Q8WWQ2 (HPSE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inactive heparanase-2
Short name=Hpa2

Gene names

Name:	HPSE2
Synonyms:	HPA2

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	592 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	Binds heparin and heparan sulfate with high affinity, but lacks heparanase activity. Inhibits HPSE, possibly by competing for its substrates (in vitro). Ref.7
Subunit structure	Interacts with HPSE. Interacts with SDC1 (via glycan chains). Ref.7
Subcellular location	Secreted › extracellular space › extracellular matrix Ref.7.
Tissue specificity	Widely expressed, with the highest expression in brain, mammary gland, prostate, small intestine, testis and uterus. In the central nervous system, expressed in the spinal chord, caudate nucleus, thalamus, substantia nigra, medulla oblongata, putamen and pons. In the urinary bladder, expressed in longitudinal and circular layers of detrusor muscle. Found both in normal and cancer tissues. Ref.1 Ref.6
Developmental stage	Expressed in the developing forebrain, diencephalon, midbrain, hind brain and spinal cord at Carnagie stage 16 (CS16, 6 weeks of gestation) and CS21 (8 weeks). Ref.6
Involvement in disease	Urofacial syndrome (UFS) [MIM:236730]: A rare autosomal recessive characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. Affected individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.6
Sequence similarities	Belongs to the glycosyl hydrolase 79 family.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Traceable author statement. Source: Reactome glycosaminoglycan catabolic process Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	intracellular Traceable author statement Ref.1. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome proteinaceous extracellular matrix Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	heparan sulfate proteoglycan binding Inferred from direct assay Ref.7. Source: UniProtKB heparanase activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8WWQ2-1)

Also known as: HPA2c;

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 2 (identifier: Q8WWQ2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     539-548: SVQLNGQPLV → TQRCQYCGII
     549-592: Missing.

Isoform 3 (identifier: Q8WWQ2-3)

Also known as: HPA2b;

The sequence of this isoform differs from the canonical sequence as follows:
     204-261: Missing.

Isoform 4 (identifier: Q8WWQ2-4)

Also known as: HPA2a;

The sequence of this isoform differs from the canonical sequence as follows:
     150-261: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 41	41	Potential
	Chain	42 – 592	551	Inactive heparanase-2		PRO_0000068140
Amino acid modifications
	Glycosylation	254	1	N-linked (GlcNAc...) Potential
	Glycosylation	392	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	150 – 261	112	Missing in isoform 4.		VSP_015850
	Alternative sequence	204 – 261	58	Missing in isoform 3.		VSP_015851
	Alternative sequence	539 – 548	10	SVQLNGQPLV → TQRCQYCGII in isoform 2.		VSP_015852
	Alternative sequence	549 – 592	44	Missing in isoform 2.		VSP_015853
	Natural variant	315	1	A → T. Corresponds to variant rs17110744 [ dbSNP | Ensembl ].		VAR_030472
	Natural variant	579	1	Y → F. Ref.1 Ref.2 Corresponds to variant rs10883100 [ dbSNP | Ensembl ].		VAR_023601
Experimental info
	Sequence conflict	12	1	P → L in CAC82492. Ref.2
	Sequence conflict	213	1	F → S in CAC82491. Ref.2
	Sequence conflict	213	1	F → S in CAC82492. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (HPA2c) [UniParc]. Last modified February 6, 2007. Version 3. Checksum: 95C384AD9A6C868E	FASTA	592	66,596
	10 20 30 40 50 60 MRVLCAFPEA MPSSNSRPPA CLAPGALYLA LLLHLSLSSQ AGDRRPLPVD RAAGLKEKTL 70 80 90 100 110 120 ILLDVSTKNP VRTVNENFLS LQLDPSIIHD GWLDFLSSKR LVTLARGLSP AFLRFGGKRT 130 140 150 160 170 180 DFLQFQNLRN PAKSRGGPGP DYYLKNYEDD IVRSDVALDK QKGCKIAQHP DVMLELQREK 190 200 210 220 230 240 AAQMHLVLLK EQFSNTYSNL ILTARSLDKL YNFADCSGLH LIFALNALRR NPNNSWNSSS 250 260 270 280 290 300 ALSLLKYSAS KKYNISWELG NEPNNYRTMH GRAVNGSQLG KDYIQLKSLL QPIRIYSRAS 310 320 330 340 350 360 LYGPNIGRPR KNVIALLDGF MKVAGSTVDA VTWQHCYIDG RVVKVMDFLK TRLLDTLSDQ 370 380 390 400 410 420 IRKIQKVVNT YTPGKKIWLE GVVTTSAGGT NNLSDSYAAG FLWLNTLGML ANQGIDVVIR 430 440 450 460 470 480 HSFFDHGYNH LVDQNFNPLP DYWLSLLYKR LIGPKVLAVH VAGLQRKPRP GRVIRDKLRI 490 500 510 520 530 540 YAHCTNHHNH NYVRGSITLF IINLHRSRKK IKLAGTLRDK LVHQYLLQPY GQEGLKSKSV 550 560 570 580 590 QLNGQPLVMV DDGTLPELKP RPLRAGRTLV IPPVTMGFYV VKNVNALACR YR
	Isoform 2 [UniParc]. Checksum: 2572C68423CD2C51	FASTA	548	61,816
	10 20 30 40 50 60 MRVLCAFPEA MPSSNSRPPA CLAPGALYLA LLLHLSLSSQ AGDRRPLPVD RAAGLKEKTL 70 80 90 100 110 120 ILLDVSTKNP VRTVNENFLS LQLDPSIIHD GWLDFLSSKR LVTLARGLSP AFLRFGGKRT 130 140 150 160 170 180 DFLQFQNLRN PAKSRGGPGP DYYLKNYEDD IVRSDVALDK QKGCKIAQHP DVMLELQREK 190 200 210 220 230 240 AAQMHLVLLK EQFSNTYSNL ILTARSLDKL YNFADCSGLH LIFALNALRR NPNNSWNSSS 250 260 270 280 290 300 ALSLLKYSAS KKYNISWELG NEPNNYRTMH GRAVNGSQLG KDYIQLKSLL QPIRIYSRAS 310 320 330 340 350 360 LYGPNIGRPR KNVIALLDGF MKVAGSTVDA VTWQHCYIDG RVVKVMDFLK TRLLDTLSDQ 370 380 390 400 410 420 IRKIQKVVNT YTPGKKIWLE GVVTTSAGGT NNLSDSYAAG FLWLNTLGML ANQGIDVVIR 430 440 450 460 470 480 HSFFDHGYNH LVDQNFNPLP DYWLSLLYKR LIGPKVLAVH VAGLQRKPRP GRVIRDKLRI 490 500 510 520 530 540 YAHCTNHHNH NYVRGSITLF IINLHRSRKK IKLAGTLRDK LVHQYLLQPY GQEGLKSKTQ RCQYCGII
	Isoform 3 (HPA2b) [UniParc]. Checksum: C3DE5E900CAB9BC4	FASTA	534	60,080
	10 20 30 40 50 60 MRVLCAFPEA MPSSNSRPPA CLAPGALYLA LLLHLSLSSQ AGDRRPLPVD RAAGLKEKTL 70 80 90 100 110 120 ILLDVSTKNP VRTVNENFLS LQLDPSIIHD GWLDFLSSKR LVTLARGLSP AFLRFGGKRT 130 140 150 160 170 180 DFLQFQNLRN PAKSRGGPGP DYYLKNYEDD IVRSDVALDK QKGCKIAQHP DVMLELQREK 190 200 210 220 230 240 AAQMHLVLLK EQFSNTYSNL ILTEPNNYRT MHGRAVNGSQ LGKDYIQLKS LLQPIRIYSR 250 260 270 280 290 300 ASLYGPNIGR PRKNVIALLD GFMKVAGSTV DAVTWQHCYI DGRVVKVMDF LKTRLLDTLS 310 320 330 340 350 360 DQIRKIQKVV NTYTPGKKIW LEGVVTTSAG GTNNLSDSYA AGFLWLNTLG MLANQGIDVV 370 380 390 400 410 420 IRHSFFDHGY NHLVDQNFNP LPDYWLSLLY KRLIGPKVLA VHVAGLQRKP RPGRVIRDKL 430 440 450 460 470 480 RIYAHCTNHH NHNYVRGSIT LFIINLHRSR KKIKLAGTLR DKLVHQYLLQ PYGQEGLKSK 490 500 510 520 530 SVQLNGQPLV MVDDGTLPEL KPRPLRAGRT LVIPPVTMGF YVVKNVNALA CRYR
	Isoform 4 (HPA2a) [UniParc]. Checksum: F75F89F67AD95C83	FASTA	480	53,917
	10 20 30 40 50 60 MRVLCAFPEA MPSSNSRPPA CLAPGALYLA LLLHLSLSSQ AGDRRPLPVD RAAGLKEKTL 70 80 90 100 110 120 ILLDVSTKNP VRTVNENFLS LQLDPSIIHD GWLDFLSSKR LVTLARGLSP AFLRFGGKRT 130 140 150 160 170 180 DFLQFQNLRN PAKSRGGPGP DYYLKNYEDE PNNYRTMHGR AVNGSQLGKD YIQLKSLLQP 190 200 210 220 230 240 IRIYSRASLY GPNIGRPRKN VIALLDGFMK VAGSTVDAVT WQHCYIDGRV VKVMDFLKTR 250 260 270 280 290 300 LLDTLSDQIR KIQKVVNTYT PGKKIWLEGV VTTSAGGTNN LSDSYAAGFL WLNTLGMLAN 310 320 330 340 350 360 QGIDVVIRHS FFDHGYNHLV DQNFNPLPDY WLSLLYKRLI GPKVLAVHVA GLQRKPRPGR 370 380 390 400 410 420 VIRDKLRIYA HCTNHHNHNY VRGSITLFII NLHRSRKKIK LAGTLRDKLV HQYLLQPYGQ 430 440 450 460 470 480 EGLKSKSVQL NGQPLVMVDD GTLPELKPRP LRAGRTLVIP PVTMGFYVVK NVNALACRYR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member." McKenzie E., Tyson K., Stamps A., Smith P., Turner P., Barry R., Hircock M., Patel S., Barry E., Stubberfield C., Terrett J., Page M. Biochem. Biophys. Res. Commun. 276:1170-1177(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), VARIANT PHE-579, TISSUE SPECIFICITY. Tissue: Heart.
[2]	Legoux P., Legoux R., O'Brien D., Salome M. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT PHE-579. Tissue: Prostate.
[3]	"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].
[4]	"Loss-of-function mutations in HPSE2 cause the autosomal recessive urofacial syndrome." Pang J., Zhang S., Yang P., Hawkins-Lee B., Zhong J., Zhang Y., Ochoa B., Agundez J.A., Voelckel M.A., Fisher R.B., Gu W., Xiong W.C., Mei L., She J.X., Wang C.Y. Am. J. Hum. Genet. 86:957-962(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN UFS.
[5]	Erratum Pang J., Zhang S., Yang P., Hawkins-Lee B., Zhong J., Zhang Y., Ochoa B., Agundez J.A., Voelckel M.A., Fisher R.B., Gu W., Xiong W.C., Mei L., She J.X., Wang C.Y. Am. J. Hum. Genet. 87:161-161(2010)
[6]	"Mutations in HPSE2 cause urofacial syndrome." Daly S.B., Urquhart J.E., Hilton E., McKenzie E.A., Kammerer R.A., Lewis M., Kerr B., Stuart H., Donnai D., Long D.A., Burgu B., Aydogdu O., Derbent M., Garcia-Minaur S., Reardon W., Gener B., Shalev S., Smith R. , Woolf A.S., Black G.C., Newman W.G. Am. J. Hum. Genet. 86:963-969(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN UFS, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[7]	"Heparanase 2 interacts with heparan sulfate with high affinity and inhibits heparanase activity." Levy-Adam F., Feld S., Cohen-Kaplan V., Shteingauz A., Gross M., Arvatz G., Naroditsky I., Ilan N., Doweck I., Vlodavsky I. J. Biol. Chem. 285:28010-28019(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HPSE, ABSENCE OF HEPARANASE ACTIVITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF282885 mRNA. Translation: AAG23421.1. AF282886 mRNA. Translation: AAG23422.1. AF282887 mRNA. Translation: AAG23423.1. AJ299719 mRNA. Translation: CAC82491.1. AJ299720 mRNA. Translation: CAC82492.1. AL590036 , AL139243, AL356220, AL356268, AL445251 Genomic DNA. Translation: CAH73137.1. AL139243 , AL356220, AL356268, AL445251, AL590036 Genomic DNA. Translation: CAI14146.1. AL356268 , AL139243, AL356220, AL445251, AL590036 Genomic DNA. Translation: CAH70448.1. AL445251 , AL139243, AL356220, AL356268, AL590036 Genomic DNA. Translation: CAI16472.1. AL356220 , AL139243, AL356268, AL445251, AL590036 Genomic DNA. Translation: CAI17160.1. AL590036 , AL139243, AL356220, AL356268, AL445251 Genomic DNA. Translation: CAH73139.1. AL356220 , AL356268, AL139243, AL445251, AL590036 Genomic DNA. Translation: CAI17162.1. AL356268 , AL139243, AL356220, AL445251, AL590036 Genomic DNA. Translation: CAH70450.1. AL445251 , AL139243, AL356220, AL356268, AL590036 Genomic DNA. Translation: CAI16474.1. AL139243 , AL356220, AL356268, AL445251, AL590036 Genomic DNA. Translation: CAI14148.1. AL590036 , AL139243, AL356220, AL356268, AL445251 Genomic DNA. Translation: CAH73138.1. AL356220 , AL139243, AL356268, AL445251, AL590036 Genomic DNA. Translation: CAI17161.1. AL356268 , AL139243, AL356220, AL445251, AL590036 Genomic DNA. Translation: CAH70449.1. AL445251 , AL139243, AL356220, AL356268, AL590036 Genomic DNA. Translation: CAI16473.1. AL139243 , AL356220, AL356268, AL445251, AL590036 Genomic DNA. Translation: CAI14147.1.
IPI	IPI00029594. IPI00157363. IPI00157364. IPI00642713.
PIR	JC7506.
RefSeq	NP_001159716.1. NM_001166244.1. NP_001159717.1. NM_001166245.1. NP_001159718.1. NM_001166246.1. NP_068600.4. NM_021828.4.
UniGene	Hs.500750. Hs.676960. Hs.689544.
3D structure databases
ProteinModelPortal	Q8WWQ2.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000359583.
PTM databases
PhosphoSite	Q8WWQ2.
Polymorphism databases
DMDM	125987832.
Proteomic databases
PaxDb	Q8WWQ2.
PRIDE	Q8WWQ2.
Protocols and materials databases
DNASU	60495.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370546; ENSP00000359577; ENSG00000172987. ENST00000370549; ENSP00000359580; ENSG00000172987. ENST00000370552; ENSP00000359583; ENSG00000172987. ENST00000404542; ENSP00000384384; ENSG00000172987.
GeneID	60495.
KEGG	hsa:60495.
UCSC	uc001kpn.2. human. uc001kpo.2. human. uc009xwc.2. human. uc009xwd.2. human.
Organism-specific databases
CTD	60495.
GeneCards	GC10M100208.
HGNC	HGNC:18374. HPSE2.
HPA	HPA044603.
MIM	236730. phenotype. 613469. gene.
neXtProt	NX_Q8WWQ2.
Orphanet	2704. Ochoa syndrome.
PharmGKB	PA38533.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG72789.
HOVERGEN	HBG081606.
InParanoid	Q8WWQ2.
KO	K07965.
OMA	VIPPLTM.
OrthoDB	EOG4JHCFC.
PhylomeDB	Q8WWQ2.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_116125. Disease.
Gene expression databases
Bgee	Q8WWQ2.
CleanEx	HS_HPSE2.
Genevestigator	Q8WWQ2.
GermOnline	ENSG00000172987. Homo sapiens.
Family and domain databases
Gene3D	3.20.20.80. 1 hit.
InterPro	IPR005199. Glyco_hydro_79. IPR013781. Glyco_hydro_catalytic_dom. IPR017853. Glycoside_hydrolase_SF. [Graphical view]
PANTHER	PTHR14363. PTHR14363. 1 hit.
Pfam	PF03662. Glyco_hydro_79n. 1 hit. [Graphical view]
SUPFAM	SSF51445. Glyco_hydro_cat. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	60495.
NextBio	65399.
SOURCE	Search...

Entry information

Entry name

HPSE2_HUMAN

Accession

Primary (citable) accession number: Q8WWQ2
Secondary accession number(s): Q5VUH4 , Q5VUH5, Q5VUH6, Q8WWQ1, Q9HB37, Q9HB38, Q9HB39

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	February 6, 2007
Last modified:	May 1, 2013
This is version 84 of the entry and version 3 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.