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Protein

C-type lectin domain family 4 member M

Gene

CLEC4M

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Probable pathogen-recognition receptor involved in peripheral immune surveillance in liver. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. Is a receptor for ICAM3, probably by binding to mannose-like carbohydrates.1 Publication
(Microbial infection) Acts as an attachment receptor for Ebolavirus.2 Publications
(Microbial infection) Acts as an attachment receptor for Hepatitis C virus.2 Publications
(Microbial infection) Acts as an attachment receptor for HIV-1.2 Publications
(Microbial infection) Acts as an attachment receptor for Human coronavirus 229E.1 Publication
(Microbial infection) Acts as an attachment receptor for Human cytomegalovirus/HHV-5.1 Publication
(Microbial infection) Acts as an attachment receptor for Influenzavirus.1 Publication
(Microbial infection) Acts as an attachment receptor for SARS coronavirus.1 Publication
(Microbial infection) Acts as an attachment receptor for West-nile virus.1 Publication
(Microbial infection) Acts as an attachment receptor for Japanese encephalitis virus.1 Publication
(Microbial infection) Acts as an attachment receptor for Marburg virus glycoprotein.1 Publication
(Microbial infection) Recognition of M.bovis by dendritic cells may occur partially via this molecule.1 Publication

Miscellaneous

In vitro, is a receptor for HIV-1 and transmits HIV-1 to permissive T-cells.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi359Calcium1
Metal bindingi361Calcium1
Metal bindingi363Calcium; via carbonyl oxygen1
Metal bindingi366Calcium1
Metal bindingi377Calcium1
Metal bindingi378Calcium1

GO - Molecular functioni

  • calcium-dependent protein binding Source: AgBase
  • carbohydrate binding Source: UniProtKB
  • ICAM-3 receptor activity Source: UniProtKB
  • mannose binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • peptide antigen binding Source: UniProtKB
  • signaling receptor activity Source: UniProtKB
  • virion binding Source: UniProtKB
  • virus receptor activity Source: CACAO

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • antigen processing and presentation Source: UniProtKB
  • cell-cell recognition Source: UniProtKB
  • endocytosis Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • intracellular signal transduction Source: UniProtKB
  • intracellular transport of virus Source: UniProtKB
  • leukocyte cell-cell adhesion Source: UniProtKB
  • modulation by virus of host morphology or physiology Source: UniProtKB
  • peptide antigen transport Source: UniProtKB
  • viral genome replication Source: UniProtKB
  • virion attachment to host cell Source: UniProtKB

Keywordsi

Molecular functionHost cell receptor for virus entry, Receptor
Biological processAdaptive immunity, Endocytosis, Host-virus interaction, Immunity, Innate immunity
LigandCalcium, Lectin, Mannose-binding, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
C-type lectin domain family 4 member M
Alternative name(s):
CD209 antigen-like protein 1
DC-SIGN-related protein
Short name:
DC-SIGNR
Dendritic cell-specific ICAM-3-grabbing non-integrin 2
Short name:
DC-SIGN2
Liver/lymph node-specific ICAM-3-grabbing non-integrin
Short name:
L-SIGN
CD_antigen: CD299
Gene namesi
Name:CLEC4M
Synonyms:CD209L, CD209L1, CD299
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000104938.16
HGNCiHGNC:13523 CLEC4M
MIMi605872 gene
neXtProtiNX_Q9H2X3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 49CytoplasmicCuratedAdd BLAST49
Transmembranei50 – 70Helical; Signal-anchor for type II membrane proteinCuratedAdd BLAST21
Topological domaini71 – 399ExtracellularCuratedAdd BLAST329

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi10332
OpenTargetsiENSG00000104938
PharmGKBiPA26200

Chemistry databases

ChEMBLiCHEMBL2176858

Polymorphism and mutation databases

BioMutaiCLEC4M
DMDMi46395990

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000466261 – 399C-type lectin domain family 4 member MAdd BLAST399

