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Protein

Heparan-sulfate 6-O-sulfotransferase 1

Gene

HS6ST1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate. Critical for normal neuronal development where it may play a role in neuron branching. May also play a role in limb development. May prefer iduronic acid.1 Publication

Catalytic activityi

3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan sulfate]-glucosamine 6-sulfate.

GO - Molecular functioni

  • heparan sulfate 6-O-sulfotransferase activity Source: GO_Central
  • sulfotransferase activity Source: ProtInc

GO - Biological processi

  • angiogenesis Source: Ensembl
  • glycosaminoglycan biosynthetic process Source: Reactome
  • heparan sulfate proteoglycan biosynthetic process, enzymatic modification Source: ProtInc
  • labyrinthine layer blood vessel development Source: Ensembl
  • lung alveolus development Source: Ensembl
  • neuron development Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000136720-MONOMER.
ZFISH:ENSG00000136720-MONOMER.
ReactomeiR-HSA-2022928. HS-GAG biosynthesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Heparan-sulfate 6-O-sulfotransferase 1 (EC:2.8.2.-)
Short name:
HS6ST-1
Gene namesi
Name:HS6ST1
Synonyms:HS6ST
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:5201. HS6ST1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini11 – 17CytoplasmicSequence analysis7
Transmembranei18 – 37Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST20
Topological domaini38 – 411LumenalSequence analysisAdd BLAST374

GO - Cellular componenti

  • Golgi membrane Source: Reactome
  • integral component of plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 15 with or without anosmia (HH15)2 Publications
The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry.
Disease descriptionA disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
See also OMIM:614880
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072980218P → S in HH15. 1 PublicationCorresponds to variant rs200268730dbSNPEnsembl.1
Natural variantiVAR_069283306R → Q in HH15; 15 to 30% reduction in enzymatic activity compared to wild-type. 2 PublicationsCorresponds to variant rs201307896dbSNPEnsembl.1
Natural variantiVAR_069284306R → W in HH15; with anosmia; results in Kallmann syndrome in the presence of FGFR1 mutation Gln-250; approximately 50% reduction in enzymatic activity compared to wild-type. 2 PublicationsCorresponds to variant rs780352591dbSNPEnsembl.1
Natural variantiVAR_069285323R → Q in HH15; approximately 30% reduction in enzymatic activity compared to wild-type when heparan sulfate is the acceptor substrate. 1 PublicationCorresponds to variant rs761325768dbSNPEnsembl.1
Natural variantiVAR_069286382R → W in HH15; with or without anosmia; results in Kallmann syndrome in the presence of NSMF mutation Ala-480; 25 to 35% reduction in enzymatic activity compared to wild-type. 1 PublicationCorresponds to variant rs199538589dbSNPEnsembl.1
Natural variantiVAR_069287404M → V in HH15; with anosmia; 30 to 70% reduction in enzymatic activity compared to wild-type. 1 Publication1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism, Kallmann syndrome

Organism-specific databases

DisGeNETi9394.
MalaCardsiHS6ST1.
MIMi614880. phenotype.
OpenTargetsiENSG00000136720.
Orphaneti478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA35102.

Polymorphism and mutation databases

BioMutaiHS6ST1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001908011 – 411Heparan-sulfate 6-O-sulfotransferase 1Add BLAST411

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi264N-linked (GlcNAc...)Sequence analysis1
Glycosylationi320N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiO60243.
MaxQBiO60243.
PaxDbiO60243.
PeptideAtlasiO60243.
PRIDEiO60243.

PTM databases

iPTMnetiO60243.
PhosphoSitePlusiO60243.

Expressioni

Tissue specificityi

Expressed in fetal brain.1 Publication

Gene expression databases

BgeeiENSG00000136720.
CleanExiHS_HS6ST1.
GenevisibleiO60243. HS.

Organism-specific databases

HPAiHPA044586.

Interactioni

Protein-protein interaction databases

BioGridi114793. 9 interactors.
IntActiO60243. 2 interactors.
STRINGi9606.ENSP00000259241.

