ID HEPC_PEDHD Reviewed; 659 AA. AC Q59289; C6XUY0; DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 12-OCT-2022, entry version 79. DE RecName: Full=Heparin-sulfate lyase; DE EC=4.2.2.8; DE AltName: Full=Heparin-sulfate eliminase; DE AltName: Full=Heparinase III; DE Short=HepIII; DE AltName: Full=Heparitin-sulfate lyase; DE Flags: Precursor; GN Name=hepC; OrderedLocusNames=Phep_3797; OS Pedobacter heparinus (strain ATCC 13125 / DSM 2366 / CIP 104194 / JCM 7457 OS / NBRC 12017 / NCIMB 9290 / NRRL B-14731 / HIM 762-3). OC Bacteria; Bacteroidetes; Sphingobacteriia; Sphingobacteriales; OC Sphingobacteriaceae; Pedobacter. OX NCBI_TaxID=485917; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF N-TERMINUS, PROTEIN RP SEQUENCE OF 99-123; 128-142 AND 414-436, FUNCTION, CATALYTIC ACTIVITY, AND RP SUBCELLULAR LOCATION. RC STRAIN=ATCC 13125 / DSM 2366 / CIP 104194 / JCM 7457 / NBRC 12017 / NCIMB RC 9290 / NRRL B-14731 / HIM 762-3; RX PubMed=8702264; DOI=10.1128/aem.62.8.2723-2734.1996; RA Su H., Blain F., Musil R.A., Zimmermann J.J., Gu K., Bennett D.C.; RT "Isolation and expression in Escherichia coli of hepB and hepC, genes RT coding for the glycosaminoglycan-degrading enzymes heparinase II and RT heparinase III, respectively, from Flavobacterium heparinum."; RL Appl. Environ. Microbiol. 62:2723-2734(1996). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 62-68; 75-88; RP 249-264; 383-390; 404-408; 459-464; 468-483; 513-519; 597-605 AND 625-631. RX PubMed=8780685; DOI=10.1006/bbrc.1996.1246; RA Godavarti R., Davis M., Venkataraman G., Cooney C., Langer R., RA Sasisekharan R.; RT "Heparinase III from Flavobacterium heparinum: cloning and recombinant RT expression in Escherichia coli."; RL Biochem. Biophys. Res. Commun. 225:751-758(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 13125 / DSM 2366 / CIP 104194 / JCM 7457 / NBRC 12017 / NCIMB RC 9290 / NRRL B-14731 / HIM 762-3; RX PubMed=21304637; DOI=10.4056/sigs.22138; RA Han C., Spring S., Lapidus A., Del Rio T.G., Tice H., Copeland A., RA Cheng J.F., Lucas S., Chen F., Nolan M., Bruce D., Goodwin L., Pitluck S., RA Ivanova N., Mavromatis K., Mikhailova N., Pati A., Chen A., Palaniappan K., RA Land M., Hauser L., Chang Y.J., Jeffries C.C., Saunders E., Chertkov O., RA Brettin T., Goker M., Rohde M., Bristow J., Eisen J.A., Markowitz V., RA Hugenholtz P., Kyrpides N.C., Klenk H.P., Detter J.C.; RT "Complete genome sequence of Pedobacter heparinus type strain (HIM 762- RT 3)."; RL Stand. Genomic Sci. 1:54-62(2009). RN [4] RP IDENTIFICATION. RX PubMed=2211596; DOI=10.1016/s0021-9258(17)44833-2; RA Nader H.B., Porcionatto M.A., Tersariol I.L., Pinhal M.A., Oliveira F.W., RA Moraes C.T., Dietrich C.P.; RT "Purification and substrate specificity of heparitinase I and heparitinase RT II from Flavobacterium heparinum. Analyses of the heparin and heparan RT sulfate degradation products by 13C NMR spectroscopy."; RL J. Biol. Chem. 265:16807-16813(1990). RN [5] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF HIS-295 AND RP HIS-510. RX PubMed=10747789; DOI=10.1021/bi992514k; RA Pojasek K., Shriver Z., Hu Y., Sasisekharan R.; RT "Histidine 295 and histidine 510 are crucial for the enzymatic degradation RT of heparan sulfate by heparinase III."; RL Biochemistry 39:4012-4019(2000). CC -!- FUNCTION: Specifically cleaves heparan sulfate-rich regions of acidic CC polysaccharides. Does not act on N,O-desulfated glucosamine or N- CC acetyl-O-sulfated glucosamine linkages. Functions in cleaving metazoan CC heparan sulfate and providing carbon, nitrogen and sulfate sources for CC microorganisms. {ECO:0000269|PubMed:10747789, CC ECO:0000269|PubMed:8702264}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Elimination of sulfate, appears to act on linkages between N- CC acetyl-D-glucosamine and uronate. Product is an unsaturated sugar.; CC EC=4.2.2.8; Evidence={ECO:0000269|PubMed:8702264}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=143 uM for heparan sulfate {ECO:0000269|PubMed:10747789}; CC KM=80 uM for heparan sulfate (with recombinant enzyme) CC {ECO:0000269|PubMed:10747789}; CC Note=kcat is 94 sec(-1). kcat is 78 sec(-1) with recombinant enzyme.; CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000269|PubMed:8702264}. CC -!- SIMILARITY: Belongs to the polysaccharide lyase 12 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=ACU05988.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U27586; AAB18278.1; -; Genomic_DNA. DR EMBL; CP001681; ACU05988.1; ALT_INIT; Genomic_DNA. DR PIR; JC4910; JC4910. DR RefSeq; WP_036674924.1; NZ_AQGK01000003.1. DR PDB; 4MMH; X-ray; 2.20 A; A=25-659. DR PDB; 4MMI; X-ray; 2.40 A; A=25-659. DR PDBsum; 4MMH; -. DR PDBsum; 4MMI; -. DR AlphaFoldDB; Q59289; -. DR SMR; Q59289; -. DR STRING; 485917.Phep_3797; -. DR CAZy; PL12; Polysaccharide Lyase Family 12. DR EnsemblBacteria; ACU05988; ACU05988; Phep_3797. DR KEGG; phe:Phep_3797; -. DR eggNOG; COG5434; Bacteria. DR HOGENOM; CLU_013047_1_0_10; -. DR BioCyc; MetaCyc:MON-19212; -. DR BRENDA; 4.2.2.8; 2286. DR Proteomes; UP000000852; Chromosome. DR GO; GO:0042597; C:periplasmic space; TAS:UniProtKB. DR GO; GO:0015021; F:heparin-sulfate lyase activity; IDA:UniProtKB. DR GO; GO:0030200; P:heparan sulfate proteoglycan catabolic process; IDA:UniProtKB. DR Gene3D; 1.50.10.100; -; 1. DR InterPro; IPR008929; Chondroitin_lyas. DR InterPro; IPR012480; Hepar_II_III. DR InterPro; IPR031680; Hepar_II_III_N. DR Pfam; PF07940; Hepar_II_III; 1. DR Pfam; PF16889; Hepar_II_III_N; 1. DR SUPFAM; SSF48230; SSF48230; 1. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Lyase; Periplasm; KW Reference proteome; Signal. FT SIGNAL 1..24 FT /evidence="ECO:0000269|PubMed:8702264" FT CHAIN 25..659 FT /note="Heparin-sulfate lyase" FT /id="PRO_5000144614" FT ACT_SITE 294 FT /note="Proton acceptor" FT /evidence="ECO:0000255" FT MUTAGEN 295 FT /note="H->A: Impaired catalytic activity." FT /evidence="ECO:0000269|PubMed:10747789" FT MUTAGEN 510 FT /note="H->A: Impaired catalytic activity." FT /evidence="ECO:0000269|PubMed:10747789" FT CONFLICT 128..129 FT /note="PV -> LI (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT HELIX 32..34 FT /evidence="ECO:0007829|PDB:4MMH" FT TURN 42..44 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 45..52 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 56..72 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 81..83 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 87..89 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 93..103 FT /evidence="ECO:0007829|PDB:4MMH" FT TURN 119..122 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 128..130 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 132..138 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 143..154 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 157..173 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 180..186 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 189..206 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 214..232 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 237..239 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 242..255 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 262..280 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 292..310 FT /evidence="ECO:0007829|PDB:4MMH" FT TURN 311..313 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 315..317 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 320..335 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 354..367 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 372..378 FT /evidence="ECO:0007829|PDB:4MMH" FT TURN 379..381 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 382..384 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 390..394 FT /evidence="ECO:0007829|PDB:4MMH" FT TURN 395..398 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 399..404 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 411..416 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 432..436 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 439..442 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 454..463 FT /evidence="ECO:0007829|PDB:4MMH" FT HELIX 466..468 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 469..474 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 485..490 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 493..505 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 508..517 FT /evidence="ECO:0007829|PDB:4MMH" FT TURN 518..520 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 521..531 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 534..541 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 549..551 FT /evidence="ECO:0007829|PDB:4MMH" FT TURN 552..555 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 556..558 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 564..571 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 578..582 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 585..589 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 592..595 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 598..605 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 607..609 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 611..624 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 628..632 FT /evidence="ECO:0007829|PDB:4MMH" FT TURN 638..641 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 642..649 FT /evidence="ECO:0007829|PDB:4MMH" FT STRAND 652..659 FT /evidence="ECO:0007829|PDB:4MMH" SQ SEQUENCE 659 AA; 75807 MW; B73EDF10A1256FE2 CRC64; MTTKIFKRII VFAVIALSSG NILAQSSSIT RKDFDHINLE YSGLEKVNKA VAAGNYDDAA KALLAYYREK SKAREPDFSN AEKPADIRQP IDKVTREMAD KALVHQFQPH KGYGYFDYGK DINWQMWPVK DNEVRWQLHR VKWWQAMALV YHATGDEKYA REWVYQYSDW ARKNPLGLSQ DNDKFVWRPL EVSDRVQSLP PTFSLFVNSP AFTPAFLMEF LNSYHQQADY LSTHYAEQGN HRLFEAQRNL FAGVSFPEFK DSPRWRQTGI SVLNTEIKKQ VYADGMQFEL SPIYHVAAID IFLKAYGSAK RVNLEKEFPQ SYVQTVENMI MALISISLPD YNTPMFGDSW ITDKNFRMAQ FASWARVFPA NQAIKYFATD GKQGKAPNFL SKALSNAGFY TFRSGWDKNA TVMVLKASPP GEFHAQPDNG TFELFIKGRN FTPDAGVFVY SGDEAIMKLR NWYRQTRIHS TLTLDNQNMV ITKARQNKWE TGNNLDVLTY TNPSYPNLDH QRSVLFINKK YFLVIDRAIG EATGNLGVHW QLKEDSNPVF DKTKNRVYTT YRDGNNLMIQ SLNADRTSLN EEEGKVSYVY NKELKRPAFV FEKPKKNAGT QNFVSIVYPY DGQKAPEISI RENKGNDFEK GKLNLTLTIN GKQQLVLVP //