CLC4M_HUMAN
ID CLC4M_HUMAN Reviewed; 399 AA.
AC Q9H2X3; A6NKI4; A8K8B3; Q69F40; Q969M4; Q96QP3; Q96QP4; Q96QP5; Q96QP6;
AC Q9BXS3; Q9H2Q9; Q9H8F0; Q9Y2A8;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=C-type lectin domain family 4 member M;
DE AltName: Full=CD209 antigen-like protein 1;
DE AltName: Full=DC-SIGN-related protein;
DE Short=DC-SIGNR;
DE AltName: Full=Dendritic cell-specific ICAM-3-grabbing non-integrin 2;
DE Short=DC-SIGN2;
DE AltName: Full=Liver/lymph node-specific ICAM-3-grabbing non-integrin;
DE Short=L-SIGN;
DE AltName: CD_antigen=CD299;
GN Name=CLEC4M; Synonyms=CD209L, CD209L1, CD299;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 9).
RC TISSUE=Liver;
RX PubMed=10072769; DOI=10.1016/s0378-1119(99)00004-9;
RA Yokoyama-Kobayashi M., Yamaguchi T., Sekine S., Kato S.;
RT "Selection of cDNAs encoding putative type II membrane proteins on the cell
RT surface from a human full-length cDNA bank.";
RL Gene 228:161-167(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=10975799; DOI=10.4049/jimmunol.165.6.2937;
RA Soilleux E.J., Barten R., Trowsdale J.;
RT "DC-SIGN, a related gene, DC-SIGNR, and CD23 form a cluster on 19p13.";
RL J. Immunol. 165:2937-2942(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 4; 5; 6 AND 7), ALTERNATIVE
RP SPLICING (ISOFORM 3), POLYMORPHISM, AND VARIANT GLN-164.
RX PubMed=11337487; DOI=10.1074/jbc.m009807200;
RA Mummidi S., Catano G., Lam L., Hoefle A., Telles V., Begum K., Jimenez F.,
RA Ahuja S.S., Ahuja S.K.;
RT "Extensive repertoire of membrane-bound and soluble dendritic cell-specific
RT ICAM-3-grabbing nonintegrin 1 (DC-SIGN1) and DC-SIGN2 isoforms. Inter-
RT individual variation in expression of DC-SIGN transcripts.";
RL J. Biol. Chem. 276:33196-33212(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8), TISSUE SPECIFICITY, FUNCTION,
RP INTERACTION WITH ICAM3 AND HIV-1 GP120, AND POLYMORPHISM.
RX PubMed=11257134; DOI=10.1084/jem.193.6.671;
RA Bashirova A.A., Geijtenbeek T.B.H., van Duijnhoven G.C.F., van Vliet S.J.,
RA Eilering J.B.G., Martin M.P., Wu L., Martin T.D., Viebig N., Knolle P.A.,
RA Kewalramani V.N., van Kooyk Y., Carrington M.;
RT "A dendritic cell-specific intercellular adhesion molecule 3-grabbing
RT nonintegrin (DC-SIGN)-related protein is highly expressed on human liver
RT sinusoidal endothelial cells and promotes HIV-1 infection.";
RL J. Exp. Med. 193:671-678(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASN-291.
RA Bruen S., Bashirova A., Carrington M., KewalRamani V.;
RT "L-SIGN interaction with HIV-1.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 8 AND 10).
RC TISSUE=Placenta, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP TISSUE SPECIFICITY, INTERACTION WITH HIV-1 GP120 (MICROBIAL INFECTION), AND
RP ROLE IN HIV-1 INFECTION (MICROBIAL INFECTION).
RX PubMed=11226297; DOI=10.1073/pnas.051631398;
RA Poehlmann S., Soilleux E.J., Baribaud F., Leslie G.J., Morris L.S.,
RA Trowsdale J., Lee B., Coleman N., Doms R.W.;
RT "DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to
RT human and simian immunodeficiency viruses and activates infection in
RT trans.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2670-2675(2001).
RN [10]
RP SUBUNIT, AND LIGAND-BINDING.
RX PubMed=11384997; DOI=10.1074/jbc.m104565200;
RA Mitchell D.A., Fadden A.J., Drickamer K.;
RT "A novel mechanism of carbohydrate recognition by the C-type lectins DC-
RT SIGN and DC-SIGNR. Subunit organization and binding to multivalent
RT ligands.";
RL J. Biol. Chem. 276:28939-28945(2001).
