HPSE2_HUMAN
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 03-AUG-2022, entry version 145.
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; 29.
DR IntAct; Q8WWQ2; 2.
DR STRING; 9606.ENSP00000359583; -.
DR GlyGen; Q8WWQ2; 2 sites.
DR iPTMnet; Q8WWQ2; -.
DR PhosphoSitePlus; Q8WWQ2; -.
DR BioMuta; HPSE2; -.
DR DMDM; 125987832; -.
DR MassIVE; Q8WWQ2; -.
DR PaxDb; Q8WWQ2; -.
DR PeptideAtlas; Q8WWQ2; -.
DR PRIDE; Q8WWQ2; -.
DR ProteomicsDB; 74920; -. [Q8WWQ2-1]
DR ProteomicsDB; 74921; -. [Q8WWQ2-2]
DR ProteomicsDB; 74922; -. [Q8WWQ2-3]
DR ProteomicsDB; 74923; -. [Q8WWQ2-4]
DR Antibodypedia; 45898; 185 antibodies from 29 providers.
DR DNASU; 60495; -.
DR Ensembl; ENST00000370546.5; ENSP00000359577.1; ENSG00000172987.13. [Q8WWQ2-2]
DR Ensembl; ENST00000370549.5; ENSP00000359580.1; ENSG00000172987.13. [Q8WWQ2-3]
DR Ensembl; ENST00000370552.8; ENSP00000359583.3; ENSG00000172987.13. [Q8WWQ2-1]
DR Ensembl; ENST00000628193.2; ENSP00000485916.1; ENSG00000172987.13. [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 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; YSRAHLY; -.
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 1068 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 96 other tissues.
DR ExpressionAtlas; Q8WWQ2; baseline and differential.
DR Genevisible; Q8WWQ2; HS.
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:0006027; P:glycosaminoglycan catabolic process; TAS:Reactome.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR InterPro; IPR005199; Glyco_hydro_79.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR Pfam; PF03662; Glyco_hydro_79n; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
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
