Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1

Details

Name
Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1
Synonyms
  • [Heparan sulfate]-glucosamine N-sulfotransferase 1
  • 2.8.2.8
  • Glucosaminyl N-deacetylase/N-sulfotransferase 1
  • HSNST 1
  • HSST
  • HSST1
  • N-heparan sulfate sulfotransferase 1
  • N-HSST 1
  • NDST-1
Gene Name
NDST1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0005024|Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1
MPALACLRRLCRHVSPQAVLFLLFIFCLFSVFISAYYLYGWKRGLEPSADAPEPDCGDPP
PVAPSRLLPLKPVQAATPSRTDPLVLVFVESLYSQLGQEVVAILESSRFKYRTEIAPGKG
DMPTLTDKGRGRFALIIYENILKYVNLDAWNRELLDKYCVAYGVGIIGFFKANENSLLSA
QLKGFPLFLHSNLGLKDCSINPKSPLLYVTRPSEVEKGVLPGEDWTVFQSNHSTYEPVLL
AKTRSSESIPHLGADAGLHAALHATVVQDLGLHDGIQRVLFGNNLNFWLHKLVFVDAVAF
LTGKRLSLPLDRYILVDIDDIFVGKEGTRMKVEDVKALFDTQNELRAHIPNFTFNLGYSG
KFFHTGTNAEDAGDDLLLSYVKEFWWFPHMWSHMQPHLFHNQSVLAEQMALNKKFAVEHG
IPTDMGYAVAPHHSGVYPVHVQLYEAWKQVWSIRVTSTEEYPHLKPARYRRGFIHNGIMV
LPRQTCGLFTHTIFYNEYPGGSSELDKIINGGELFLTVLLNPISIFMTHLSNYGNDRLGL
YTFKHLVRFLHSWTNLRLQTLPPVQLAQKYFQIFSEEKDPLWQDPCEDKRHKDIWSKEKT
CDRFPKLLIIGPQKTGTTALYLFLGMHPDLSSNYPSSETFEEIQFFNGHNYHKGIDWYME
FFPIPSNTTSDFYFEKSANYFDSEVAPRRAAALLPKAKVLTILINPADRAYSWYQHQRAH
DDPVALKYTFHEVITAGSDASSKLRALQNRCLVPGWYATHIERWLSAYHANQILVLDGKL
LRTEPAKVMDMVQKFLGVTNTIDYHKTLAFDPKKGFWCQLLEGGKTKCLGKSKGRKYPEM
DLDSRAFLKDYYRDHNIELSKLLYKMGQTLPTWLREDLQNTR
Number of residues
882
Molecular Weight
100867.015
Theoretical pI
8.07
GO Classification
Functions
[heparan sulfate]-glucosamine N-sulfotransferase activity / deacetylase activity
Processes
carbohydrate metabolic process / embryonic neurocranium morphogenesis / embryonic viscerocranium morphogenesis / fibroblast growth factor receptor signaling pathway / forebrain development / glycosaminoglycan biosynthetic process / glycosaminoglycan metabolic process / heparan sulfate proteoglycan biosynthetic process / heparin biosynthetic process / inflammatory response / MAPK cascade / midbrain development / polysaccharide biosynthetic process / respiratory gaseous exchange / small molecule metabolic process / smoothened signaling pathway
Components
Golgi membrane / integral component of membrane
General Function
Deacetylase activity
Specific Function
Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis. Plays a role in determining the extent and pattern of sulfation of heparan sulfate. Compared to other NDST enzymes, its presence is absolutely required. Participates in biosynthesis of heparan sulfate that can ultimately serve as L-selectin ligands, thereby playing a role in inflammatory response.
Pfam Domain Function
Transmembrane Regions
18-39
Cellular Location
Golgi apparatus membrane
Gene sequence
>lcl|BSEQ0021332|Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1 (NDST1)
ATGCCTGCCCTGGCATGCCTCCGGAGGCTGTGTCGGCACGTGTCCCCGCAGGCTGTCCTT
TTCCTGCTGTTCATCTTCTGCCTGTTCAGCGTTTTCATCTCGGCCTACTACCTATATGGC
TGGAAGCGAGGCCTGGAGCCCTCGGCGGATGCCCCCGAGCCTGACTGCGGGGACCCGCCG
CCTGTGGCCCCCAGTCGCCTGCTGCCACTCAAGCCTGTGCAGGCAGCCACCCCTTCCCGC
ACAGACCCGTTGGTGCTGGTCTTTGTGGAGAGCCTCTACTCGCAACTGGGCCAGGAGGTG
GTGGCCATCCTGGAGTCCAGCCGCTTCAAATACCGCACAGAGATTGCGCCGGGCAAGGGT
GACATGCCCACGCTCACTGACAAGGGCCGTGGCCGCTTCGCCCTCATCATCTATGAGAAC
ATCCTCAAGTATGTCAACCTGGACGCCTGGAACCGGGAGCTGCTGGACAAGTACTGTGTG
GCCTACGGCGTGGGCATCATTGGCTTCTTCAAGGCCAATGAGAACAGCCTGCTGAGTGCG
CAGCTCAAGGGCTTCCCCCTGTTCCTGCACTCAAACCTGGGCCTGAAGGACTGCAGCATC
AACCCCAAGTCCCCGCTGCTCTACGTGACGCGACCTAGCGAGGTGGAGAAAGGTGTGCTC
CCCGGCGAGGACTGGACGGTTTTCCAGTCAAATCACTCCACCTATGAGCCAGTGCTGCTG
GCCAAGACGCGCTCGTCTGAGTCCATCCCACACCTGGGCGCAGACGCCGGCCTGCATGCT
GCACTGCACGCCACTGTGGTCCAGGACCTGGGCCTGCACGACGGCATCCAGCGCGTGCTG
TTTGGCAACAACCTGAACTTCTGGCTGCACAAGCTTGTCTTCGTGGATGCCGTGGCCTTC
CTCACGGGGAAGCGCCTCTCCCTGCCATTGGACCGCTACATCCTGGTGGACATTGATGAC
ATCTTCGTGGGCAAGGAGGGCACACGCATGAAGGTGGAGGACGTGAAGGCCCTGTTTGAC
ACACAGAACGAACTACGCGCACACATCCCAAACTTCACCTTCAACCTGGGCTACTCAGGG
AAATTCTTCCACACAGGTACCAATGCTGAGGACGCTGGGGATGATCTGCTGCTGTCGTAT
GTGAAGGAGTTCTGGTGGTTCCCCCACATGTGGAGCCACATGCAGCCCCACCTTTTCCAC
AACCAGTCCGTGTTGGCCGAGCAGATGGCCTTGAACAAGAAGTTCGCTGTCGAGCATGGC
ATTCCCACAGACATGGGGTATGCAGTGGCGCCCCACCACTCGGGCGTGTACCCCGTGCAC
GTGCAGCTGTACGAGGCTTGGAAGCAGGTGTGGAGCATCCGCGTGACCAGCACGGAGGAG
TACCCCCACCTGAAGCCAGCCCGCTACCGCCGTGGCTTCATCCACAATGGCATCATGGTT
CTCCCACGGCAGACCTGCGGCCTCTTCACACACACCATCTTCTACAACGAGTACCCTGGC
GGCTCCAGTGAGCTGGACAAGATCATCAACGGGGGCGAGCTCTTCCTCACCGTGCTCCTC
AATCCTATCAGCATCTTCATGACGCACCTGTCCAACTATGGGAATGACCGCCTGGGCCTG
TACACCTTCAAGCACCTGGTGCGCTTCCTGCACTCCTGGACGAACCTCCGGCTGCAGACA
CTGCCCCCTGTGCAGTTGGCGCAGAAGTACTTCCAGATCTTCTCCGAGGAGAAGGACCCG
CTCTGGCAGGACCCCTGCGAGGACAAACGTCACAAAGACATCTGGTCCAAGGAGAAGACG
TGTGACCGCTTCCCAAAGCTCCTCATCATCGGCCCCCAGAAAACAGGCACCACTGCCCTC
TACCTGTTCCTGGGCATGCACCCTGACCTAAGCAGCAACTACCCCAGCTCTGAGACCTTT
GAGGAGATCCAGTTTTTTAATGGCCACAACTATCACAAAGGCATCGACTGGTACATGGAG
TTCTTCCCCATCCCTTCCAACACCACCTCCGACTTCTACTTTGAGAAAAGCGCCAACTAC
TTTGATTCAGAAGTGGCGCCCCGGCGGGCAGCAGCCCTCTTGCCCAAAGCCAAGGTCCTG
ACCATCCTCATCAACCCCGCGGACCGGGCCTATTCCTGGTACCAGATTCTGGTCTTGGAT
GGCAAACTGCTTCGCACAGAACCTGCCAAAGTGATGGACATGGTGCAGAAGTTCCTTGGG
GTGACCAACACCATTGACTACCACAAAACCTTGGCGTTTGATCCAAAGAAAGGATTTTGG
TGCCAACTGCTTGAAGGAGGAAAAACCAAGTGTCTGGGCAAAAGCAAGGGCCGGAAATAT
CCCGAGATGGACTTGGATTCCCGAGCCTTCCTGAAGGACTATTACCGGGACCACAACATC
GAGCTCTCCAAGCTGCTGTATAAGATGGGCCAGACACTTCCCACTTGGCTACGAGAGGAC
CTCCAGAACACCAGGTAG
Chromosome Location
5
Locus
5q33.1
External Identifiers
ResourceLink
UniProtKB IDP52848
UniProtKB Entry NameNDST1_HUMAN
GenBank Gene IDU18918
GenAtlas IDNDST1
HGNC IDHGNC:7680
General References
  1. Dixon J, Loftus SK, Gladwin AJ, Scambler PJ, Wasmuth JJ, Dixon MJ: Cloning of the human heparan sulfate-N-deacetylase/N-sulfotransferase gene from the Treacher Collins syndrome candidate region at 5q32-q33.1. Genomics. 1995 Mar 20;26(2):239-44. [Article]
  2. Humphries DE, Sullivan BM, Aleixo MD, Stow JL: Localization of human heparan glucosaminyl N-deacetylase/N-sulphotransferase to the trans-Golgi network. Biochem J. 1997 Jul 15;325 ( Pt 2):351-7. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Sueyoshi T, Kakuta Y, Pedersen LC, Wall FE, Pedersen LG, Negishi M: A role of Lys614 in the sulfotransferase activity of human heparan sulfate N-deacetylase/N-sulfotransferase. FEBS Lett. 1998 Aug 21;433(3):211-4. [Article]
  5. Pikas DS, Eriksson I, Kjellen L: Overexpression of different isoforms of glucosaminyl N-deacetylase/N-sulfotransferase results in distinct heparan sulfate N-sulfation patterns. Biochemistry. 2000 Apr 18;39(15):4552-8. [Article]
  6. van den Born J, Pikas DS, Pisa BJ, Eriksson I, Kjellen L, Berden JH: Antibody-based assay for N-deacetylase activity of heparan sulfate/heparin N-deacetylase/N-sulfotransferase (NDST): novel characteristics of NDST-1 and -2. Glycobiology. 2003 Jan;13(1):1-10. Epub 2002 Nov 1. [Article]
  7. Kakuta Y, Sueyoshi T, Negishi M, Pedersen LC: Crystal structure of the sulfotransferase domain of human heparan sulfate N-deacetylase/ N-sulfotransferase 1. J Biol Chem. 1999 Apr 16;274(16):10673-6. [Article]
  8. Reuter MS, Musante L, Hu H, Diederich S, Sticht H, Ekici AB, Uebe S, Wienker TF, Bartsch O, Zechner U, Oppitz C, Keleman K, Jamra RA, Najmabadi H, Schweiger S, Reis A, Kahrizi K: NDST1 missense mutations in autosomal recessive intellectual disability. Am J Med Genet A. 2014 Nov;164A(11):2753-63. doi: 10.1002/ajmg.a.36723. Epub 2014 Aug 14. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01812Adenosine 3',5'-diphosphateexperimentalunknownDetails