RN [11]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HUMAN
RP CYTOMEGALOVIRUS/HHV-5 GB PROTEIN (MICROBIAL INFECTION).
RX PubMed=12433371; DOI=10.1016/s1074-7613(02)00447-8;
RA Halary F., Amara A., Lortat-Jacob H., Messerle M., Delaunay T., Houles C.,
RA Fieschi F., Arenzana-Seisdedos F., Moreau J.-F., Dechanet-Merville J.;
RT "Human cytomegalovirus binding to DC-SIGN is required for dendritic cell
RT infection and target cell trans-infection.";
RL Immunity 17:653-664(2002).
RN [12]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH EBOLAVIRUS
RP GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=12050398; DOI=10.1128/jvi.76.13.6841-6844.2002;
RA Alvarez C.P., Lasala F., Carrillo J., Muniz O., Corbi A.L., Delgado R.;
RT "C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in
RT cis and in trans.";
RL J. Virol. 76:6841-6844(2002).
RN [13]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HIV-1 GP120; HIV-2
RP GP120; SIV GP120 AND EBOLA GLYCOPROTEINS (MICROBIAL INFECTION).
RX PubMed=12502850; DOI=10.1128/jvi.77.2.1337-1346.2003;
RA Lin G., Simmons G., Poehlmann S., Baribaud F., Ni H., Leslie G.J.,
RA Haggarty B.S., Bates P., Weissman D., Hoxie J.A., Doms R.W.;
RT "Differential N-linked glycosylation of human immunodeficiency virus and
RT Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and
RT DC-SIGNR.";
RL J. Virol. 77:1337-1346(2003).
RN [14]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH SARS-COV SPIKE
RP GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=15479853; DOI=10.1128/jvi.78.21.12090-12095.2004;
RA Marzi A., Gramberg T., Simmons G., Moeller P., Rennekamp A.J.,
RA Krumbiegel M., Geier M., Eisemann J., Turza N., Saunier B.,
RA Steinkasserer A., Becker S., Bates P., Hofmann H., Poehlmann S.;
RT "DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and
RT the S protein of severe acute respiratory syndrome coronavirus.";
RL J. Virol. 78:12090-12095(2004).
RN [15]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HEPATITIS C VIRUS E2
RP PROTEIN (MICROBIAL INFECTION).
RX PubMed=15371595; DOI=10.1073/pnas.0405695101;
RA Cormier E.G., Durso R.J., Tsamis F., Boussemart L., Manix C., Olson W.C.,
RA Gardner J.P., Dragic T.;
RT "L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells
RT by hepatitis C virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:14067-14072(2004).
RN [16]
RP INTERACTION WITH SARS-COV SPIKE GLYCOPROTEIN (MICROBIAL INFECTION), AND
RP TISSUE SPECIFICITY.
RX PubMed=15496474; DOI=10.1073/pnas.0403812101;
RA Jeffers S.A., Tusell S.M., Gillim-Ross L., Hemmila E.M., Achenbach J.E.,
RA Babcock G.J., Thomas W.D. Jr., Thackray L.B., Young M.D., Mason R.J.,
RA Ambrosino D.M., Wentworth D.E., Demartini J.C., Holmes K.V.;
RT "CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome
RT coronavirus.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15748-15753(2004).
RN [17]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HEPATITIS C VIRUS E1
RP AND E2 PROTEINS (MICROBIAL INFECTION).
RX PubMed=16816373; DOI=10.2353/ajpath.2006.051191;
RA Lai W.K., Sun P.J., Zhang J., Jennings A., Lalor P.F., Hubscher S.,
RA McKeating J.A., Adams D.H.;
RT "Expression of DC-SIGN and DC-SIGNR on human sinusoidal endothelium: a role
RT for capturing hepatitis C virus particles.";
RL Am. J. Pathol. 169:200-208(2006).
RN [18]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HUMAN CORONAVIRUS 229E
RP SPIKE GLYCOPROTEIN (MICROBIAL INFECTION).
RX PubMed=17037540; DOI=10.1007/978-0-387-33012-9_44;
RA Jeffers S.A., Hemmila E.M., Holmes K.V.;
RT "Human coronavirus 229E can use CD209L (L-SIGN) to enter cells.";
RL Adv. Exp. Med. Biol. 581:265-269(2006).
RN [19]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH WEST-NILE VIRUS
RP ENVELOPE PROTEIN (MICROBIAL INFECTION).
RX PubMed=16415006; DOI=10.1128/jvi.80.3.1290-1301.2006;
RA Davis C.W., Nguyen H.Y., Hanna S.L., Sanchez M.D., Doms R.W., Pierson T.C.;
RT "West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular
RT attachment and infection.";
RL J. Virol. 80:1290-1301(2006).
RN [20]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH M.BOVIS LPRG
RP (MICROBIAL INFECTION).
RX PubMed=21203928; DOI=10.1007/s13238-010-0101-3;
RA Carroll M.V., Sim R.B., Bigi F., Jaekel A., Antrobus R., Mitchell D.A.;
RT "Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG.";
RL Protein Cell 1:859-870(2010).
RN [21]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HIV-1 GP120 (MICROBIAL
RP INFECTION).
RX PubMed=21277928; DOI=10.1016/j.humimm.2011.01.012;
RA da Silva R.C., Segat L., Crovella S.;
RT "Role of DC-SIGN and L-SIGN receptors in HIV-1 vertical transmission.";
RL Hum. Immunol. 72:305-311(2011).
RN [22]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH INFLUENZAVIRUS A
RP HEMAGGLUTININ (MICROBIAL INFECTION).
RX PubMed=21191006; DOI=10.1128/jvi.01705-10;
RA Londrigan S.L., Turville S.G., Tate M.D., Deng Y.M., Brooks A.G.,
RA Reading P.C.;
RT "N-linked glycosylation facilitates sialic acid-independent attachment and
RT entry of influenza A viruses into cells expressing DC-SIGN or L-SIGN.";
RL J. Virol. 85:2990-3000(2011).
RN [23]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH JAPANESE ENCEPHALITIS
RP VIRUS E PROTEIN (MICROBIALINFECTION).
RX PubMed=24623090; DOI=10.1007/s00705-014-2042-2;
RA Shimojima M., Takenouchi A., Shimoda H., Kimura N., Maeda K.;
RT "Distinct usage of three C-type lectins by Japanese encephalitis virus: DC-
RT SIGN, DC-SIGNR, and LSECtin.";
RL Arch. Virol. 159:2023-2031(2014).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 265-394 IN COMPLEX WITH
RP GLCNAC(2)-MAN(3) PENTASACCHARIDE.
RX PubMed=11739956; DOI=10.1126/science.1066371;
RA Feinberg H., Mitchell D.A., Drickamer K., Weis W.I.;
RT "Structural basis for selective recognition of oligosaccharides by DC-SIGN
RT and DC-SIGNR.";
RL Science 294:2163-2166(2001).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 216-399, AND DISULFIDE BONDS.
RX PubMed=15509576; DOI=10.1074/jbc.m409925200;
RA Feinberg H., Guo Y., Mitchell D.A., Drickamer K., Weis W.I.;
RT "Extended neck regions stabilize tetramers of the receptors DC-SIGN and DC-
RT SIGNR.";
RL J. Biol. Chem. 280:1327-1335(2005).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.41 ANGSTROMS) OF 250-399, AND DISULFIDE BONDS.
RX PubMed=15784257; DOI=10.1016/j.jmb.2005.01.063;
RA Snyder G.A., Colonna M., Sun P.D.;
RT "The structure of DC-SIGNR with a portion of its repeat domain lends
RT insights to modeling of the receptor tetramer.";
RL J. Mol. Biol. 347:979-989(2005).
CC -!- FUNCTION: Probable pathogen-recognition receptor involved in peripheral
CC immune surveillance in liver. May mediate the endocytosis of pathogens
CC which are subsequently degraded in lysosomal compartments. Is a
CC receptor for ICAM3, probably by binding to mannose-like carbohydrates.
CC {ECO:0000269|PubMed:11257134}.
CC -!- FUNCTION: (Microbial infection) Acts as an attachment receptor for
CC Ebolavirus. {ECO:0000269|PubMed:12050398, ECO:0000269|PubMed:12502850}.
CC -!- FUNCTION: (Microbial infection) Acts as an attachment receptor for
CC Hepatitis C virus. {ECO:0000269|PubMed:15371595,
CC ECO:0000269|PubMed:16816373}.
CC -!- FUNCTION: (Microbial infection) Acts as an attachment receptor for HIV-
CC 1. {ECO:0000269|PubMed:12502850, ECO:0000269|PubMed:21203928}.
CC -!- FUNCTION: (Microbial infection) Acts as an attachment receptor for
CC Human coronavirus 229E. {ECO:0000269|PubMed:17037540}.
CC -!- FUNCTION: (Microbial infection) Acts as an attachment receptor for
CC Human cytomegalovirus/HHV-5. {ECO:0000269|PubMed:12433371}.
CC -!- FUNCTION: (Microbial infection) Acts as an attachment receptor for
CC Influenzavirus. {ECO:0000269|PubMed:21191006}.
CC -!- FUNCTION: (Microbial infection) Acts as an attachment receptor for
CC SARS-CoV. {ECO:0000269|PubMed:15479853}.
CC -!- FUNCTION: (Microbial infection) Acts as an attachment receptor for
CC West-nile virus. {ECO:0000269|PubMed:15479853}.
CC -!- FUNCTION: (Microbial infection) Acts as an attachment receptor for
CC Japanese encephalitis virus. {ECO:0000269|PubMed:24623090}.
CC -!- FUNCTION: (Microbial infection) Acts as an attachment receptor for
CC Marburg virus glycoprotein. {ECO:0000269|PubMed:15479853}.
CC -!- FUNCTION: (Microbial infection) Recognition of M.bovis by dendritic
CC cells may occur partially via this molecule.
CC {ECO:0000269|PubMed:21277928}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:11384997,
CC ECO:0000269|PubMed:11739956}.
CC -!- SUBUNIT: (Microbial infection) Interacts with ebola virus glycoprotein
CC (PubMed:12050398, PubMed:12502850). {ECO:0000269|PubMed:12050398,
CC ECO:0000269|PubMed:12502850}.
CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C virus E1 and
CC E2 protein (PubMed:15371595, PubMed:16816373).
CC {ECO:0000269|PubMed:15371595, ECO:0000269|PubMed:16816373}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 gp120
CC (PubMed:21277928, PubMed:12502850). {ECO:0000269|PubMed:12502850,
CC ECO:0000269|PubMed:21277928}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human coronavirus 229E
CC spike glycoprotein. {ECO:0000269|PubMed:17037540}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human
CC cytomegalovirus/HHV-5 gB protein. {ECO:0000269|PubMed:12433371}.
CC -!- SUBUNIT: (Microbial infection) Interacts with influenzavirus
CC hemagglutinin. {ECO:0000269|PubMed:21191006}.
CC -!- SUBUNIT: (Microbial infection) Interacts with SARS-CoV spike
CC glycoprotein. {ECO:0000269|PubMed:15479853}.
CC -!- SUBUNIT: (Microbial infection) Interacts with west-nile virus envelope
CC protein E. {ECO:0000269|PubMed:16415006}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Japanese encephalitis
CC virus E protein. {ECO:0000269|PubMed:24623090}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Marburg virus
CC glycoprotein. {ECO:0000269|PubMed:15479853}.
CC -!- SUBUNIT: (Microbial infection) Interacts with M.bovis LprG.
CC {ECO:0000269|PubMed:21203928}.
CC -!- INTERACTION:
CC Q9H2X3; Q9BYF1: ACE2; NbExp=3; IntAct=EBI-1391211, EBI-7730807;
CC Q9H2X3; Q8IY31-3: IFT20; NbExp=3; IntAct=EBI-1391211, EBI-9091197;
CC Q9H2X3; Q8IY26: PLPP6; NbExp=3; IntAct=EBI-1391211, EBI-11721828;
CC Q9H2X3; P0DTC2: S; Xeno; NbExp=12; IntAct=EBI-1391211, EBI-25474821;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000305}; Single-
CC pass type II membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000305}; Single-
CC pass type II membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane {ECO:0000305}; Single-
CC pass type II membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 6]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 7]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 10]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=10;
CC Comment=Additional isoforms seem to exist. Several splicing events
CC may occur independently in a modular way. Deletion of the
CC transmembrane domain encoding exon through alternative splicing
CC produces soluble isoforms.;
CC Name=1; Synonyms=mDC-SIGN2 type I;
CC IsoId=Q9H2X3-1; Sequence=Displayed;
CC Name=2; Synonyms=mDC-SIGN2 type III, mDC-SIGN2 type IV;
CC IsoId=Q9H2X3-2; Sequence=VSP_010063, VSP_010064;
CC Name=3; Synonyms=mDC-SIGN2 type V;
CC IsoId=Q9H2X3-3; Sequence=VSP_010065, VSP_010066;
CC Name=4; Synonyms=mDC-SIGN2 type VI;
CC IsoId=Q9H2X3-4; Sequence=VSP_010060, VSP_010062, VSP_010065,
CC VSP_010066;
CC Name=5; Synonyms=sDC-SIGN2 type I;
CC IsoId=Q9H2X3-5; Sequence=VSP_010058, VSP_010061, VSP_010062;
CC Name=6; Synonyms=sDC-SIGN2 type II;
CC IsoId=Q9H2X3-6; Sequence=VSP_010058, VSP_010063, VSP_010064;
CC Name=7; Synonyms=sDC-SIGN2 type III;
CC IsoId=Q9H2X3-7; Sequence=VSP_010058, VSP_010059;
CC Name=8;
CC IsoId=Q9H2X3-8; Sequence=VSP_010061;
CC Name=9;
CC IsoId=Q9H2X3-9; Sequence=VSP_010056, VSP_010065, VSP_010066;
CC Name=10;
CC IsoId=Q9H2X3-10; Sequence=VSP_010056, VSP_010057, VSP_010063,
CC VSP_010064;
CC -!- TISSUE SPECIFICITY: Predominantly highly expressed in liver sinusoidal
CC endothelial cells and in lymph node. Found in placental endothelium but
CC not in macrophages. Expressed in type II alveolar cells and lung
CC endothelial cells. {ECO:0000269|PubMed:11226297,
CC ECO:0000269|PubMed:11257134, ECO:0000269|PubMed:15496474}.
CC -!- DOMAIN: The tandem repeat domain, also called neck domain, mediates
CC oligomerization.
CC -!- POLYMORPHISM: The number of repeats in the tandem repeat domain is
CC shown to vary between 3 and 9 per allele thus contributing to a further
CC variability in addition to alternative splicing. The shown 7 repeat-
CC containing form has been shown to be the most frequent one (53.9%) in a
CC study with 350 Caucasian individuals.
CC -!- MISCELLANEOUS: In vitro, is a receptor for HIV-1 and transmits HIV-1 to
CC permissive T-cells.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to intron retention.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: May be due to intron retention.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 8]: Non-canonical intron-exon splice junction.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 10]: May be due to intron retention.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAR04559.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=DC-SIGNR;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_00122";
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DR EMBL; AB015629; BAA76496.1; -; mRNA.
DR EMBL; AF245219; AAG13848.2; -; mRNA.
DR EMBL; AF209481; AAG13815.2; -; Genomic_DNA.
DR EMBL; AF209480; AAG13815.2; JOINED; Genomic_DNA.
DR EMBL; AY042234; AAK91859.1; -; mRNA.
DR EMBL; AY042235; AAK91860.1; -; mRNA.
DR EMBL; AY042236; AAK91861.1; -; mRNA.
DR EMBL; AY042237; AAK91862.1; -; mRNA.
DR EMBL; AY042238; AAK91863.1; -; mRNA.
DR EMBL; AY042239; AAK91864.1; -; mRNA.
DR EMBL; AY042240; AAK91865.1; -; mRNA.
DR EMBL; AF290887; AAK20998.1; -; mRNA.
DR EMBL; AY343913; AAR04559.1; ALT_SEQ; mRNA.
DR EMBL; AK023750; BAB14667.1; -; mRNA.
DR EMBL; AK292278; BAF84967.1; -; mRNA.
DR EMBL; AC008812; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC038851; AAH38851.1; -; mRNA.
DR CCDS; CCDS12187.1; -. [Q9H2X3-1]
DR CCDS; CCDS59346.1; -. [Q9H2X3-4]
DR CCDS; CCDS59347.1; -. [Q9H2X3-7]
DR CCDS; CCDS59348.1; -. [Q9H2X3-9]
DR RefSeq; NP_001138377.1; NM_001144905.1.
DR RefSeq; NP_001138378.1; NM_001144906.1. [Q9H2X3-7]
DR RefSeq; NP_001138379.1; NM_001144907.1. [Q9H2X3-5]
DR RefSeq; NP_001138380.1; NM_001144908.1. [Q9H2X3-4]
DR RefSeq; NP_001138381.1; NM_001144909.1.
DR RefSeq; NP_001138382.1; NM_001144910.1. [Q9H2X3-8]
DR RefSeq; NP_001138383.1; NM_001144911.1. [Q9H2X3-9]
DR RefSeq; NP_055072.3; NM_014257.4. [Q9H2X3-1]
DR RefSeq; XP_006722678.1; XM_006722615.2.
DR PDB; 1K9J; X-ray; 1.90 A; A/B=262-399.
DR PDB; 1SL6; X-ray; 2.25 A; A/B/C/D/E/F=216-399.
DR PDB; 1XAR; X-ray; 2.25 A; A/B=216-399.
DR PDB; 1XPH; X-ray; 1.41 A; A=250-399.
DR PDB; 3JQH; X-ray; 2.20 A; A=101-264.
DR PDBsum; 1K9J; -.
DR PDBsum; 1SL6; -.
DR PDBsum; 1XAR; -.
DR PDBsum; 1XPH; -.
DR PDBsum; 3JQH; -.
DR AlphaFoldDB; Q9H2X3; -.
DR BMRB; Q9H2X3; -.
DR SMR; Q9H2X3; -.
DR BioGRID; 115615; 21.
DR ComplexPortal; CPX-5696; SARS-CoV Spike - human CLEC4M lectin complex.
DR ComplexPortal; CPX-6761; SARS-CoV-2 Spike - human CLEC4M lectin complex.
DR IntAct; Q9H2X3; 10.
DR MINT; Q9H2X3; -.
DR STRING; 9606.ENSP00000316228; -.
DR ChEMBL; CHEMBL2176858; -.
DR TCDB; 1.C.111.1.15; the regiiiGama (regiiiGama) family.
DR UniLectin; Q9H2X3; -.
DR GlyGen; Q9H2X3; 2 sites.
DR iPTMnet; Q9H2X3; -.
DR PhosphoSitePlus; Q9H2X3; -.
DR BioMuta; CLEC4M; -.
DR DMDM; 46395990; -.
DR jPOST; Q9H2X3; -.
DR MassIVE; Q9H2X3; -.
DR PaxDb; Q9H2X3; -.
DR PeptideAtlas; Q9H2X3; -.
DR PRIDE; Q9H2X3; -.
DR ProteomicsDB; 80616; -. [Q9H2X3-1]
DR ProteomicsDB; 80617; -. [Q9H2X3-10]
DR ProteomicsDB; 80619; -. [Q9H2X3-2]
DR ProteomicsDB; 80620; -. [Q9H2X3-3]
DR ProteomicsDB; 80621; -. [Q9H2X3-4]
DR ProteomicsDB; 80622; -. [Q9H2X3-5]
DR ProteomicsDB; 80623; -. [Q9H2X3-6]
DR ProteomicsDB; 80624; -. [Q9H2X3-7]
DR ProteomicsDB; 80625; -. [Q9H2X3-8]
DR ProteomicsDB; 80626; -. [Q9H2X3-9]
DR ABCD; Q9H2X3; 46 sequenced antibodies.
DR Antibodypedia; 12235; 442 antibodies from 31 providers.
DR DNASU; 10332; -.
DR Ensembl; ENST00000327325.10; ENSP00000316228.4; ENSG00000104938.18. [Q9H2X3-1]
DR Ensembl; ENST00000596363.5; ENSP00000471125.1; ENSG00000104938.18. [Q9H2X3-9]
DR GeneID; 10332; -.
DR KEGG; hsa:10332; -.
DR MANE-Select; ENST00000327325.10; ENSP00000316228.4; NM_014257.5; NP_055072.3.
DR UCSC; uc002mhz.4; human. [Q9H2X3-1]
DR CTD; 10332; -.
DR DisGeNET; 10332; -.
DR GeneCards; CLEC4M; -.
DR HGNC; HGNC:13523; CLEC4M.
DR HPA; ENSG00000104938; Group enriched (liver, lymphoid tissue).
DR MIM; 605872; gene.
DR neXtProt; NX_Q9H2X3; -.
