LOCUS       NM_001098540            4581 bp    mRNA    linear   PRI 01-AUG-2024
DEFINITION  Homo sapiens heparanase (HPSE), transcript variant 2, mRNA.
ACCESSION   NM_001098540
VERSION     NM_001098540.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4581)
  AUTHORS   Lee,C.S., Shang,R., Wang,F., Khayambashi,P., Wang,H., Araujo,G.,
            Puri,K., Vlodavsky,I., Hussein,B. and Rodrigues,B.
  TITLE     Heparanase Stimulation of Physiologic Cardiac Hypertrophy Is
            Suppressed After Chronic Diabetes, Resulting in Cardiac Remodeling
            and Dysfunction
  JOURNAL   Diabetes 73 (8), 1300-1316 (2024)
   PUBMED   38771953
  REMARK    GeneRIF: Heparanase Stimulation of Physiologic Cardiac Hypertrophy
            Is Suppressed After Chronic Diabetes, Resulting in Cardiac
            Remodeling and Dysfunction.
REFERENCE   2  (bases 1 to 4581)
  AUTHORS   Martinez,H.A., Koliesnik,I., Kaber,G., Reid,J.K., Nagy,N.,
            Barlow,G., Falk,B.A., Medina,C.O., Hargil,A., Zihsler,S.,
            Vlodavsky,I., Li,J.P., Perez-Cruz,M., Tang,S.W., Meyer,E.H.,
            Wrenshall,L.E., Lord,J.D., Garcia,K.C., Palmer,T.D., Steinman,L.,
            Nepom,G.T., Wight,T.N., Bollyky,P.L. and Kuipers,H.F.
  TITLE     Regulatory T cells use heparanase to access IL-2 bound to
            extracellular matrix in inflamed tissue
  JOURNAL   Nat Commun 15 (1), 1564 (2024)
   PUBMED   38378682
  REMARK    GeneRIF: Regulatory T cells use heparanase to access IL-2 bound to
            extracellular matrix in inflamed tissue.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 4581)
  AUTHORS   Wang,C., Huang,Y., Jia,B., Huang,Y. and Chen,J.
  TITLE     Heparanase promotes malignant phenotypes of human oral squamous
            carcinoma cells by regulating the epithelial-mesenchymal
            transition-related molecules and infiltrated levels of natural
            killer cells
  JOURNAL   Arch Oral Biol 154, 105775 (2023)
   PUBMED   37481997
  REMARK    GeneRIF: Heparanase promotes malignant phenotypes of human oral
            squamous carcinoma cells by regulating the epithelial-mesenchymal
            transition-related molecules and infiltrated levels of natural
            killer cells.
REFERENCE   4  (bases 1 to 4581)
  AUTHORS   Ostrovsky,O., Beider,K., Magen,H., Leiba,M., Sanderson,R.D.,
            Vlodavsky,I. and Nagler,A.
  TITLE     Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary
            Paraskeletal Multiple Myeloma
  JOURNAL   Cells 12 (6), 913 (2023)
   PUBMED   36980254
  REMARK    GeneRIF: Effect of HPSE and HPSE2 SNPs on the Risk of Developing
            Primary Paraskeletal Multiple Myeloma.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 4581)
  AUTHORS   van der Velden,A.I.M., van den Berg,B.M., van den Born,B.J.,
            Galenkamp,H., Ijpelaar,D.H.T. and Rabelink,T.J.
  TITLE     Ethnic differences in urinary monocyte chemoattractant protein-1
            and heparanase-1 levels in individuals with type 2 diabetes: the
            HELIUS study
  JOURNAL   BMJ Open Diabetes Res Care 10 (6) (2022)
   PUBMED   36564084
  REMARK    GeneRIF: Ethnic differences in urinary monocyte chemoattractant
            protein-1 and heparanase-1 levels in individuals with type 2
            diabetes: the HELIUS study.
REFERENCE   6  (bases 1 to 4581)
  AUTHORS   Nasser,N.J., Avivi,A., Shushy,M., Vlodavsky,I. and Nevo,E.
  TITLE     Cloning, expression, and characterization of an alternatively
            spliced variant of human heparanase
  JOURNAL   Biochem Biophys Res Commun 354 (1), 33-38 (2007)
   PUBMED   17208203
  REMARK    GeneRIF: Splice 5 escaped proteolytic cleavage, was devoid of HS
            degradation activity and exhibited diffused rather than granular
            cellular localization.
REFERENCE   7  (bases 1 to 4581)
  AUTHORS   Kussie,P.H., Hulmes,J.D., Ludwig,D.L., Patel,S., Navarro,E.C.,
            Seddon,A.P., Giorgio,N.A. and Bohlen,P.
