O00182 (LEG9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Galectin-9
Short name=Gal-9

Alternative name(s):
Ecalectin
Tumor antigen HOM-HD-21

Gene names

Name:

LGALS9

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	355 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds galactosides. Has high affinity for the Forssman pentasaccharide. May play a role in thymocyte-epithelial interactions relevant to the biology of the thymus. Inhibits cell proliferation. It is a ligand for HAVCR2/TIM3. Induces T-helper type 1 lymphocyte (Th1) death. Isoform Short acts as an eosinophil chemoattractant. Ref.10 Ref.11 Ref.13
Subunit structure	Monomer Probable. Ref.11
Subcellular location	Cytoplasm By similarity. Secreted By similarity. Note: May also be secreted by a non-classical secretory pathway By similarity.
Tissue specificity	Peripheral blood leukocytes and lymphatic tissues. Overexpressed in Hodgkin disease tissue.
Domain	Contains two homologous but distinct carbohydrate-binding domains.
Sequence similarities	Contains 2 galectin domains.

Ontologies

Keywords
Cellular component	Cytoplasm Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	Lectin
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype PubMed 12761501. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	galactose binding Traceable author statement Ref.1. Source: ProtInc signal transducer activity Inferred from mutant phenotype PubMed 12761501. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform Long (identifier: O00182-1)

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 Short (identifier: O00182-2)

The sequence of this isoform differs from the canonical sequence as follows:
     149-180: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 355

355

Galectin-9

PRO_0000076946

Regions

Domain

17 – 148

132

Galectin 1

Domain

227 – 355

129

Galectin 2

Region

82 – 88

7

Beta-galactoside binding 1

Region

287 – 293

7

Beta-galactoside binding 2 By similarity

Sites

Binding site

48

1

Beta-galactoside 1

Binding site

61

1

Beta-galactoside 1

Binding site

65

1

Beta-galactoside 1

Binding site

75

1

Beta-galactoside 1

Binding site

267

1

Beta-galactoside 2

Binding site

271

1

Beta-galactoside 2

Binding site

281

1

Beta-galactoside 2 By similarity

Natural variations

Alternative sequence

149 – 180

32

Missing in isoform Short.

VSP_003096

Natural variant

5

1

G → S. Ref.3 Ref.7
Corresponds to variant rs3751093 [ dbSNP | Ensembl ].

VAR_020453

Experimental info

Sequence conflict

48

1

N → D in CAB93851. Ref.6

Sequence conflict

79 – 81

3

NGS → KGR in CAB93851. Ref.6

Sequence conflict

88

1

K → R in CAA88922. Ref.1

Sequence conflict

89

1

T → M in CAB93851. Ref.6

Sequence conflict

93

1

F → S in BAD96952. Ref.7

Sequence conflict

135

1

S → F in CAA88922. Ref.1

Sequence conflict

270

1

P → L in CAA88922. Ref.1

Sequence conflict

313

1

E → G in CAA88922. Ref.1

Sequence conflict

326

1

L → V in CAB93851. Ref.6

Sequence conflict

341

1

R → K in CAB93851. Ref.6

Secondary structure

1

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355

Helix Strand Turn

Details...

Beta strand

5 – 7

3

Beta strand

10 – 12

3

Beta strand

15 – 20

6

Beta strand

30 – 37

8

Beta strand

39 – 41

3

Beta strand

43 – 56

14

Beta strand

58 – 65

8

Beta strand

71 – 78

8

Beta strand

86 – 89

4

Beta strand

98 – 105

8

Beta strand

107 – 114

8

Beta strand

117 – 123

7

Helix

128 – 130

3

Beta strand

133 – 146

14

Beta strand

225 – 230

6

Beta strand

240 – 247

8

Beta strand

253 – 260

8

Beta strand

263 – 271

9

Turn

272 – 275

4

Beta strand

276 – 283

8

Beta strand

295 – 297

3

Beta strand

305 – 312

8

Beta strand

314 – 321

8

Beta strand

324 – 330

7

Helix

336 – 338

3

Beta strand

341 – 354

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 4748C22FCAFA536A	FASTA	355	39,518
	10 20 30 40 50 60 MAFSGSQAPY LSPAVPFSGT IQGGLQDGLQ ITVNGTVLSS SGTRFAVNFQ TGFSGNDIAF 70 80 90 100 110 120 HFNPRFEDGG YVVCNTRQNG SWGPEERKTH MPFQKGMPFD LCFLVQSSDF KVMVNGILFV 130 140 150 160 170 180 QYFHRVPFHR VDTISVNGSV QLSYISFQNP RTVPVQPAFS TVPFSQPVCF PPRPRGRRQK 190 200 210 220 230 240 PPGVWPANPA PITQTVIHTV QSAPGQMFST PAIPPMMYPH PAYPMPFITT ILGGLYPSKS 250 260 270 280 290 300 ILLSGTVLPS AQRFHINLCS GNHIAFHLNP RFDENAVVRN TQIDNSWGSE ERSLPRKMPF 310 320 330 340 350 VRGQSFSVWI LCEAHCLKVA VDGQHLFEYY HRLRNLPTIN RLEVGGDIQL THVQT
	Isoform Short [UniParc]. Checksum: 1A3EB2941FC7F377	FASTA	323	35,888
	10 20 30 40 50 60 MAFSGSQAPY LSPAVPFSGT IQGGLQDGLQ ITVNGTVLSS SGTRFAVNFQ TGFSGNDIAF 70 80 90 100 110 120 HFNPRFEDGG YVVCNTRQNG SWGPEERKTH MPFQKGMPFD LCFLVQSSDF KVMVNGILFV 130 140 150 160 170 180 QYFHRVPFHR VDTISVNGSV QLSYISFQPP GVWPANPAPI TQTVIHTVQS APGQMFSTPA 190 200 210 220 230 240 IPPMMYPHPA YPMPFITTIL GGLYPSKSIL LSGTVLPSAQ RFHINLCSGN HIAFHLNPRF 250 260 270 280 290 300 DENAVVRNTQ IDNSWGSEER SLPRKMPFVR GQSFSVWILC EAHCLKVAVD GQHLFEYYHR 310 320 LRNLPTINRL EVGGDIQLTH VQT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular definition of a novel human galectin which is immunogenic in patients with Hodgkin's disease." Tuereci O., Schmitt H., Fadle N., Pfreundschuh M., Sahin U. J. Biol. Chem. 272:6416-6422(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). Tissue: Spleen.
[2]	"Human galectin-9 isoform full-length cDNA from gastric adenocarcinoma." Kato S. Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: Gastric carcinoma.
[3]	"Human ecalectin, a variant of human galectin-9, is a novel eosinophil chemoattractant produced by T lymphocytes." Matsumoto R., Matsumoto H., Seki M., Hata M., Asano Y., Kanegasaki S., Stevens R.L., Hirashima M. J. Biol. Chem. 273:16976-16984(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), VARIANT SER-5.
[4]	"Cloning and expression of human urate transporter mRNA." Nakajima H., Shichiri M., Hamaguchi T. Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT). Tissue: Kidney and Stomach.
[5]	"Homo sapiens galectin-9 (LGALS9) / ecalectin gene, exon 2 through 11." Akiyama S. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Genomic organization of the human galectin-9 gene." Graessler J., Spitzenberger F., Schroeder H.E. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT), VARIANT SER-5. Tissue: Gastric mucosa.
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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 SHORT). Tissue: Colon.
[10]	"The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity." Zhu C., Anderson A.C., Schubart A., Xiong H., Imitola J., Khoury S.J., Zheng X.X., Strom T.B., Kuchroo V.K. Nat. Immunol. 6:1245-1252(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS LIGAND FOR HAVCR2/TIM3.
[11]	"Structural analysis of the human galectin-9 N-terminal carbohydrate recognition domain reveals unexpected properties that differ from the mouse orthologue." Nagae M., Nishi N., Nakamura-Tsuruta S., Hirabayashi J., Wakatsuki S., Kato R. J. Mol. Biol. 375:119-135(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1-148 IN COMPLEXES WITH LACTOSE AND COMPLEX BETA-GALACTOSIDE, SUBUNIT, CARBOHYDRATE SPECIFICITY, FUNCTION.
[12]	"Crystal structure of N-terminal domain of human galectin-9 containing L-acetyllactosamine." RIKEN structural genomics initiative (RSGI) Submitted (APR-2008) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.17 ANGSTROMS) OF 1-150 IN COMPLEX WITH L-ACETYLLACTOSAMINE.
[13]	"Structural analysis of the recognition mechanism of poly-N-acetyllactosamine by the human galectin-9 N-terminal carbohydrate recognition domain." Nagae M., Nishi N., Murata T., Usui T., Nakamura T., Wakatsuki S., Kato R. Glycobiology 19:112-117(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 1-148 IN COMPLEXES WITH N-ACETYLLACTOSAMINE OLIGOMERS, FUNCTION.
[14]	"X-ray structures of human galectin-9 C-terminal domain in complexes with a biantennary oligosaccharide and sialyllactose." Yoshida H., Teraoka M., Nishi N., Nakakita S., Nakamura T., Hirashima M., Kamitori S. J. Biol. Chem. 285:36969-36976(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 186-323 IN COMPLEXES WITH OLIGOSACCHARIDES.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - Glycan Binding

