicz E. Clin. Genet. 72:538-542(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT AGD PRO-349.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J03077 mRNA. Translation: AAA52560.1.
D00422 mRNA. Translation: BAA00321.1.
BT006849 mRNA. Translation: AAP35495.1.
CR456746 mRNA. Translation: CAG33027.1.
AL731541, AC073370 Genomic DNA. Translation: CAI40837.1.
CH471083 Genomic DNA. Translation: EAW54437.1.
BC001503 mRNA. Translation: AAH01503.1.
BC004275 mRNA. Translation: AAH04275.1.
BC007612 mRNA. Translation: AAH07612.1.
M86181 Genomic DNA. No translation available.
X57107 Genomic DNA. Translation: CAA40391.1.
X57108 Genomic DNA. Translation: CAA40392.1.
M12710 mRNA. No translation available.
J03015 mRNA. Translation: AAB59494.1.
M32221 mRNA. Translation: AAA60303.1.
M60257 mRNA. Translation: AAA36595.1.
M60258 mRNA. Translation: AAA36596.1.
M60255 mRNA. Translation: AAA36594.1.

IPI

IPI00012503.
IPI00219825.
IPI00744835.

PIR

SAHUP. JX0061.

RefSeq

NP_001035930.1. NM_001042465.1.
NP_001035931.1. NM_001042466.1.
NP_002769.1. NM_002778.2.

UniGene

Hs.523004.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M12	NMR	-	A	311-390	[»]
1N69	X-ray	2.20	A/B/C	195-273	[»]
1SN6	NMR	-	A	311-390	[»]
2DOB	X-ray	2.00	A	60-140	[»]
2GTG	X-ray	2.40	A	311-391	[»]
2QYP	X-ray	2.45	A/B	311-392	[»]
2R0R	X-ray	2.50	A/B	407-484	[»]
2R1Q	X-ray	2.50	A	407-484	[»]
2RB3	X-ray	2.10	A/B/C/D	407-484	[»]
2Z9A	X-ray	2.50	A/B	311-389	[»]
3BQP	X-ray	1.30	A/B	405-484	[»]
3BQQ	X-ray	2.00	A/B/C/D	405-484	[»]
4DDJ	X-ray	1.90	A	60-140	[»]

ProteinModelPortal

P07602.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29803N.

IntAct

P07602. 10 interactions.

MINT

MINT-1193270.

Protein family/group databases

TCDB

1.C.35.2.1. amoebapore family.

PTM databases

GlycoSuiteDB

P07602.

PhosphoSite

P07602.

Polymorphism databases

DMDM

134218.

Proteomic databases

PaxDb

P07602.

PRIDE

P07602.

Protocols and materials databases

DNASU

5660.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000394936; ENSP00000378394; ENSG00000197746.

GeneID

5660.

KEGG

hsa:5660.

UCSC

uc001jsm.3. human.

Organism-specific databases

CTD

5660.

GeneCards

GC10M073576.

HGNC

HGNC:9498. PSAP.

HPA

CAB004647.
HPA004426.

MIM

176801. gene.
249900. phenotype.
610539. phenotype.
611721. phenotype.
611722. phenotype.

neXtProt

NX_P07602.

Orphanet

139406. Encephalopathy due to prosaposin deficiency.
512. Metachromatic leukodystrophy.

PharmGKB

PA33845.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG269151.

HOVERGEN

HBG002617.

KO

K12382.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P07602.

Bgee

P07602.

CleanEx

HS_PSAP.

Genevestigator

P07602.

GermOnline

ENSG00000197746. Homo sapiens.

Family and domain databases

Gene3D

1.10.225.10. 4 hits.

InterPro

IPR003119. SapA.
IPR007856. SapB_1.
IPR008138. SapB_2.
IPR008373. Saposin.
IPR011001. Saposin-like.
IPR021165. Saposin_chordata.
IPR008139. SaposinB.
[Graphical view]

Pfam

PF02199. SapA. 2 hits.
PF05184. SapB_1. 4 hits.
PF03489. SapB_2. 4 hits.
[Graphical view]

PIRSF

PIRSF002431. Saposin. 1 hit.

PRINTS

PR01797. SAPOSIN.

SMART

SM00162. SAPA. 2 hits.
SM00741. SapB. 4 hits.
[Graphical view]

SUPFAM

SSF47862. Saposin_like. 4 hits.

PROSITE

PS51110. SAP_A. 2 hits.
PS50015. SAP_B. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PSAP. human.

EvolutionaryTrace

P07602.

GenomeRNAi

5660.

NextBio

21992.

SOURCE

Search...

Entry information

Entry name

SAP_HUMAN

Accession

Primary (citable) accession number: P07602
Secondary accession number(s): P07292 , P15793, P78538, P78541, P78546, P78547, P78558, Q53Y86, Q6IBQ6, Q92739, Q92740, Q92741, Q92742

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	August 1, 1990
Last modified:	May 1, 2013
This is version 171 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.