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O60243

- H6ST1_HUMAN

UniProt

O60243 - H6ST1_HUMAN

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Protein

Heparan-sulfate 6-O-sulfotransferase 1

Gene
HS6ST1, HS6ST
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. sulfotransferase activity Source: ProtInc

GO - Biological processi

  1. angiogenesis Source: Ensembl
  2. carbohydrate metabolic process Source: Reactome
  3. glycosaminoglycan biosynthetic process Source: Reactome
  4. glycosaminoglycan metabolic process Source: Reactome
  5. heparan sulfate proteoglycan biosynthetic process, enzymatic modification Source: ProtInc
  6. labyrinthine layer blood vessel development Source: Ensembl
  7. lung alveolus development Source: Ensembl
  8. neuron development Source: UniProtKB
  9. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000136720-MONOMER.
ReactomeiREACT_121248. 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
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:5201. HS6ST1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini11 – 177Cytoplasmic Reviewed prediction
Transmembranei18 – 3720Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini38 – 411374Lumenal Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. Golgi membrane Source: Reactome
  2. 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) [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.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti306 – 3061R → Q in HH15; 15 to 30% reduction in enzymatic activity compared to wild-type. 1 Publication
VAR_069283
Natural varianti306 – 3061R → 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. 1 Publication
VAR_069284
Natural varianti323 – 3231R → Q in HH15; approximately 30% reduction in enzymatic activity compared to wild-type when heparan sulfate is the acceptor substrate. 1 Publication
VAR_069285
Natural varianti382 – 3821R → 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 Publication
VAR_069286
Natural varianti404 – 4041M → V in HH15; with anosmia; 30 to 70% reduction in enzymatic activity compared to wild-type. 1 Publication
VAR_069287

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism, Kallmann syndrome

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 411411Heparan-sulfate 6-O-sulfotransferase 1PRO_0000190801Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi264 – 2641N-linked (GlcNAc...) Reviewed prediction
Glycosylationi320 – 3201N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

N-glycosylated By similarity.

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiO60243.
PRIDEiO60243.

PTM databases

PhosphoSiteiO60243.

Expressioni

Tissue specificityi

Expressed in fetal brain.1 Publication

Gene expression databases

ArrayExpressiO60243.
BgeeiO60243.
CleanExiHS_HS6ST1.
GenevestigatoriO60243.

Organism-specific databases

HPAiHPA044586.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000259241.

Structurei

3D structure databases

ProteinModelPortaliO60243.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni96 – 10275'-phosphosulfate-binding Reviewed prediction
Regioni185 – 19393'-phosphate binding Reviewed prediction

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili352 – 38736 Reviewed predictionAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi2 – 54Poly-Arg

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG302961.
HOGENOMiHOG000007772.
HOVERGENiHBG083012.
InParanoidiO60243.
KOiK02514.
OMAiPTEDYMN.
OrthoDBiEOG75MVW3.
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. Align

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

MRRRRAGGRT MVERASKFVL VVAGSVCFML ILYQYAGPGL SLGAPGGRAP    50
PDDLDLFPTP DPHYEKKYYF PVRELERSLR FDMKGDDVIV FLHIQKTGGT 100
TFGRHLVQNV RLEVPCDCRP GQKKCTCYRP NRRETWLFSR FSTGWSCGLH 150
ADWTELTNCV PGVLDRRDSA ALRTPRKFYY ITLLRDPVSR YLSEWRHVQR 200
GATWKTSLHM CDGRTPTPEE LPPCYEGTDW SGCTLQEFMD CPYNLANNRQ 250
VRMLADLSLV GCYNLSFIPE GKRAQLLLES AKKNLRGMAF FGLTEFQRKT 300
QYLFERTFNL KFIRPFMQYN STRAGGVEVD EDTIRRIEEL NDLDMQLYDY 350
AKDLFQQRYQ YKRQLERREQ RLRSREERLL HRAKEALPRE DADEPGRVPT 400
EDYMSHIIEK W 411
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 BAA25760.1 differs from that shown. Reason: Frameshift at positions 5 and 7.
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 BAG57153.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti306 – 3061R → Q in HH15; 15 to 30% reduction in enzymatic activity compared to wild-type. 1 Publication
VAR_069283
Natural varianti306 – 3061R → 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. 1 Publication
VAR_069284
Natural varianti323 – 3231R → Q in HH15; approximately 30% reduction in enzymatic activity compared to wild-type when heparan sulfate is the acceptor substrate. 1 Publication
VAR_069285
Natural varianti382 – 3821R → 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 Publication
VAR_069286
Natural varianti404 – 4041M → V in HH15; with anosmia; 30 to 70% reduction in enzymatic activity compared to wild-type. 1 Publication
VAR_069287

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 162162Missing in isoform 2. VSP_037048Add
BLAST
Alternative sequencei163 – 17513VLDRR…ALRTP → MFSWCLWPVVGES in isoform 2. VSP_037049Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti55 – 551D → Y in BAA25760. 1 Publication
Sequence conflicti191 – 1911Y → C in BAG57153. 1 Publication
Sequence conflicti255 – 2551A → T in BAG57153. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Genome annotation databases

EnsembliENST00000259241; ENSP00000259241; ENSG00000136720. [O60243-1]
GeneIDi9394.
KEGGihsa:9394.
UCSCiuc002tpt.4. human. [O60243-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS42748.1. [O60243-1 ]
RefSeqi NP_004798.3. NM_004807.2. [O60243-1 ]
UniGenei Hs.512841.

3D structure databases

ProteinModelPortali O60243.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000259241.

PTM databases

PhosphoSitei O60243.

Proteomic databases

PaxDbi O60243.
PRIDEi O60243.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000259241 ; ENSP00000259241 ; ENSG00000136720 . [O60243-1 ]
GeneIDi 9394.
KEGGi hsa:9394.
UCSCi uc002tpt.4. human. [O60243-1 ]

Organism-specific databases

CTDi 9394.
GeneCardsi GC02M128929.
HGNCi HGNC:5201. HS6ST1.
HPAi HPA044586.
MIMi 604846. gene.
614880. phenotype.
neXtProti NX_O60243.
Orphaneti 478. Kallmann syndrome.
432. Normosmic congenital hypogonadotropic hypogonadism.
PharmGKBi PA35102.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG302961.
HOGENOMi HOG000007772.
HOVERGENi HBG083012.
InParanoidi O60243.
KOi K02514.
OMAi PTEDYMN.
OrthoDBi EOG75MVW3.
PhylomeDBi O60243.
TreeFami TF312835.

Enzyme and pathway databases

BioCyci MetaCyc:ENSG00000136720-MONOMER.
Reactomei REACT_121248. HS-GAG biosynthesis.

Miscellaneous databases

ChiTaRSi HS6ST1. human.
GenomeRNAii 9394.
NextBioi 35195.
PROi O60243.
SOURCEi Search...

Gene expression databases

ArrayExpressi O60243.
Bgeei O60243.
CleanExi HS_HS6ST1.
Genevestigatori O60243.

Family and domain databases

InterProi IPR010635. Heparan_SO4-6-sulfoTrfase.
IPR027417. P-loop_NTPase.
IPR005331. Sulfotransferase.
[Graphical view ]
PANTHERi PTHR12812. PTHR12812. 1 hit.
Pfami PF03567. Sulfotransfer_2. 1 hit.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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.

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: September 3, 2014
This is version 103 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

External Data

Dasty 3

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