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Protein

Sialin

Gene

SLC17A5

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

Functioni

Transports glucuronic acid and free sialic acid out of the lysosome after it is cleaved from sialoglycoconjugates undergoing degradation, this is required for normal CNS myelination. Mediates aspartate and glutamate membrane potential-dependent uptake into synaptic vesicles and synaptic-like microvesicles. Also functions as an electrogenic 2NO3-/H+ cotransporter in the plasma membrane of salivary gland acinar cells, mediating the physiological nitrate efflux, 25% of the circulating nitrate ions is typically removed and secreted in saliva.5 Publications

GO - Molecular functioni

  • sialic acid:proton symporter activity Source: Reactome
  • sialic acid transmembrane transporter activity Source: MGI
  • sugar:proton symporter activity Source: ProtInc

GO - Biological processi

  • amino acid transport Source: UniProtKB-KW
  • anion transport Source: ProtInc
  • ion transport Source: Reactome
  • sialic acid transport Source: MGI
Complete GO annotation...

Keywords - Biological processi

Amino-acid transport, Symport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-4085001. Sialic acid metabolism.
R-HSA-428643. Organic anion transporters.

Protein family/group databases

TCDBi2.A.1.14.10. the major facilitator superfamily (mfs).

Names & Taxonomyi

Protein namesi
Recommended name:
Sialin
Alternative name(s):
H(+)/nitrate cotransporter
H(+)/sialic acid cotransporter
Short name:
AST
Membrane glycoprotein HP59
Solute carrier family 17 member 5
Vesicular H(+)/Aspartate-glutamate cotransporter
Gene namesi
Name:SLC17A5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:10933. SLC17A5.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 41CytoplasmicSequence analysisAdd BLAST41
Transmembranei42 – 62HelicalSequence analysisAdd BLAST21
Topological domaini63 – 109LumenalSequence analysisAdd BLAST47
Transmembranei110 – 130HelicalSequence analysisAdd BLAST21
Topological domaini131 – 136CytoplasmicSequence analysis6
Transmembranei137 – 157HelicalSequence analysisAdd BLAST21
Topological domaini158LumenalSequence analysis1
Transmembranei159 – 179HelicalSequence analysisAdd BLAST21
Topological domaini180 – 200CytoplasmicSequence analysisAdd BLAST21
Transmembranei201 – 221HelicalSequence analysisAdd BLAST21
Topological domaini222 – 227LumenalSequence analysis6
Transmembranei228 – 248HelicalSequence analysisAdd BLAST21
Topological domaini249 – 279CytoplasmicSequence analysisAdd BLAST31
Transmembranei280 – 300HelicalSequence analysisAdd BLAST21
Topological domaini301 – 328LumenalSequence analysisAdd BLAST28
Transmembranei329 – 349HelicalSequence analysisAdd BLAST21
Topological domaini350 – 365CytoplasmicSequence analysisAdd BLAST16
Transmembranei366 – 386HelicalSequence analysisAdd BLAST21
Topological domaini387 – 391LumenalSequence analysis5
Transmembranei392 – 412HelicalSequence analysisAdd BLAST21
Topological domaini413 – 423CytoplasmicSequence analysisAdd BLAST11
Transmembranei424 – 444HelicalSequence analysisAdd BLAST21
Topological domaini445 – 457LumenalSequence analysisAdd BLAST13
Transmembranei458 – 478HelicalSequence analysisAdd BLAST21
Topological domaini479 – 495CytoplasmicSequence analysisAdd BLAST17