Structurei

3D structure databases

ProteinModelPortaliO60243.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni96 – 1025'-phosphosulfate-bindingSequence analysis7
Regioni185 – 1933'-phosphate bindingSequence analysis9

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili352 – 387Sequence analysisAdd BLAST36

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi2 – 5Poly-Arg4

Sequence similaritiesi

Belongs to the sulfotransferase 6 family.Curated

Keywords - Domaini

Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3955. Eukaryota.
ENOG410XSW4. LUCA.
GeneTreeiENSGT00390000013468.
HOGENOMiHOG000007772.
HOVERGENiHBG083012.
InParanoidiO60243.
KOiK02514.
OMAiQNLRPDQ.
OrthoDBiEOG091G08UD.
PhylomeDBiO60243.
TreeFamiTF312835.

Family and domain databases

InterProiIPR010635. Heparan_SO4-6-sulfoTrfase.
IPR027417. P-loop_NTPase.
IPR005331. Sulfotransferase.
[Graphical view]
PANTHERiPTHR12812. PTHR12812. 1 hit.
PfamiPF03567. Sulfotransfer_2. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O60243-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRRRRAGGRT MVERASKFVL VVAGSVCFML ILYQYAGPGL SLGAPGGRAP
60 70 80 90 100
PDDLDLFPTP DPHYEKKYYF PVRELERSLR FDMKGDDVIV FLHIQKTGGT
110 120 130 140 150
TFGRHLVQNV RLEVPCDCRP GQKKCTCYRP NRRETWLFSR FSTGWSCGLH
160 170 180 190 200
ADWTELTNCV PGVLDRRDSA ALRTPRKFYY ITLLRDPVSR YLSEWRHVQR
210 220 230 240 250
GATWKTSLHM CDGRTPTPEE LPPCYEGTDW SGCTLQEFMD CPYNLANNRQ
260 270 280 290 300
VRMLADLSLV GCYNLSFIPE GKRAQLLLES AKKNLRGMAF FGLTEFQRKT
310 320 330 340 350
QYLFERTFNL KFIRPFMQYN STRAGGVEVD EDTIRRIEEL NDLDMQLYDY
360 370 380 390 400
AKDLFQQRYQ YKRQLERREQ RLRSREERLL HRAKEALPRE DADEPGRVPT
410
EDYMSHIIEK W
Length:411
Mass (Da):48,226
Last modified:May 5, 2009 - v5
Checksum:iFCBF7AFAF1F3325D
GO
Isoform 2 (identifier: O60243-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-162: Missing.
     163-175: VLDRRDSAALRTP → MFSWCLWPVVGES

Note: No experimental confirmation available.
Show »
Length:249
Mass (Da):29,870
Checksum:i8579B4F4EE555A99
GO

Sequence cautioni

The sequence AAY14736 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA25760 differs from that shown. Reason: Frameshift at positions 5 and 7.Curated
The sequence BAA25760 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG57153 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55D → Y in BAA25760 (PubMed:9535912).Curated1
Sequence conflicti191Y → C in BAG57153 (PubMed:14702039).Curated1
Sequence conflicti255A → T in BAG57153 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072980218P → S in HH15. 1 PublicationCorresponds to variant rs200268730dbSNPEnsembl.1
Natural variantiVAR_069283306R → Q in HH15; 15 to 30% reduction in enzymatic activity compared to wild-type. 2 PublicationsCorresponds to variant rs201307896dbSNPEnsembl.1
Natural variantiVAR_069284306R → W in HH15; with anosmia; results in Kallmann syndrome in the presence of FGFR1 mutation Gln-250; approximately 50% reduction in enzymatic activity compared to wild-type. 2 PublicationsCorresponds to variant rs780352591dbSNPEnsembl.1
Natural variantiVAR_069285323R → Q in HH15; approximately 30% reduction in enzymatic activity compared to wild-type when heparan sulfate is the acceptor substrate. 1 PublicationCorresponds to variant rs761325768dbSNPEnsembl.1
Natural variantiVAR_069286382R → W in HH15; with or without anosmia; results in Kallmann syndrome in the presence of NSMF mutation Ala-480; 25 to 35% reduction in enzymatic activity compared to wild-type. 1 PublicationCorresponds to variant rs199538589dbSNPEnsembl.1
Natural variantiVAR_069287404M → V in HH15; with anosmia; 30 to 70% reduction in enzymatic activity compared to wild-type. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0370481 – 162Missing in isoform 2. 1 PublicationAdd BLAST162
Alternative sequenceiVSP_037049163 – 175VLDRR…ALRTP → MFSWCLWPVVGES in isoform 2. 1 PublicationAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006179 mRNA. Translation: BAA25760.1. Sequence problems.
AK293724 mRNA. Translation: BAG57153.1. Different initiation.
AK295898 mRNA. Translation: BAG58691.1.
AC017079 Genomic DNA. Translation: AAY14736.1. Different initiation.
BC001196 mRNA. Translation: AAH01196.1.
BC096239 mRNA. Translation: AAH96239.4.
BC096240 mRNA. Translation: AAH96240.4.
BC099638 mRNA. Translation: AAH99638.4.
BC099639 mRNA. Translation: AAH99639.4.
CCDSiCCDS42748.1. [O60243-1]
RefSeqiNP_004798.3. NM_004807.2. [O60243-1]
UniGeneiHs.512841.
Hs.715359.

Genome annotation databases

EnsembliENST00000259241; ENSP00000259241; ENSG00000136720. [O60243-1]
GeneIDi9394.
KEGGihsa:9394.
UCSCiuc002tpt.5. human. [O60243-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006179 mRNA. Translation: BAA25760.1. Sequence problems.
AK293724 mRNA. Translation: BAG57153.1. Different initiation.
AK295898 mRNA. Translation: BAG58691.1.
AC017079 Genomic DNA. Translation: AAY14736.1. Different initiation.
BC001196 mRNA. Translation: AAH01196.1.
BC096239 mRNA. Translation: AAH96239.4.
BC096240 mRNA. Translation: AAH96240.4.
BC099638 mRNA. Translation: AAH99638.4.
BC099639 mRNA. Translation: AAH99639.4.
CCDSiCCDS42748.1. [O60243-1]
RefSeqiNP_004798.3. NM_004807.2. [O60243-1]
UniGeneiHs.512841.
Hs.715359.

3D structure databases

ProteinModelPortaliO60243.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114793. 9 interactors.
IntActiO60243. 2 interactors.
STRINGi9606.ENSP00000259241.

PTM databases

iPTMnetiO60243.
PhosphoSitePlusiO60243.

Polymorphism and mutation databases

BioMutaiHS6ST1.

Proteomic databases

EPDiO60243.
MaxQBiO60243.
PaxDbiO60243.
PeptideAtlasiO60243.
PRIDEiO60243.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000259241; ENSP00000259241; ENSG00000136720. [O60243-1]
GeneIDi9394.
KEGGihsa:9394.
UCSCiuc002tpt.5. human. [O60243-1]

Organism-specific databases

CTDi9394.
DisGeNETi9394.
GeneCardsiHS6ST1.
HGNCiHGNC:5201. HS6ST1.
HPAiHPA044586.
MalaCardsiHS6ST1.
MIMi604846. gene.
614880. phenotype.
neXtProtiNX_O60243.
OpenTargetsiENSG00000136720.
Orphaneti478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBiPA35102.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3955. Eukaryota.
ENOG410XSW4. LUCA.
GeneTreeiENSGT00390000013468.
HOGENOMiHOG000007772.
HOVERGENiHBG083012.
InParanoidiO60243.
KOiK02514.
OMAiQNLRPDQ.
OrthoDBiEOG091G08UD.
PhylomeDBiO60243.
TreeFamiTF312835.

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000136720-MONOMER.
ZFISH:ENSG00000136720-MONOMER.
ReactomeiR-HSA-2022928. HS-GAG biosynthesis.

Miscellaneous databases

ChiTaRSiHS6ST1. human.
GenomeRNAii9394.
PROiO60243.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136720.
CleanExiHS_HS6ST1.
GenevisibleiO60243. HS.

Family and domain databases

InterProiIPR010635. Heparan_SO4-6-sulfoTrfase.
IPR027417. P-loop_NTPase.
IPR005331. Sulfotransferase.
[Graphical view]
PANTHERiPTHR12812. PTHR12812. 1 hit.
PfamiPF03567. Sulfotransfer_2. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiH6ST1_HUMAN
AccessioniPrimary (citable) accession number: O60243
Secondary accession number(s): B4DEP2
, B4DJ29, Q53SL2, Q9BVI1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: May 5, 2009
Last modified: November 30, 2016
This is version 122 of the entry and version 5 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.