Q96E93 (KLRG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Killer cell lectin-like receptor subfamily G member 1

Alternative name(s):
C-type lectin domain family 15 member A
ITIM-containing receptor MAFA-L
MAFA-like receptor
Mast cell function-associated antigen

Gene names

Name:	KLRG1
Synonyms:	CLEC15A, MAFA, MAFAL

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	195 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays an inhibitory role on natural killer (NK) cells and T-cell functions upon binding to their non-MHC ligands. May mediate missing self recognition by binding to a highly conserved site on classical cadherins, enabling it to monitor expression of E-cadherin/CDH1, N-cadherin/CDH2 and R-cadherin/CDH4 on target cells. Ref.8
Subunit structure	Forms monomer and homodimer; disulfide-linked By similarity. Interacts (via ITIM motif) with PTPN11 and INPP5D By similarity. Ref.8
Subcellular location	Cell membrane; Single-pass type II membrane protein Ref.8.
Tissue specificity	Expressed specifically on natural killer (NK) cells and T-cells, mainly CD8 T-cells. Ref.2 Ref.6
Induction	By pathogens and viruses infections. Ref.6
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. Upon phosphorylation of ITIM motif KLRG1 associates with the two phosphatases PTPN11 and INPP5D By similarity.
Sequence similarities	Contains 1 C-type lectin domain.

Ontologies

Keywords
Biological process	Immunity Innate immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Lectin
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell surface receptor linked signaling pathway Traceable author statement. Source: ProtInc cellular defense response Traceable author statement. Source: ProtInc inflammatory response Traceable author statement. Source: ProtInc innate immune response Inferred from electronic annotation. Source: UniProtKB-KW regulation of immune response Traceable author statement. Source: Reactome
Cellular component	integral to membrane Traceable author statement. Source: ProtInc plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	receptor activity Traceable author statement. Source: ProtInc sugar binding Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q96E93-1)

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 2 (identifier: Q96E93-2)

The sequence of this isoform differs from the canonical sequence as follows:
     187-195: CPFADQALF → VRL

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 195

195

Killer cell lectin-like receptor subfamily G member 1

PRO_0000331256

Regions

Topological domain

1 – 38

38

Cytoplasmic Potential

Transmembrane

39 – 59

21

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

60 – 195

136

Extracellular Potential

Domain

82 – 185

104

C-type lectin

Motif

5 – 10

6

ITIM motif

Compositional bias

28 – 31

4

Poly-Ser

Amino acid modifications

Glycosylation

65

1

N-linked (GlcNAc...) Potential

Glycosylation

97

1

N-linked (GlcNAc...) Potential

Glycosylation

137

1

N-linked (GlcNAc...) Potential

Glycosylation

150

1

N-linked (GlcNAc...) Potential

Disulfide bond

75 ↔ 86

Ref.8

Disulfide bond

103 ↔ 184

Ref.8

Disulfide bond

163 ↔ 176

Ref.8

Natural variations

Alternative sequence

187 – 195

9

CPFADQALF → VRL in isoform 2.

VSP_033151

Natural variant

58

1

W → R.
Corresponds to variant rs1805749 [ dbSNP | Ensembl ].

VAR_042750

Experimental info

Sequence conflict

32

1

R → K in AAC34731. Ref.1

Sequence conflict

42

1

A → T in AAC34731. Ref.1

Sequence conflict

182

1

W → G in AAC34731. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

195

Helix Strand Turn

Details...

