Q6UVW9 (CLC2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-type lectin domain family 2 member A

Alternative name(s):
Keratinocyte-associated C-type lectin
Short name=KACL
Proliferation-induced lymphocyte-associated receptor
Short name=PILAR

Gene names

Name:	CLEC2A
Synonyms:	KACL
ORF Names:	UNQ5792/PRO19597

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

General annotation (Comments)

Function	Plays a role in modulating the extent of T-cell expansion. Enhances the expansion of TCR-stimulated T-cells by increasing their survival through enhanced expression of anti-apoptotic proteins. May modulate the capacity of T-cells to home to lymph nodes through SELL. Facilitates dedicated immune recognition of keratinocytes via interaction with its receptor KLRF2 by stimulating natural killer cell mediated cytotoxicity. Ref.1 Ref.4
Subunit structure	Homodimer; non disulfide-linked. Interacts with KLRB1. Interacts with KLRF2. Ref.1 Ref.4
Subcellular location	Cell membrane; Single-pass type II membrane protein Ref.1 Ref.3.
Tissue specificity	Mainly expressed in skin. Also expressed in keratinocytes, spleen, thymus, small intestine, peripheral blood monocytes, bone marrow, ovary, testis and skin. High expression in CD8+, B-lymphocytes and naive CD4+ T-cells. Restricted mostly to proliferating lymphocytes. Not detected in myeloid leukocytes or natural killer (NK) cells. Ref.1 Ref.3 Ref.4
Induction	By phytohemagglutinin (PHA) in peripheral CD8+ T cells.
Post-translational modification	N-glycosylated. Ref.4
Sequence similarities	Contains 1 C-type lectin domain.

Ontologies

Keywords
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
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	natural killer cell mediated cytotoxicity Traceable author statement Ref.4. Source: UniProtKB
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	carbohydrate binding Inferred from electronic annotation. Source: InterPro protein homodimerization activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q6UVW9-1)

Also known as: CLEC2A1;

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: Q6UVW9-2)

Also known as: CLEC2A2;

The sequence of this isoform differs from the canonical sequence as follows:
     138-174: FEIIGNGSFAFLSADGVHSSRGFIDIKWICSKPKYFL → PSNSKWSCNWSLRQWLLLLGPLR

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 174	174	C-type lectin domain family 2 member A		PRO_0000264240
Regions
	Topological domain	1 – 27	27	Cytoplasmic Potential
	Transmembrane	28 – 48	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	49 – 174	126	Extracellular Potential
	Domain	65 – 174	110	C-type lectin
Amino acid modifications
	Glycosylation	78	1	N-linked (GlcNAc...) Potential
	Glycosylation	130	1	N-linked (GlcNAc...) Potential
	Glycosylation	143	1	N-linked (GlcNAc...) Potential
	Disulfide bond	58 ↔ 69		By similarity
	Disulfide bond	86 ↔ 167		By similarity
Natural variations
	Alternative sequence	138 – 174	37	FEIIG…PKYFL → PSNSKWSCNWSLRQWLLLLG PLR in isoform 2.		VSP_035643
	Natural variant	136	1	G → D. Ref.3 Corresponds to variant rs526680 [ dbSNP | Ensembl ].		VAR_029629

