Q8IZT8 (HS3S5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	HS3ST5
Synonyms:	3OST5, HS3OST5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	346 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.1
Catalytic activity	3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 3-sulfate. Ref.8
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein Probable.
Tissue specificity	Highly expressed in skeletal muscle and fetal brain, and also found in adult brain, spinal cord, cerebellum and colon. Ref.1 Ref.5
Sequence similarities	Belongs to the sulfotransferase 1 family.

Ontologies

Keywords
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Transferase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Traceable author statement. Source: Reactome glycosaminoglycan biosynthetic process Traceable author statement. Source: Reactome heparan sulfate proteoglycan biosynthetic process, enzymatic modification Inferred from direct assay Ref.1. Source: UniProtKB negative regulation of coagulation Inferred from direct assay Ref.1. Source: UniProtKB protein sulfation Inferred from direct assay Ref.1. Source: UniProtKB regulation of viral entry into host cell Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular_function	3'-phosphoadenosine 5'-phosphosulfate binding Non-traceable author statement Ref.1. Source: UniProtKB [heparan sulfate]-glucosamine 3-sulfotransferase 1 activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 346

346

Heparan sulfate glucosamine 3-O-sulfotransferase 5

PRO_0000085222

Regions

Topological domain

1 – 12

12

Cytoplasmic Potential

Transmembrane

13 – 32

20

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

33 – 346

314

Lumenal Potential

Nucleotide binding

100 – 104

5

PAPS By similarity

Nucleotide binding

309 – 313

5

PAPS By similarity

Region

122 – 128

7

Substrate binding By similarity

Region

155 – 158

4

Substrate binding By similarity

Region

226 – 227

2

Substrate binding By similarity

Sites

Binding site

183

1

PAPS By similarity

Binding site

191

1

PAPS By similarity

Binding site

293

1

PAPS By similarity

Amino acid modifications

Glycosylation

287

1

N-linked (GlcNAc...) Potential

Disulfide bond

294 ↔ 304

By similarity

Natural variations

Natural variant

247

1

I → N.
Corresponds to variant rs17793043 [ dbSNP | Ensembl ].

VAR_052531

Experimental info

Mutagenesis

99

1

R → A: Reduces enzyme activity by over 99%. Ref.8

Mutagenesis

104

1

R → A: Reduces enzyme activity by 93%,. Ref.8

Mutagenesis

155

1

K → A: Reduces enzyme activity by over 99%. Ref.8

Mutagenesis

195

1

Q → A: Reduces enzyme activity by over 99%. Ref.8

Mutagenesis

309

1

K → A: Loss of enzyme activity. Ref.8

Mutagenesis

311

1

R → A: Reduces enzyme activity by 98%. Ref.8

Secondary structure

1

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346

Helix Strand Turn

Details...

Beta strand

92 – 97

6

Helix

103 – 110

8

Beta strand

116 – 118

3

Helix

129 – 133

5

Helix

136 – 140

5

Beta strand

151 – 155

5

Helix

157 – 160

4

Helix

165 – 172

8

Beta strand

177 – 182

6

Helix

185 – 202

18

Helix

210 – 214

5

Turn

217 – 219

3

Helix

227 – 231

5

Helix

234 – 242

9

Helix

247 – 249

3

Beta strand

250 – 254

5

Helix

255 – 260

6

Helix

262 – 272

11

Helix

281 – 283

3

Beta strand

284 – 287

4

Turn

288 – 291

4

Beta strand

292 – 296

5

Beta strand

298 – 300

3

Helix

318 – 339

22

Sequences

	Sequence		Length	Mass (Da)
	Q8IZT8 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: C763F70793FDB156	FASTA	346	40,408
	10 20 30 40 50 60 MLFKQQAWLR QKLLVLGSLA VGSLLYLVAR VGSLDRLQPI CPIEGRLGGA RTQAEFPLRA 70 80 90 100 110 120 LQFKRGLLHE FRKGNASKEQ VRLHDLVQQL PKAIIIGVRK GGTRALLEML NLHPAVVKAS 130 140 150 160 170 180 QEIHFFDNDE NYGKGIEWYR KKMPFSYPQQ ITIEKSPAYF ITEEVPERIY KMNSSIKLLI 190 200 210 220 230 240 IVREPTTRAI SDYTQVLEGK ERKNKTYYKF EKLAIDPNTC EVNTKYKAVR TSIYTKHLER 250 260 270 280 290 300 WLKYFPIEQF HVVDGDRLIT EPLPELQLVE KFLNLPPRIS QYNLYFNATR GFYCLRFNII 310 320 330 340 FNKCLAGSKG RIHPEVDPSV ITKLRKFFHP FNQKFYQITG RTLNWP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Heparan sulfate 3-O-sulfotransferase isoform 5 generates both an antithrombin-binding site and an entry receptor for herpes simplex virus, type 1." Xia G., Chen J., Tiwari V., Ju W., Li J.-P., Malmstroem A., Shukla D., Liu J. J. Biol. Chem. 277:37912-37919(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CHARACTERIZATION, FUNCTION IN HSV-1 ENTRY. Tissue: Placenta.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Caudate nucleus and Corpus callosum.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"Characterization of a heparan sulfate 3-O-sulfotransferase-5, an enzyme synthesizing a tetrasulfated disaccharide." Mochizuki H., Yoshida K., Gotoh M., Sugioka S., Kikuchi N., Kwon Y.-D., Tawada A., Maeyama K., Inaba N., Hiruma T., Kimata K., Narimatsu H. J. Biol. Chem. 278:26780-26787(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION, TISSUE SPECIFICITY.
[6]	"The biosynthesis of anticoagulant heparan sulfate by the heparan sulfate 3-O-sulfotransferase isoform 5." Duncan M.B., Chen J., Krise J.P., Liu J. Biochim. Biophys. Acta 1671:34-43(2004) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[7]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Engineering sulfotransferases to modify heparan sulfate." Xu D., Moon A.F., Song D., Pedersen L.C., Liu J. Nat. Chem. Biol. 4:200-202(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 88-346 IN COMPLEX WITH ADENOSINE-3'-5'-DIPHOSPHATE, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-99; ARG-104; LYS-155; GLN-195; LYS-309 AND ARG-311.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00218071.

RefSeq

NP_705840.2. NM_153612.3.

UniGene

Hs.645477.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BD9	X-ray	2.30	A	88-346	[»]

ProteinModelPortal

Q8IZT8.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000387653.

PTM databases

PhosphoSite

Q8IZT8.

Polymorphism databases

DMDM

61214369.

Proteomic databases

PaxDb

Q8IZT8.

PeptideAtlas

Q8IZT8.

PRIDE

Q8IZT8.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000312719; ENSP00000427888; ENSG00000249853.
ENST00000411826; ENSP00000440332; ENSG00000249853.

GeneID

222537.

KEGG

hsa:222537.

UCSC

uc003pwg.4. human.

Organism-specific databases

CTD

222537.

GeneCards

GC06M114376.

HGNC

HGNC:19419. HS3ST5.

HPA

HPA021823.

MIM

609407. gene.

neXtProt

NX_Q8IZT8.

PharmGKB

PA164741639.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG282030.

HOGENOM

HOG000036663.

HOVERGEN

HBG053377.

InParanoid

Q8IZT8.

KO

K08104.

OMA

GRTFNWP.

OrthoDB

EOG4XKV77.

PhylomeDB

Q8IZT8.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

Bgee

Q8IZT8.

CleanEx

HS_HS3ST5.

Genevestigator

Q8IZT8.

GermOnline

ENSG00000175818. Homo sapiens.

Family and domain databases

InterPro

IPR000863. Sulfotransferase_dom.
[Graphical view]

Pfam

PF00685. Sulfotransfer_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8IZT8.

GenomeRNAi

222537.

NextBio

91615.

SOURCE

Search...

Entry information

Entry name

HS3S5_HUMAN

Accession

Primary (citable) accession number: Q8IZT8
Secondary accession number(s): A8K1J2, Q52LI2, Q8N285

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.