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Q9UJ71 (CLC4K_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
C-type lectin domain family 4 member K
Alternative name(s):
Langerin
CD_antigen=CD207
Gene names
Name:CD207
Synonyms:CLEC4K
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length328 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium-dependent lectin displaying mannose-binding specificity. Induces the formation of Birbeck granules (BGs); is a potent regulator of membrane superimposition and zippering. Binds to sulfated as well as mannosylated glycans, keratan sulfate (KS) and beta-glucans. Facilitates uptake of antigens and is involved in the routing and/or processing of antigen for presentation to T cells. Major receptor on primary Langerhans cells for Candida species, Saccharomyces species, and Malassezia furfur. Protects against human immunodeficiency virus-1 (HIV-1) infection. Binds to high-mannose structures present on the envelope glycoprotein which is followed by subsequent targeting of the virus to the Birbeck granules leading to its rapid degradation. Ref.1 Ref.6 Ref.8 Ref.9

Subunit structure

Homotrimer. Ref.4

Subcellular location

Membrane; Single-pass type II membrane protein. Note: Found in Birbeck granules (BGs), which are organelles consisting of superimposed and zippered membranes. Ref.1

Tissue specificity

Exclusively expressed by Langerhans cells. Expressed in astrocytoma and malignant ependymoma, but not in normal brain tissues. Ref.1 Ref.8

Domain

The C-type lectin domain mediates dual recognition of both sulfated and mannosylated glycans. Ref.8

Involvement in disease

Birbeck granule deficiency (BIRGD) [MIM:613393]: A condition characterized by the absence of Birbeck granules in epidermal Langerhans cells. Despite the lack of Birbeck granules, Langerhans cells are present in normal numbers and have normal morphologic characteristics and antigen-presenting capacity.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12

Sequence similarities

Contains 1 C-type lectin domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 328328C-type lectin domain family 4 member K
PRO_0000223693

Regions

Topological domain1 – 4343Cytoplasmic Potential
Transmembrane44 – 6421Helical; Signal-anchor for type II membrane protein; Potential
Topological domain65 – 328264Extracellular Potential
Domain202 – 320119C-type lectin
Coiled coil145 – 19046 Potential

Amino acid modifications

Modified residue2371Phosphoserine Ref.7
Modified residue2431Phosphotyrosine Ref.7
Glycosylation871N-linked (GlcNAc...) Potential
Glycosylation1131N-linked (GlcNAc...) Potential
Glycosylation1801N-linked (GlcNAc...) Potential
Disulfide bond223 ↔ 319 Ref.10
Disulfide bond295 ↔ 311 Ref.10

Natural variations

Natural variant551A → V.
Corresponds to variant rs10489990 [ dbSNP | Ensembl ].
VAR_054781
Natural variant1361Q → E.
Corresponds to variant rs17718987 [ dbSNP | Ensembl ].
VAR_056151
Natural variant2131P → S.
Corresponds to variant rs17006436 [ dbSNP | Ensembl ].
VAR_054782
Natural variant2641W → R in BIRGD; abolishes mannose-binding ability. Ref.11 Ref.12
VAR_063828
Natural variant2781V → A No effect on mannose-binding ability. Ref.1 Ref.12
Corresponds to variant rs741326 [ dbSNP | Ensembl ].
VAR_054783
Natural variant2881N → D Significant reduction in mannose-binding ability. Ref.12
Corresponds to variant rs13383830 [ dbSNP | Ensembl ].
VAR_054784
Natural variant3001A → P Significant reduction in mannose-binding ability; significant decrease in thermal stability; increased sensitivity of sugar binding to pH change. Ref.12
Corresponds to variant rs2080391 [ dbSNP | Ensembl ].
VAR_059448

Experimental info

Mutagenesis2851E → A: Loss of binding to 6'-sulfo-LacNAc and invertase. Ref.8
Mutagenesis2871N → A: Loss of binding to 6'-sulfo-LacNAc and invertase. Ref.8
Mutagenesis2991K → A: Loss of binding to 6'-sulfo-LacNAc. Ref.8
Mutagenesis3131K → A: Loss of binding to 6'-sulfo-LacNAc and 6-sulfo-GlcNAc. Ref.8

Secondary structure

............................. 328
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UJ71 [UniParc].

Last modified March 24, 2009. Version 2.
Checksum: 83DF432682BF4B62

FASTA32836,725
        10         20         30         40         50         60 
MTVEKEAPDA HFTVDKQNIS LWPREPPPKS GPSLVPGKTP TVRAALICLT LVLVASVLLQ 

        70         80         90        100        110        120 
AVLYPRFMGT ISDVKTNVQL LKGRVDNIST LDSEIKKNSD GMEAAGVQIQ MVNESLGYVR 

       130        140        150        160        170        180 
SQFLKLKTSV EKANAQIQIL TRSWEEVSTL NAQIPELKSD LEKASALNTK IRALQGSLEN 

       190        200        210        220        230        240 
MSKLLKRQND ILQVVSQGWK YFKGNFYYFS LIPKTWYSAE QFCVSRNSHL TSVTSESEQE 

       250        260        270        280        290        300 
FLYKTAGGLI YWIGLTKAGM EGDWSWVDDT PFNKVQSVRF WIPGEPNNAG NNEHCGNIKA 

       310        320 
PSLQAWNDAP CDKTFLFICK RPYVPSEP 

« Hide

References

« Hide 'large scale' references
[1]"Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules."
Valladeau J., Ravel O., Dezutter-Dambuyant C., Moore K., Kleijmeer M., Liu Y., Duvert-Frances V., Vincent C., Schmitt D., Davoust J., Caux C., Lebecque S., Saeland S.
Immunity 12:71-81(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT ALA-278.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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].
Tissue: Lung.
[4]"Characterization of carbohydrate recognition by langerin, a C-type lectin of Langerhans cells."
Stambach N.S., Taylor M.E.
Glycobiology 13:401-410(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[5]"Langerin/CD207 sheds light on formation of Birbeck granules and their possible function in Langerhans cells."
Valladeau J., Dezutter-Dambuyant C., Saeland S.
Immunol. Res. 28:93-107(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[6]"Langerin is a natural barrier to HIV-1 transmission by Langerhans cells."
de Witte L., Nabatov A., Pion M., Fluitsma D., de Jong M.A., de Gruijl T., Piguet V., van Kooyk Y., Geijtenbeek T.B.
Nat. Med. 13:367-371(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-237 AND TYR-243, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[8]"Dual specificity of langerin to sulfated and mannosylated glycans via a single C-type carbohydrate recognition domain."
Tateno H., Ohnishi K., Yabe R., Hayatsu N., Sato T., Takeya M., Narimatsu H., Hirabayashi J.
J. Biol. Chem. 285:6390-6400(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DOMAIN C-TYPE LECTIN, MUTAGENESIS OF GLU-285; ASN-287; LYS-299 AND LYS-313.
[9]"C-type lectin Langerin is a beta-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungi."
de Jong M.A., Vriend L.E., Theelen B., Taylor M.E., Fluitsma D., Boekhout T., Geijtenbeek T.B.
Mol. Immunol. 47:1216-1225(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Structural studies of langerin and Birbeck granule: a macromolecular organization model."
Thepaut M., Valladeau J., Nurisso A., Kahn R., Arnou B., Vives C., Saeland S., Ebel C., Monnier C., Dezutter-Dambuyant C., Imberty A., Fieschi F.
Biochemistry 48:2684-2698(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 188-328, DISULFIDE BONDS.
[11]"A lack of Birbeck granules in Langerhans cells is associated with a naturally occurring point mutation in the human Langerin gene."
Verdijk P., Dijkman R., Plasmeijer E.I., Mulder A.A., Zoutman W.H., Mieke Mommaas A., Tensen C.P.
J. Invest. Dermatol. 124:714-717(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BIRGD ARG-264.
[12]"Polymorphisms in human langerin affect stability and sugar binding activity."
Ward E.M., Stambach N.S., Drickamer K., Taylor M.E.
J. Biol. Chem. 281:15450-15456(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-278; ASP-288 AND PRO-300, CHARACTERIZATION OF VARIANT BIRGD ARG-264, CHARACTERIZATION OF VARIANTS ALA-278; ASP-288 AND PRO-300.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ242859 mRNA. Translation: CAB62403.1.
AC007395 Genomic DNA. No translation available.
BC022278 mRNA. Translation: AAH22278.1.
RefSeqNP_056532.4. NM_015717.4.
UniGeneHs.199731.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3C22X-ray1.50A/B/C/D188-328[»]
3KQGX-ray2.30A/B/C/D/E/F147-328[»]
3P5DX-ray1.80A/B/C/D193-328[»]
3P5EX-ray1.70A/B/C/D193-328[»]
3P5FX-ray1.75A/B/C/D193-328[»]
3P5GX-ray1.60A/B/C/D193-328[»]
3P5HX-ray1.61A/B/C/D193-328[»]
3P5IX-ray1.80A/B/C/D193-328[»]
3P7FX-ray2.50A/B/C/D193-328[»]
3P7GX-ray1.60A/B/C/D193-328[»]
3P7HX-ray2.30A/B/C/D193-328[»]
4AK8X-ray1.40A/B/C/D188-328[»]
4N32X-ray1.75A/B/C/D193-328[»]
4N33X-ray1.85A/B/C/D193-328[»]
4N34X-ray1.75A/B/C/D193-328[»]
4N35X-ray1.85A/B/C/D193-328[»]
4N36X-ray1.85A/B/C/D193-328[»]
4N37X-ray2.00A/B/C/D193-328[»]
4N38X-ray2.00A/B/C/D193-328[»]
ProteinModelPortalQ9UJ71.
SMRQ9UJ71. Positions 159-328.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9UJ71. 1 interaction.
MINTMINT-6631688.
STRING9606.ENSP00000386378.

