Q9MYY0 (HPSE_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Heparanase
EC=3.2.-.-

Cleaved into the following 2 chains:

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

Gene names

Name:

HPSE

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	545 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. 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. Acts as procoagulant by enhancing the generation of activated factor X/F10 in the presence of tissue factor/TF and activated factor VII/F7. Independent of its enzymatic activity, increases cell adhesion to the extracellular matrix (ECM). Enhances AKT1/PKB phosphorylation, possibly via interaction with a lipid raft-resident receptor. Plays a role in the regulation of 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.
Enzyme regulation	Inhibited by laminarin sulfate and, to a lower extent, by heparin, sulfamin and EDTA. Activated by calcium and magnesium By similarity.
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. Associates with lipid rafts. Colocalizes with SDC1 in endosomal/lysosomal vesicles. Accumulates in perinuclear lysosomal vesicles. Heparin retains proheparanase in the extracellular medium By similarity.
Tissue specificity	Highly expressed in placenta and weakly in the kidney, lung, spleen and uterus. Ref.1
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 the 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 hydrolase activity, acting on glycosyl bonds Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 37	37	By similarity
	Chain	38 – 111	74	Heparanase 8 kDa subunit By similarity		PRO_0000042256
	Propeptide	112 – 159	48	Linker peptide		PRO_0000042257
	Chain	160 – 545	386	Heparanase 50 kDa subunit By similarity		PRO_0000042258
Regions
	Region	160 – 164	5	Heparin/HS-binding Potential
	Region	272 – 282	11	Heparin/HS-binding Potential
	Region	529 – 545	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	227	1	Proton donor Potential
	Active site	345	1	Nucleophile Potential
Amino acid modifications
	Glycosylation	164	1	N-linked (GlcNAc...) Potential
	Glycosylation	219	1	N-linked (GlcNAc...) Potential
	Glycosylation	461	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	Q9MYY0 [UniParc]. Last modified June 1, 2001. Version 2. Checksum: FAC4BDFFD855B933	FASTA	545	61,077
	10 20 30 40 50 60 MLACRKPGLR PPLLLLLPLL GPLGPCSPGT PAAAAPADDA AELEFFTERP LHLVSPAFLS 70 80 90 100 110 120 FTIDANLATD PRFFTFLGSS KLRTLARGLA PAYLRFGGNK GDFLIFDPKK EPAFEERSYW 130 140 150 160 170 180 LSQSNQDICK SGSIPSDVEE KLRLEWPFQE QVLLREQYQK KFTNSTYSRS SVDMLYTFAS 190 200 210 220 230 240 CSGLNLIFGV NALLRTTDMH WDSSNAQLLL DYCSSKNYNI SWELGNEPNS FQRKAGIFIN 250 260 270 280 290 300 GRQLGEDFIE FRKLLGKSAF KNAKLYGPDI GQPRRNTVKM LKSFLKAGGE VIDSVTWHHY 310 320 330 340 350 360 YVNGRIATKE DFLNPDILDT FISSVQKTLR IVEKIRPLKK VWLGETSSAF GGGAPFLSNT 370 380 390 400 410 420 FAAGFMWLDK LGLSARMGIE VVMRQVLFGA GNYHLVDGNF EPLPDYWLSL LFKKLVGNKV 430 440 450 460 470 480 LMASVKGPDR SKFRVYLHCT NTKHPRYKEG DLTLYALNLH NVTKHLELPH HLFNKQVDKY 490 500 510 520 530 540 LIKPSGTDGL LSKSVQLNGQ ILKMVDEQTL PALTEKPLHP GSSLGMPPFS YGFFVIRNAK VAACI

References

[1]	"Expression of heparanase mRNA in bovine placenta during gestation." Kizaki K., Nakano H., Nakano H., Takahashi T., Imai K., Hashizume K. Reproduction 121:573-580(2001) [PubMed: 11277877] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Placenta.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF281160 mRNA. Translation: AAF87301.2.
IPI	IPI00696957.
RefSeq	NP_776507.1. NM_174082.2.
UniGene	Bt.8127.
3D structure databases
ProteinModelPortal	Q9MYY0.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9MYY0.
Protein family/group databases
CAZy	GH79. Glycoside Hydrolase Family 79.
Proteomic databases
PRIDE	Q9MYY0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	281230.
KEGG	bta:281230.
Organism-specific databases
CTD	10855.
Phylogenomic databases
eggNOG	maNOG15282.
GeneTree	ENSGT00390000004874.
HOVERGEN	HBG081606.
InParanoid	Q9MYY0.
OrthoDB	EOG45MN5C.
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...

Entry information

Entry name

HPSE_BOVIN

Accession

Primary (citable) accession number: Q9MYY0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2005
Last sequence update:	June 1, 2001
Last modified:	November 16, 2011
This is version 55 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program