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Q8IWU6

- SULF1_HUMAN

UniProt

Q8IWU6 - SULF1_HUMAN

Protein

Extracellular sulfatase Sulf-1

Gene

SULF1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      Previous versions | rss
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    Functioni

    Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity. It can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin. Diminishes HSPG (heparan sulfate proteoglycans) sulfation, inhibits signaling by heparin-dependent growth factors, diminishes proliferation, and facilitates apoptosis in response to exogenous stimulation.

    Cofactori

    Binds 1 calcium ion per subunit.By similarity

    pH dependencei

    Optimum pH is 7.0-8.0.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi51 – 511CalciumBy similarity
    Metal bindingi52 – 521CalciumBy similarity
    Metal bindingi87 – 871Calcium; via 3-oxoalanineBy similarity
    Metal bindingi316 – 3161CalciumBy similarity
    Metal bindingi317 – 3171CalciumBy similarity

    GO - Molecular functioni

    1. arylsulfatase activity Source: UniProtKB
    2. calcium ion binding Source: InterPro
    3. N-acetylglucosamine-6-sulfatase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. bone development Source: BHF-UCL
    3. cartilage development Source: UniProtKB
    4. chondrocyte development Source: UniProtKB
    5. embryonic skeletal system development Source: UniProtKB
    6. esophagus smooth muscle contraction Source: UniProtKB
    7. glial cell-derived neurotrophic factor receptor signaling pathway Source: UniProtKB
    8. glomerular basement membrane development Source: UniProtKB
    9. glomerular filtration Source: UniProtKB
    10. heparan sulfate proteoglycan metabolic process Source: UniProtKB
    11. innervation Source: UniProtKB
    12. kidney development Source: BHF-UCL
    13. negative regulation of angiogenesis Source: UniProtKB
    14. negative regulation of cell migration Source: UniProtKB
    15. negative regulation of endothelial cell proliferation Source: UniProtKB
    16. negative regulation of fibroblast growth factor receptor signaling pathway Source: UniProtKB
    17. negative regulation of prostatic bud formation Source: UniProtKB
    18. positive regulation of BMP signaling pathway Source: UniProtKB
    19. positive regulation of Wnt signaling pathway Source: UniProtKB
    20. positive regulation vascular endothelial growth factor production Source: UniProtKB
    21. regulation of fibroblast growth factor receptor signaling pathway Source: UniProtKB
    22. vascular endothelial growth factor receptor signaling pathway Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Apoptosis

    Keywords - Ligandi

    Calcium, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Extracellular sulfatase Sulf-1 (EC:3.1.6.-)
    Short name:
    hSulf-1
    Gene namesi
    Name:SULF1
    Synonyms:KIAA1077
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:20391. SULF1.

    Subcellular locationi

    Endoplasmic reticulum By similarity. Golgi apparatusGolgi stack By similarity. Cell surface By similarity
    Note: Also localized on the cell surface.By similarity

    GO - Cellular componenti

    1. cell surface Source: UniProtKB
    2. endoplasmic reticulum Source: UniProtKB
    3. extracellular space Source: UniProtKB
    4. Golgi apparatus Source: UniProtKB
    5. Golgi stack Source: UniProtKB-SubCell
    6. membrane raft Source: UniProtKB
    7. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Endoplasmic reticulum, Golgi apparatus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi87 – 882CC → AA: Loss of arylsulfatase activity and loss of ability to modulate apoptosis. 2 Publications

    Organism-specific databases

    Orphaneti2496. Mesomelia-synostoses syndrome.
    PharmGKBiPA134861022.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2222Sequence AnalysisAdd
    BLAST
    Chaini23 – 871849Extracellular sulfatase Sulf-1PRO_0000033434Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi64 – 641N-linked (GlcNAc...)Sequence Analysis
    Modified residuei87 – 8713-oxoalanine (Cys)By similarity
    Glycosylationi111 – 1111N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi131 – 1311N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi148 – 1481N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi170 – 1701N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi197 – 1971N-linked (GlcNAc...)1 Publication
    Glycosylationi240 – 2401N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi623 – 6231N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi773 – 7731N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi783 – 7831N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity.By similarity

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiQ8IWU6.
    PRIDEiQ8IWU6.

    PTM databases

    PhosphoSiteiQ8IWU6.

    Expressioni

    Tissue specificityi

    Expressed at highest levels in testis, stomach, skeletal muscle, lung, kidney, pancreas, small intestine and colon. It is also detected in normal ovarian surface epithelial cells. Down-regulation seen in ovarian carcinoma cell lines, ovarian cancers, breast, pancreatic, renal and hepatocellular carcinoma cell lines.

