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Protein

Sialic acid-binding Ig-like lectin 8

Gene

SIGLEC8

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

Functioni

Putative adhesion molecule that mediates sialic-acid dependent binding to red blood cells (PubMed:10856141, PubMed:10625619). 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 (PubMed:10625619). Recognizes simultaneously epitopes having a terminal N-acetylneuraminic acid (sialic acid) and an underlying 6-O-sulfated galactose. Preferentially binds to Gal-6-sulfated sialyl-Lewis X glycan epitopes (PubMed:27357658).3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei23CarbohydrateCombined sources1 Publication1
Binding sitei125CarbohydrateCombined sources1 Publication1
Sitei125Indispensable role in 6'-sulfo sialyl-Lewis X1 Publication1

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Biological processCell adhesion
LigandLectin

Enzyme and pathway databases

ReactomeiR-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

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
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105366.15
HGNCiHGNC:10877 SIGLEC8
MIMi605639 gene
neXtProtiNX_Q9NYZ4

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini17 – 363ExtracellularSequence analysisAdd BLAST347
Transmembranei364 – 384HelicalSequence analysisAdd BLAST21
Topological domaini385 – 499CytoplasmicSequence analysisAdd BLAST115

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi72R → A: Strongly impaired binding to 6'-sulfo sialyl-Lewis X. 1 Publication1
Mutagenesisi74Y → A: Modestly affected binding to 6'-sulfo sialyl-Lewis X. 1 Publication1
Mutagenesisi75Q → A: Modestly affected binding to 6'-sulfo sialyl-Lewis X. 1 Publication1
Mutagenesisi125R → A: Abolishes binding to 6'-sulfo sialyl-Lewis X. 1 Publication1
Mutagenesisi132K → A: Strongly impaired binding to 6'-sulfo sialyl-Lewis X. 1 Publication1
Mutagenesisi136K → A: Strongly impaired binding to 6'-sulfo sialyl-Lewis X. 1 Publication1
Mutagenesisi138Q → A: Minor effects on binding to 6'-sulfo sialyl-Lewis X. 1 Publication1

Organism-specific databases

DisGeNETi27181
OpenTargetsiENSG00000105366
PharmGKBiPA35778

Polymorphism and mutation databases

BioMutaiSIGLEC8
DMDMi25009268

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
ChainiPRO_000001494817 – 499Sialic acid-binding Ig-like lectin 8Add BLAST483

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi42 ↔ 181PROSITE-ProRule annotation
Disulfide bondi47 ↔ 107PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi172N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi175 ↔ 224PROSITE-ProRule annotation
Glycosylationi249N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi267N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi283 ↔ 328PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9NYZ4
PaxDbiQ9NYZ4
PeptideAtlasiQ9NYZ4
PRIDEiQ9NYZ4
ProteomicsDBi83307
83308 [Q9NYZ4-2]
83309 [Q9NYZ4-3]

PTM databases

iPTMnetiQ9NYZ4
PhosphoSitePlusiQ9NYZ4

Expressioni

Tissue specificityi

Expressed specifically on red blood cells namely basophil, mast cells and eosinophils.2 Publications

Gene expression databases

BgeeiENSG00000105366 Expressed in 94 organ(s), highest expression level in substantia nigra
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 interactor
IntActiQ9NYZ4, 1 interactor
STRINGi9606.ENSP00000321077

Structurei

Secondary structure

1499
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9NYZ4
SMRiQ9NYZ4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini40 – 123Ig-like V-typeAdd BLAST84
Domaini157 – 240Ig-like C2-type 1Add BLAST84
Domaini246 – 344Ig-like C2-type 2Add BLAST99

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni72 – 75Carbohydrate bindingCombined sources1 Publication4
Regioni134 – 138Carbohydrate bindingCombined sources1 Publication5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi445 – 450ITIM motif6
Motifi468 – 473SLAM-like motif6

Domaini

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IJT6 Eukaryota
ENOG410YKZU LUCA
GeneTreeiENSGT00760000119139
HOGENOMiHOG000236324
HOVERGENiHBG036161
InParanoidiQ9NYZ4
KOiK06748
OMAiWFRAGDR
OrthoDBiEOG091G0445
PhylomeDBiQ9NYZ4
TreeFamiTF332441

Family and domain databases

Gene3Di2.60.40.10, 3 hits
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR013106 Ig_V-set
PfamiView protein in Pfam
PF07686 V-set, 1 hit
SMARTiView protein in SMART
SM00409 IG, 3 hits
SM00408 IGc2, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 2 hits

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

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JT30C9JT30_HUMAN
Sialic acid-binding Ig-like lectin ...
SIGLEC8
390Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021487170S → P1 PublicationCorresponds to variant dbSNP:rs10409962Ensembl.1
Natural variantiVAR_064751282V → L Found in a renal cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_049930388R → G. Corresponds to variant dbSNP:rs3829659Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002559152 – 245ALTHR…LDVSY → D in isoform 2. 1 PublicationAdd BLAST94
Alternative sequenceiVSP_002560416 – 499GPLTE…KEVRG → VSDVGFSTPSIQPGHL in isoform 3. 2 PublicationsAdd BLAST84

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]
CCDS86797.1 [Q9NYZ4-2]
RefSeqiNP_055257.2, NM_014442.2 [Q9NYZ4-1]
XP_011525037.1, XM_011526735.2 [Q9NYZ4-2]
UniGeneiHs.447899

Genome annotation databases

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

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

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]
CCDS86797.1 [Q9NYZ4-2]
RefSeqiNP_055257.2, NM_014442.2 [Q9NYZ4-1]
XP_011525037.1, XM_011526735.2 [Q9NYZ4-2]
UniGeneiHs.447899

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N7ANMR-A17-155[»]
2N7BNMR-A17-155[»]
ProteinModelPortaliQ9NYZ4
SMRiQ9NYZ4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118057, 1 interactor
IntActiQ9NYZ4, 1 interactor
STRINGi9606.ENSP00000321077

PTM databases

iPTMnetiQ9NYZ4
PhosphoSitePlusiQ9NYZ4

Polymorphism and mutation databases

BioMutaiSIGLEC8
DMDMi25009268

Proteomic databases

EPDiQ9NYZ4
PaxDbiQ9NYZ4
PeptideAtlasiQ9NYZ4
PRIDEiQ9NYZ4
ProteomicsDBi83307
83308 [Q9NYZ4-2]
83309 [Q9NYZ4-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi27181
DisGeNETi27181
EuPathDBiHostDB:ENSG00000105366.15
GeneCardsiSIGLEC8
H-InvDBiHIX0027458
HGNCiHGNC:10877 SIGLEC8
HPAiHPA012556
MIMi605639 gene
neXtProtiNX_Q9NYZ4
OpenTargetsiENSG00000105366
PharmGKBiPA35778
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJT6 Eukaryota
ENOG410YKZU LUCA
GeneTreeiENSGT00760000119139
HOGENOMiHOG000236324
HOVERGENiHBG036161
InParanoidiQ9NYZ4
KOiK06748
OMAiWFRAGDR
OrthoDBiEOG091G0445
PhylomeDBiQ9NYZ4
TreeFamiTF332441

Enzyme and pathway databases

ReactomeiR-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Miscellaneous databases

GeneWikiiSIGLEC8
GenomeRNAii27181
PROiPR:Q9NYZ4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105366 Expressed in 94 organ(s), highest expression level in substantia nigra
CleanExiHS_SIGLEC8
ExpressionAtlasiQ9NYZ4 baseline and differential
GenevisibleiQ9NYZ4 HS

Family and domain databases

Gene3Di2.60.40.10, 3 hits
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR003598 Ig_sub2
IPR013106 Ig_V-set
PfamiView protein in Pfam
PF07686 V-set, 1 hit
SMARTiView protein in SMART
SM00409 IG, 3 hits
SM00408 IGc2, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiSIGL8_HUMAN
AccessioniPrimary (citable) accession number: Q9NYZ4
Secondary accession number(s): Q7Z728
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: November 8, 2002
Last modified: September 12, 2018
This is version 154 of the entry and version 2 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  7. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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