Q9UJ71 (CLC4K_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-type lectin domain family 4 member K

Alternative name(s):
Langerin
CD_antigen=CD207

Gene names

Name:	CD207
Synonyms:	CLEC4K

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	328 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Coiled coil Signal-anchor Transmembrane Transmembrane helix
Ligand	Lectin
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Traceable author statement. Source: Reactome defense response to virus Inferred from direct assay Ref.6. Source: UniProtKB
Cellular_component	clathrin-coated endocytic vesicle membrane Traceable author statement. Source: Reactome early endosome membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	mannose binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 328

328

C-type lectin domain family 4 member K

PRO_0000223693

Regions

Topological domain

1 – 43

43

Cytoplasmic Potential

Transmembrane

44 – 64

21

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

Topological domain

65 – 328

264

Extracellular Potential

Domain

202 – 320

119

C-type lectin

Coiled coil

145 – 190

46

Potential

Amino acid modifications

Modified residue

237

1

Phosphoserine Ref.7

Modified residue

243

1

Phosphotyrosine Ref.7

Glycosylation

87

1

N-linked (GlcNAc...) Potential

Glycosylation

113

1

N-linked (GlcNAc...) Potential

Glycosylation

180

1

N-linked (GlcNAc...) Potential

Disulfide bond

223 ↔ 319

Ref.10

Disulfide bond

295 ↔ 311

Ref.10

Natural variations

Natural variant

55

1

A → V.
Corresponds to variant rs10489990 [ dbSNP | Ensembl ].

VAR_054781

Natural variant

136

1

Q → E.
Corresponds to variant rs17718987 [ dbSNP | Ensembl ].

VAR_056151

Natural variant

213

1

P → S.
Corresponds to variant rs17006436 [ dbSNP | Ensembl ].

VAR_054782

Natural variant

264

1

W → R in BIRGD; abolishes mannose-binding ability. Ref.11 Ref.12

VAR_063828

Natural variant

278

1

V → A No effect on mannose-binding ability. Ref.1 Ref.12
Corresponds to variant rs741326 [ dbSNP | Ensembl ].

VAR_054783

Natural variant

288

1

N → D Significant reduction in mannose-binding ability. Ref.12
Corresponds to variant rs13383830 [ dbSNP | Ensembl ].

VAR_054784

Natural variant

300

1

A → 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

Mutagenesis

285

1

E → A: Loss of binding to 6'-sulfo-LacNAc and invertase. Ref.8

Mutagenesis

287

1

N → A: Loss of binding to 6'-sulfo-LacNAc and invertase. Ref.8

Mutagenesis

299

1

K → A: Loss of binding to 6'-sulfo-LacNAc. Ref.8

Mutagenesis

313

1

K → A: Loss of binding to 6'-sulfo-LacNAc and 6-sulfo-GlcNAc. Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

.

.

.

.

.

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.

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.

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.

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.

328

Helix Strand Turn

Details...

Helix

160 – 195

36

Turn

196 – 198

3

Beta strand

200 – 202

3

Beta strand

205 – 209

5

Helix

216 – 225

10

Helix

236 – 246

11

Beta strand

251 – 258

8

Turn

259 – 262

4

Beta strand

263 – 266

4

Helix

274 – 277

4

Helix

278 – 280

3

Helix

289 – 291

3

Beta strand

295 – 298

4

Beta strand

300 – 304

5

Beta strand

306 – 309

4

Beta strand

315 – 322

8

Sequences

	Sequence		Length	Mass (Da)
	Q9UJ71 [UniParc]. Last modified March 24, 2009. Version 2. Checksum: 83DF432682BF4B62	FASTA	328	36,725
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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.

Web resources

Functional Glycomics Gateway - Glycan Binding

Langerin

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ242859 mRNA. Translation: CAB62403.1.
AC007395 Genomic DNA. No translation available.
BC022278 mRNA. Translation: AAH22278.1.

IPI

IPI00296527.

RefSeq

NP_056532.3. NM_015717.3.

UniGene

Hs.199731.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3C22	X-ray	1.50	A/B/C/D	188-328	[»]
3KQG	X-ray	2.30	A/B/C/D/E/F	148-328	[»]
3P5D	X-ray	1.80	A/B/C/D	193-328	[»]
3P5E	X-ray	1.70	A/B/C/D	193-328	[»]
3P5F	X-ray	1.75	A/B/C/D	193-328	[»]
3P5G	X-ray	1.60	A/B/C/D	193-328	[»]
3P5H	X-ray	1.61	A/B/C/D	193-328	[»]
3P5I	X-ray	1.80	A/B/C/D	193-328	[»]
3P7F	X-ray	2.50	A/B/C/D	193-328	[»]
3P7G	X-ray	1.60	A/B/C/D	193-328	[»]
3P7H	X-ray	2.30	A/B/C/D	193-328	[»]

ProteinModelPortal

Q9UJ71.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UJ71. 1 interaction.

STRING

9606.ENSP00000386378.

PTM databases

PhosphoSite

Q9UJ71.

Polymorphism databases

DMDM

229784129.

Proteomic databases

PaxDb

Q9UJ71.

PRIDE

Q9UJ71.

Protocols and materials databases

DNASU

50489.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000410009; ENSP00000386378; ENSG00000116031.

GeneID

50489.

KEGG

hsa:50489.

UCSC

uc002shg.3. human.

Organism-specific databases

CTD

50489.

GeneCards

GC02M071057.

HGNC

HGNC:17935. CD207.

HPA

CAB002222.
HPA011216.

MIM

604862. gene.
613393. phenotype.

neXtProt

NX_Q9UJ71.

PharmGKB

PA134986203.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG311341.

HOGENOM

HOG000064516.

HOVERGEN

HBG073250.

InParanoid

Q9UJ71.

KO

K06561.

OMA

LFICKRP.

OrthoDB

EOG4ZPDVN.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

Bgee

Q9UJ71.

CleanEx

HS_CD207.

Genevestigator

Q9UJ71.

GermOnline

ENSG00000116031. Homo sapiens.

Family and domain databases

Gene3D

3.10.100.10. 1 hit.

InterPro

IPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
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. 1 hit.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UJ71.

GenomeRNAi

50489.

NextBio

53062.

SOURCE

Search...

Entry information

Entry name

CLC4K_HUMAN

Accession

Primary (citable) accession number: Q9UJ71

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2006
Last sequence update:	March 24, 2009
Last modified:	May 1, 2013
This is version 101 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.