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Q9NYZ4 (SIGL8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sialic acid-binding Ig-like lectin 8

Short name=Siglec-8
Alternative name(s):
Sialoadhesin family member 2
Short name=SAF-2
Gene names
Name:SIGLEC8
Synonyms:SAF2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length499 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Expressed specifically on eosinophils.

Domain

Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.

Sequence similarities

Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TFF1P041553EBI-4314991,EBI-743871

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NYZ4-1)

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.
Isoform 2 (identifier: Q9NYZ4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     152-245: ALTHRPDILI...TSTVRLDVSY → D
Isoform 3 (identifier: Q9NYZ4-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Potential
Chain17 – 499483Sialic acid-binding Ig-like lectin 8
PRO_0000014948

Regions

Topological domain17 – 363347Extracellular Potential
Transmembrane364 – 38421Helical; Potential
Topological domain385 – 499115Cytoplasmic Potential
Domain40 – 12384Ig-like V-type
Domain157 – 24084Ig-like C2-type 1
Domain246 – 34499Ig-like C2-type 2
Motif445 – 4506ITIM motif
Motif468 – 4736SLAM-like motif

Sites

Binding site1251Sialic acid By similarity

Amino acid modifications

Glycosylation1721N-linked (GlcNAc...) Potential
Glycosylation2491N-linked (GlcNAc...) Potential
Glycosylation2671N-linked (GlcNAc...) Potential
Disulfide bond42 ↔ 181 By similarity
Disulfide bond47 ↔ 107 By similarity
Disulfide bond175 ↔ 224 By similarity
Disulfide bond283 ↔ 328 By similarity

Natural variations

Alternative sequence152 – 24594ALTHR…LDVSY → D in isoform 2.
VSP_002559
Alternative sequence416 – 49984GPLTE…KEVRG → VSDVGFSTPSIQPGHL in isoform 3.
VSP_002560
Natural variant1701S → P. Ref.5
Corresponds to variant rs10409962 [ dbSNP | Ensembl ].
VAR_021487
Natural variant2821V → L Found in a renal cell carcinoma sample; somatic mutation. Ref.6
VAR_064751
Natural variant3881R → G.
Corresponds to variant rs3829659 [ dbSNP | Ensembl ].
VAR_049930

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) [UniParc].

Last modified November 8, 2002. Version 2.
Checksum: 086EFF989B74123C

FASTA49954,042
        10         20         30         40         50         60 
MLLLLLLLPL LWGTKGMEGD RQYGDGYLLQ VQELVTVQEG LCVHVPCSFS YPQDGWTDSD 

        70         80         90        100        110        120 
PVHGYWFRAG DRPYQDAPVA TNNPDREVQA ETQGRFQLLG DIWSNDCSLS IRDARKRDKG 

       130        140        150        160        170        180 
SYFFRLERGS MKWSYKSQLN YKTKQLSVFV TALTHRPDIL ILGTLESGHS RNLTCSVPWA 

       190        200        210        220        230        240 
CKQGTPPMIS WIGASVSSPG PTTARSSVLT LTPKPQDHGT SLTCQVTLPG TGVTTTSTVR 

       250        260        270        280        290        300 
LDVSYPPWNL TMTVFQGDAT ASTALGNGSS LSVLEGQSLR LVCAVNSNPP ARLSWTRGSL 

       310        320        330        340        350        360 
TLCPSRSSNP GLLELPRVHV RDEGEFTCRA QNAQGSQHIS LSLSLQNEGT GTSRPVSQVT 

       370        380        390        400        410        420 
LAAVGGAGAT ALAFLSFCII FIIVRSCRKK SARPAAGVGD TGMEDAKAIR GSASQGPLTE 

       430        440        450        460        470        480 
SWKDGNPLKK PPPAVAPSSG EEGELHYATL SFHKVKPQDP QGQEATDSEY SEIKIHKRET 

       490 
AETQACLRNH NPSSKEVRG 

« Hide

Isoform 2 [UniParc].

Checksum: B23D94FA1DB4741A
Show »

FASTA40644,360
Isoform 3 [UniParc].

Checksum: 49B91B84CE67B118
Show »

FASTA43146,434

References

« Hide 'large scale' references
[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]"Identification of SAF-2, a novel siglec expressed on eosinophils, mast cells, and basophils."
Kikly K.K., Bochner B.S., Freeman S.D., Tan K.B., Gallagher K.T., D'Alessio K.J., Holmes S.D., Abrahamson J.A., Erickson-Miller C.L., Murdock P.R., Tachimoto H., Schleimer R.P., White J.R.
J. Allergy Clin. Immunol. 105:1093-1100(2000) [PubMed] [Europe PMC] [Abstract]
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]"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma."
Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. expand/collapse author list , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.
Nature 469:539-542(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LEU-282.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_055257.2. NM_014442.2.
UniGeneHs.447899.

3D structure databases

ProteinModelPortalQ9NYZ4.
SMRQ9NYZ4. Positions 27-244, 269-350.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118057. 1 interaction.
IntActQ9NYZ4. 1 interaction.
STRING9606.ENSP00000321077.

Protein family/group databases

MEROPSI43.001.

PTM databases

PhosphoSiteQ9NYZ4.

Polymorphism databases

DMDM25009268.

Proteomic databases

PaxDbQ9NYZ4.
PRIDEQ9NYZ4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000321424; ENSP00000321077; ENSG00000105366. [Q9NYZ4-1]
ENST00000340550; ENSP00000339448; ENSG00000105366. [Q9NYZ4-2]
GeneID27181.
KEGGhsa:27181.
UCSCuc002pwt.3. human. [Q9NYZ4-1]
uc010eox.2. human. [Q9NYZ4-2]

Organism-specific databases

CTD27181.
GeneCardsGC19M051956.
H-InvDBHIX0027458.
HGNCHGNC:10877. SIGLEC8.
HPAHPA012556.
MIM605639. gene.
neXtProtNX_Q9NYZ4.
PharmGKBPA35778.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG147919.
HOGENOMHOG000236324.
HOVERGENHBG036161.
InParanoidQ9NYZ4.
KOK06748.
OMALERGSMK.
PhylomeDBQ9NYZ4.
TreeFamTF332441.

Gene expression databases

ArrayExpressQ9NYZ4.
BgeeQ9NYZ4.
CleanExHS_SIGLEC8.
GenevestigatorQ9NYZ4.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
IPR013151. Immunoglobulin.
[Graphical view]
PfamPF00047. ig. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSIGLEC8.
GenomeRNAi27181.
NextBio50012.
PROQ9NYZ4.
SOURCESearch...

Entry information

Entry nameSIGL8_HUMAN
AccessionPrimary (citable) accession number: Q9NYZ4
Secondary accession number(s): Q7Z728
Entry history
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: November 8, 2002
Last modified: April 16, 2014
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries