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Protein

Heparan sulfate glucosamine 3-O-sulfotransferase 5

Gene

HS3ST5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to position 3 of glucosamine residues in heparan. Catalyzes the rate limiting step in the biosynthesis of heparan sulfate (HSact). This modification is a crucial step in the biosynthesis of anticoagulant heparan sulfate as it completes the structure of the antithrombin pentasaccharide binding site. Also generates GlcUA-GlcNS or IdoUA-GlcNS and IdoUA2S-GlcNH2. The substrate-specific O-sulfation generates an enzyme-modified heparan sulfate which acts as a binding receptor to Herpes simplex virus-1 (HSV-1) and permits its entry.1 Publication

Catalytic activityi

3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei183PAPSBy similarity1
Binding sitei191PAPSBy similarity1
Binding sitei293PAPSBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi100 – 104PAPSBy similarity5
Nucleotide bindingi309 – 313PAPSBy similarity5

GO - Molecular functioni

  • [heparan sulfate]-glucosamine 3-sulfotransferase 1 activity Source: UniProtKB
  • 3'-phosphoadenosine 5'-phosphosulfate binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionTransferase

Enzyme and pathway databases

ReactomeiR-HSA-2022928 HS-GAG biosynthesis

Names & Taxonomyi

Protein namesi
Recommended name:
Heparan sulfate glucosamine 3-O-sulfotransferase 5 (EC:2.8.2.23)
Alternative name(s):
Heparan sulfate D-glucosaminyl 3-O-sulfotransferase 5
Short name:
3-OST-5
Short name:
Heparan sulfate 3-O-sulfotransferase 5
Short name:
h3-OST-5
Gene namesi
Name:HS3ST5
Synonyms:3OST5, HS3OST5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000249853.7
HGNCiHGNC:19419 HS3ST5
MIMi609407 gene
neXtProtiNX_Q8IZT8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 12CytoplasmicSequence analysisAdd BLAST12
Transmembranei13 – 32Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST20
Topological domaini33 – 346LumenalSequence analysisAdd BLAST314

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi99R → A: Reduces enzyme activity by over 99%. 1 Publication1
Mutagenesisi104R → A: Reduces enzyme activity by 93%,. 1 Publication1
Mutagenesisi155K → A: Reduces enzyme activity by over 99%. 1 Publication1
Mutagenesisi195Q → A: Reduces enzyme activity by over 99%. 1 Publication1
Mutagenesisi309K → A: Loss of enzyme activity. 1 Publication1
Mutagenesisi311R → A: Reduces enzyme activity by 98%. 1 Publication1

Organism-specific databases

DisGeNETi222537
OpenTargetsiENSG00000249853
PharmGKBiPA164741639

Polymorphism and mutation databases

BioMutaiHS3ST5
DMDMi61214369

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000852221 – 346Heparan sulfate glucosamine 3-O-sulfotransferase 5Add BLAST346

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi287N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi294 ↔ 304By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ8IZT8
PRIDEiQ8IZT8
ProteomicsDBi71426

PTM databases

iPTMnetiQ8IZT8
PhosphoSitePlusiQ8IZT8

Expressioni

Tissue specificityi

Highly expressed in skeletal muscle and fetal brain, and also found in adult brain, spinal cord, cerebellum and colon.2 Publications

Gene expression databases

BgeeiENSG00000249853 Expressed in 98 organ(s), highest expression level in caudate nucleus
CleanExiHS_HS3ST5
GenevisibleiQ8IZT8 HS

Organism-specific databases

HPAiHPA021823
HPA064677

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000427888

Structurei

Secondary structure

1346
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8IZT8
SMRiQ8IZT8
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8IZT8

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni122 – 128Substrate bindingBy similarity7
Regioni155 – 158Substrate bindingBy similarity4
Regioni226 – 227Substrate bindingBy similarity2

Sequence similaritiesi

Belongs to the sulfotransferase 1 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3704 Eukaryota
ENOG410XS59 LUCA
GeneTreeiENSGT00760000119023
HOGENOMiHOG000036663
HOVERGENiHBG053377
InParanoidiQ8IZT8
KOiK08104
OMAiGRTFNWP
OrthoDBiEOG091G0CS5
PhylomeDBiQ8IZT8
TreeFamiTF350755

Family and domain databases

InterProiView protein in InterPro
IPR037359 NST/OST
IPR027417 P-loop_NTPase
IPR000863 Sulfotransferase_dom
PANTHERiPTHR10605 PTHR10605, 1 hit
PfamiView protein in Pfam
PF00685 Sulfotransfer_1, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit

Sequencei

Sequence statusi: Complete.

Q8IZT8-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLFKQQAWLR QKLLVLGSLA VGSLLYLVAR VGSLDRLQPI CPIEGRLGGA
60 70 80 90 100
RTQAEFPLRA LQFKRGLLHE FRKGNASKEQ VRLHDLVQQL PKAIIIGVRK
110 120 130 140 150
GGTRALLEML NLHPAVVKAS QEIHFFDNDE NYGKGIEWYR KKMPFSYPQQ
160 170 180 190 200
ITIEKSPAYF ITEEVPERIY KMNSSIKLLI IVREPTTRAI SDYTQVLEGK
210 220 230 240 250
ERKNKTYYKF EKLAIDPNTC EVNTKYKAVR TSIYTKHLER WLKYFPIEQF
260 270 280 290 300
HVVDGDRLIT EPLPELQLVE KFLNLPPRIS QYNLYFNATR GFYCLRFNII
310 320 330 340
FNKCLAGSKG RIHPEVDPSV ITKLRKFFHP FNQKFYQITG RTLNWP
Length:346
Mass (Da):40,408
Last modified:March 1, 2003 - v1
Checksum:iC763F70793FDB156
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052531247I → N. Corresponds to variant dbSNP:rs17793043Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF503292 mRNA Translation: AAN37737.1
AK091074 mRNA No translation available.
AK289907 mRNA Translation: BAF82596.1
CH471051 Genomic DNA Translation: EAW48251.1
BC093911 mRNA Translation: AAH93911.1
BC093913 mRNA Translation: AAH93913.1
CCDSiCCDS34517.1
RefSeqiNP_705840.2, NM_153612.3
XP_006715442.1, XM_006715379.2
XP_011533890.1, XM_011535588.2
XP_016865959.1, XM_017010470.1
XP_016865960.1, XM_017010471.1
XP_016865961.1, XM_017010472.1
XP_016865962.1, XM_017010473.1
XP_016865963.1, XM_017010474.1
UniGeneiHs.645477

Genome annotation databases

EnsembliENST00000312719; ENSP00000427888; ENSG00000249853
ENST00000411826; ENSP00000440332; ENSG00000249853
GeneIDi222537
KEGGihsa:222537
UCSCiuc003pwg.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF503292 mRNA Translation: AAN37737.1
AK091074 mRNA No translation available.
AK289907 mRNA Translation: BAF82596.1
CH471051 Genomic DNA Translation: EAW48251.1
BC093911 mRNA Translation: AAH93911.1
BC093913 mRNA Translation: AAH93913.1
CCDSiCCDS34517.1
RefSeqiNP_705840.2, NM_153612.3
XP_006715442.1, XM_006715379.2
XP_011533890.1, XM_011535588.2
XP_016865959.1, XM_017010470.1
XP_016865960.1, XM_017010471.1
XP_016865961.1, XM_017010472.1
XP_016865962.1, XM_017010473.1
XP_016865963.1, XM_017010474.1
UniGeneiHs.645477

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BD9X-ray2.30A88-346[»]
ProteinModelPortaliQ8IZT8
SMRiQ8IZT8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000427888

PTM databases

iPTMnetiQ8IZT8
PhosphoSitePlusiQ8IZT8

Polymorphism and mutation databases

BioMutaiHS3ST5
DMDMi61214369

Proteomic databases

PaxDbiQ8IZT8
PRIDEiQ8IZT8
ProteomicsDBi71426

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000312719; ENSP00000427888; ENSG00000249853
ENST00000411826; ENSP00000440332; ENSG00000249853
GeneIDi222537
KEGGihsa:222537
UCSCiuc003pwg.4 human

Organism-specific databases

CTDi222537
DisGeNETi222537
EuPathDBiHostDB:ENSG00000249853.7
GeneCardsiHS3ST5
HGNCiHGNC:19419 HS3ST5
HPAiHPA021823
HPA064677
MIMi609407 gene
neXtProtiNX_Q8IZT8
OpenTargetsiENSG00000249853
PharmGKBiPA164741639
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3704 Eukaryota
ENOG410XS59 LUCA
GeneTreeiENSGT00760000119023
HOGENOMiHOG000036663
HOVERGENiHBG053377
InParanoidiQ8IZT8
KOiK08104
OMAiGRTFNWP
OrthoDBiEOG091G0CS5
PhylomeDBiQ8IZT8
TreeFamiTF350755

Enzyme and pathway databases

ReactomeiR-HSA-2022928 HS-GAG biosynthesis

Miscellaneous databases

ChiTaRSiHS3ST5 human
EvolutionaryTraceiQ8IZT8
GenomeRNAii222537
PROiPR:Q8IZT8
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000249853 Expressed in 98 organ(s), highest expression level in caudate nucleus
CleanExiHS_HS3ST5
GenevisibleiQ8IZT8 HS

Family and domain databases

InterProiView protein in InterPro
IPR037359 NST/OST
IPR027417 P-loop_NTPase
IPR000863 Sulfotransferase_dom
PANTHERiPTHR10605 PTHR10605, 1 hit
PfamiView protein in Pfam
PF00685 Sulfotransfer_1, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHS3S5_HUMAN
AccessioniPrimary (citable) accession number: Q8IZT8
Secondary accession number(s): A8K1J2, Q52LI2, Q8N285
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: March 1, 2003
Last modified: November 7, 2018
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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