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Information on EC 3.10.1.1 - N-sulfoglucosamine sulfohydrolase
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3.10.1.1 N-sulfoglucosamine sulfohydrolaseSpecify your search results
Word Map
- 3.10.1.1
- mucopolysaccharidosis
- lysosomal
-
sanfilippo
-
mps-iiia
- naglu
-
n-sulfate
-
sulfate-derived
- heparinum
- medicine
- oestrone
- hgsnat
- sumf1
-
iduronate
-
sulfatases
-
ubiquitin-positive
- drug development
- pharmacology
- diagnostics
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
sulfamidase, sgsh, sulphamidase, sulphohydrolase, n-sulfoglucosamine sulfohydrolase, heparin sulfamidase, n-sulphoglucosamine, heparan-n-sulfatase, sulphamate sulphohydrolase, heparan-n-sulphatase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-desoxy-2-sulphamido-D-glucose sulphamidase
-
-
-
-
2-desoxy-D-glucoside-2-sulphamate sulphohydrolase
-
-
-
-
heparin sulfamidase
-
-
-
-
N-sulfoglucosamine sulfohydrolase
SGSH
sulfamidase
sulfoglucosamine sulfamidase
-
-
-
-
sulphamate sulphohydrolase
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-
-
-
sulphamidase
sulphamidase
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-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
N-sulfo-D-glucosamine + H2O = D-glucosamine + sulfate
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-
-
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N-sulfo-D-glucosamine + H2O = D-glucosamine + sulfate
catalytic reaction mechanism: the active-site formylglycine (FGly70), which is intrinsically reactive, undergoes hydration to form the resting state of the enzyme with a gem-diol group (step 1). Coordination of one of the hydroxyl groups of the gem-diol to a Ca2+ ion facilitates the development of a negative charge on the O atom as its proton is lost to a base. The negatively charged O atom nucleophilically attacks the sulfur centre of the N-linked sulfate group on the glucosamine substrate (step 2), resulting in a covalently bound enzyme-substrate complex with a pentavalent sulfur transition state. An acid (possibly His181) facilitates the cleavage of the S-N bond by protonating the bridging N atom to form an amine leaving group on the N-desulfated substrate, which diffuses away, leaving an O-sulfated enzyme (step 3). Finally, in a step that underlines the importance of the formylglycine residue, another base (His125) deprotonates the second hydroxyl group, resulting in a negatively charged O atom (step 4) that forms a double bond with the C atom as the C-O bond between it and the bridging O atom of the sulfate group breaks, eliminating the sulfate ion and regenerating the formylglycine residue (step 5)
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis
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hydrolysis of an N-linked sulfate group from the non-reducing terminal glucosaminide residues of heparan sulfate
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
N-sulfo-D-glucosamine sulfohydrolase
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CAS REGISTRY NUMBER
COMMENTARY
37289-41-1
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-deoxy-2-sulfamido-D-glucose + H2O
2-deoxy-2-amino-D-glucose + sulfate
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-
-
-
ir
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
O-(alpha-2-sulfamino-2-deoxy-D-glucopyranosyl)-(1-3)-L-idonic acid
O-(alpha-2-amino-2-deoxy-D-glucopyranosyl)-(1-3)-L-idonic acid + sulfate
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-
-
-
?
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
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-
-
?
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
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-
-
-
?
4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide + H2O
4-methylumbelliferyl alpha-D-glucosaminide + sulfate
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-
-
-
?
glucosamine 2,6-disulfate + H2O
D-glucosamine 6-sulfate + sulfate
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-
-
-
ir
glucosamine 2,6-disulfate + H2O
D-glucosamine 6-sulfate + sulfate
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no activity with purified enzyme
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-
?
additional information
?
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enzyme defiency leads to defective lysosomal degradation of the glycosaminoglycan heparan sulfate, mutations of the enzyme are responsible for mucopolysaccharidosis type IIIA, i.e. Sanfilippo A syndrome, onset and progression of the disease, overview
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?
additional information
?
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reduced activity of sulfamidase results in intracellular accumulation of heparan sulfate, with the brain the primary site of pathology, e.g. in mucopolysaccharidosis type IIIA, or Sanfilippo syndrome, an inherited neurodegenerative lysosomal storage disorder, progressive loss of learned skills, sleep disturbance and behavioural problems occur. A potential therapy method is the repeated injection of the enzyme into cerebrospinal fluid via cisterna magna leading to a reduction of the number of lysosomal storage inclusions in the brain with a significant decrease in the immunohistochemical staining of a lysosomal membrane marker, and to reduced numbers of activated isolectin-B4-positive microglia and GFAP-positive astrocytes in some brain regions, phenotype, mouse model, overview
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-
?
additional information
?
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-
repeated human enzyme injection into murine cerebrospinal fluid via cisterna magna leads to a reduction of heparan sulfate-derived monosulfated disaccharide in the brain and spinal cord, reduced lysosomal vesicle formation in various cell types, reduced axonal spheroids, and improved behaviour of treated mice, mouse model, overview
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-
?
additional information
?
-
the enzymatic activity of the enzyme is measured in a two-step reaction: 4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide is desulfated by the enzyme to become a substrate for alpha-glucosidase, which converts 4-methylumbelliferyl-alpha-D-N-sulfoglucosamine to methylumbelliferone, which is a fluorescent compound
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?
additional information
?
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congenital deficiency of sulfamidase leads to mucopolysaccharidosis type IIIA or Sanfilippo syndrome, a lysosomal storage disorder, with consequent accumulation of partially degraded heparan sulfate in lysosomes and the central nervous system as the predominant site of tissue damage, overview
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-
?
additional information
?
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the enzymatic activity of the enzyme is measured in a two-step reaction: 4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide is desulfated by the enzyme to become a substrate for alpha-glucosidase from Bacillus stearothermophilus, which converts 4-methylumbelliferyl-alpha-D-N-sulfoglucosamine to methylumbelliferone, which is a fluorescent compound. Method evaluation
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-
?
additional information
?
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the enzymatic activity of the enzyme is measured in a two-step reaction: 4-methylumbelliferyl-alpha-D-N-sulfoglucosaminide is desulfated by the enzyme to become a substrate for alpha-glucosidase from Bacillus stearothermophilus, which converts 4-methylumbelliferyl-alpha-D-N-sulfoglucosamine to methylumbelliferone, which is a fluorescent compound. Method evaluation
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?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
enzyme defiency leads to defective lysosomal degradation of the glycosaminoglycan heparan sulfate, mutations of the enzyme are responsible for mucopolysaccharidosis type IIIA, i.e. Sanfilippo A syndrome, onset and progression of the disease, overview
-
-
?
additional information
?
-
-
reduced activity of sulfamidase results in intracellular accumulation of heparan sulfate, with the brain the primary site of pathology, e.g. in mucopolysaccharidosis type IIIA, or Sanfilippo syndrome, an inherited neurodegenerative lysosomal storage disorder, progressive loss of learned skills, sleep disturbance and behavioural problems occur. A potential therapy method is the repeated injection of the enzyme into cerebrospinal fluid via cisterna magna leading to a reduction of the number of lysosomal storage inclusions in the brain with a significant decrease in the immunohistochemical staining of a lysosomal membrane marker, and to reduced numbers of activated isolectin-B4-positive microglia and GFAP-positive astrocytes in some brain regions, phenotype, mouse model, overview
-
-
?
additional information
?
-
-
repeated human enzyme injection into murine cerebrospinal fluid via cisterna magna leads to a reduction of heparan sulfate-derived monosulfated disaccharide in the brain and spinal cord, reduced lysosomal vesicle formation in various cell types, reduced axonal spheroids, and improved behaviour of treated mice, mouse model, overview
-
-
?
additional information
?