DR OpenTargets; ENSG00000104938; -.
DR PharmGKB; PA26200; -.
DR VEuPathDB; HostDB:ENSG00000104938; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000167383; -.
DR InParanoid; Q9H2X3; -.
DR OMA; QLQTCNT; -.
DR OrthoDB; 1509611at2759; -.
DR PhylomeDB; Q9H2X3; -.
DR TreeFam; TF333341; -.
DR PathwayCommons; Q9H2X3; -.
DR SignaLink; Q9H2X3; -.
DR SIGNOR; Q9H2X3; -.
DR BioGRID-ORCS; 10332; 6 hits in 1066 CRISPR screens.
DR EvolutionaryTrace; Q9H2X3; -.
DR GeneWiki; CLEC4M; -.
DR GenomeRNAi; 10332; -.
DR Pharos; Q9H2X3; Tbio.
DR PRO; PR:Q9H2X3; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9H2X3; protein.
DR Bgee; ENSG00000104938; Expressed in right lobe of liver and 95 other tissues.
DR ExpressionAtlas; Q9H2X3; baseline and differential.
DR Genevisible; Q9H2X3; HS.
DR GO; GO:0005737; C:cytoplasm; NAS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0043657; C:host cell; IEA:GOC.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; TAS:UniProtKB.
DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:AgBase.
DR GO; GO:0030246; F:carbohydrate binding; IBA:GO_Central.
DR GO; GO:0030369; F:ICAM-3 receptor activity; NAS:UniProtKB.
DR GO; GO:0005537; F:mannose binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042605; F:peptide antigen binding; NAS:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; NAS:UniProtKB.
DR GO; GO:0046790; F:virion binding; TAS:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; IDA:FlyBase.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0019882; P:antigen processing and presentation; NAS:UniProtKB.
DR GO; GO:0009988; P:cell-cell recognition; TAS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; NAS:UniProtKB.
DR GO; GO:0075733; P:intracellular transport of virus; TAS:UniProtKB.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; NAS:UniProtKB.
DR GO; GO:0046968; P:peptide antigen transport; NAS:UniProtKB.
DR GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; IC:ComplexPortal.
DR GO; GO:0046813; P:receptor-mediated virion attachment to host cell; IDA:ComplexPortal.
DR GO; GO:0046718; P:viral entry into host cell; IDA:FlyBase.
DR GO; GO:0019079; P:viral genome replication; NAS:UniProtKB.
DR GO; GO:0019062; P:virion attachment to host cell; TAS:UniProtKB.
DR CDD; cd03590; CLECT_DC-SIGN_like; 1.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR001304; C-type_lectin-like.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR018378; C-type_lectin_CS.
DR InterPro; IPR033989; CD209-like_CTLD.
DR InterPro; IPR016187; CTDL_fold.
DR Pfam; PF00059; Lectin_C; 1.
DR SMART; SM00034; CLECT; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS00615; C_TYPE_LECTIN_1; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Calcium;
KW Cell membrane; Disulfide bond; Endocytosis; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction; Immunity;
KW Innate immunity; Lectin; Mannose-binding; Membrane; Metal-binding;
KW Receptor; Reference proteome; Repeat; Secreted; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..399
FT /note="C-type lectin domain family 4 member M"
FT /id="PRO_0000046626"
FT TOPO_DOM 1..49
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 50..70
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000305"
FT TOPO_DOM 71..399
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT REPEAT 108..130
FT /note="1"
FT REPEAT 131..153
FT /note="2"
FT REPEAT 154..176
FT /note="3"
FT REPEAT 177..199
FT /note="4"
FT REPEAT 200..222
FT /note="5"
FT REPEAT 223..245
FT /note="6"
FT REPEAT 246..268
FT /note="7"
FT DOMAIN 274..390
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT REGION 108..269
FT /note="7 X approximate tandem repeats"
FT MOTIF 14..15
FT /note="Endocytosis signal"
FT /evidence="ECO:0000250"
FT BINDING 359
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 361
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 363
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 366
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 377
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 378
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 361
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 265..395
FT DISULFID 268..279
FT DISULFID 296..389
FT DISULFID 368..381
FT VAR_SEQ 16..43
FT /note="Missing (in isoform 9 and isoform 10)"
FT /evidence="ECO:0000303|PubMed:10072769,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_010056"
FT VAR_SEQ 44..71
FT /note="Missing (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_010057"
FT VAR_SEQ 44..71
FT /note="GCLGHGALVLQLLSFMLLAGVLVAILVQ -> VPFLLGP (in isoform
FT 5, isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:11337487"
FT /id="VSP_010058"
FT VAR_SEQ 147..261
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:11337487"
FT /id="VSP_010059"
FT VAR_SEQ 170..238
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11337487"
FT /id="VSP_010060"
FT VAR_SEQ 177..199
FT /note="Missing (in isoform 5 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:11257134,
FT ECO:0000303|PubMed:11337487, ECO:0000303|PubMed:14702039"
FT /id="VSP_010061"
FT VAR_SEQ 239..261
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:11337487"
FT /id="VSP_010062"
FT VAR_SEQ 262..272
FT /note="ERLCRHCPKDW -> GEFLHIKGPWA (in isoform 2, isoform 6
FT and isoform 10)"
FT /evidence="ECO:0000303|PubMed:11337487,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_010063"
FT VAR_SEQ 273..399
FT /note="Missing (in isoform 2, isoform 6 and isoform 10)"
FT /evidence="ECO:0000303|PubMed:11337487,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_010064"
FT VAR_SEQ 313..324
FT /note="NFLQLQTSRSNR -> LPAVLEQWRTQQ (in isoform 3, isoform
FT 4 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:10072769,
FT ECO:0000303|PubMed:11337487"
FT /id="VSP_010065"
FT VAR_SEQ 325..399
FT /note="Missing (in isoform 3, isoform 4 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:10072769,
FT ECO:0000303|PubMed:11337487"
FT /id="VSP_010066"
FT VARIANT 164
FT /note="R -> Q (in dbSNP:rs11465376)"
FT /evidence="ECO:0000269|PubMed:11337487"
FT /id="VAR_050107"
FT VARIANT 205
FT /note="Y -> C (in dbSNP:rs479448)"
FT /id="VAR_050108"
FT VARIANT 251
FT /note="Y -> C (in dbSNP:rs479448)"
FT /id="VAR_050109"
FT VARIANT 291
FT /note="D -> N (in dbSNP:rs2277998)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_021957"
FT CONFLICT 99
FT /note="A -> T (in Ref. 5; BAB14667)"
FT /evidence="ECO:0000305"
FT HELIX 220..232
FT /evidence="ECO:0007829|PDB:1SL6"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:1XPH"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:1XPH"
FT STRAND 278..282
FT /evidence="ECO:0007829|PDB:1XPH"
FT HELIX 289..298
FT /evidence="ECO:0007829|PDB:1XPH"
FT HELIX 309..322
FT /evidence="ECO:0007829|PDB:1XPH"
FT STRAND 326..331
FT /evidence="ECO:0007829|PDB:1XPH"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:1K9J"
FT HELIX 349..354
FT /evidence="ECO:0007829|PDB:1XPH"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:1XAR"
FT STRAND 368..372
FT /evidence="ECO:0007829|PDB:1XPH"
FT STRAND 375..379
FT /evidence="ECO:0007829|PDB:1XPH"
FT STRAND 385..392
FT /evidence="ECO:0007829|PDB:1XPH"
SQ SEQUENCE 399 AA; 45350 MW; 0FADC99F72AEA593 CRC64;
MSDSKEPRVQ QLGLLEEDPT TSGIRLFPRD FQFQQIHGHK SSTGCLGHGA LVLQLLSFML
LAGVLVAILV QVSKVPSSLS QEQSEQDAIY QNLTQLKAAV GELSEKSKLQ EIYQELTQLK
AAVGELPEKS KLQEIYQELT RLKAAVGELP EKSKLQEIYQ ELTRLKAAVG ELPEKSKLQE
IYQELTRLKA AVGELPEKSK LQEIYQELTE LKAAVGELPE KSKLQEIYQE LTQLKAAVGE
LPDQSKQQQI YQELTDLKTA FERLCRHCPK DWTFFQGNCY FMSNSQRNWH DSVTACQEVR
AQLVVIKTAE EQNFLQLQTS RSNRFSWMGL SDLNQEGTWQ WVDGSPLSPS FQRYWNSGEP
NNSGNEDCAE FSGSGWNDNR CDVDNYWICK KPAACFRDE
