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O60243 (H6ST1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Heparan-sulfate 6-O-sulfotransferase 1

Short name=HS6ST-1
EC=2.8.2.-
Gene names
Name:HS6ST1
Synonyms:HS6ST
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length411 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5

Catalytic activity

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

Subcellular location

Membrane; Single-pass type II membrane protein Potential.

Tissue specificity

Expressed in fetal brain. Ref.1

Post-translational modification

N-glycosylated By similarity.

Involvement in disease

Hypogonadotropic hypogonadism 15 with or without anosmia (HH15) [MIM:614880]: A 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).
Note: The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Ref.5

Sequence similarities

Belongs to the sulfotransferase 6 family.

Sequence caution

The sequence AAY14736.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAA25760.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAA25760.1 differs from that shown. Reason: Frameshift at positions 5 and 7.

The sequence BAG57153.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60243-1)

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.
Isoform 2 (identifier: O60243-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-162: Missing.
     163-175: VLDRRDSAALRTP → MFSWCLWPVVGES
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 411411Heparan-sulfate 6-O-sulfotransferase 1
PRO_0000190801

Regions

Topological domain11 – 177Cytoplasmic Potential
Transmembrane18 – 3720Helical; Signal-anchor for type II membrane protein; Potential
Topological domain38 – 411374Lumenal Potential
Region96 – 10275'-phosphosulfate-binding Potential
Region185 – 19393'-phosphate binding Potential
Coiled coil352 – 38736 Potential
Compositional bias2 – 54Poly-Arg

Amino acid modifications

Glycosylation2641N-linked (GlcNAc...) Potential
Glycosylation3201N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 162162Missing in isoform 2.
VSP_037048
Alternative sequence163 – 17513VLDRR…ALRTP → MFSWCLWPVVGES in isoform 2.
VSP_037049
Natural variant3061R → Q in HH15; 15 to 30% reduction in enzymatic activity compared to wild-type. Ref.5
VAR_069283
Natural variant3061R → 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. Ref.5
VAR_069284
Natural variant3231R → Q in HH15; approximately 30% reduction in enzymatic activity compared to wild-type when heparan sulfate is the acceptor substrate. Ref.5
VAR_069285
Natural variant3821R → 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. Ref.5
VAR_069286
Natural variant4041M → V in HH15; with anosmia; 30 to 70% reduction in enzymatic activity compared to wild-type. Ref.5
VAR_069287

Experimental info

Sequence conflict551D → Y in BAA25760. Ref.1
Sequence conflict1911Y → C in BAG57153. Ref.2
Sequence conflict2551A → T in BAG57153. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 5, 2009. Version 5.
Checksum: FCBF7AFAF1F3325D

FASTA41148,226
        10         20         30         40         50         60 
MRRRRAGGRT MVERASKFVL VVAGSVCFML ILYQYAGPGL SLGAPGGRAP PDDLDLFPTP 

        70         80         90        100        110        120 
DPHYEKKYYF PVRELERSLR FDMKGDDVIV FLHIQKTGGT TFGRHLVQNV RLEVPCDCRP 

       130        140        150        160        170        180 
GQKKCTCYRP NRRETWLFSR FSTGWSCGLH ADWTELTNCV PGVLDRRDSA ALRTPRKFYY 

       190        200        210        220        230        240 
ITLLRDPVSR YLSEWRHVQR GATWKTSLHM CDGRTPTPEE LPPCYEGTDW SGCTLQEFMD 

       250        260        270        280        290        300 
CPYNLANNRQ VRMLADLSLV GCYNLSFIPE GKRAQLLLES AKKNLRGMAF FGLTEFQRKT 

       310        320        330        340        350        360 
QYLFERTFNL KFIRPFMQYN STRAGGVEVD EDTIRRIEEL NDLDMQLYDY AKDLFQQRYQ 

       370        380        390        400        410 
YKRQLERREQ RLRSREERLL HRAKEALPRE DADEPGRVPT EDYMSHIIEK W 

« Hide

Isoform 2 [UniParc].

Checksum: 8579B4F4EE555A99
Show »

FASTA24929,870

References

« Hide 'large scale' references
[1]"Molecular characterization and expression of heparan-sulfate 6-sulfotransferase."
Habuchi H., Kobayashi M., Kimata K.
J. Biol. Chem. 273:9208-9213(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Fetal brain.
[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. expand/collapse author list , 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] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 171-411 (ISOFORM 1).
Tissue: Cerebellum and Hippocampus.
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
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] (ISOFORM 1).
Tissue: Eye.
[5]"Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism."
Tornberg J., Sykiotis G.P., Keefe K., Plummer L., Hoang X., Hall J.E., Quinton R., Seminara S.B., Hughes V., Van Vliet G., Van Uum S., Crowley W.F., Habuchi H., Kimata K., Pitteloud N., Bulow H.E.
Proc. Natl. Acad. Sci. U.S.A. 108:11524-11529(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANTS HH15 TRP-306; GLN-306; GLN-323; TRP-382 AND VAL-404, CHARACTERIZATION OF VARIANTS HH15 TRP-306; GLN-306; GLN-323; TRP-382 AND VAL-404.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS42748.1. [O60243-1]
RefSeqNP_004798.3. NM_004807.2. [O60243-1]
UniGeneHs.512841.

3D structure databases

ProteinModelPortalO60243.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000259241.

PTM databases

PhosphoSiteO60243.

Proteomic databases

PaxDbO60243.
PRIDEO60243.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000259241; ENSP00000259241; ENSG00000136720. [O60243-1]
GeneID9394.
KEGGhsa:9394.
UCSCuc002tpt.4. human. [O60243-1]

Organism-specific databases

CTD9394.
GeneCardsGC02M128929.
HGNCHGNC:5201. HS6ST1.
HPAHPA044586.
MIM604846. gene.
614880. phenotype.
neXtProtNX_O60243.
Orphanet478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBPA35102.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG302961.
HOGENOMHOG000007772.
HOVERGENHBG083012.
InParanoidO60243.
KOK02514.
OMAPTEDYMN.
OrthoDBEOG75MVW3.
PhylomeDBO60243.
TreeFamTF312835.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000136720-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

ArrayExpressO60243.
BgeeO60243.
CleanExHS_HS6ST1.
GenevestigatorO60243.

Family and domain databases

InterProIPR010635. Heparan_SO4-6-sulfoTrfase.
IPR027417. P-loop_NTPase.
IPR005331. Sulfotransferase.
[Graphical view]
PANTHERPTHR12812. PTHR12812. 1 hit.
PfamPF03567. Sulfotransfer_2. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
ProtoNetSearch...

Other

ChiTaRSHS6ST1. human.
GenomeRNAi9394.
NextBio35195.
PROO60243.
SOURCESearch...

Entry information

Entry nameH6ST1_HUMAN
AccessionPrimary (citable) accession number: O60243
Secondary accession number(s): B4DEP2 expand/collapse secondary AC list , B4DJ29, Q53SL2, Q9BVI1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: May 5, 2009
Last modified: July 9, 2014
This is version 102 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM