Q71RP1 (HPSE_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Heparanase
EC=3.2.-.-

Alternative name(s):
Endo-glucoronidase

Cleaved into the following 2 chains:

1. Heparanase 8 kDa subunit
2. Heparanase 50 kDa subunit

Gene names

Name:	Hpse
Synonyms:	Hep

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	536 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Highly selective enzyme cleaving HSPGs at specific intrachain sites. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extacellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis By similarity. Ref.3
Enzyme regulation	Inhibited by laminarin sulfate and, to a lower extent, by heparin and sulfamin By similarity. Activated by calcium and magnesium. Inhibited by EDTA. Ref.2
Subunit structure	Heterodimer; heterodimer formation between the 8 kDa and the 50 kDa subunits is required for enzyme activity By similarity. Interacts with TF; the interaction, inhibited by heparin, enhances the generation of activated factor X and activates coagulation. Interacts with HRG; the interaction is enhanced at acidic pH, partially inhibits binding of HPSE to cell surface receptors and modulates its enzymatic activity. Interacts with SDC1; the interaction enhances the shedding of SDC1 By similarity.
Subcellular location	Lysosome membrane; Peripheral membrane protein By similarity. Secreted By similarity. Nucleus By similarity. Note: Proheparanase is secreted via vesicles of the Golgi. Interacts with cell membrane heparan sulfate proteoglycans (HSPGs). Endocytosed and accumulates in endosomes. Transferred to lysosomes where it is proteolytically cleaved to produce the active enzyme. Under certain stimuli, transferred to the cell surface. Colocalizes with SDC1 in endosomal/lysosomal vesicles. Accumulates in perinuclear lysosomal vesicles. Heparin retains proheparanase in the extracellular medium. Associates with lipid rafts By similarity.
Post-translational modification	Proteolytically processed. The cleavage of the 65 kDa form leads to the generation of a linker peptide, and the 8 kDa and 50 kDa products. The active form, the 8/50 kDa heterodimer, is resistant to degradation. Complete removal of the linker peptide appears to be a prerequisite to the complete activation of the enzyme By similarity. N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility By similarity.
Sequence similarities	Belongs to the glycosyl hydrolase 79 family.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Lysosome Membrane Nucleus Secreted
Domain	Signal
Ligand	Calcium Magnesium
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	cation binding Inferred from electronic annotation. Source: InterPro heparanase activity Inferred from direct assay Ref.2. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28	By similarity
	Chain	29 – 102	74	Heparanase 8 kDa subunit		PRO_0000042266
	Propeptide	103 – 150	48	Linker peptide By similarity		PRO_0000042267
	Chain	151 – 536	386	Heparanase 50 kDa subunit		PRO_0000042268
Regions
	Region	151 – 155	5	Heparin/HS-binding By similarity
	Region	263 – 273	11	Heparin/HS-binding By similarity
	Region	520 – 536	17	Required for transferring proheparanase to the Golgi apparatus, secretion and subsequent enzyme activity and for enhancement of PKB/AKT1 phosphorylation By similarity
Sites
	Active site	218	1	Proton donor Potential
	Active site	336	1	Nucleophile Potential
Amino acid modifications
	Glycosylation	155	1	N-linked (GlcNAc...) By similarity
	Glycosylation	193	1	N-linked (GlcNAc...) By similarity
	Glycosylation	210	1	N-linked (GlcNAc...) By similarity
	Glycosylation	452	1	N-linked (GlcNAc...) By similarity
Experimental info
	Sequence conflict	15	1	G → R in AAF04563. Ref.2
	Sequence conflict	227	1	H → Q in AAF04563. Ref.2
	Sequence conflict	350	1	D → N in AAF04563. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q71RP1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: C434E04CF536EA4D	FASTA	536	60,480
	10 20 30 40 50 60 MLRPLLLLWL WGRLGALTQG TPAGTAPTKD VVDLEFYTKR LFQSVSPSFL SITIDASLAT 70 80 90 100 110 120 DPRFLTFLGS PRLRALARGL SPAYLRFGGT KTDFLIFDPN KEPTSEERSY WQSQDNNDIC 130 140 150 160 170 180 GSERVSADVL RKLQMEWPFQ ELLLLREQYQ REFKNSTYSR SSVDMLYSFA KCSRLDLIFG 190 200 210 220 230 240 LNALLRTPDL RWNSSNAQLL LNYCSSKGYN ISWELGNEPN SFWKKAHISI DGLQLGEDFV 250 260 270 280 290 300 ELHKLLQKSA FQNAKLYGPD IGQPRGKTVK LLRSFLKAGG EVIDSLTWHH YYLNGRVATK 310 320 330 340 350 360 EDFLSSDVLD TFILSVQKIL KVTKEMTPGK KVWLGETSSA YGGGAPLLSD TFAAGFMWLD 370 380 390 400 410 420 KLGLSAQLGI EVVMRQVFFG AGNYHLVDEN FEPLPDYWLS LLFKKLVGPK VLMSRVKGPD 430 440 450 460 470 480 RSKLRVYLHC TNVYHPRYRE GDLTLYVLNL HNVTKHLKLP PPMFSRPVDK YLLKPFGSDG 490 500 510 520 530 LLSKSVQLNG QTLKMVDEQT LPALTEKPLP AGSSLSVPAF SYGFFVIRNA KIAACI

References

[1]	"Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis." Hulett M.D., Freeman C., Hamdorf B.J., Baker R.T., Harris M.J., Parish C.R. Nat. Med. 5:803-809(1999) [PubMed: 10395326] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Characterization of heparanase from a rat parathyroid cell line." Podyma-Inoue K.A., Yokote H., Sakaguchi K., Ikuta M., Yanagishita M. J. Biol. Chem. 277:32459-32465(2002) [PubMed: 12077130] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME REGULATION.
[3]	"Heparanase accelerates wound angiogenesis and wound healing in mouse and rat models." Zcharia E., Zilka R., Yaar A., Yacoby-Zeevi O., Zetser A., Metzger S., Sarid R., Naggi A., Casu B., Ilan N., Vlodavsky I., Abramovitch R. FASEB J. 19:211-221(2005) [PubMed: 15677344] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF359508 mRNA. Translation: AAQ15189.1. AF184967 mRNA. Translation: AAF04563.1.
IPI	IPI00214945.
RefSeq	NP_072127.1. NM_022605.1.
UniGene	Rn.6392.
3D structure databases
ProteinModelPortal	Q71RP1.
ModBase	Search...
Protein-protein interaction databases
STRING	Q71RP1.
Protein family/group databases
CAZy	GH79. Glycoside Hydrolase Family 79.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	64537.
KEGG	rno:64537.
Organism-specific databases
CTD	10855.
RGD	61969. Hpse.
Phylogenomic databases
eggNOG	maNOG15282.
HOVERGEN	HBG081606.
InParanoid	Q71RP1.
Gene expression databases
ArrayExpress	Q71RP1.
Genevestigator	Q71RP1.
GermOnline	ENSRNOG00000002188. Rattus norvegicus.
Family and domain databases
InterPro	IPR005199. Glyco_hydro_79. IPR013781. Glyco_hydro_subgr_catalytic. IPR017853. Glycoside_hydrolase_SF. [Graphical view]
Gene3D	G3DSA:3.20.20.80. Glyco_hydro_cat. 1 hit.
KO	K07964.
PANTHER	PTHR14363. Glyco_hydro_79_N. 1 hit.
Pfam	PF03662. Glyco_hydro_79n. 1 hit. [Graphical view]
SUPFAM	SSF51445. Glyco_hydro_cat. 1 hit.
ProtoNet	Search...
Other
NextBio	613394.

Entry information

Entry name

HPSE_RAT

Accession

Primary (citable) accession number: Q71RP1
Secondary accession number(s): Q9QZF8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2005
Last sequence update:	July 5, 2004
Last modified:	November 16, 2011
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program