Galectin-9

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z49107 mRNA. Translation: CAA88922.1.
AB006782 mRNA. Translation: BAA22166.1.
AB005894 mRNA. Translation: BAA31542.1.
AB003517 mRNA. Translation: BAF76327.1.
AB008492 mRNA. Translation: BAF76328.1.
AB040130 Genomic DNA. Translation: BAB83625.1.
AB040130 Genomic DNA. Translation: BAB83624.1.
AJ288083 , AJ288084, AJ288085, AJ288086, AJ288087, AJ288088, AJ288089, AJ288090 Genomic DNA. Translation: CAB93851.1.
AK223232 mRNA. Translation: BAD96952.1.
CH471159 Genomic DNA. Translation: EAW51037.1.
CH471159 Genomic DNA. Translation: EAW51044.1.
BC105942 mRNA. Translation: AAI05943.1.
BC105944 mRNA. Translation: AAI05945.1.
BC110340 mRNA. Translation: AAI10341.1.

IPI

IPI00010477.
IPI00293267.

RefSeq

NP_002299.2. NM_002308.3.
NP_033665.1. NM_009587.2.

UniGene

Hs.81337.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EAK	X-ray	1.97	A/B/C	1-148	[»]
2EAL	X-ray	1.85	A/B	1-148	[»]
2YY1	X-ray	2.17	A	1-147	[»]
2ZHK	X-ray	1.80	A/B	1-148	[»]
2ZHL	X-ray	1.75	A/B/C/D	1-148	[»]
2ZHM	X-ray	1.84	A/B/C/D	1-148	[»]
2ZHN	X-ray	1.30	A	1-148	[»]
3LSD	X-ray	2.03	A	6-148	[»]
3LSE	X-ray	2.69	A	6-148	[»]
3NV1	X-ray	1.50	A	218-355	[»]
3NV2	X-ray	2.34	A	218-355	[»]
3NV3	X-ray	1.57	A	218-355	[»]
3NV4	X-ray	1.99	A	218-355	[»]

ProteinModelPortal

O00182.

ModBase

Search...

Protein-protein interaction databases

IntAct

O00182. 12 interactions.

STRING

9606.ENSP00000378856.

PTM databases

PhosphoSite

O00182.

Proteomic databases

PRIDE

O00182.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000302228; ENSP00000306228; ENSG00000168961.
ENST00000395473; ENSP00000378856; ENSG00000168961.

GeneID

3965.

KEGG

hsa:3965.

UCSC

uc002gzp.3. human.

Organism-specific databases

CTD

3965.

GeneCards

GC17P025956.

HGNC

HGNC:6570. LGALS9.

MIM

601879. gene.

neXtProt

NX_O00182.

PharmGKB

PA30347.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HOG000290194.

HOVERGEN

HBG002412.

InParanoid

O00182.

KO

K10093.

OMA

VCNTRQN.

OrthoDB

EOG49GKH7.

PhylomeDB

O00182.

Gene expression databases

ArrayExpress

O00182.

Bgee

O00182.

CleanEx

HS_LGALS9.

Genevestigator

O00182.

GermOnline

ENSG00000168961. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.200. 2 hits.

InterPro

IPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR001079. Galectin_CRD.
[Graphical view]

Pfam

PF00337. Gal-bind_lectin. 2 hits.
[Graphical view]

SMART

SM00908. Gal-bind_lectin. 2 hits.
SM00276. GLECT. 2 hits.
[Graphical view]

SUPFAM

SSF49899. ConA_like_lec_gl. 2 hits.

PROSITE

PS51304. GALECTIN. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

O00182.

ChEMBL

CHEMBL5474.

ChiTaRS

lgals9. human.

EvolutionaryTrace

O00182.

GenomeRNAi

3965.

NextBio

15562.

SOURCE

Search...

Entry information

Entry name

LEG9_HUMAN

Accession

Primary (citable) accession number: O00182
Secondary accession number(s): A7VJG6 , O14532, O75028, Q3B8N1, Q53FQ0, Q9NQ58

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.