Chemistry

ChEMBLCHEMBL2176853.

PTM databases

PhosphoSiteQ9UJ71.

Polymorphism databases

DMDM229784129.

Proteomic databases

PaxDbQ9UJ71.
PRIDEQ9UJ71.

Protocols and materials databases

DNASU50489.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000410009; ENSP00000386378; ENSG00000116031.
ENST00000605949; ENSP00000476003; ENSG00000272210.
GeneID50489.
KEGGhsa:50489.
UCSCuc002shg.3. human.

Organism-specific databases

CTD50489.
GeneCardsGC02M071057.
HGNCHGNC:17935. CD207.
HPACAB002222.
HPA011216.
MIM604862. gene.
613393. phenotype.
neXtProtNX_Q9UJ71.
PharmGKBPA134986203.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG311341.
HOGENOMHOG000064516.
HOVERGENHBG073250.
InParanoidQ9UJ71.
KOK06561.
OMAFKGNFYY.
OrthoDBEOG7QZGBX.
PhylomeDBQ9UJ71.
TreeFamTF333341.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeQ9UJ71.
CleanExHS_CD207.
GenevestigatorQ9UJ71.

Family and domain databases

Gene3D3.10.100.10. 1 hit.
InterProIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
IPR016187. C-type_lectin_fold.
[Graphical view]
PfamPF00059. Lectin_C. 1 hit.
[Graphical view]
SMARTSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMSSF56436. SSF56436. 1 hit.
PROSITEPS00615. C_TYPE_LECTIN_1. 1 hit.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9UJ71.
GeneWikiLangerin.
GenomeRNAi50489.
NextBio53062.
PROQ9UJ71.
SOURCESearch...

Entry information

Entry nameCLC4K_HUMAN
AccessionPrimary (citable) accession number: Q9UJ71
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: March 24, 2009
Last modified: July 9, 2014
This is version 112 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 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries