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Protein

Sialic acid-binding Ig-like lectin 8

Gene

SIGLEC8

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

Functioni

Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3-linked sialic acid. Also binds to alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei125 – 1251Sialic acidBy similarity

GO - Molecular functioni

  • carbohydrate binding Source: ProtInc
  • transmembrane signaling receptor activity Source: ProtInc

GO - Biological processi

  • cell adhesion Source: UniProtKB-KW
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Lectin

Protein family/group databases

MEROPSiI43.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Sialic acid-binding Ig-like lectin 8
Short name:
Siglec-8
Alternative name(s):
Sialoadhesin family member 2
Short name:
SAF-2
Gene namesi
Name:SIGLEC8
Synonyms:SAF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:10877. SIGLEC8.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini17 – 363347ExtracellularSequence AnalysisAdd
BLAST
Transmembranei364 – 38421HelicalSequence AnalysisAdd
BLAST
Topological domaini385 – 499115CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35778.

Polymorphism and mutation databases

BioMutaiSIGLEC8.
DMDMi25009268.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1616Sequence AnalysisAdd
BLAST
Chaini17 – 499483Sialic acid-binding Ig-like lectin 8PRO_0000014948Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi42 ↔ 181PROSITE-ProRule annotation
Disulfide bondi47 ↔ 107PROSITE-ProRule annotation
Glycosylationi172 – 1721N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi175 ↔ 224PROSITE-ProRule annotation
Glycosylationi249 – 2491N-linked (GlcNAc...)Sequence Analysis
Glycosylationi267 – 2671N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi283 ↔ 328PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9NYZ4.
PRIDEiQ9NYZ4.

PTM databases

PhosphoSiteiQ9NYZ4.

Expressioni

Tissue specificityi

Expressed specifically on eosinophils.

Gene expression databases

BgeeiQ9NYZ4.
CleanExiHS_SIGLEC8.
ExpressionAtlasiQ9NYZ4. baseline and differential.
GenevisibleiQ9NYZ4. HS.

Organism-specific databases

HPAiHPA012556.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TFF1P041553EBI-4314991,EBI-743871

Protein-protein interaction databases

BioGridi118057. 1 interaction.
IntActiQ9NYZ4. 1 interaction.
STRINGi9606.ENSP00000321077.

Structurei

3D structure databases

ProteinModelPortaliQ9NYZ4.
SMRiQ9NYZ4. Positions 27-244, 271-346.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini40 – 12384Ig-like V-typeAdd
BLAST
Domaini157 – 24084Ig-like C2-type 1Add
BLAST
Domaini246 – 34499Ig-like C2-type 2Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi445 – 4506ITIM motif
Motifi468 – 4736SLAM-like motif

Domaini

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG147919.
GeneTreeiENSGT00760000119139.
HOGENOMiHOG000236324.
HOVERGENiHBG036161.
InParanoidiQ9NYZ4.
KOiK06748.
OMAiWFRAGDR.
PhylomeDBiQ9NYZ4.
TreeFamiTF332441.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
IPR013151. Immunoglobulin.
[Graphical view]
PfamiPF00047. ig. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NYZ4-1) [UniParc]FASTAAdd to basket

Also known as: Long

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
MLLLLLLLPL LWGTKGMEGD RQYGDGYLLQ VQELVTVQEG LCVHVPCSFS
60 70 80 90 100
YPQDGWTDSD PVHGYWFRAG DRPYQDAPVA TNNPDREVQA ETQGRFQLLG
110 120 130 140 150
DIWSNDCSLS IRDARKRDKG SYFFRLERGS MKWSYKSQLN YKTKQLSVFV
160 170 180 190 200
TALTHRPDIL ILGTLESGHS RNLTCSVPWA CKQGTPPMIS WIGASVSSPG
210 220 230 240 250
PTTARSSVLT LTPKPQDHGT SLTCQVTLPG TGVTTTSTVR LDVSYPPWNL
260 270 280 290 300
TMTVFQGDAT ASTALGNGSS LSVLEGQSLR LVCAVNSNPP ARLSWTRGSL
310 320 330 340 350
TLCPSRSSNP GLLELPRVHV RDEGEFTCRA QNAQGSQHIS LSLSLQNEGT
360 370 380 390 400
GTSRPVSQVT LAAVGGAGAT ALAFLSFCII FIIVRSCRKK SARPAAGVGD
410 420 430 440 450
TGMEDAKAIR GSASQGPLTE SWKDGNPLKK PPPAVAPSSG EEGELHYATL
460 470 480 490
SFHKVKPQDP QGQEATDSEY SEIKIHKRET AETQACLRNH NPSSKEVRG
Length:499
Mass (Da):54,042
Last modified:November 8, 2002 - v2
Checksum:i086EFF989B74123C
GO
Isoform 2 (identifier: Q9NYZ4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     152-245: ALTHRPDILI...TSTVRLDVSY → D

Show »
Length:406
Mass (Da):44,360
Checksum:iB23D94FA1DB4741A
GO
Isoform 3 (identifier: Q9NYZ4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     416-499: GPLTESWKDG...HNPSSKEVRG → VSDVGFSTPSIQPGHL

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:431
Mass (Da):46,434
Checksum:i49B91B84CE67B118
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti170 – 1701S → P.1 Publication
Corresponds to variant rs10409962 [ dbSNP | Ensembl ].
VAR_021487
Natural varianti282 – 2821V → L Found in a renal cell carcinoma sample; somatic mutation. 1 Publication
VAR_064751
Natural varianti388 – 3881R → G.
Corresponds to variant rs3829659 [ dbSNP | Ensembl ].
VAR_049930

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei152 – 24594ALTHR…LDVSY → D in isoform 2. 1 PublicationVSP_002559Add
BLAST
Alternative sequencei416 – 49984GPLTE…KEVRG → VSDVGFSTPSIQPGHL in isoform 3. 2 PublicationsVSP_002560Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF287892 Genomic DNA. Translation: AAG00573.1.
AF223403 mRNA. Translation: AAF34702.1.
AF195092 mRNA. Translation: AAF27622.1.
AF310234 mRNA. Translation: AAK55140.1.
BC053319 mRNA. Translation: AAH53319.1.
CCDSiCCDS33086.1. [Q9NYZ4-1]
RefSeqiNP_055257.2. NM_014442.2. [Q9NYZ4-1]
XP_011525037.1. XM_011526735.1. [Q9NYZ4-2]
UniGeneiHs.447899.

Genome annotation databases

EnsembliENST00000321424; ENSP00000321077; ENSG00000105366.
ENST00000340550; ENSP00000339448; ENSG00000105366. [Q9NYZ4-2]
GeneIDi27181.
KEGGihsa:27181.
UCSCiuc002pwt.3. human. [Q9NYZ4-1]
uc010eox.2. human. [Q9NYZ4-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - Glycan Binding

Siglec-8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF287892 Genomic DNA. Translation: AAG00573.1.
AF223403 mRNA. Translation: AAF34702.1.
AF195092 mRNA. Translation: AAF27622.1.
AF310234 mRNA. Translation: AAK55140.1.
BC053319 mRNA. Translation: AAH53319.1.
CCDSiCCDS33086.1. [Q9NYZ4-1]
RefSeqiNP_055257.2. NM_014442.2. [Q9NYZ4-1]
XP_011525037.1. XM_011526735.1. [Q9NYZ4-2]
UniGeneiHs.447899.

3D structure databases

ProteinModelPortaliQ9NYZ4.
SMRiQ9NYZ4. Positions 27-244, 271-346.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118057. 1 interaction.
IntActiQ9NYZ4. 1 interaction.
STRINGi9606.ENSP00000321077.

Protein family/group databases

MEROPSiI43.001.

PTM databases

PhosphoSiteiQ9NYZ4.

Polymorphism and mutation databases

BioMutaiSIGLEC8.
DMDMi25009268.

Proteomic databases

PaxDbiQ9NYZ4.
PRIDEiQ9NYZ4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000321424; ENSP00000321077; ENSG00000105366.
ENST00000340550; ENSP00000339448; ENSG00000105366. [Q9NYZ4-2]
GeneIDi27181.
KEGGihsa:27181.
UCSCiuc002pwt.3. human. [Q9NYZ4-1]
uc010eox.2. human. [Q9NYZ4-2]

Organism-specific databases

CTDi27181.
GeneCardsiGC19M051956.
H-InvDBHIX0027458.
HGNCiHGNC:10877. SIGLEC8.
HPAiHPA012556.
MIMi605639. gene.
neXtProtiNX_Q9NYZ4.
PharmGKBiPA35778.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG147919.
GeneTreeiENSGT00760000119139.
HOGENOMiHOG000236324.
HOVERGENiHBG036161.
InParanoidiQ9NYZ4.
KOiK06748.
OMAiWFRAGDR.
PhylomeDBiQ9NYZ4.
TreeFamiTF332441.

Miscellaneous databases

GeneWikiiSIGLEC8.
GenomeRNAii27181.
NextBioi50012.
PROiQ9NYZ4.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NYZ4.
CleanExiHS_SIGLEC8.
ExpressionAtlasiQ9NYZ4. baseline and differential.
GenevisibleiQ9NYZ4. HS.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
IPR013151. Immunoglobulin.
[Graphical view]
PfamiPF00047. ig. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular characterization of a siglec8 variant containing cytoplasmic tyrosine-based motifs, and mapping of the siglec8 gene."
    Foussias G., Yousef G.M., Diamandis E.P.
    Biochem. Biophys. Res. Commun. 278:775-781(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
  3. "Siglec-8. A novel eosinophil-specific member of the immunoglobulin superfamily."
    Floyd H., Ni J., Cornish A.L., Zeng Z., Liu D., Carter K.C., Steel J., Crocker P.R.
    J. Biol. Chem. 275:861-866(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
    Tissue: Eosinophil.
  4. Floyd H., Zhang J.Q., Crocker P.R.
    Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT PRO-170.
    Tissue: Spleen.
  6. Cited for: VARIANT LEU-282.

Entry informationi

Entry nameiSIGL8_HUMAN
AccessioniPrimary (citable) accession number: Q9NYZ4
Secondary accession number(s): Q7Z728
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: November 8, 2002
Last modified: July 22, 2015
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 cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.