SAP_BOVIN
ID SAP_BOVIN Reviewed; 525 AA.
AC P26779; Q2HJG9; Q9N2G4;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 3.
DT 25-MAY-2022, entry version 148.
DE RecName: Full=Prosaposin;
DE AltName: Full=Proactivator polypeptide;
DE Contains:
DE RecName: Full=Saposin-A;
DE AltName: Full=Protein A;
DE Contains:
DE RecName: Full=Saposin-B;
DE AltName: Full=Cerebroside sulfate activator;
DE Short=CSAct;
DE AltName: Full=Dispersin;
DE AltName: Full=Sphingolipid activator protein 1;
DE Short=SAP-1;
DE AltName: Full=Sulfatide/GM1 activator;
DE Contains:
DE RecName: Full=Saposin-C;
DE AltName: Full=A1 activator;
DE AltName: Full=Co-beta-glucosidase;
DE AltName: Full=Glucosylceramidase activator;
DE AltName: Full=Sphingolipid activator protein 2;
DE Short=SAP-2;
DE Contains:
DE RecName: Full=Saposin-D;
DE AltName: Full=Component C;
DE AltName: Full=Protein C;
DE Flags: Precursor;
GN Name=PSAP;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT ARG-127.
RC TISSUE=Mammary gland;
RA Azuma N., Yoshida K.;
RT "RT-PCR cloning of bovine prosaposin.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Hereford; TISSUE=Heart ventricle;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 312-391.
RC TISSUE=Spleen;
RX PubMed=1554743; DOI=10.1016/0167-4838(92)90426-e;
RA Sano A., Mizuno T., Kondoh K., Hineno T., Ueno S., Kakimoto Y., Morita N.;
RT "Saposin-C from bovine spleen; complete amino acid sequence and relation
RT between the structure and its biological activity.";
RL Biochim. Biophys. Acta 1120:75-80(1992).
CC -!- FUNCTION: Saposin-A and saposin-C stimulate the hydrolysis of
CC glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and
CC galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-
CC C apparently acts by combining with the enzyme and acidic lipid to form
CC an activated complex, rather than by solubilizing the substrate.
CC {ECO:0000250|UniProtKB:P07602}.
CC -!- FUNCTION: Saposin-B stimulates the hydrolysis of galacto-cerebroside
CC sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-
CC galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-
CC galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex
CC with the substrates of the sphingolipid hydrolases.
CC {ECO:0000250|UniProtKB:P07602}.
CC -!- FUNCTION: Saposin-D is a specific sphingomyelin phosphodiesterase
CC activator (EC 3.1.4.12). {ECO:0000250|UniProtKB:P07602}.
CC -!- FUNCTION: [Prosaposin]: Behaves as a myelinotrophic and neurotrophic
CC factor, these effects are mediated by its G-protein-coupled receptors,
CC GPR37 and GPR37L1, undergoing ligand-mediated internalization followed
CC by ERK phosphorylation signaling. {ECO:0000250|UniProtKB:P07602}.
CC -!- FUNCTION: Saposins are specific low-molecular mass non-enzymatic
CC proteins, they participate in the lysosomal degradation of
CC sphingolipids, which takes place by the sequential action of specific
CC hydrolases. {ECO:0000250|UniProtKB:P07602}.
CC -!- SUBUNIT: Saposin-B is a homodimer. Prosaposin exists as a roughly half-
CC half mixture of monomers and disulfide-linked dimers. Monomeric
CC prosaposin interacts (via C-terminus) with sortilin/SORT1, the
CC interaction is required for targeting to lysosomes. Interacts with GRN;
CC facilitates lysosomal delivery of progranulin from the extracellular
CC space and the biosynthetic pathway (By similarity).
CC {ECO:0000250|UniProtKB:P07602}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P07602}.
CC -!- SUBCELLULAR LOCATION: [Prosaposin]: Secreted
CC {ECO:0000250|UniProtKB:Q61207}. Note=Secreted as a fully glycosylated
CC 70 kDa protein composed of complex glycans.
CC {ECO:0000250|UniProtKB:Q61207}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P26779-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P26779-2; Sequence=VSP_020782;
CC -!- PTM: The lysosomal precursor is proteolytically processed to 4 small
CC peptides, which are similar to each other and are sphingolipid
CC hydrolase activator proteins. {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB036791; BAA95677.1; -; mRNA.
DR EMBL; BC105409; AAI05410.1; -; mRNA.
DR RefSeq; NP_776586.1; NM_174161.3. [P26779-1]
DR AlphaFoldDB; P26779; -.
DR SMR; P26779; -.
DR STRING; 9913.ENSBTAP00000044260; -.
DR PaxDb; P26779; -.
DR PeptideAtlas; P26779; -.
DR PRIDE; P26779; -.
DR GeneID; 281433; -.
DR KEGG; bta:281433; -.
DR CTD; 5660; -.
DR eggNOG; KOG1340; Eukaryota.
DR InParanoid; P26779; -.
DR OrthoDB; 865505at2759; -.
DR TreeFam; TF316942; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0060742; P:epithelial cell differentiation involved in prostate gland development; IBA:GO_Central.
DR GO; GO:0007041; P:lysosomal transport; ISS:UniProtKB.
DR GO; GO:0060736; P:prostate gland growth; IBA:GO_Central.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IBA:GO_Central.
DR GO; GO:0006665; P:sphingolipid metabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR003119; SAP_A.
DR InterPro; IPR007856; SapB_1.
DR InterPro; IPR008138; SapB_2.
DR InterPro; IPR008373; Saposin.
DR InterPro; IPR011001; Saposin-like.
DR InterPro; IPR021165; Saposin_chordata.
DR InterPro; IPR008139; SaposinB_dom.
DR Pfam; PF02199; SapA; 2.
DR Pfam; PF05184; SapB_1; 4.
DR Pfam; PF03489; SapB_2; 4.
DR PIRSF; PIRSF002431; Saposin; 1.
DR PRINTS; PR01797; SAPOSIN.
DR SMART; SM00162; SAPA; 2.
DR SMART; SM00741; SapB; 4.
DR SUPFAM; SSF47862; SSF47862; 4.
DR PROSITE; PS51110; SAP_A; 2.
DR PROSITE; PS50015; SAP_B; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Lipid metabolism;
KW Lysosome; Reference proteome; Repeat; Secreted; Signal;
KW Sphingolipid metabolism.
FT SIGNAL 1..16
FT /evidence="ECO:0000250|UniProtKB:P07602"
FT CHAIN 17..525
FT /note="Prosaposin"
FT /evidence="ECO:0000250|UniProtKB:P07602"
FT /id="PRO_0000424773"
FT PROPEP 17..59
FT /evidence="ECO:0000250|UniProtKB:P07602"
FT /id="PRO_0000031607"
FT CHAIN 60..142
FT /note="Saposin-A"
FT /evidence="ECO:0000250|UniProtKB:P07602"
FT /id="PRO_0000031608"
FT PROPEP 143..195
FT /evidence="ECO:0000250|UniProtKB:P07602"
FT /id="PRO_0000031609"
FT CHAIN 196..275
FT /note="Saposin-B"
FT /evidence="ECO:0000250|UniProtKB:P07602"
FT /id="PRO_0000031610"
FT PROPEP 276..311
FT /evidence="ECO:0000269|PubMed:1554743"
FT /id="PRO_0000031611"
FT CHAIN 312..391
FT /note="Saposin-C"
FT /evidence="ECO:0000269|PubMed:1554743"
FT /id="PRO_0000031612"
FT PROPEP 392..405
FT /evidence="ECO:0000269|PubMed:1554743"
FT /id="PRO_0000031613"
FT CHAIN 406..487
FT /note="Saposin-D"
FT /evidence="ECO:0000250|UniProtKB:P07602"
FT /id="PRO_0000031614"
FT PROPEP 488..525
FT /evidence="ECO:0000250|UniProtKB:P07602"
FT /id="PRO_0000031615"
FT DOMAIN 18..58
FT /note="Saposin A-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00414"
FT DOMAIN 59..142
FT /note="Saposin B-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DOMAIN 195..276
FT /note="Saposin B-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DOMAIN 312..393
FT /note="Saposin B-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DOMAIN 406..487
FT /note="Saposin B-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DOMAIN 489..525
FT /note="Saposin A-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00414"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 427
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 63..138
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 66..132
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 94..106
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 199..272
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 202..266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 231..242
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 316..389
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 319..383
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 347..358
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 410..483
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 413..477
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT DISULFID 441..452
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00415"
FT VAR_SEQ 261
FT /note="Q -> QDQQ (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1, ECO:0000303|Ref.2"
FT /id="VSP_020782"
FT VARIANT 127
FT /note="H -> R"
FT /evidence="ECO:0000269|Ref.1"
FT CONFLICT 71
FT /note="T -> I (in Ref. 2; AAI05410)"
FT /evidence="ECO:0000305"
FT CONFLICT 317
FT /note="E -> Q (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 367
FT /note="S -> R (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 525 AA; 58051 MW; 2734E6BFB86FE092 CRC64;
MYSFFVLASL LGGALASPVL GLRECTRGSA VWCQNVKTAA DCGAVQHCLQ TVWSKPTVKS
LPCDICKDVI TAAGNLLKDN ATEQEILMYL ERTCDWLPKP NMSASCKEIV DSYLPVILDM
IKGQMSHPGE VCSALNLCES LQKHLAELNH QKQLESNQIP ELDMAEVVAP FMANIPFLLY
PQDGSHSKPQ PKKANGNVCQ DCIQLVTDVQ EALRTNSTFV EALVDHAKEE CDRLGPGMSD
MCKNYINQYS EVAIQMVMHM QPKEICVLAG FCDEVKEMPM KTLVPAEVVS ENVIPALGLV
EPIKKDPAPA KADIYCEVCE FVVKEVAKLI DNNRTEEEIL HALDKVCSKL PTSLAEQCQE
VVDTYGSSIL SILLDEASPE LVCSMLHLCS SRGLPAATVR VMPRKDGGFC EVCKKLVGYL
DRNLEKNSTK EQILAALEKG CSFLPDQYRK QCDQFVTEYE PVLIEILVEV MDPSFVCLKI
GACPAAHKPL LGAEKCVWGP SYWCQNMESA ALCNAVEHCR RHVWN