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi92N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi265 ↔ 395
Disulfide bondi268 ↔ 279
Disulfide bondi296 ↔ 389
Glycosylationi361N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi368 ↔ 381

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9H2X3
PeptideAtlasiQ9H2X3
PRIDEiQ9H2X3
ProteomicsDBi80616
80617 [Q9H2X3-10]
80619 [Q9H2X3-2]
80620 [Q9H2X3-3]
80621 [Q9H2X3-4]
80622 [Q9H2X3-5]
80623 [Q9H2X3-6]
80624 [Q9H2X3-7]
80625 [Q9H2X3-8]
80626 [Q9H2X3-9]

PTM databases

iPTMnetiQ9H2X3
PhosphoSitePlusiQ9H2X3

Expressioni

Tissue specificityi

Predominantly highly expressed in liver sinusoidal endothelial cells and in lymph node. Found in placental endothelium but not in macrophages. Expressed in type II alveolar cells and lung endothelial cells.3 Publications

Gene expression databases

BgeeiENSG00000104938
ExpressionAtlasiQ9H2X3 baseline and differential
GenevisibleiQ9H2X3 HS

Organism-specific databases

HPAiCAB033689
CAB033691
HPA042661

Interactioni

Subunit structurei

Homotetramer.2 Publications
(Microbial infection) Interacts with ebola virus glycoprotein (PubMed:12050398, PubMed:12502850).2 Publications
(Microbial infection) Interacts with hepatitis C virus E1 and E2 protein (PubMed:15371595, PubMed:16816373).2 Publications
(Microbial infection) Interacts with HIV-1 gp120 (PubMed:21277928, PubMed:12502850).2 Publications
(Microbial infection) Interacts with human coronavirus 229E spike glycoprotein.1 Publication
(Microbial infection) Interacts with human cytomegalovirus/HHV-5 gB protein.1 Publication
(Microbial infection) Interacts with influenzavirus hemagglutinin.1 Publication
(Microbial infection) Interacts with SARS coronavirus spike glycoprotein.1 Publication
(Microbial infection) Interacts with west-nile virus envelope protein E.1 Publication
(Microbial infection) Interacts with Japanese encephalitis virus E protein.1 Publication
(Microbial infection) Interacts with Marburg virus glycoprotein.1 Publication
(Microbial infection) Interacts with M.bovis LprG.1 Publication

GO - Molecular functioni

  • calcium-dependent protein binding Source: AgBase

Protein-protein interaction databases

BioGridi115615, 7 interactors
IntActiQ9H2X3, 3 interactors
MINTiQ9H2X3
STRINGi9606.ENSP00000316228

Structurei

Secondary structure

1399
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi220 – 232Combined sources13
Helixi262 – 264Combined sources3
Beta strandi273 – 275Combined sources3
Beta strandi278 – 282Combined sources5
Helixi289 – 298Combined sources10
Helixi309 – 322Combined sources14
Beta strandi326 – 331Combined sources6
Beta strandi333 – 335Combined sources3
Helixi349 – 354Combined sources6
Beta strandi362 – 365Combined sources4
Beta strandi368 – 372Combined sources5
Beta strandi375 – 379Combined sources5
Beta strandi385 – 392Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K9JX-ray1.90A/B262-399[»]
1SL6X-ray2.25A/B/C/D/E/F216-399[»]
1XARX-ray2.25A/B216-399[»]
1XPHX-ray1.41A250-399[»]
1Z0Ymodel-A/B/C/D85-399[»]
3JQHX-ray2.20A101-264[»]
ProteinModelPortaliQ9H2X3
SMRiQ9H2X3
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H2X3

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati108 – 1301Add BLAST23
Repeati131 – 1532Add BLAST23
Repeati154 – 1763Add BLAST23
Repeati177 – 1994Add BLAST23
Repeati200 – 2225Add BLAST23
Repeati223 – 2456Add BLAST23
Repeati246 – 2687Add BLAST23
Domaini274 – 390C-type lectinPROSITE-ProRule annotationAdd BLAST117

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni108 – 2697 X approximate tandem repeatsAdd BLAST162

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi14 – 15Endocytosis signalBy similarity2

Domaini

The tandem repeat domain, also called neck domain, mediates oligomerization.

Keywords - Domaini

Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4297 Eukaryota
ENOG410XPJ1 LUCA
GeneTreeiENSGT00760000118924
HOVERGENiHBG050992
InParanoidiQ9H2X3
KOiK06563
OMAiDNYWICK
OrthoDBiEOG091G0G9W
PhylomeDBiQ9H2X3
TreeFamiTF333341

Family and domain databases

CDDicd03590 CLECT_DC-SIGN_like, 1 hit
Gene3Di3.10.100.10, 1 hit
InterProiView protein in InterPro
IPR001304 C-type_lectin-like
IPR016186 C-type_lectin-like/link_sf
IPR018378 C-type_lectin_CS
IPR033989 CD209-like_CTLD
IPR016187 CTDL_fold
PfamiView protein in Pfam
PF00059 Lectin_C, 1 hit
SMARTiView protein in SMART
SM00034 CLECT, 1 hit
SUPFAMiSSF56436 SSF56436, 1 hit
PROSITEiView protein in PROSITE
PS00615 C_TYPE_LECTIN_1, 1 hit
PS50041 C_TYPE_LECTIN_2, 1 hit

Sequences (10)i

Sequence statusi: Complete.

This entry describes 10 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist. Several splicing events may occur independently in a modular way. Deletion of the transmembrane domain encoding exon through alternative splicing produces soluble isoforms.
Isoform 1 (identifier: Q9H2X3-1) [UniParc]FASTAAdd to basket
Also known as: mDC-SIGN2 type I

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

        10         20         30         40         50
MSDSKEPRVQ QLGLLEEDPT TSGIRLFPRD FQFQQIHGHK SSTGCLGHGA
60 70 80 90 100
LVLQLLSFML LAGVLVAILV QVSKVPSSLS QEQSEQDAIY QNLTQLKAAV
110 120 130 140 150
GELSEKSKLQ EIYQELTQLK AAVGELPEKS KLQEIYQELT RLKAAVGELP
160 170 180 190 200
EKSKLQEIYQ ELTRLKAAVG ELPEKSKLQE IYQELTRLKA AVGELPEKSK
210 220 230 240 250
LQEIYQELTE LKAAVGELPE KSKLQEIYQE LTQLKAAVGE LPDQSKQQQI
260 270 280 290 300
YQELTDLKTA FERLCRHCPK DWTFFQGNCY FMSNSQRNWH DSVTACQEVR
310 320 330 340 350
AQLVVIKTAE EQNFLQLQTS RSNRFSWMGL SDLNQEGTWQ WVDGSPLSPS
360 370 380 390
FQRYWNSGEP NNSGNEDCAE FSGSGWNDNR CDVDNYWICK KPAACFRDE
Length:399
Mass (Da):45,350
Last modified:March 1, 2001 - v1
Checksum:i0FADC99F72AEA593
GO
Isoform 2 (identifier: Q9H2X3-2) [UniParc]FASTAAdd to basket
Also known as: mDC-SIGN2 type III, mDC-SIGN2 type IV

The sequence of this isoform differs from the canonical sequence as follows:
     262-272: ERLCRHCPKDW → GEFLHIKGPWA
     273-399: Missing.

Note: May be due to intron retention.
Show »
Length:272
Mass (Da):30,481
Checksum:iB26BE2F2DE541F5E
GO
Isoform 3 (identifier: Q9H2X3-3) [UniParc]FASTAAdd to basket
Also known as: mDC-SIGN2 type V

The sequence of this isoform differs from the canonical sequence as follows:
     313-324: NFLQLQTSRSNR → LPAVLEQWRTQQ
     325-399: Missing.

Show »
Length:324
Mass (Da):36,769
Checksum:iB22BD6E0C926649A
GO
Isoform 4 (identifier: Q9H2X3-4) [UniParc]FASTAAdd to basket
Also known as: mDC-SIGN2 type VI

The sequence of this isoform differs from the canonical sequence as follows:
     170-238: Missing.
     239-261: Missing.
     313-324: NFLQLQTSRSNR → LPAVLEQWRTQQ
     325-399: Missing.

Show »
Length:232
Mass (Da):26,283
Checksum:iB50EB1500097CB70
GO
Isoform 5 (identifier: Q9H2X3-5) [UniParc]FASTAAdd to basket
Also known as: sDC-SIGN2 type I

The sequence of this isoform differs from the canonical sequence as follows:
     44-71: GCLGHGALVLQLLSFMLLAGVLVAILVQ → VPFLLGP
     177-199: Missing.
     239-261: Missing.

Show »
Length:332
Mass (Da):37,954
Checksum:iC6FDEF92C1B073C6
GO
Isoform 6 (identifier: Q9H2X3-6) [UniParc]FASTAAdd to basket
Also known as: sDC-SIGN2 type II

The sequence of this isoform differs from the canonical sequence as follows:
     44-71: GCLGHGALVLQLLSFMLLAGVLVAILVQ → VPFLLGP
     262-272: ERLCRHCPKDW → GEFLHIKGPWA
     273-399: Missing.

Note: May be due to intron retention.
Show »
Length:251
Mass (Da):28,373
Checksum:i86F69F6CD6055D6E
GO
Isoform 7 (identifier: Q9H2X3-7) [UniParc]FASTAAdd to basket
Also known as: sDC-SIGN2 type III

The sequence of this isoform differs from the canonical sequence as follows:
     44-71: GCLGHGALVLQLLSFMLLAGVLVAILVQ → VPFLLGP
     147-261: Missing.

Show »
Length:263
Mass (Da):30,131
Checksum:i2BB0AAF2C506495E
GO
Isoform 8 (identifier: Q9H2X3-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     177-199: Missing.

Note: Non-canonical intron-exon splice junction.
Show »
Length:376
Mass (Da):42,724
Checksum:i36CB19991F23BE90
GO
Isoform 9 (identifier: Q9H2X3-9) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     16-43: Missing.
     313-324: NFLQLQTSRSNR → LPAVLEQWRTQQ
     325-399: Missing.

Show »
Length:296
Mass (Da):33,528
Checksum:i70228F848F2DE64F
GO
Isoform 10 (identifier: Q9H2X3-10) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     16-43: Missing.
     44-71: Missing.
     262-272: ERLCRHCPKDW → GEFLHIKGPWA
     273-399: Missing.

Note: May be due to intron retention.
Show »
Length:216
Mass (Da):24,408
Checksum:i45F01AD20E279619
GO

Sequence cautioni

The sequence AAR04559 differs from that shown. Aberrant splicing.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti99A → T in BAB14667 (Ref. 5) Curated1

Polymorphismi

The number of repeats in the tandem repeat domain is shown to vary between 3 and 9 per allele thus contributing to a further variability in addition to alternative splicing. The shown 7 repeat-containing form has been shown to be the most frequent one (53.9%) in a study with 350 Caucasian individuals.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050107164R → Q1 PublicationCorresponds to variant dbSNP:rs11465376Ensembl.1
Natural variantiVAR_050108205Y → C. Corresponds to variant dbSNP:rs479448Ensembl.1
Natural variantiVAR_050109251Y → C. Corresponds to variant dbSNP:rs479448Ensembl.1
Natural variantiVAR_021957291D → N1 PublicationCorresponds to variant dbSNP:rs2277998Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01005616 – 43Missing in isoform 9 and isoform 10. 2 PublicationsAdd BLAST28
Alternative sequenceiVSP_01005744 – 71Missing in isoform 10. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_01005844 – 71GCLGH…AILVQ → VPFLLGP in isoform 5, isoform 6 and isoform 7. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_010059147 – 261Missing in isoform 7. 1 PublicationAdd BLAST115
Alternative sequenceiVSP_010060170 – 238Missing in isoform 4. 1 PublicationAdd BLAST69
Alternative sequenceiVSP_010061177 – 199Missing in isoform 5 and isoform 8. 3 PublicationsAdd BLAST23
Alternative sequenceiVSP_010062239 – 261Missing in isoform 4 and isoform 5. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_010063262 – 272ERLCRHCPKDW → GEFLHIKGPWA in isoform 2, isoform 6 and isoform 10. 2 PublicationsAdd BLAST11
Alternative sequenceiVSP_010064273 – 399Missing in isoform 2, isoform 6 and isoform 10. 2 PublicationsAdd BLAST127
Alternative sequenceiVSP_010065313 – 324NFLQL…SRSNR → LPAVLEQWRTQQ in isoform 3, isoform 4 and isoform 9. 2 PublicationsAdd BLAST12
Alternative sequenceiVSP_010066325 – 399Missing in isoform 3, isoform 4 and isoform 9. 2 PublicationsAdd BLAST75

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB015629 mRNA Translation: BAA76496.1
AF245219 mRNA Translation: AAG13848.2
AF209481, AF209480 Genomic DNA Translation: AAG13815.2
AY042234 mRNA Translation: AAK91859.1
AY042235 mRNA Translation: AAK91860.1
AY042236 mRNA Translation: AAK91861.1
AY042237 mRNA Translation: AAK91862.1
AY042238 mRNA Translation: AAK91863.1
AY042239 mRNA Translation: AAK91864.1
AY042240 mRNA Translation: AAK91865.1
AF290887 mRNA Translation: AAK20998.1
AY343913 mRNA Translation: AAR04559.1 Sequence problems.
AK023750 mRNA Translation: BAB14667.1
AK292278 mRNA Translation: BAF84967.1
AC008812 Genomic DNA No translation available.
BC038851 mRNA Translation: AAH38851.1
CCDSiCCDS12187.1 [Q9H2X3-1]
CCDS59346.1 [Q9H2X3-4]
CCDS59347.1 [Q9H2X3-7]
CCDS59348.1 [Q9H2X3-9]
RefSeqiNP_001138377.1, NM_001144905.1
NP_001138378.1, NM_001144906.1 [Q9H2X3-7]
NP_001138379.1, NM_001144907.1 [Q9H2X3-5]
NP_001138380.1, NM_001144908.1 [Q9H2X3-4]
NP_001138381.1, NM_001144909.1
NP_001138382.1, NM_001144910.1 [Q9H2X3-8]
NP_001138383.1, NM_001144911.1 [Q9H2X3-9]
NP_055072.3, NM_014257.4 [Q9H2X3-1]
XP_006722678.1, XM_006722615.2 [Q9H2X3-3]
UniGeneiHs.421437

Genome annotation databases

EnsembliENST00000248228; ENSP00000248228; ENSG00000104938 [Q9H2X3-8]
ENST00000327325; ENSP00000316228; ENSG00000104938 [Q9H2X3-1]
ENST00000359059; ENSP00000351954; ENSG00000104938 [Q9H2X3-5]
ENST00000595496; ENSP00000470132; ENSG00000104938 [Q9H2X3-7]
ENST00000596363; ENSP00000471125; ENSG00000104938 [Q9H2X3-9]
ENST00000597522; ENSP00000471132; ENSG00000104938 [Q9H2X3-4]
GeneIDi10332
KEGGihsa:10332
UCSCiuc002mhz.4 human [Q9H2X3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCLC4M_HUMAN
AccessioniPrimary (citable) accession number: Q9H2X3
Secondary accession number(s): A6NKI4
, A8K8B3, Q69F40, Q969M4, Q96QP3, Q96QP4, Q96QP5, Q96QP6, Q9BXS3, Q9H2Q9, Q9H8F0, Q9Y2A8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: March 1, 2001
Last modified: June 20, 2018
This is version 170 of the entry and version 1 of the sequence. See 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 cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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