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Q6UVW9 (CLC2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length174 AA.
Sequence statusComplete.
Protein existenceEvidence 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 Ref.5

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 Ref.5

Sequence similarities

Contains 1 C-type lectin domain.

Ontologies

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 174174C-type lectin domain family 2 member A
PRO_0000264240

Regions

Topological domain1 – 2727Cytoplasmic Potential
Transmembrane28 – 4821Helical; Signal-anchor for type II membrane protein; Potential
Topological domain49 – 174126Extracellular Potential
Domain65 – 174110C-type lectin

Amino acid modifications

Glycosylation781N-linked (GlcNAc...) Ref.5
Glycosylation1301N-linked (GlcNAc...) Ref.5
Glycosylation1431N-linked (GlcNAc...) Potential
Disulfide bond58 ↔ 69 Ref.5
Disulfide bond86 ↔ 167 Ref.5

Natural variations

Alternative sequence138 – 17437FEIIG…PKYFL → PSNSKWSCNWSLRQWLLLLG PLR in isoform 2.
VSP_035643
Natural variant1361G → D. Ref.3
Corresponds to variant rs526680 [ dbSNP | Ensembl ].
VAR_029629

Experimental info

Mutagenesis1481F → A: Reduces affinity for KLRF2 40-fold. Ref.5
Mutagenesis1521D → A: No effect on affinity for KLRF2. Ref.5
Mutagenesis1551H → A: Slightly reduces affinity for KLRF2. Ref.5
Mutagenesis157 – 1582SR → AA: Reduces affinity for KLRF2 over 10'000-fold.
Mutagenesis160 – 1612FI → AA: Reduces affinity for KLRF2 550-fold.
Mutagenesis1621D → A: Reduces affinity for KLRF2 360-fold. Ref.5

Secondary structure

..................... 174
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CLEC2A1) [UniParc].

Last modified November 4, 2008. Version 2.
Checksum: 76E137A5053361B9

FASTA17419,972
        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 

« Hide

Isoform 2 (CLEC2A2) [UniParc].

Checksum: 6689FAF3B31AE2DE
Show »

FASTA16018,576

References

« Hide '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. expand/collapse author list , 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.
[5]"Structure of NKp65 bound to its keratinocyte ligand reveals basis for genetically linked recognition in natural killer gene complex."
Li Y., Wang Q., Chen S., Brown P.H., Mariuzza R.A.
Proc. Natl. Acad. Sci. U.S.A. 110:11505-11510(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 46-174 IN COMPLEX WITH KLRF2, SUBUNIT, INTERACTION WITH KLRF2, MUTAGENESIS OF PHE-148; ASP-152; HIS-155; 157-SER-ARG-158 AND ASP-162, GLYCOSYLATION AT ASN-78 AND ASN-130, DISULFIDE BOND.

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.
RefSeqNP_001124183.1. NM_001130711.1.
XP_005253423.1. XM_005253366.1.
UniGeneHs.527665.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4IOPX-ray3.20A46-174[»]
ProteinModelPortalQ6UVW9.
SMRQ6UVW9. Positions 56-172.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-58611N.
STRING9606.ENSP00000396163.

Protein family/group databases

MEROPSI63.001.

Polymorphism databases

DMDM212276429.

Proteomic databases

PaxDbQ6UVW9.
PRIDEQ6UVW9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000339766; ENSP00000339732; ENSG00000188393. [Q6UVW9-2]
ENST00000455827; ENSP00000396163; ENSG00000188393. [Q6UVW9-1]
GeneID387836.
KEGGhsa:387836.
UCSCuc009zhb.2. human. [Q6UVW9-2]
uc009zhc.2. human. [Q6UVW9-1]

Organism-specific databases

CTD387836.
GeneCardsGC12M010051.
H-InvDBHIX0036770.
HGNCHGNC:24191. CLEC2A.
HPAHPA048530.
MIM612087. gene.
neXtProtNX_Q6UVW9.
PharmGKBPA142672099.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG259216.
HOGENOMHOG000059595.
HOVERGENHBG107718.
OMADIKWICS.
OrthoDBEOG7R833G.
PhylomeDBQ6UVW9.
TreeFamTF351467.

Gene expression databases

CleanExHS_CLEC2A.
GenevestigatorQ6UVW9.

Family and domain databases

Gene3D3.10.100.10. 1 hit.
InterProIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR016187. C-type_lectin_fold.
[Graphical view]
PfamPF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMSSF56436. SSF56436. 1 hit.
PROSITEPS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi387836.
NextBio101654.
PROQ6UVW9.
SOURCESearch...

Entry information

Entry nameCLC2A_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 83 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM