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Q6UVW9

- CLC2A_HUMAN

UniProt

Q6UVW9 - CLC2A_HUMAN

Protein

C-type lectin domain family 2 member A

Gene

CLEC2A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 87 (01 Oct 2014)
      Sequence version 2 (04 Nov 2008)
      Previous versions | rss
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    Functioni

    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.2 Publications

    GO - Molecular functioni

    1. carbohydrate binding Source: InterPro
    2. protein binding Source: UniProtKB
    3. protein homodimerization activity Source: UniProtKB

    GO - Biological processi

    1. natural killer cell mediated cytotoxicity Source: UniProtKB

    Keywords - Molecular functioni

    Receptor

    Keywords - Ligandi

    Lectin

    Protein family/group databases

    MEROPSiI63.001.

    Names & Taxonomyi

    Protein namesi
    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 namesi
    Name:CLEC2A
    Synonyms:KACL
    ORF Names:UNQ5792/PRO19597
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:24191. CLEC2A.

    Subcellular locationi

    Cell membrane 2 Publications; Single-pass type II membrane protein 2 Publications

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi148 – 1481F → A: Reduces affinity for KLRF2 40-fold. 1 Publication
    Mutagenesisi152 – 1521D → A: No effect on affinity for KLRF2. 1 Publication
    Mutagenesisi155 – 1551H → A: Slightly reduces affinity for KLRF2. 1 Publication
    Mutagenesisi157 – 1582SR → AA: Reduces affinity for KLRF2 over 10'000-fold.
    Mutagenesisi160 – 1612FI → AA: Reduces affinity for KLRF2 550-fold.
    Mutagenesisi162 – 1621D → A: Reduces affinity for KLRF2 360-fold. 1 Publication

    Organism-specific databases

    PharmGKBiPA142672099.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 174174C-type lectin domain family 2 member APRO_0000264240Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi58 ↔ 691 PublicationPROSITE-ProRule annotation
    Glycosylationi78 – 781N-linked (GlcNAc...)2 Publications
    Disulfide bondi86 ↔ 1671 PublicationPROSITE-ProRule annotation
    Glycosylationi130 – 1301N-linked (GlcNAc...)2 Publications
    Glycosylationi143 – 1431N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    N-glycosylated.2 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ6UVW9.
    PRIDEiQ6UVW9.

    Expressioni

    Tissue specificityi

    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.3 Publications

    Inductioni

    By phytohemagglutinin (PHA) in peripheral CD8+ T cells.

    Gene expression databases

    CleanExiHS_CLEC2A.
    GenevestigatoriQ6UVW9.

    Organism-specific databases

    HPAiHPA048530.

    Interactioni

    Subunit structurei

    Homodimer; non disulfide-linked. Interacts with KLRB1. Interacts with KLRF2.3 Publications

    Protein-protein interaction databases

    DIPiDIP-58611N.
    STRINGi9606.ENSP00000396163.

    Structurei

    Secondary structure

    1
    174
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi60 – 656
    Beta strandi68 – 725
    Helixi79 – 879
    Turni88 – 903
    Helixi99 – 1079
    Turni108 – 1114
    Beta strandi114 – 1218
    Beta strandi129 – 1313
    Beta strandi143 – 1497
    Beta strandi154 – 1574
    Beta strandi163 – 1708

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4IOPX-ray3.20A46-174[»]
    ProteinModelPortaliQ6UVW9.
    SMRiQ6UVW9. Positions 56-172.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2727CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini49 – 174126ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei28 – 4821Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini65 – 174110C-type lectinPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 C-type lectin domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG259216.
    HOGENOMiHOG000059595.
    HOVERGENiHBG107718.
    OMAiEAWISFI.
    OrthoDBiEOG7R833G.
    PhylomeDBiQ6UVW9.
    TreeFamiTF351467.

    Family and domain databases

    Gene3Di3.10.100.10. 1 hit.
    InterProiIPR001304. C-type_lectin.
    IPR016186. C-type_lectin-like.
    IPR016187. C-type_lectin_fold.
    [Graphical view]
    PfamiPF00059. Lectin_C. 1 hit.
    [Graphical view]
    SMARTiSM00034. CLECT. 1 hit.
    [Graphical view]
    SUPFAMiSSF56436. SSF56436. 1 hit.
    PROSITEiPS50041. C_TYPE_LECTIN_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q6UVW9-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MINPELRDGR ADGFIHRIVP KLIQNWKIGL MCFLSIIITT VCIIMIATWS    50
    KHAKPVACSG DWLGVRDKCF YFSDDTRNWT ASKIFCSLQK AELAQIDTQE 100
    DMEFLKRYAG TDMHWIGLSR KQGDSWKWTN GTTFNGWFEI IGNGSFAFLS 150
    ADGVHSSRGF IDIKWICSKP KYFL 174
    Length:174
    Mass (Da):19,972
    Last modified:November 4, 2008 - v2
    Checksum:i76E137A5053361B9
    GO
    Isoform 2 (identifier: Q6UVW9-2) [UniParc]FASTAAdd to Basket

    Also known as: CLEC2A2

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

    Show »
    Length:160
    Mass (Da):18,576
    Checksum:i6689FAF3B31AE2DE
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti136 – 1361G → D.1 Publication
    Corresponds to variant rs526680 [ dbSNP | Ensembl ].
    VAR_029629

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei138 – 17437FEIIG…PKYFL → PSNSKWSCNWSLRQWLLLLG PLR in isoform 2. 2 PublicationsVSP_035643Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    EF127467 mRNA. Translation: ABO33172.1.
    AY359126 mRNA. Translation: AAQ89483.1.
    EU095393 mRNA. Translation: ABW79912.1.
    EU095394 mRNA. Translation: ABW79913.1.
    CCDSiCCDS44829.1. [Q6UVW9-1]
    RefSeqiNP_001124183.1. NM_001130711.1. [Q6UVW9-1]
    XP_005253423.1. XM_005253366.1.
    UniGeneiHs.527665.

    Genome annotation databases

    EnsembliENST00000339766; ENSP00000339732; ENSG00000188393. [Q6UVW9-2]
    ENST00000455827; ENSP00000396163; ENSG00000188393. [Q6UVW9-1]
    GeneIDi387836.
    KEGGihsa:387836.
    UCSCiuc009zhb.2. human. [Q6UVW9-2]
    uc009zhc.2. human. [Q6UVW9-1]

    Polymorphism databases

    DMDMi212276429.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    EF127467 mRNA. Translation: ABO33172.1 .
    AY359126 mRNA. Translation: AAQ89483.1 .
    EU095393 mRNA. Translation: ABW79912.1 .
    EU095394 mRNA. Translation: ABW79913.1 .
    CCDSi CCDS44829.1. [Q6UVW9-1 ]
    RefSeqi NP_001124183.1. NM_001130711.1. [Q6UVW9-1 ]
    XP_005253423.1. XM_005253366.1.
    UniGenei Hs.527665.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4IOP X-ray 3.20 A 46-174 [» ]
    ProteinModelPortali Q6UVW9.
    SMRi Q6UVW9. Positions 56-172.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-58611N.
    STRINGi 9606.ENSP00000396163.

    Protein family/group databases

    MEROPSi I63.001.

    Polymorphism databases

    DMDMi 212276429.

    Proteomic databases

    PaxDbi Q6UVW9.
    PRIDEi Q6UVW9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000339766 ; ENSP00000339732 ; ENSG00000188393 . [Q6UVW9-2 ]
    ENST00000455827 ; ENSP00000396163 ; ENSG00000188393 . [Q6UVW9-1 ]
    GeneIDi 387836.
    KEGGi hsa:387836.
    UCSCi uc009zhb.2. human. [Q6UVW9-2 ]
    uc009zhc.2. human. [Q6UVW9-1 ]

    Organism-specific databases

    CTDi 387836.
    GeneCardsi GC12M010051.
    H-InvDB HIX0036770.
    HGNCi HGNC:24191. CLEC2A.
    HPAi HPA048530.
    MIMi 612087. gene.
    neXtProti NX_Q6UVW9.
    PharmGKBi PA142672099.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG259216.
    HOGENOMi HOG000059595.
    HOVERGENi HBG107718.
    OMAi EAWISFI.
    OrthoDBi EOG7R833G.
    PhylomeDBi Q6UVW9.
    TreeFami TF351467.

    Miscellaneous databases

    GenomeRNAii 387836.
    NextBioi 101654.
    PROi Q6UVW9.
    SOURCEi Search...

    Gene expression databases

    CleanExi HS_CLEC2A.
    Genevestigatori Q6UVW9.

    Family and domain databases

    Gene3Di 3.10.100.10. 1 hit.
    InterProi IPR001304. C-type_lectin.
    IPR016186. C-type_lectin-like.
    IPR016187. C-type_lectin_fold.
    [Graphical view ]
    Pfami PF00059. Lectin_C. 1 hit.
    [Graphical view ]
    SMARTi SM00034. CLECT. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56436. SSF56436. 1 hit.
    PROSITEi PS50041. C_TYPE_LECTIN_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH KLRB1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Tissue: Spleen.
    2. 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.

    Entry informationi

    Entry nameiCLC2A_HUMAN
    AccessioniPrimary (citable) accession number: Q6UVW9
    Secondary accession number(s): A5Y4G5, A9QKS2, A9QKS3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 12, 2006
    Last sequence update: November 4, 2008
    Last modified: October 1, 2014
    This is version 87 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3