ID   HPSE2_HUMAN             Reviewed;         592 AA.
AC   Q8WWQ2; Q5VUH4; Q5VUH5; Q5VUH6; Q8WWQ1; Q9HB37; Q9HB38; Q9HB39;
DT   25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT   06-FEB-2007, sequence version 3.
DT   27-MAR-2024, entry version 154.
DE   RecName: Full=Inactive heparanase-2;
DE            Short=Hpa2;
DE   Flags: Precursor;
GN   Name=HPSE2; Synonyms=HPA2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), VARIANT PHE-579, AND
RP   TISSUE SPECIFICITY.
RC   TISSUE=Heart;
RX   PubMed=11027606; DOI=10.1006/bbrc.2000.3586;
RA   McKenzie E., Tyson K., Stamps A., Smith P., Turner P., Barry R.,
RA   Hircock M., Patel S., Barry E., Stubberfield C., Terrett J., Page M.;
RT   "Cloning and expression profiling of Hpa2, a novel mammalian heparanase
RT   family member.";
RL   Biochem. Biophys. Res. Commun. 276:1170-1177(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT PHE-579.
RC   TISSUE=Prostate;
RA   Legoux P., Legoux R., O'Brien D., Salome M.;
RL   Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [4]
RP   INVOLVEMENT IN UFS1.
RX   PubMed=20560209; DOI=10.1016/j.ajhg.2010.04.016;
RA   Pang J., Zhang S., Yang P., Hawkins-Lee B., Zhong J., Zhang Y., Ochoa B.,
RA   Agundez J.A., Voelckel M.A., Fisher R.B., Gu W., Xiong W.C., Mei L.,
RA   She J.X., Wang C.Y.;
RT   "Loss-of-function mutations in HPSE2 cause the autosomal recessive
RT   urofacial syndrome.";
RL   Am. J. Hum. Genet. 86:957-962(2010).
RN   [5]
RP   ERRATUM OF PUBMED:20560209.
RA   Pang J., Zhang S., Yang P., Hawkins-Lee B., Zhong J., Zhang Y., Ochoa B.,
RA   Agundez J.A., Voelckel M.A., Fisher R.B., Gu W., Xiong W.C., Mei L.,
RA   She J.X., Wang C.Y.;
RL   Am. J. Hum. Genet. 87:161-161(2010).
RN   [6]
RP   INVOLVEMENT IN UFS1, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=20560210; DOI=10.1016/j.ajhg.2010.05.006;
RA   Daly S.B., Urquhart J.E., Hilton E., McKenzie E.A., Kammerer R.A.,
RA   Lewis M., Kerr B., Stuart H., Donnai D., Long D.A., Burgu B., Aydogdu O.,
RA   Derbent M., Garcia-Minaur S., Reardon W., Gener B., Shalev S., Smith R.,
RA   Woolf A.S., Black G.C., Newman W.G.;
RT   "Mutations in HPSE2 cause urofacial syndrome.";
RL   Am. J. Hum. Genet. 86:963-969(2010).
RN   [7]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HPSE, AND ABSENCE OF
RP   HEPARANASE ACTIVITY.
RX   PubMed=20576607; DOI=10.1074/jbc.m110.116384;
RA   Levy-Adam F., Feld S., Cohen-Kaplan V., Shteingauz A., Gross M., Arvatz G.,
RA   Naroditsky I., Ilan N., Doweck I., Vlodavsky I.;
RT   "Heparanase 2 interacts with heparan sulfate with high affinity and
RT   inhibits heparanase activity.";
RL   J. Biol. Chem. 285:28010-28019(2010).
CC   -!- FUNCTION: Binds heparin and heparan sulfate with high affinity, but
CC       lacks heparanase activity. Inhibits HPSE, possibly by competing for its
CC       substrates (in vitro). {ECO:0000269|PubMed:20576607}.
CC   -!- SUBUNIT: Interacts with HPSE. Interacts with SDC1 (via glycan chains).
CC       {ECO:0000269|PubMed:20576607}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000269|PubMed:20576607}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1; Synonyms=HPA2c;
CC         IsoId=Q8WWQ2-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8WWQ2-2; Sequence=VSP_015852, VSP_015853;
CC       Name=3; Synonyms=HPA2b;
CC         IsoId=Q8WWQ2-3; Sequence=VSP_015851;
CC       Name=4; Synonyms=HPA2a;
CC         IsoId=Q8WWQ2-4; Sequence=VSP_015850;
CC   -!- TISSUE SPECIFICITY: Widely expressed, with the highest expression in
CC       brain, mammary gland, prostate, small intestine, testis and uterus. In
CC       the central nervous system, expressed in the spinal chord, caudate
CC       nucleus, thalamus, substantia nigra, medulla oblongata, putamen and
CC       pons. In the urinary bladder, expressed in longitudinal and circular
CC       layers of detrusor muscle. Found both in normal and cancer tissues.
CC       {ECO:0000269|PubMed:11027606, ECO:0000269|PubMed:20560210}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in the developing forebrain,
CC       diencephalon, midbrain, hind brain and spinal cord at Carnagie stage 16
CC       (CS16, 6 weeks of gestation) and CS21 (8 weeks).
CC       {ECO:0000269|PubMed:20560210}.
CC   -!- DISEASE: Urofacial syndrome 1 (UFS1) [MIM:236730]: A rare autosomal
CC       recessive disorder characterized by facial grimacing when attempting to
CC       smile and failure of the urinary bladder to void completely despite a
CC       lack of anatomical bladder outflow obstruction or overt neurological
CC       damage. Affected individuals often have reflux of infected urine from
CC       the bladder to the upper renal tract, with a risk of kidney damage and
CC       renal failure. {ECO:0000269|PubMed:20560209,
CC       ECO:0000269|PubMed:20560210}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 79 family. {ECO:0000305}.
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DR   EMBL; AF282885; AAG23421.1; -; mRNA.
DR   EMBL; AF282886; AAG23422.1; -; mRNA.
DR   EMBL; AF282887; AAG23423.1; -; mRNA.
DR   EMBL; AJ299719; CAC82491.1; -; mRNA.
DR   EMBL; AJ299720; CAC82492.1; -; mRNA.
DR   EMBL; AL590036; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL139243; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL356268; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL445251; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL356220; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS53566.1; -. [Q8WWQ2-4]
DR   CCDS; CCDS53567.1; -. [Q8WWQ2-3]
DR   CCDS; CCDS53568.1; -. [Q8WWQ2-2]
DR   CCDS; CCDS7477.1; -. [Q8WWQ2-1]
DR   PIR; JC7506; JC7506.
DR   RefSeq; NP_001159716.1; NM_001166244.1. [Q8WWQ2-3]
DR   RefSeq; NP_001159717.1; NM_001166245.1. [Q8WWQ2-4]
DR   RefSeq; NP_001159718.1; NM_001166246.1. [Q8WWQ2-2]
DR   RefSeq; NP_068600.4; NM_021828.4. [Q8WWQ2-1]
DR   AlphaFoldDB; Q8WWQ2; -.
DR   SMR; Q8WWQ2; -.
DR   BioGRID; 121926; 30.
DR   IntAct; Q8WWQ2; 2.
DR   STRING; 9606.ENSP00000359583; -.
DR   GlyCosmos; Q8WWQ2; 2 sites, No reported glycans.
DR   GlyGen; Q8WWQ2; 2 sites.
DR   iPTMnet; Q8WWQ2; -.
DR   PhosphoSitePlus; Q8WWQ2; -.
DR   BioMuta; HPSE2; -.
DR   DMDM; 125987832; -.
DR   MassIVE; Q8WWQ2; -.
DR   PaxDb; 9606-ENSP00000359583; -.
DR   PeptideAtlas; Q8WWQ2; -.
DR   ProteomicsDB; 74920; -. [Q8WWQ2-1]
DR   ProteomicsDB; 74921; -. [Q8WWQ2-2]
DR   ProteomicsDB; 74922; -. [Q8WWQ2-3]
DR   ProteomicsDB; 74923; -. [Q8WWQ2-4]
DR   Antibodypedia; 45898; 197 antibodies from 29 providers.
DR   DNASU; 60495; -.
DR   Ensembl; ENST00000370546.5; ENSP00000359577.1; ENSG00000172987.14. [Q8WWQ2-2]
DR   Ensembl; ENST00000370549.5; ENSP00000359580.1; ENSG00000172987.14. [Q8WWQ2-3]
DR   Ensembl; ENST00000370552.8; ENSP00000359583.3; ENSG00000172987.14. [Q8WWQ2-1]
DR   Ensembl; ENST00000628193.2; ENSP00000485916.1; ENSG00000172987.14. [Q8WWQ2-4]
DR   GeneID; 60495; -.
DR   KEGG; hsa:60495; -.
DR   MANE-Select; ENST00000370552.8; ENSP00000359583.3; NM_021828.5; NP_068600.4.
DR   UCSC; uc001kpn.3; human. [Q8WWQ2-1]
DR   AGR; HGNC:18374; -.
DR   CTD; 60495; -.
DR   DisGeNET; 60495; -.
DR   GeneCards; HPSE2; -.
DR   GeneReviews; HPSE2; -.
DR   HGNC; HGNC:18374; HPSE2.
DR   HPA; ENSG00000172987; Tissue enhanced (brain, cervix, vagina).
DR   MalaCards; HPSE2; -.
DR   MIM; 236730; phenotype.
DR   MIM; 613469; gene.
DR   neXtProt; NX_Q8WWQ2; -.
DR   OpenTargets; ENSG00000172987; -.
DR   Orphanet; 2704; Ochoa syndrome.
DR   PharmGKB; PA38533; -.
DR   VEuPathDB; HostDB:ENSG00000172987; -.
DR   eggNOG; ENOG502QQST; Eukaryota.
DR   GeneTree; ENSGT00390000004874; -.
DR   InParanoid; Q8WWQ2; -.
DR   OMA; YMRGSIT; -.
DR   OrthoDB; 1054039at2759; -.
DR   PhylomeDB; Q8WWQ2; -.
DR   TreeFam; TF328999; -.
DR   PathwayCommons; Q8WWQ2; -.
DR   Reactome; R-HSA-2024096; HS-GAG degradation.
DR   SignaLink; Q8WWQ2; -.
DR   SIGNOR; Q8WWQ2; -.
DR   BioGRID-ORCS; 60495; 10 hits in 1146 CRISPR screens.
DR   ChiTaRS; HPSE2; human.
DR   GeneWiki; HPSE2; -.
DR   GenomeRNAi; 60495; -.
DR   Pharos; Q8WWQ2; Tbio.
DR   PRO; PR:Q8WWQ2; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q8WWQ2; Protein.
DR   Bgee; ENSG00000172987; Expressed in calcaneal tendon and 98 other cell types or tissues.
DR   ExpressionAtlas; Q8WWQ2; baseline and differential.
DR   GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0043395; F:heparan sulfate proteoglycan binding; IDA:UniProtKB.
DR   GO; GO:0030305; F:heparanase activity; TAS:UniProtKB.
DR   GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR   Gene3D; 3.20.20.80; Glycosidases; 1.
DR   InterPro; IPR005199; Glyco_hydro_79.
DR   InterPro; IPR017853; Glycoside_hydrolase_SF.
DR   PANTHER; PTHR46145; HEPARANASE; 1.
DR   PANTHER; PTHR46145:SF1; INACTIVE HEPARANASE-2; 1.
DR   Pfam; PF03662; Glyco_hydro_79n; 1.
DR   SUPFAM; SSF51445; (Trans)glycosidases; 1.
DR   Genevisible; Q8WWQ2; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Extracellular matrix; Glycoprotein;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..41
FT                   /evidence="ECO:0000255"
FT   CHAIN           42..592
FT                   /note="Inactive heparanase-2"
FT                   /id="PRO_0000068140"
FT   CARBOHYD        254
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         150..261
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:11027606"
FT                   /id="VSP_015850"
FT   VAR_SEQ         204..261
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:11027606"
FT                   /id="VSP_015851"
FT   VAR_SEQ         539..548
FT                   /note="SVQLNGQPLV -> TQRCQYCGII (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_015852"
FT   VAR_SEQ         549..592
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_015853"
FT   VARIANT         315
FT                   /note="A -> T (in dbSNP:rs17110744)"
FT                   /id="VAR_030472"
FT   VARIANT         579
FT                   /note="Y -> F (in dbSNP:rs10883100)"
FT                   /evidence="ECO:0000269|PubMed:11027606, ECO:0000269|Ref.2"
FT                   /id="VAR_023601"
FT   CONFLICT        12
FT                   /note="P -> L (in Ref. 2; CAC82492)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        213
FT                   /note="F -> S (in Ref. 2; CAC82491/CAC82492)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   592 AA;  66596 MW;  95C384AD9A6C868E CRC64;
     MRVLCAFPEA MPSSNSRPPA CLAPGALYLA LLLHLSLSSQ AGDRRPLPVD RAAGLKEKTL
     ILLDVSTKNP VRTVNENFLS LQLDPSIIHD GWLDFLSSKR LVTLARGLSP AFLRFGGKRT
     DFLQFQNLRN PAKSRGGPGP DYYLKNYEDD IVRSDVALDK QKGCKIAQHP DVMLELQREK
     AAQMHLVLLK EQFSNTYSNL ILTARSLDKL YNFADCSGLH LIFALNALRR NPNNSWNSSS
     ALSLLKYSAS KKYNISWELG NEPNNYRTMH GRAVNGSQLG KDYIQLKSLL QPIRIYSRAS
     LYGPNIGRPR KNVIALLDGF MKVAGSTVDA VTWQHCYIDG RVVKVMDFLK TRLLDTLSDQ
     IRKIQKVVNT YTPGKKIWLE GVVTTSAGGT NNLSDSYAAG FLWLNTLGML ANQGIDVVIR
     HSFFDHGYNH LVDQNFNPLP DYWLSLLYKR LIGPKVLAVH VAGLQRKPRP GRVIRDKLRI
     YAHCTNHHNH NYVRGSITLF IINLHRSRKK IKLAGTLRDK LVHQYLLQPY GQEGLKSKSV
     QLNGQPLVMV DDGTLPELKP RPLRAGRTLV IPPVTMGFYV VKNVNALACR YR
//