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Q8IWU6

- SULF1_HUMAN

UniProt

Q8IWU6 - SULF1_HUMAN

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Protein

Extracellular sulfatase Sulf-1

Gene
SULF1, KIAA1077
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 – 511Calcium By similarity
Metal bindingi52 – 521Calcium By similarity
Metal bindingi87 – 871Calcium; via 3-oxoalanine By similarity
Metal bindingi316 – 3161Calcium By similarity
Metal bindingi317 – 3171Calcium By 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
Complete GO annotation...

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
Complete GO annotation...

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 – 2222 Reviewed predictionAdd
BLAST
Chaini23 – 871849Extracellular sulfatase Sulf-1PRO_0000033434Add
BLAST

Amino acid modifications

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

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.

Family & Domainsi

Sequence similaritiesi

Belongs to the sulfatase family.

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

« Hide

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti49 – 491L → P in AAO33315. 1 Publication
Sequence conflicti728 – 7281K → R in BAC11258. 1 Publication

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

« Hide 'large scale' publications
  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: July 9, 2014
This is version 104 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

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