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (CLEC2A1) [UniParc]. Last modified November 4, 2008. Version 2. Checksum: 76E137A5053361B9	FASTA	174	19,972
	10 20 30 40 50 60 MINPELRDGR ADGFIHRIVP KLIQNWKIGL MCFLSIIITT VCIIMIATWS KHAKPVACSG 70 80 90 100 110 120 DWLGVRDKCF YFSDDTRNWT ASKIFCSLQK AELAQIDTQE DMEFLKRYAG TDMHWIGLSR 130 140 150 160 170 KQGDSWKWTN GTTFNGWFEI IGNGSFAFLS ADGVHSSRGF IDIKWICSKP KYFL
	Isoform 2 (CLEC2A2) [UniParc]. Checksum: 6689FAF3B31AE2DE	FASTA	160	18,576
	10 20 30 40 50 60 MINPELRDGR ADGFIHRIVP KLIQNWKIGL MCFLSIIITT VCIIMIATWS KHAKPVACSG 70 80 90 100 110 120 DWLGVRDKCF YFSDDTRNWT ASKIFCSLQK AELAQIDTQE DMEFLKRYAG TDMHWIGLSR 130 140 150 160 KQGDSWKWTN GTTFNGWPSN SKWSCNWSLR QWLLLLGPLR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PILAR is a novel modulator of human T-cell expansion." Huarte E., Cubillos-Ruiz J.R., Nesbeth Y.C., Scarlett U.K., Martinez D.G., Engle X.A., Rigby W.F., Pioli P.A., Guyre P.M., Conejo-Garcia J.R. Blood 112:1259-1268(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH KLRB1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Spleen.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]	"CLEC2A: a novel, alternatively spliced and skin-associated member of the NKC-encoded AICL-CD69-LLT1 family." Spreu J., Kienle E.C., Schrage B., Steinle A. Immunogenetics 59:903-912(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-166 (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 8-154 (ISOFORM 2), VARIANT ASP-136, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Histiocytic lymphoma.
[4]	"Interaction of C-type lectin-like receptors NKp65 and KACL facilitates dedicated immune recognition of human keratinocytes." Spreu J., Kuttruff S., Stejfova V., Dennehy K.M., Schittek B., Steinle A. Proc. Natl. Acad. Sci. U.S.A. 107:5100-5105(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, GLYCOSYLATION, TISSUE SPECIFICITY.

Cross-references

Sequence databases
EMBL GenBank DDBJ	EF127467 mRNA. Translation: ABO33172.1. AY359126 mRNA. Translation: AAQ89483.1. EU095393 mRNA. Translation: ABW79912.1. EU095394 mRNA. Translation: ABW79913.1.
IPI	IPI00398946. IPI00914678.
RefSeq	NP_001124183.1. NM_001130711.1.
UniGene	Hs.527665.
3D structure databases
HSSP	HSSP built from PDB template 1FM5 based on UniProtKB Q07108.
ProteinModelPortal	Q6UVW9.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-58611N.
STRING	9606.ENSP00000396163.
Polymorphism databases
DMDM	212276429.
Proteomic databases
PaxDb	Q6UVW9.
PRIDE	Q6UVW9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000339766; ENSP00000339732; ENSG00000188393. ENST00000455827; ENSP00000396163; ENSG00000188393.
GeneID	387836.
KEGG	hsa:387836.
UCSC	uc009zhb.2. human. uc009zhc.2. human.
Organism-specific databases
CTD	387836.
GeneCards	GC12M010051.
H-InvDB	HIX0036770.
HGNC	HGNC:24191. CLEC2A.
HPA	HPA048530.
MIM	612087. gene.
neXtProt	NX_Q6UVW9.
PharmGKB	PA142672099.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG259216.
HOGENOM	HOG000059595.
HOVERGEN	HBG107718.
OMA	DIKWICS.
Gene expression databases
CleanEx	HS_CLEC2A.
Genevestigator	Q6UVW9.
Family and domain databases
Gene3D	3.10.100.10. 1 hit.
InterPro	IPR001304. C-type_lectin. IPR016186. C-type_lectin-like. IPR016187. C-type_lectin_fold. [Graphical view]
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
GenomeRNAi	387836.
NextBio	101654.
SOURCE	Search...

Entry information

Entry name

CLC2A_HUMAN

Accession

Primary (citable) accession number: Q6UVW9
Secondary accession number(s): A5Y4G5, A9QKS2, A9QKS3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 12, 2006
Last sequence update:	November 4, 2008
Last modified:	May 1, 2013
This is version 74 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.