  TITLE     Cloning and functional expression of a human heparanase gene
  JOURNAL   Biochem Biophys Res Commun 261 (1), 183-187 (1999)
   PUBMED   10405343
REFERENCE   8  (bases 1 to 4581)
  AUTHORS   Hulett,M.D., Freeman,C., Hamdorf,B.J., Baker,R.T., Harris,M.J. and
            Parish,C.R.
  TITLE     Cloning of mammalian heparanase, an important enzyme in tumor
            invasion and metastasis
  JOURNAL   Nat Med 5 (7), 803-809 (1999)
   PUBMED   10395326
REFERENCE   9  (bases 1 to 4581)
  AUTHORS   Vlodavsky,I., Friedmann,Y., Elkin,M., Aingorn,H., Atzmon,R.,
            Ishai-Michaeli,R., Bitan,M., Pappo,O., Peretz,T., Michal,I.,
            Spector,L. and Pecker,I.
  TITLE     Mammalian heparanase: gene cloning, expression and function in
            tumor progression and metastasis
  JOURNAL   Nat Med 5 (7), 793-802 (1999)
   PUBMED   10395325
REFERENCE   10 (bases 1 to 4581)
  AUTHORS   Pikas,D.S., Li,J.P., Vlodavsky,I. and Lindahl,U.
  TITLE     Substrate specificity of heparanases from human hepatoma and
            platelets
  JOURNAL   J Biol Chem 273 (30), 18770-18777 (1998)
   PUBMED   9668050
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF144325.1, AC114781.2,
            AF152376.1 and AW293069.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_001098540.2.
            
            Summary: Heparan sulfate proteoglycans are major components of the
            basement membrane and extracellular matrix. The protein encoded by
            this gene is an enzyme that cleaves heparan sulfate proteoglycans
            to permit cell movement through remodeling of the extracellular
            matrix. In addition, this cleavage can release bioactive molecules
            from the extracellular matrix. Several transcript variants encoding
            different isoforms have been found for this gene. [provided by
            RefSeq, Sep 2011].
            
            Transcript Variant: This variant (2) differs in the 5' UTR compared
            to variant 1. Variants 1 and 2 encode the same protein (isoform 1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR14038196.2457477.1, AF144325.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000311412.10/ ENSP00000308107.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-983               AF144325.1         34-1016
            984-988             AC114781.2         73865-73869         c
            989-1440            AF144325.1         1022-1473
            1441-1727           AF152376.1         1389-1675
            1728-4294           AC114781.2         57149-59715         c
            4295-4581           AW293069.1         17-303              c
FEATURES             Location/Qualifiers
     source          1..4581
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q21.23"
     gene            1..4581
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /note="heparanase"
                     /db_xref="GeneID:10855"
                     /db_xref="HGNC:HGNC:5164"
                     /db_xref="MIM:604724"
     exon            1..293
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     CDS             67..1698
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /EC_number="3.2.1.166"
                     /note="isoform 1 preproprotein is encoded by transcript
                     variant 2; heparanase-1; endo-glucoronidase"
                     /codon_start=1
                     /product="heparanase isoform 1 preproprotein"
                     /protein_id="NP_001092010.1"
                     /db_xref="CCDS:CCDS3602.1"
                     /db_xref="GeneID:10855"
                     /db_xref="HGNC:HGNC:5164"
                     /db_xref="MIM:604724"
                     /translation="MLLRSKPALPPPLMLLLLGPLGPLSPGALPRPAQAQDVVDLDFF
                     TQEPLHLVSPSFLSVTIDANLATDPRFLILLGSPKLRTLARGLSPAYLRFGGTKTDFL
                     IFDPKKESTFEERSYWQSQVNQDICKYGSIPPDVEEKLRLEWPYQEQLLLREHYQKKF
                     KNSTYSRSSVDVLYTFANCSGLDLIFGLNALLRTADLQWNSSNAQLLLDYCSSKGYNI
                     SWELGNEPNSFLKKADIFINGSQLGEDFIQLHKLLRKSTFKNAKLYGPDVGQPRRKTA
                     KMLKSFLKAGGEVIDSVTWHHYYLNGRTATKEDFLNPDVLDIFISSVQKVFQVVESTR
                     PGKKVWLGETSSAYGGGAPLLSDTFAAGFMWLDKLGLSARMGIEVVMRQVFFGAGNYH
                     LVDENFDPLPDYWLSLLFKKLVGTKVLMASVQGSKRRKLRVYLHCTNTDNPRYKEGDL
                     TLYAINLHNVTKYLRLPYPFSNKQVDKYLLRPLGPHGLLSKSVQLNGLTLKMVDDQTL
                     PPLMEKPLRPGSSLGLPAFSYSFFVIRNAKVAACI"
     exon            294..439
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     exon            440..565
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     exon            566..739
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     exon            740..908
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     exon            909..956
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     exon            957..1050
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1051..1157
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1158..1272
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1273..1391
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1392..1538
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     exon            1539..4581
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1700..1705
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /note="hexamer: AATAAA"
     regulatory      1705..1710
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /note="hexamer: AATATA"
     polyA_site      1720
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /note="major polyA site"
     polyA_site      1727
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
     regulatory      4557..4562
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
                     /note="hexamer: AATAAA"
     polyA_site      4581
                     /gene="HPSE"
                     /gene_synonym="HPA; HPA1; HPR1; HPSE1; HSE1"
ORIGIN      
        1 agtgctagag ctctcgactc tccgctgcgc ggcagctggc ggggggagca gccaggtgag
       61 cccaagatgc tgctgcgctc gaagcctgcg ctgccgccgc cgctgatgct gctgctcctg
      121 gggccgctgg gtcccctctc ccctggcgcc ctgccccgac ctgcgcaagc acaggacgtc
      181 gtggacctgg acttcttcac ccaggagccg ctgcacctgg tgagcccctc gttcctgtcc
      241 gtcaccattg acgccaacct ggccacggac ccgcggttcc tcatcctcct gggttctcca
      301 aagcttcgta ccttggccag aggcttgtct cctgcgtacc tgaggtttgg tggcaccaag
      361 acagacttcc taattttcga tcccaagaag gaatcaacct ttgaagagag aagttactgg
      421 caatctcaag tcaaccagga tatttgcaaa tatggatcca tccctcctga tgtggaggag
      481 aagttacggt tggaatggcc ctaccaggag caattgctac tccgagaaca ctaccagaaa
      541 aagttcaaga acagcaccta ctcaagaagc tctgtagatg tgctatacac ttttgcaaac
      601 tgctcaggac tggacttgat ctttggccta aatgcgttat taagaacagc agatttgcag
      661 tggaacagtt ctaatgctca gttgctcctg gactactgct cttccaaggg gtataacatt
      721 tcttgggaac taggcaatga acctaacagt ttccttaaga aggctgatat tttcatcaat
      781 gggtcgcagt taggagaaga ttttattcaa ttgcataaac ttctaagaaa gtccaccttc
      841 aaaaatgcaa aactctatgg tcctgatgtt ggtcagcctc gaagaaagac ggctaagatg
      901 ctgaagagct tcctgaaggc tggtggagaa gtgattgatt cagttacatg gcatcactac
      961 tatttgaatg gacggactgc taccaaggaa gattttctaa accctgatgt attggacatt
     1021 tttatttcat ctgtgcaaaa agttttccag gtggttgaga gcaccaggcc tggcaagaag
     1081 gtctggttag gagaaacaag ctctgcatat ggaggcggag cgcccttgct atccgacacc
     1141 tttgcagctg gctttatgtg gctggataaa ttgggcctgt cagcccgaat gggaatagaa
     1201 gtggtgatga ggcaagtatt ctttggagca ggaaactacc atttagtgga tgaaaacttc
     1261 gatcctttac ctgattattg gctatctctt ctgttcaaga aattggtggg caccaaggtg
     1321 ttaatggcaa gcgtgcaagg ttcaaagaga aggaagcttc gagtatacct tcattgcaca
     1381 aacactgaca atccaaggta taaagaagga gatttaactc tgtatgccat aaacctccat
     1441 aatgtcacca agtacttgcg gttaccctat cctttttcta acaagcaagt ggataaatac
     1501 cttctaagac ctttgggacc tcatggatta ctttccaaat ctgtccaact caatggtcta
     1561 actctaaaga tggtggatga tcaaaccttg ccacctttaa tggaaaaacc tctccggcca
     1621 ggaagttcac tgggcttgcc agctttctca tatagttttt ttgtgataag aaatgccaaa
     1681 gttgctgctt gcatctgaaa ataaaatata ctagtcctga cactgaattt ttcaagtata
     1741 ctaagagtaa agcaactcaa gttataggaa aggaagcaga taccttgcaa agcaactagt
     1801 gggtgcttga gagacactgg gacactgtca gtgctagatt tagcacagta ttttgatctc
     1861 gctaggtaga acactgctaa taataatagc taataatacc ttgttccaaa tactgcttag
     1921 cattttgcat gttttacttt tatctaaagt tttgttttgt tttattattt atttatttat
     1981 ttattttgag acagaatctc tctctgtcac ccaggctgga gtgccatggt gcgatcttgg
     2041 ctcactgcaa ctttaagcaa ttctcctgcc tcagcttcct gagtagctgg gattataggc
     2101 gtgtgccacc acgcccagct actttctata ttttttgtag agatggagtt tcgccatatt
     2161 ggccaagctg gtctcgaact cctgtcctcg aactcctgtc ctcaagtgat ccacccgcct
     2221 cagcctctca aagtgctggg attacaggtg tgagccacca cacccagcag tgttttattt
     2281 ttgagacagg gtatcattct gttgcccagg cttgagtgca gtggtgcaat catagatcac
     2341 tgcagccttt taactcctgg gctcaagtca tcctcctgct tagcctccca agtagctagg
     2401 accacagaca catgccatca cacttggcta tttttaaaaa attttttgta gagatggggt
     2461 ctcgctatgt tacccaaact ggtcctgaac tcctggactc aattgatcct cccaccttgg
     2521 ccttccaggt gctgggattt ctttgggagt acagcatggt acagcaggag atcatttgat
     2581 gttacctctg tgcagtgttg ctagtcagcg aaagactata atacctgtgg ggacagcgat
     2641 tagccaccac aaccagtctt tatttaaagt tattaaaaat ggctgggcgc agtggctcac
     2701 acctgtaatc ctagcacttt gggaggccga ggcagatgga tcacctgacg tgaggaattt
     2761 gataccagcc tggccaacat ggtgaaaccc catctctact aaaaaataca aaaattagct
     2821 gggtgtggtc ctgtagtccc agctacttgg gaggctgggg caggagaatt acttgaaccc
     2881 aggaggcaga ggttgcagtg agccgagatt gtgccactgc actccagcct gggtgacaga
     2941 gagagattcc atctcaaaaa aacaagttat taaaaatgta tatgaatgct cctaatatgg
     3001 tcaggaagca aggaagcgaa ggatatatta tgagttttaa gaaggtgctt agctgtatat
     3061 ttatctttca aaatgtatta gaagatttta gaattctttc cttcatgtgc catctctaca
     3121 ggcacccatc agaaaaagca tactgccgtt accgtgaaac tggttgtaaa agagaaacta
     3181 tctatttgca ccttaaaaga cagctagatt ttgctgattt tcttctttcg gttttctttg
     3241 tcagcaataa tatgtgagag gacagattgt tagatatgat agtataaaaa atggttaatg
     3301 acaattcaga ggcgaggaga ttctgtaaac ttaaaattac tataaatgaa attgatttgt
     3361 caagaggata aattttagaa aacacccaat accttataac tgtctgttaa tgcttgcttt
     3421 ttctctacct ttcttccttg tttcagttgg gaagcttttg gctgcaagta acagaaactc
     3481 ctaattcaaa tggcttaagc aataaggaaa tgtatattcc cacataacta gacgttcaaa
     3541 caggccaggc tccagcactt cagtacgtca ccagggatct gggttcttcc cagctctctg
     3601 ctctgccatc tttagcgctg gcttcattct cagactctgg tagcatgatg gctgtagctg
     3661 tttcatgggc cccttcaaac ctcatagcaa ccagaggaag aaaatgagcc attttttgag
     3721 tctccttcat agacttgaat aactcttttt cagagcttct cacagcaaac ctctcctcat
     3781 gtctcctcat gtcttattgt tcagaaatgg gtaatgtggc catttcacca gtcactgcca
     3841 acaacaacga ggttcctata attgtctctg agtaaccctt tggaatggag agggtgttgg
     3901 tcagtctaca aactgaacac tgcagttctg cgctttttac cagtgaaaaa atgtaattat
     3961 tttcccctct taaggattaa tattcttcaa atgtatgcct gttatggata tagtatcttt
     4021 aaaatttttt attttaatag ctttaggggt acacactttt tgcttacagg ggtgaattgt
     4081 gtagtggtga agactcggct tttaatgtac ttgtcacctg agtgatgtac attgtaccca
     4141 ataggtaatt tttcatccat taccctcctt ccgccctctt cccttctgag tctccaacat
     4201 cccttatacc actgtgtatg ttcttgtgta cctacagcta agcttccact tataagtgag
     4261 aacatgcagt atttggtttt ccattcctga gttacttccc ttaggataac agcccccagt
     4321 tccgtccaag ttgctgcaaa atacattatt cttctttatg gctgagtaat agtccatggt
     4381 acatatatac cacattttct ttatccactt atcagttgat ggacacttag gttaattcca
     4441 ttcaatttca ttcaatttaa gtatatttgt aaggagctaa agctgaaaat taaattttag
     4501 atctttcaat actcttaaat tttatatgta agtggttttt atattttcac atttgaaata
     4561 aagtaatttt tataatcttg a
//
