Reviewed, UniProtKB/Swiss-Prot Q9Y286 (SIGL7_HUMAN)

Names and origin

Protein names

Recommended name:
    Sialic acid-binding Ig-like lectin 7
      Short name=Siglec-7
Alternative name(s):
    QA79 membrane protein
    Adhesion inhibitory receptor molecule 1
      Short name=AIRM-1
    p75
    D-siglec
    CDw328
    CD_antigen=CD328

Gene names

Name:	SIGLEC7
Synonyms:	AIRM1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	467 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- and alpha-2,6-linked sialic acid. Also binds disialogangliosides (disialogalactosyl globoside, disialyl lactotetraosylceramide and disialyl GalNAc lactotetraoslylceramide). The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. Mediates inhibition of natural killer cells cytotoxicity. May play a role in hemopoiesis. Inhibits differentiation of CD34+ cell precursors towards myelomonocytic cell lineage and proliferation of leukemic myeloid cells (in vitro). Ref.5
Subunit structure	Interacts with PTPN6/SHP-1 upon phosphorylation. Ref.2
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Predominantly expressed by resting and activated natural killer cells and at lower levels by granulocytes and monocytes. High expression found in placenta, liver, lung, spleen, and peripheral blood leukocytes.
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.
Post-translational modification	Tyrosine phosphorylated. Ref.2
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.
Sequence caution	The sequence AAF44346.1 differs from that shown. Reason: Frameshift at position 406.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Ligand	Lectin
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from electronic annotation. Source: UniProtKB-KW receptor activity Ref.2 Traceable author statement. Source: ProtInc sugar binding Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y286-1)

Also known as: AIRM-1b;

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: Q9Y286-2)

Also known as: AIRM-2;

The sequence of this isoform differs from the canonical sequence as follows:
     145-238: ALTHRPNILI...NRTIQLNVSY → D

Isoform 3 (identifier: Q9Y286-3)

Also known as: AIRM-3;

The sequence of this isoform differs from the canonical sequence as follows:
     145-145: A → E
     146-467: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q9Y286-4)

The sequence of this isoform differs from the canonical sequence as follows:
     145-145: A → G
     146-467: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 467

449

Sialic acid-binding Ig-like lectin 7

PRO_0000014947

Regions

Topological domain

19 – 353

335

Extracellular Potential

Transmembrane

354 – 376

23

Potential

Topological domain

377 – 467

91

Cytoplasmic Potential

Domain

39 – 122

84

Ig-like V-type

Domain

150 – 233

84

Ig-like C2-type 1

Domain

240 – 336

97

Ig-like C2-type 2

Motif

435 – 440

6

ITIM motif

Sites

Binding site

124

1

Sialic acid By similarity

Amino acid modifications

Glycosylation

105

1

N-linked (GlcNAc...) Potential

Glycosylation

142

1

N-linked (GlcNAc...) Potential

Glycosylation

165

1

N-linked (GlcNAc...) Potential

Glycosylation

229

1

N-linked (GlcNAc...) Potential

Glycosylation

235

1

N-linked (GlcNAc...) Potential

Glycosylation

242

1

N-linked (GlcNAc...) Potential

Glycosylation

260

1

N-linked (GlcNAc...) Potential

Glycosylation

334

1

N-linked (GlcNAc...) Potential

Disulfide bond

46 ↔ 106

By similarity

Disulfide bond

168 ↔ 217

By similarity

Disulfide bond

276 ↔ 320

By similarity

Natural variations

Alternative sequence

145 – 238

94

ALTHR…LNVSY → D in isoform 2.

VSP_002555

Alternative sequence

145

1

A → E in isoform 3.

VSP_002556

Alternative sequence

145

1

A → G in isoform 4.

VSP_002557

Alternative sequence

146 – 467

322

Missing in isoform 3 and isoform 4.

VSP_002558

Natural variant

215

1

L → P in a colorectal cancer sample; somatic mutation. Ref.7

VAR_035523

Experimental info

Sequence conflict

42

1

V → A in AAF44346. Ref.4

Secondary structure

1

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467

Helix Strand Turn

Details...

Helix

23 – 25

3

Beta strand

27 – 30

4

Beta strand

32 – 37

6

Beta strand

42 – 44

3

Beta strand

46 – 49

4

Turn

54 – 58

5

Beta strand

62 – 67

6

Beta strand

78 – 81

4

Helix

89 – 91

3

Turn

92 – 94

3

Beta strand

95 – 97

3

Helix

101 – 103

3

Beta strand

108 – 110

3

Helix

115 – 117

3

Beta strand

119 – 127

9

Beta strand

130 – 133

4

Beta strand

139 – 144

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (AIRM-1b) [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 8AFE44462B001F52	FASTA	467	51,143
	10 20 30 40 50 60 MLLLLLLPLL WGRERVEGQK SNRKDYSLTM QSSVTVQEGM CVHVRCSFSY PVDSQTDSDP 70 80 90 100 110 120 VHGYWFRAGN DISWKAPVAT NNPAWAVQEE TRDRFHLLGD PQTKNCTLSI RDARMSDAGR 130 140 150 160 170 180 YFFRMEKGNI KWNYKYDQLS VNVTALTHRP NILIPGTLES GCFQNLTCSV PWACEQGTPP 190 200 210 220 230 240 MISWMGTSVS PLHPSTTRSS VLTLIPQPQH HGTSLTCQVT LPGAGVTTNR TIQLNVSYPP 250 260 270 280 290 300 QNLTVTVFQG EGTASTALGN SSSLSVLEGQ SLRLVCAVDS NPPARLSWTW RSLTLYPSQP 310 320 330 340 350 360 SNPLVLELQV HLGDEGEFTC RAQNSLGSQH VSLNLSLQQE YTGKMRPVSG VLLGAVGGAG 370 380 390 400 410 420 ATALVFLSFC VIFIVVRSCR KKSARPAADV GDIGMKDANT IRGSASQGNL TESWADDNPR 430 440 450 460 HHGLAAHSSG EEREIQYAPL SFHKGEPQDL SGQEATNNEY SEIKIPK
	Isoform 2 (AIRM-2). Checksum: 4E37C43130E19527	FASTA	374	41,237
	10 20 30 40 50 60 MLLLLLLPLL WGRERVEGQK SNRKDYSLTM QSSVTVQEGM CVHVRCSFSY PVDSQTDSDP 70 80 90 100 110 120 VHGYWFRAGN DISWKAPVAT NNPAWAVQEE TRDRFHLLGD PQTKNCTLSI RDARMSDAGR 130 140 150 160 170 180 YFFRMEKGNI KWNYKYDQLS VNVTDPPQNL TVTVFQGEGT ASTALGNSSS LSVLEGQSLR 190 200 210 220 230 240 LVCAVDSNPP ARLSWTWRSL TLYPSQPSNP LVLELQVHLG DEGEFTCRAQ NSLGSQHVSL 250 260 270 280 290 300 NLSLQQEYTG KMRPVSGVLL GAVGGAGATA LVFLSFCVIF IVVRSCRKKS ARPAADVGDI 310 320 330 340 350 360 GMKDANTIRG SASQGNLTES WADDNPRHHG LAAHSSGEER EIQYAPLSFH KGEPQDLSGQ 370 EATNNEYSEI KIPK
	Isoform 3 (AIRM-3). Checksum: B2754D9627528108	FASTA	145	16,812
	10 20 30 40 50 60 MLLLLLLPLL WGRERVEGQK SNRKDYSLTM QSSVTVQEGM CVHVRCSFSY PVDSQTDSDP 70 80 90 100 110 120 VHGYWFRAGN DISWKAPVAT NNPAWAVQEE TRDRFHLLGD PQTKNCTLSI RDARMSDAGR 130 140 YFFRMEKGNI KWNYKYDQLS VNVTE
	Isoform 4. Checksum: B1154D9627528108	FASTA	145	16,740
	10 20 30 40 50 60 MLLLLLLPLL WGRERVEGQK SNRKDYSLTM QSSVTVQEGM CVHVRCSFSY PVDSQTDSDP 70 80 90 100 110 120 VHGYWFRAGN DISWKAPVAT NNPAWAVQEE TRDRFHLLGD PQTKNCTLSI RDARMSDAGR 130 140 YFFRMEKGNI KWNYKYDQLS VNVTG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a novel siglec, siglec-7, expressed by human natural killer cells and monocytes." Nicoll G., Ni J., Liu D., Klenerman P., Munday J., Dubock S., Mattei M.-G., Crocker P.R. J. Biol. Chem. 274:34089-34095(1999) [PubMed: 10567377] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Dendritic cell.
[2]	"Identification and molecular cloning of p75/AIRM1, a novel member of the sialoadhesin family that functions as an inhibitory receptor in human natural killer cells." Falco M., Biassoni R., Bottino C., Vitale M., Sivori S., Augugliaro R., Moretta L., Moretta A. J. Exp. Med. 190:793-802(1999) [PubMed: 10499918] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), PHOSPHORYLATION, INTERACTION WITH PTPN6. Tissue: Lymphoid.
[3]	"Characterization of a novel siglec from dendritic cells." Zhang W., Wan T., Cao X. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Dendritic cell.
[4]	"Siglec-7: a sialic acid-binding lectin of the immunoglobulin superfamily." Angata T., Varki A. Glycobiology 10:431-438(2000) [PubMed: 10764831] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]	"Engagement of p75/AIRM1 or CD33 inhibits the proliferation of normal or leukemic myeloid cells." Vitale C., Romagnani C., Falco M., Ponte M., Vitale M., Moretta A., Bacigalupo A., Moretta L., Mingari M.C. Proc. Natl. Acad. Sci. U.S.A. 96:15091-15096(1999) [PubMed: 10611343] [Abstract] Cited for: FUNCTION.
[6]	"Binding specificity of siglec7 to disialogangliosides of renal cell carcinoma: possible role of disialogangliosides in tumor progression." Ito A., Handa K., Withers D.A., Satoh M., Hakomori S. FEBS Lett. 498:116-120(2001) [PubMed: 11389909] [Abstract] Cited for: DISIALOGANGLIOSIDE-BINDING.
[7]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PRO-215.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - Glycan Binding

Siglec-7

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF170485 mRNA. Translation: AAF12759.1.
AJ007395 mRNA. Translation: CAB46011.1.
AJ130710 mRNA. Translation: CAB51126.1.
AJ130711 mRNA. Translation: CAB51127.1.
AJ130712 mRNA. Translation: CAB51128.1.
AJ130713 mRNA. Translation: CAB51129.1.
AF178981 mRNA. Translation: AAF44346.1. Frameshift.
AF193441 mRNA. Translation: AAF06790.1.

IPI

IPI00004288.
IPI00220858.
IPI00220860.
IPI00220862.

RefSeq

NP_055200.1.
NP_057627.2.

UniGene

Hs.655393

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NKO	X-ray	1.45	A	19-150	[»]
1O7S	X-ray	1.75	A	18-144	[»]
1O7V	X-ray	1.90	A	18-144	[»]
2DF3	X-ray	1.90	A	18-144	[»]
2G5R	X-ray	1.60	A	18-144	[»]
2HRL	X-ray	1.85	A	18-144	[»]

ModBase

Search...

Proteomic databases

PRIDE

Q9Y286.

Genome annotation databases

Ensembl

ENSG00000168995. Homo sapiens. [Contig view]

GeneID

27036.

KEGG

hsa:27036.

Organism-specific databases

GeneCards

GC19P056337.

H-InvDB

HIX0015378.
HIX0040323.

HGNC

HGNC:10876. SIGLEC7.

MIM

604410. gene.

PharmGKB

PA35777.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9Y286.

HOVERGEN

Q9Y286.

OMA

Q9Y286. ANTIRGS.

Gene expression databases

ArrayExpress

Q9Y286.

Bgee

Q9Y286.

CleanEx

HS_SIGLEC7.

GermOnline

ENSG00000168995. Homo sapiens.

Family and domain databases

InterPro

IPR013151. Ig.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013106. Ig_V-set.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 2 hits.

Pfam

PF07679. I-set. 1 hit.
PF00047. ig. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]

SMART

SM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

49592.

SOURCE

Search...

Entry information

Entry name

SIGL7_HUMAN

Accession

Primary (citable) accession number: Q9Y286
Secondary accession number(s): Q9NZQ1 , Q9UJ86, Q9UJ87, Q9Y502

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2002
Last sequence update:	November 1, 1999
Last modified:	June 16, 2009
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)