Beta strand

86 – 89

4

Helix

96 – 104

9

Turn

105 – 107

3

Helix

116 – 123

8

Beta strand

180 – 185

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 178EE98E08EEC473	FASTA	195	21,831
	10 20 30 40 50 60 MTDSVIYSML ELPTATQAQN DYGPQQKSSS SRPSCSCLVA IALGLLTAVL LSVLLYQWIL 70 80 90 100 110 120 CQGSNYSTCA SCPSCPDRWM KYGNHCYYFS VEEKDWNSSL EFCLARDSHL LVITDNQEMS 130 140 150 160 170 180 LLQVFLSEAF CWIGLRNNSG WRWEDGSPLN FSRISSNSFV QTCGAINKNG LQASSCEVPL 190 HWVCKKCPFA DQALF
	Isoform 2 [UniParc]. Checksum: FA9023F1523656A8	FASTA	189	21,206
	10 20 30 40 50 60 MTDSVIYSML ELPTATQAQN DYGPQQKSSS SRPSCSCLVA IALGLLTAVL LSVLLYQWIL 70 80 90 100 110 120 CQGSNYSTCA SCPSCPDRWM KYGNHCYYFS VEEKDWNSSL EFCLARDSHL LVITDNQEMS 130 140 150 160 170 180 LLQVFLSEAF CWIGLRNNSG WRWEDGSPLN FSRISSNSFV QTCGAINKNG LQASSCEVPL HWVCKKVRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human MAFA has alternatively spliced variants." Lamers M.B.A.C., Lamont A.G., Williams D.H. Biochim. Biophys. Acta 1399:209-212(1998) [PubMed: 9765598] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"MAFA-L, an ITIM-containing receptor encoded by the human NK cell gene complex and expressed by basophils and NK cells." Butcher S., Arney K.L., Cook G.P. Eur. J. Immunol. 28:3755-3762(1998) [PubMed: 9842918] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Spleen.
[4]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Bone marrow.
[6]	"Expression of killer cell lectin-like receptor G1 on antigen-specific human CD8+ T lymphocytes during active, latent, and resolved infection and its relation with CD57." Ibegbu C.C., Xu Y.X., Harris W., Maggio D., Miller J.D., Kourtis A.P. J. Immunol. 174:6088-6094(2005) [PubMed: 15879103] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION BY VIRUSES AND PATHOGENS INFECTIONS.
[7]	"Tumor-associated E-cadherin mutations affect binding to the killer cell lectin-like receptor G1 in humans." Schwartzkopff S., Gruendemann C., Schweier O., Rosshart S., Karjalainen K.E., Becker K.-F., Pircher H. J. Immunol. 179:1022-1029(2007) [PubMed: 17617594] [Abstract] Cited for: LIGAND-BINDING.
[8]	"Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition." Li Y., Hofmann M., Wang Q., Teng L., Chlewicki L.K., Pircher H., Mariuzza R.A. Immunity 31:35-46(2009) [PubMed: 19604491] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 75-186 IN COMPLEX WITH CDH1, FUNCTION, SUBCELLULAR LOCATION, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF034952 mRNA. Translation: AAC34731.1.
AF081675 mRNA. Translation: AAC32200.1.
AF097358 mRNA. Translation: AAD03719.1.
AK316337 mRNA. Translation: BAH14708.1.
CH471116 Genomic DNA. Translation: EAW88594.1.
CH471116 Genomic DNA. Translation: EAW88595.1.
BC012621 mRNA. Translation: AAH12621.1.

IPI

IPI00153018.
IPI00478141.

RefSeq

NP_005801.3. NM_005810.3.

UniGene

Hs.558446.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3FF7	X-ray	1.80	C/D	75-186	[»]

ProteinModelPortal

Q96E93.

SMR

Q96E93. Positions 75-186.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96E93. 1 interaction.

MINT

MINT-1465786.

STRING

Q96E93.

Polymorphism databases

DMDM

74731536.

Proteomic databases

PRIDE

Q96E93.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000266551; ENSP00000266551; ENSG00000139187.
ENST00000356986; ENSP00000349477; ENSG00000139187.

GeneID

10219.

KEGG

hsa:10219.

UCSC

uc001qvg.1. human.
uc001qvh.2. human.

Organism-specific databases

CTD

10219.

GeneCards

GC12P009142.

HGNC

HGNC:6380. KLRG1.

MIM

604874. gene.

neXtProt

NX_Q96E93.

PharmGKB

PA30170.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06786.

GeneTree

ENSGT00550000074413.

HOGENOM

HBG126616.

HOVERGEN

HBG103557.

InParanoid

Q96E93.

OMA

KDWNSSL.

OrthoDB

EOG4ZS94B.

PhylomeDB

Q96E93.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q96E93.

Bgee

Q96E93.

CleanEx

HS_KLRG1.
HS_MAFA.

Genevestigator

Q96E93.

Family and domain databases

InterPro

IPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR016187. C-type_lectin_fold.
[Graphical view]

Gene3D

G3DSA:3.10.100.10. C-type_lectin-like. 1 hit.

KO

K10076.

Pfam

PF00059. Lectin_C. 1 hit.
[Graphical view]

SMART

SM00034. CLECT. 1 hit.
[Graphical view]

SUPFAM

SSF56436. C-type_lectin_fold. 1 hit.

PROSITE

PS00615. C_TYPE_LECTIN_1. False negative.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

38696.

SOURCE

Search...

Entry information

Entry name

KLRG1_HUMAN

Accession

Primary (citable) accession number: Q96E93
Secondary accession number(s): B7ZAM2, O43198, O75613

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 29, 2008
Last sequence update:	December 1, 2001
Last modified:	January 25, 2012
This is version 73 of the entry and version 1 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.