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: HPA
  • integral component of plasma membrane Source: ProtInc
  • lysosomal membrane Source: UniProtKB
  • membrane Source: ProtInc
  • plasma membrane Source: HPA
  • synaptic vesicle membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasmic vesicle, Lysosome, Membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Salla disease (SD)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSialic acid storage disease (SASD). SASDs are autosomal recessive neurodegenerative disorders characterized by hypotonia, cerebellar ataxia and mental retardation. They are caused by a defect in the metabolism of sialic acid which results in increased urinary excretion of unconjugated sialic acid, specifically N-acetylneuraminic acid. Enlarged lysosomes are seen on electron microscopic studies. Clinical symptoms of SD present usually at age less than 1 year and progression is slow.
See also OMIM:604369
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01868439R → C in SD; completely devoid of aspartate and glutamate transport activity, but retains appreciable H(+)/sialic acid cotransport activity, frequent mutation in Finland. 4 PublicationsCorresponds to variant rs80338794dbSNPEnsembl.1
Natural variantiVAR_018685136K → E in SD. 1 PublicationCorresponds to variant rs80338795dbSNPEnsembl.1
Natural variantiVAR_018686183H → R in ISSD. 2 PublicationsCorresponds to variant rs119491109dbSNPEnsembl.1
Natural variantiVAR_018687268 – 272Missing in ISSD. 2 Publications5
Natural variantiVAR_018688334P → R in ISSD. 2 PublicationsCorresponds to variant rs119491110dbSNPEnsembl.1
Natural variantiVAR_018689371G → V in ISSD. 1 Publication1
Infantile sialic acid storage disorder (ISSD)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSevere form of sialic acid storage disease. Affected newborns exhibit visceromegaly, coarse features and failure to thrive immediately after birth. These patients have a shortened life span, usually less than 2 years.
See also OMIM:269920
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_018686183H → R in ISSD. 2 PublicationsCorresponds to variant rs119491109dbSNPEnsembl.1
Natural variantiVAR_018687268 – 272Missing in ISSD. 2 Publications5
Natural variantiVAR_018688334P → R in ISSD. 2 PublicationsCorresponds to variant rs119491110dbSNPEnsembl.1
Natural variantiVAR_018689371G → V in ISSD. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi22 – 23LL → GG: Targeted to plasma membrane; sialic acid uptake strongly activated at acidic pH. 1 Publication2
Mutagenesisi179F → C: 15 fold increase in affinity for glucuronic acid. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi26503.
MalaCardsiSLC17A5.
MIMi269920. phenotype.
604369. phenotype.
OpenTargetsiENSG00000119899.
Orphaneti309324. Free sialic acid storage disease, infantile form.
309331. Intermediate severe Salla disease.
309334. Salla disease.
PharmGKBiPA35824.

Polymorphism and mutation databases

BioMutaiSLC17A5.
DMDMi48428688.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002209471 – 495SialinAdd BLAST495

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3PhosphoserineCombined sources1
Glycosylationi71N-linked (GlcNAc...)Sequence analysis1
Glycosylationi77N-linked (GlcNAc...)Sequence analysis1
Glycosylationi95N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9NRA2.
MaxQBiQ9NRA2.
PaxDbiQ9NRA2.
PeptideAtlasiQ9NRA2.
PRIDEiQ9NRA2.

PTM databases

iPTMnetiQ9NRA2.
PhosphoSitePlusiQ9NRA2.
SwissPalmiQ9NRA2.

Expressioni

Tissue specificityi

Found in fetal lung and small intestine, and at lower level in fetal skin and muscle. In the adult, detected in placenta, kidney and pancreas. Abundant in the endothelial cells of tumors from ovary, colon, breast and lung, but is not detected in endothelial cells from the corresponding normal tissues.2 Publications

Gene expression databases

BgeeiENSG00000119899.
CleanExiHS_SLC17A5.
GenevisibleiQ9NRA2. HS.

Organism-specific databases

HPAiHPA044479.

Interactioni

Protein-protein interaction databases

BioGridi117710. 3 interactors.
IntActiQ9NRA2. 1 interactor.
STRINGi9606.ENSP00000348019.

Structurei

3D structure databases

ProteinModelPortaliQ9NRA2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi22 – 23Dileucine internalization motif2

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2532. Eukaryota.
ENOG410XPWC. LUCA.
GeneTreeiENSGT00760000119079.
HOGENOMiHOG000230811.
HOVERGENiHBG008834.
InParanoidiQ9NRA2.
KOiK12301.
OMAiRSSPNED.
OrthoDBiEOG091G06DG.
PhylomeDBiQ9NRA2.
TreeFamiTF313535.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR011701. MFS.
IPR020846. MFS_dom.
[Graphical view]
PfamiPF07690. MFS_1. 1 hit.
[Graphical view]
SUPFAMiSSF103473. SSF103473. 2 hits.
PROSITEiPS50850. MFS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NRA2-1) [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

        10         20         30         40         50
MRSPVRDLAR NDGEESTDRT PLLPGAPRAE AAPVCCSARY NLAILAFFGF
60 70 80 90 100
FIVYALRVNL SVALVDMVDS NTTLEDNRTS KACPEHSAPI KVHHNQTGKK
110 120 130 140 150
YQWDAETQGW ILGSFFYGYI ITQIPGGYVA SKIGGKMLLG FGILGTAVLT
160 170 180 190 200
LFTPIAADLG VGPLIVLRAL EGLGEGVTFP AMHAMWSSWA PPLERSKLLS
210 220 230 240 250
ISYAGAQLGT VISLPLSGII CYYMNWTYVF YFFGTIGIFW FLLWIWLVSD
260 270 280 290 300
TPQKHKRISH YEKEYILSSL RNQLSSQKSV PWVPILKSLP LWAIVVAHFS
310 320 330 340 350
YNWTFYTLLT LLPTYMKEIL RFNVQENGFL SSLPYLGSWL CMILSGQAAD
360 370 380 390 400
NLRAKWNFST LCVRRIFSLI GMIGPAVFLV AAGFIGCDYS LAVAFLTIST
410 420 430 440 450
TLGGFCSSGF SINHLDIAPS YAGILLGITN TFATIPGMVG PVIAKSLTPD
460 470 480 490
NTVGEWQTVF YIAAAINVFG AIFFTLFAKG EVQNWALNDH HGHRH
Length:495
Mass (Da):54,640
Last modified:June 7, 2004 - v2
Checksum:i5C6C154B3E93A19E
GO
Isoform 2 (identifier: Q9NRA2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     274-276: LSS → AGV
     278-495: Missing.

Show »
Length:277
Mass (Da):30,667
Checksum:i1BF03EA560AB80DB
GO

Sequence cautioni

The sequence AAF97769 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01868439R → C in SD; completely devoid of aspartate and glutamate transport activity, but retains appreciable H(+)/sialic acid cotransport activity, frequent mutation in Finland. 4 PublicationsCorresponds to variant rs80338794dbSNPEnsembl.1
Natural variantiVAR_018685136K → E in SD. 1 PublicationCorresponds to variant rs80338795dbSNPEnsembl.1
Natural variantiVAR_018686183H → R in ISSD. 2 PublicationsCorresponds to variant rs119491109dbSNPEnsembl.1
Natural variantiVAR_018687268 – 272Missing in ISSD. 2 Publications5
Natural variantiVAR_034746296V → I.Corresponds to variant rs16883930dbSNPEnsembl.1
Natural variantiVAR_018688334P → R in ISSD. 2 PublicationsCorresponds to variant rs119491110dbSNPEnsembl.1
Natural variantiVAR_018689371G → V in ISSD. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010482274 – 276LSS → AGV in isoform 2. 2 Publications3
Alternative sequenceiVSP_010483278 – 495Missing in isoform 2. 2 PublicationsAdd BLAST218

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF244577 mRNA. Translation: AAF97769.1. Different initiation.
AJ387747 mRNA. Translation: CAB62540.1.
AK075320 mRNA. Translation: BAC11546.1.
AL590428, AL121972 Genomic DNA. Translation: CAI15635.1.
AL121972, AL590428 Genomic DNA. Translation: CAI20417.1.
BC020961 mRNA. Translation: AAH20961.1.
CCDSiCCDS4981.1. [Q9NRA2-1]
RefSeqiNP_036566.1. NM_012434.4. [Q9NRA2-1]
UniGeneiHs.597422.

Genome annotation databases

EnsembliENST00000355773; ENSP00000348019; ENSG00000119899. [Q9NRA2-1]
GeneIDi26503.
KEGGihsa:26503.
UCSCiuc003phn.5. human. [Q9NRA2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF244577 mRNA. Translation: AAF97769.1. Different initiation.
AJ387747 mRNA. Translation: CAB62540.1.
AK075320 mRNA. Translation: BAC11546.1.
AL590428, AL121972 Genomic DNA. Translation: CAI15635.1.
AL121972, AL590428 Genomic DNA. Translation: CAI20417.1.
BC020961 mRNA. Translation: AAH20961.1.
CCDSiCCDS4981.1. [Q9NRA2-1]
RefSeqiNP_036566.1. NM_012434.4. [Q9NRA2-1]
UniGeneiHs.597422.

3D structure databases

ProteinModelPortaliQ9NRA2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117710. 3 interactors.
IntActiQ9NRA2. 1 interactor.
STRINGi9606.ENSP00000348019.

Protein family/group databases

TCDBi2.A.1.14.10. the major facilitator superfamily (mfs).

PTM databases

iPTMnetiQ9NRA2.
PhosphoSitePlusiQ9NRA2.
SwissPalmiQ9NRA2.

Polymorphism and mutation databases

BioMutaiSLC17A5.
DMDMi48428688.

Proteomic databases

EPDiQ9NRA2.
MaxQBiQ9NRA2.
PaxDbiQ9NRA2.
PeptideAtlasiQ9NRA2.
PRIDEiQ9NRA2.

Protocols and materials databases

DNASUi26503.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000355773; ENSP00000348019; ENSG00000119899. [Q9NRA2-1]
GeneIDi26503.
KEGGihsa:26503.
UCSCiuc003phn.5. human. [Q9NRA2-1]

Organism-specific databases

CTDi26503.
DisGeNETi26503.
GeneCardsiSLC17A5.
GeneReviewsiSLC17A5.
HGNCiHGNC:10933. SLC17A5.
HPAiHPA044479.
MalaCardsiSLC17A5.
MIMi269920. phenotype.
604322. gene.
604369. phenotype.
neXtProtiNX_Q9NRA2.
OpenTargetsiENSG00000119899.
Orphaneti309324. Free sialic acid storage disease, infantile form.
309331. Intermediate severe Salla disease.
309334. Salla disease.
PharmGKBiPA35824.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2532. Eukaryota.
ENOG410XPWC. LUCA.
GeneTreeiENSGT00760000119079.
HOGENOMiHOG000230811.
HOVERGENiHBG008834.
InParanoidiQ9NRA2.
KOiK12301.
OMAiRSSPNED.
OrthoDBiEOG091G06DG.
PhylomeDBiQ9NRA2.
TreeFamiTF313535.

Enzyme and pathway databases

ReactomeiR-HSA-4085001. Sialic acid metabolism.
R-HSA-428643. Organic anion transporters.

Miscellaneous databases

ChiTaRSiSLC17A5. human.
GeneWikiiHP59.
SLC17A5.
GenomeRNAii26503.
PROiQ9NRA2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119899.
CleanExiHS_SLC17A5.
GenevisibleiQ9NRA2. HS.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR011701. MFS.
IPR020846. MFS_dom.
[Graphical view]
PfamiPF07690. MFS_1. 1 hit.
[Graphical view]
SUPFAMiSSF103473. SSF103473. 2 hits.
PROSITEiPS50850. MFS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS17A5_HUMAN
AccessioniPrimary (citable) accession number: Q9NRA2
Secondary accession number(s): Q5SZ76, Q8NBR5, Q9UGH0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: November 30, 2016
This is version 134 of the entry and version 2 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 6
    Human chromosome 6: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.