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FLASH GENE

Symbol

SULF1

contributors: mct/npt - updated : 31-05-2017

HGNC name	sulfatase 1
HGNC id	20391

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	194.29 kb     22 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	all variants encode the same protein

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001128204 22 - 5548 NP_001121676 - 871 - 2008 19373441 NM_001128205 23 - 5716 NP_001121677 - 871 - 2008 19373441 NM_001128206 22 - 5554 NP_001121678 - 871 - 2008 19373441 NM_015170 23 - 5710 NP_055985 - 871 - 2008 19373441

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue     highly Hearing/Equilibrium ear inner cochlea Corti highly Homo sapiens Respiratory respiratory tract larynx     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective cartilage     highly Homo sapiens Fetal

cells

System Cell Pubmed Species Stage Rna symbol not specific chondrocyte Homo sapiens Fetal Skeleton osteoblast

cell lineage

cell lines

fluid/secretion

at STAGE

Text	fetal kidney and brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	catalytic center residing in the N-terminal 75-kDa subunit
	C-terminal 50-kDa subunit indispensable for both arylsufatase and glucosamine 6-O-sulfate-endosulfatase activity (Tang 2009)

isoforms

Precursor

synthesized as prepro-enzymes and cleaved by a furin-type proteinase to form disulfide-bond linked heterodimers of 75- and 50-kDa subunits.

HOMOLOGY

Homologene

FAMILY

sulfatase family

CATEGORY

enzyme , tumor suppressor

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
text	secreted into conditioned medium, as well as retained on the cell membrane (Tang 2009)

basic FUNCTION	facilitating apoptosis in response to exogenous stimulation
	playing a potential role of down-regulation in mammary carcinogenesis (Narita 2007)
	promotes drug-induced apoptosis of cancer cells and inhibits tumorigenesis and angiogenesis (Lai 2008)
	extracellular sulfatase acting on internal glucosamine 6-O-sulfate modifications within heparan sulfate proteoglycans and regulating their interactions with various signaling molecules, including Wnt ligands (Tang 2009)
	extracellular sulfatases SULF1 and SULF2 remove specific 6-O-sulfate groups from heparan sulfate, thereby modulating numerous signalling pathways underlying development and homeostasis
	SULF1 and SULF2 differentially contribute to the generation of organ-specific sulfation patterns of heparan sulfate
	is a TGFB1)-responsive gene in normal human lung fibroblasts and functions as a negative feedback regulator of TGFB1
	plays a crucial role in modulating both BMP and FGF signaling along the developing myoseptum to coordinate the morphogenesis of trunk musculature, associated pigment cells, and lateral line neuromasts
	key role of SULF1 in regulating SHH-dependent neural cell diversity
	SULF1, SULF2 plays an important role in the development of the inner ear
	SULF1, SULF2 and EGFR are likely involved in the signalling pathway from chondroitin sulphate proteoglycans (CSPGs)that leads to inhibition of neurite outgrowth and may regulate structural plasticity and regeneration in the nervous system
	plays a key role in cell signaling involving in cell growth, differentiation, proliferation, and migration
	acts extracellularly to modify the structure of heparan sulfate chains to affect the bio-availability of WNT ligands
	SULF1/SULF2 enzymes regulate cell signalling that impacts the growth and differentiation of many tissues
	SULF1 and SULF2 play indispensable roles to maintain glomerular integrity and protective roles in diabetic nephropathy, probably by growth factor modulation
	acts as a regulator of sonic hedgehog (SHH) signaling during embryonic ventral spinal cord development

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein

BMP4 and BMP7 limit likely FGF10 action in the developing prostate at least in part by inducing SULF1

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

DEL8Q13

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in the majority of cancer cell lines examined, and forced expression of SULF1 decreases cell proliferation, migration, and invasion (Lai 2008) constitutional     --over   in degenerative intervertebral disc cells

Susceptibility

to recurrent miscarriage

Variant & Polymorphism

Candidate gene
Marker
Therapy target	targeting SULF1 or the interaction between SULF1 and the related sulfatase 2 will potentially be important in developing novel cancer therapies (Lai 2008)

ANIMAL & CELL MODELS