-
-
congenital deficiency of sulfamidase leads to mucopolysaccharidosis type IIIA or Sanfilippo syndrome, a lysosomal storage disorder, with consequent accumulation of partially degraded heparan sulfate in lysosomes and the central nervous system as the predominant site of tissue damage, overview
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SUMF1
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i.e. sulfatase modifying factor 1, exhibits an enhancing effect on sulfatase activity when coexpressed with sulfatases, overview
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0107
tetrasaccharides
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substrates deriving from heparan sulfate, unamplified recombinant enzyme
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0.01225
tetrasaccharides
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substrates deriving from heparan sulfate, gene-amplified recombinant enzyme
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.7
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 6
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
an adult Sanfilippo type A patient with homozygous mutation R206P in the sulfamidase gene shows a mild clinical phenotype characterized essentially by a moderate nonevolving metal retardation, polymorphism R456H is also found
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brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
sulphamidase activity is undetectable in liver, kidney, brain, and spleen from untreated mucopolysaccharidosis type IIIA mice, whereas levels of sulphamidase activity in the liver, kidney, and spleen of mucopolysaccharidosis type IIIA mice treated with the sulphamidase vector averaged 68%, 5%, and 186% of normal activity, respectively
brenda
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newborn and adult mucopolysaccharidosis type IIIA brain cells have approximately 5.7% of the sulfamidase activity present in primary neural cells cultured from unaffected newborn and adult mice
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
despite the low sequence identity between the unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. A highly conserved lysine in O-sulfatases is replaced in the N-sulfoglucosamine sulfohydrolase by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate
malfunction
additional information
the enzyme shows low structural flexibility. The consensus active site lies in domain 1 in a narrow pocket at the bottom of a surface cleft and close to the end of the first beta-strand, active site structure, overview. Proposed interactions between the terminal N-sulfoglucosamine residue of the substrate with the enzyme in the active site
malfunction
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mutation S298P leads to 97.7% reduced enzyme activity and proteasomal degradation of the mutant enzyme causing the mild clinical phenotype of Sanfilippo A syndrome or Mucopolysaccharidosis type IIIA, a fatal inherited lysosomal storage disease accompanied by progressive neurologic degeneration, overview. PPatients are objects for early sulfamidase replacement therapy or treatment with selective pharmacological chaperones. Treatments with several pharmacological chaperones, such as nojirimycin, deoxygalactonojirimycin, deoxymannojirimycin, N-butyldeoxynojirimycin, phenylbutyric acid, at various concentrations do not increase the sulfamidase activity in S298P mutant expressing cells
malfunction
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deficient N-sulfoglucosamine sulfohydrolase enzyme activity causes mucopolysaccharidosis (MPS) type IIIA
malfunction
-
deficient N-sulfoglucosamine sulfohydrolase enzyme activity causes mucopolysaccharidosis (MPS) type IIIA
malfunction
mucopolysaccharidoses are a group of recessively inherited lysosomal storage disorders caused by a deficiency of enzymes involved in the metabolic breakdown of glycosaminoglycans. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase, more than 100 mutations in the SGSH gene are found to reduce or eliminate its enzymatic activity. The Sanfilippo syndrome signs of neurodegeneration are the initial symptoms and comprise of hyperactivity, developmental stagnation and psychomotor regression
malfunction
mucopolysaccharidosis IIIA (MPS IIIA, Sanfilippo syndrome type A) is a lysosomal storage disorder caused by a deficiency of the enzyme heparan-N-sulfatase (EC 3.10.1.1), leading to accumulation of the glycosaminoglycan, heparan sulfate, in the lysosomes
malfunction
mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A) is a neurodegenerative lysosomal storage disorder caused by the deficiency of sulphamidase enzyme (SGSH) leading to accumulation of heparan sulfate
malfunction
mucopolysaccharidosis Type IIIA (MPSIIIA, Sanfilippo A syndrome), is an inherited neurodegenerative disease caused by mutations in the lysosomal enzyme, N-sulfoglucosamine sulfohydrolase. Mutations in the SGSH enzyme, the only mammalian heparan N-sulfatase, cause accumulation of lysosomal inclusion bodies in brain cells comprising heparan sulfate glycosaminoglycans. Systemic administration of MPSIIIA mice with the cTfRMAb-SGSH (IgG-SGSH fusion protein, where the IgG domain is a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR)) fusion protein causes a 70% reduction in brain heparan sulfate, the pathologic glycosaminoglycan of the central nervous system in MPSIIIA
malfunction
Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA) is a lysosomal disorder wherein deficient heparan-N-sulfatase (HNS) activity results in the accumulation of heparan sulfate in the central nervous system and is associated with progressive neurodegeneration in early childhood
malfunction
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deficient N-sulfoglucosamine sulfohydrolase enzyme activity causes mucopolysaccharidosis (MPS) type IIIA
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SPHM_HUMAN
502
0
56695
Swiss-Prot
Secretory Pathway (Reliability: 1)
A0A142B9N1_9GAMM
506
0
57589
TrEMBL
-
A0A8B6HQQ5_MYTGA
510
0
58733
TrEMBL
Secretory Pathway (Reliability: 1)
F0SKD6_RUBBR
Rubinisphaera brasiliensis (strain ATCC 49424 / DSM 5305 / JCM 21570 / IAM 15109 / NBRC 103401 / IFAM 1448)
485
0
54504
TrEMBL
-
F0SNG8_RUBBR
Rubinisphaera brasiliensis (strain ATCC 49424 / DSM 5305 / JCM 21570 / IAM 15109 / NBRC 103401 / IFAM 1448)
474
0
53234
TrEMBL
-
G0L5L8_ZOBGA
Zobellia galactanivorans (strain DSM 12802 / CCUG 47099 / CIP 106680 / NCIMB 13871 / Dsij)
499
0
56649
TrEMBL
-
B0BML2_XENTR
503
0
57856
TrEMBL
Secretory Pathway (Reliability: 1)
F8DAA6_HALXS
Halopiger xanaduensis (strain DSM 18323 / JCM 14033 / SH-6)
458
0
50948
TrEMBL
-
Q9VE24_DROME
524
0
59906
TrEMBL
Secretory Pathway (Reliability: 1)
A0A6J8CCS4_MYTCO
210
0
25256
TrEMBL
other Location (Reliability: 2)
G0L5M7_ZOBGA
Zobellia galactanivorans (strain DSM 12802 / CCUG 47099 / CIP 106680 / NCIMB 13871 / Dsij)
514
0
58461
TrEMBL
-
A0A1J0LJG7_9FLAO
734
0
82485
TrEMBL
-
Q9GJU7_CANLF
507
1
57180
TrEMBL
Secretory Pathway (Reliability: 4)
Q9JHK6_MOUSE
502
0
56839
TrEMBL
Secretory Pathway (Reliability: 1)
G0LBQ5_ZOBGA
Zobellia galactanivorans (strain DSM 12802 / CCUG 47099 / CIP 106680 / NCIMB 13871 / Dsij)
525
0
60428
TrEMBL
-
B7PQU3_IXOSC
107
0
11790
TrEMBL
Secretory Pathway (Reliability: 4)
A0A812DGJ5_SEPPH
396
0
44302
TrEMBL
Secretory Pathway (Reliability: 2)
F0SJR4_RUBBR
Rubinisphaera brasiliensis (strain ATCC 49424 / DSM 5305 / JCM 21570 / IAM 15109 / NBRC 103401 / IFAM 1448)
494
0
55894
TrEMBL
-
A0A7R8CTA9_LEPSM
513
0
59778
TrEMBL
other Location (Reliability: 1)
A0A7U3ZL74_RUNSL
Runella slithyformis (strain ATCC 29530 / DSM 19594 / LMG 11500 / NCIMB 11436 / LSU 4)
470
0
53124
TrEMBL
-
F0SFJ5_RUBBR
Rubinisphaera brasiliensis (strain ATCC 49424 / DSM 5305 / JCM 21570 / IAM 15109 / NBRC 103401 / IFAM 1448)
532
1
59065
TrEMBL
-
B7PQU4_IXOSC
280
0
31378
TrEMBL
other Location (Reliability: 3)
B5X3L3_SALSA
512
0
57617
TrEMBL
Secretory Pathway (Reliability: 1)
B7PZX1_IXOSC
136
0
15409
TrEMBL
Mitochondrion (Reliability: 5)
A0A6J8CD70_MYTCO
312
0
34755
TrEMBL
Secretory Pathway (Reliability: 1)
G0L8N6_ZOBGA
Zobellia galactanivorans (strain DSM 12802 / CCUG 47099 / CIP 106680 / NCIMB 13871 / Dsij)
622
0
71253
TrEMBL
-
G0LA74_ZOBGA
Zobellia galactanivorans (strain DSM 12802 / CCUG 47099 / CIP 106680 / NCIMB 13871 / Dsij)
534
0
60888
TrEMBL
-
F4L8B6_HALH1
Haliscomenobacter hydrossis (strain ATCC 27775 / DSM 1100 / LMG 10767 / O)
501
1
56717
TrEMBL
-