    Gene expression databases

    ArrayExpressiQ8IWU6.
    BgeeiQ8IWU6.
    CleanExiHS_SULF1.
    GenevestigatoriQ8IWU6.

    Organism-specific databases

    HPAiHPA054728.

    Interactioni

    Protein-protein interaction databases

    BioGridi116820. 2 interactions.
    STRINGi9606.ENSP00000260128.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8IWU6.
    SMRiQ8IWU6. Positions 42-411.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the sulfatase family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiCOG3119.
    HOGENOMiHOG000290161.
    HOVERGENiHBG056431.
    InParanoidiQ8IWU6.
    KOiK14607.
    OMAiKPDECDC.
    OrthoDBiEOG7FR7H6.
    PhylomeDBiQ8IWU6.
    TreeFamiTF313545.

    Family and domain databases

    Gene3Di3.40.720.10. 3 hits.
    InterProiIPR017849. Alkaline_Pase-like_a/b/a.
    IPR017850. Alkaline_phosphatase_core.
    IPR014615. Extracellular_sulfatase.
    IPR024609. Extracellular_sulfatase_C.
    IPR000917. Sulfatase.
    IPR024607. Sulfatase_CS.
    [Graphical view]
    PfamiPF12548. DUF3740. 1 hit.
    PF00884. Sulfatase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF036665. Sulf1. 1 hit.
    SUPFAMiSSF53649. SSF53649. 3 hits.
    PROSITEiPS00523. SULFATASE_1. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q8IWU6-1 [UniParc]FASTAAdd to Basket

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    MKYSCCALVL AVLGTELLGS LCSTVRSPRF RGRIQQERKN IRPNIILVLT    50
    DDQDVELGSL QVMNKTRKIM EHGGATFINA FVTTPMCCPS RSSMLTGKYV 100
    HNHNVYTNNE NCSSPSWQAM HEPRTFAVYL NNTGYRTAFF GKYLNEYNGS 150
    YIPPGWREWL GLIKNSRFYN YTVCRNGIKE KHGFDYAKDY FTDLITNESI 200
    NYFKMSKRMY PHRPVMMVIS HAAPHGPEDS APQFSKLYPN ASQHITPSYN 250
    YAPNMDKHWI MQYTGPMLPI HMEFTNILQR KRLQTLMSVD DSVERLYNML 300
    VETGELENTY IIYTADHGYH IGQFGLVKGK SMPYDFDIRV PFFIRGPSVE 350
    PGSIVPQIVL NIDLAPTILD IAGLDTPPDV DGKSVLKLLD PEKPGNRFRT 400
    NKKAKIWRDT FLVERGKFLR KKEESSKNIQ QSNHLPKYER VKELCQQARY 450
    QTACEQPGQK WQCIEDTSGK LRIHKCKGPS DLLTVRQSTR NLYARGFHDK 500
    DKECSCRESG YRASRSQRKS QRQFLRNQGT PKYKPRFVHT RQTRSLSVEF 550
    EGEIYDINLE EEEELQVLQP RNIAKRHDEG HKGPRDLQAS SGGNRGRMLA 600
    DSSNAVGPPT TVRVTHKCFI LPNDSIHCER ELYQSARAWK DHKAYIDKEI 650
    EALQDKIKNL REVRGHLKRR KPEECSCSKQ SYYNKEKGVK KQEKLKSHLH 700
    PFKEAAQEVD SKLQLFKENN RRRKKERKEK RRQRKGEECS LPGLTCFTHD 750
    NNHWQTAPFW NLGSFCACTS SNNNTYWCLR TVNETHNFLF CEFATGFLEY 800
    FDMNTDPYQL TNTVHTVERG ILNQLHVQLM ELRSCQGYKQ CNPRPKNLDV 850
    GNKDGGSYDL HRGQLWDGWE G 871
    Length:871
    Mass (Da):101,027
    Last modified:March 1, 2003 - v1
    Checksum:i9A90ADB280304364
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti49 – 491L → P in AAO33315. (PubMed:12686563)Curated
    Sequence conflicti728 – 7281K → R in BAC11258. (PubMed:14702039)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY101175 mRNA. Translation: AAM76860.1.
    AF545571 mRNA. Translation: AAO33315.1.
    AB029000 mRNA. Translation: BAA83029.1.
    AK074873 mRNA. Translation: BAC11258.1.
    CCDSiCCDS6204.1.
    RefSeqiNP_001121676.1. NM_001128204.1.
    NP_001121677.1. NM_001128205.1.
    NP_001121678.1. NM_001128206.1.
    NP_055985.2. NM_015170.2.
    UniGeneiHs.409602.

    Genome annotation databases

    EnsembliENST00000260128; ENSP00000260128; ENSG00000137573.
    ENST00000402687; ENSP00000385704; ENSG00000137573.
    ENST00000419716; ENSP00000390315; ENSG00000137573.
    ENST00000458141; ENSP00000403040; ENSG00000137573.
    GeneIDi23213.
    KEGGihsa:23213.
    UCSCiuc003xyd.2. human.

    Polymorphism databases

    DMDMi33112447.

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY101175 mRNA. Translation: AAM76860.1 .
    AF545571 mRNA. Translation: AAO33315.1 .
    AB029000 mRNA. Translation: BAA83029.1 .
    AK074873 mRNA. Translation: BAC11258.1 .
    CCDSi CCDS6204.1.
    RefSeqi NP_001121676.1. NM_001128204.1.
    NP_001121677.1. NM_001128205.1.
    NP_001121678.1. NM_001128206.1.
    NP_055985.2. NM_015170.2.
    UniGenei Hs.409602.

    3D structure databases

    ProteinModelPortali Q8IWU6.
    SMRi Q8IWU6. Positions 42-411.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116820. 2 interactions.
    STRINGi 9606.ENSP00000260128.

    PTM databases

    PhosphoSitei Q8IWU6.

    Polymorphism databases

    DMDMi 33112447.

    Proteomic databases

    PaxDbi Q8IWU6.
    PRIDEi Q8IWU6.

    Protocols and materials databases

    DNASUi 23213.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000260128 ; ENSP00000260128 ; ENSG00000137573 .
    ENST00000402687 ; ENSP00000385704 ; ENSG00000137573 .
    ENST00000419716 ; ENSP00000390315 ; ENSG00000137573 .
    ENST00000458141 ; ENSP00000403040 ; ENSG00000137573 .
    GeneIDi 23213.
    KEGGi hsa:23213.
    UCSCi uc003xyd.2. human.

    Organism-specific databases

    CTDi 23213.
    GeneCardsi GC08P070428.
    HGNCi HGNC:20391. SULF1.
    HPAi HPA054728.
    MIMi 610012. gene.
    neXtProti NX_Q8IWU6.
    Orphaneti 2496. Mesomelia-synostoses syndrome.
    PharmGKBi PA134861022.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG3119.
    HOGENOMi HOG000290161.
    HOVERGENi HBG056431.
    InParanoidi Q8IWU6.
    KOi K14607.
    OMAi KPDECDC.
    OrthoDBi EOG7FR7H6.
    PhylomeDBi Q8IWU6.
    TreeFami TF313545.

    Miscellaneous databases

    ChiTaRSi SULF1. human.
    GeneWikii SULF1.
    GenomeRNAii 23213.
    NextBioi 44771.
    PROi Q8IWU6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8IWU6.
    Bgeei Q8IWU6.
    CleanExi HS_SULF1.
    Genevestigatori Q8IWU6.

    Family and domain databases

    Gene3Di 3.40.720.10. 3 hits.
    InterProi IPR017849. Alkaline_Pase-like_a/b/a.
    IPR017850. Alkaline_phosphatase_core.
    IPR014615. Extracellular_sulfatase.
    IPR024609. Extracellular_sulfatase_C.
    IPR000917. Sulfatase.
    IPR024607. Sulfatase_CS.
    [Graphical view ]
    Pfami PF12548. DUF3740. 1 hit.
    PF00884. Sulfatase. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF036665. Sulf1. 1 hit.
    SUPFAMi SSF53649. SSF53649. 3 hits.
    PROSITEi PS00523. SULFATASE_1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and characterization of two extracellular heparin-degrading endosulfatases in mice and humans."
      Morimoto-Tomita M., Uchimura K., Werb Z., Hemmerich S., Rosen S.D.
      J. Biol. Chem. 277:49175-49185(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, MUTAGENESIS OF 87-CYS-CYS-88.
      Tissue: Prostate.
    2. "Loss of HSulf-1 up-regulates heparin-binding growth factor signaling in cancer."
      Lai J., Chien J., Staub J., Avula R., Greene E.L., Matthews T.A., Smith D.I., Kaufmann S.H., Roberts L.R., Shridhar V.
      J. Biol. Chem. 278:23107-23117(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF 87-CYS-CYS-88.
    3. "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
      Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
      DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 54-871.
      Tissue: Brain.
    4. "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] OF 312-871.
      Tissue: Teratocarcinoma.
    5. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-197.
      Tissue: Liver.

    Entry informationi

    Entry nameiSULF1_HUMAN
    AccessioniPrimary (citable) accession number: Q8IWU6
    Secondary accession number(s): Q86YV8, Q8NCA2, Q9UPS5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2003
    Last sequence update: March 1, 2003
    Last modified: October 1, 2014
    This is version 105 of the entry and version 1 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 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3