CD166_HUMAN
ID CD166_HUMAN Reviewed; 583 AA.
AC Q13740; B2RNS3; B4DTU0; O60892; Q1HGM8; Q1HGM9; Q6PEY4; Q6ZS95;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=CD166 antigen;
DE AltName: Full=Activated leukocyte cell adhesion molecule;
DE AltName: CD_antigen=CD166;
DE Flags: Precursor;
GN Name=ALCAM; Synonyms=MEMD {ECO:0000303|PubMed:9502422};
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 1), VARIANT MET-301, PARTIAL PROTEIN
RP SEQUENCE, INTERACTION WITH CD6, SUBUNIT, SUBCELLULAR LOCATION, FUNCTION,
RP AND TISSUE SPECIFICITY.
RX PubMed=7760007; DOI=10.1084/jem.181.6.2213;
RA Bowen M.A., Patel D.D., Li X., Modrell B., Malacko A.R., Wang W.-C.,
RA Marquardt H., Neubauer M., Pesando J.M., Francke U., Haynes B.F.,
RA Aruffo A.;
RT "Cloning, mapping, and characterization of activated leukocyte-cell
RT adhesion molecule (ALCAM), a CD6 ligand.";
RL J. Exp. Med. 181:2213-2220(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION (ISOFORM 3),
RP FUNCTION (ISOFORMS 1 AND 3), GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX PubMed=15496415; DOI=10.1074/jbc.m407776200;
RA Ikeda K., Quertermous T.;
RT "Molecular isolation and characterization of a soluble isoform of activated
RT leukocyte cell adhesion molecule that modulates endothelial cell
RT function.";
RL J. Biol. Chem. 279:55315-55323(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Abe Y., Bui-Thanh N.-A., Smith C.W., Ballantyne C.M., Burns A.R.;
RT "A novel alternatively spliced variant of activated leukocyte cell adhesion
RT molecule (ALCAM/CD166) resulting from a deletion in the extracellular
RT membrane proximal stem.";
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Lung, and Placenta;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, and Lung;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-583 (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=9502422;
RA Degen W.G., van Kempen L.C., Gijzen E.G., van Groningen J.J., van Kooyk Y.,
RA Bloemers H.P.J., Swart G.W.;
RT "MEMD, a new cell adhesion molecule in metastasizing human melanoma cell
RT lines, is identical to ALCAM (activated leukocyte cell adhesion
RT molecule).";
RL Am. J. Pathol. 152:805-813(1998).
RN [8]
RP DOMAIN CD6 BINDING, AND INTERACTION WITH CD6.
RX PubMed=8823162; DOI=10.1021/bi961038k;
RA Skonier J.E., Bowen M.A., Emswiler J., Aruffo A., Bajorath J.;
RT "Recognition of diverse proteins by members of the immunoglobulin
RT superfamily: delineation of the receptor binding site in the human CD6
RT ligand ALCAM.";
RL Biochemistry 35:12287-12291(1996).
RN [9]
RP GLYCOSYLATION AT ASN-91; ASN-167; ASN-480 AND ASN-499.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [10]
RP FUNCTION, INTERACTION WITH CD6, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=15048703; DOI=10.1002/eji.200424856;
RA Hassan N.J., Barclay A.N., Brown M.H.;
RT "Frontline: Optimal T cell activation requires the engagement of CD6 and
RT CD166.";
RL Eur. J. Immunol. 34:930-940(2004).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=15294938; DOI=10.4049/jimmunol.173.4.2262;
RA Gimferrer I., Calvo M., Mittelbrunn M., Farnos M., Sarrias M.R., Enrich C.,
RA Vives J., Sanchez-Madrid F., Lozano F.;
RT "Relevance of CD6-mediated interactions in T cell activation and
RT proliferation.";
RL J. Immunol. 173:2262-2270(2004).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-95; ASN-265 AND ASN-499.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CD6, SUBUNIT, AND TISSUE
RP SPECIFICITY.
RX PubMed=16352806; DOI=10.1182/blood-2005-09-3881;
RA Zimmerman A.W., Joosten B., Torensma R., Parnes J.R., van Leeuwen F.N.,
RA Figdor C.G.;
RT "Long-term engagement of CD6 and ALCAM is essential for T-cell
RT proliferation induced by dendritic cells.";
RL Blood 107:3212-3220(2006).
RN [14]
RP INTERACTION WITH CD6.
RX PubMed=16914752; DOI=10.1128/mcb.00688-06;
RA Hassan N.J., Simmonds S.J., Clarkson N.G., Hanrahan S., Puklavec M.J.,
RA Bomb M., Barclay A.N., Brown M.H.;
RT "CD6 regulates T-cell responses through activation-dependent recruitment of
RT the positive regulator SLP-76.";
RL Mol. Cell. Biol. 26:6727-6738(2006).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-91; ASN-95; ASN-457 AND
RP ASN-480.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-457.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INDUCTION BY TNF
RP AND IFNG.
RX PubMed=23169771; DOI=10.1096/fj.12-217844;
RA Iolyeva M., Karaman S., Willrodt A.H., Weingartner S., Vigl B., Halin C.;
RT "Novel role for ALCAM in lymphatic network formation and function.";
RL FASEB J. 27:978-990(2013).
RN [19]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=24740813; DOI=10.1182/blood-2014-03-565721;
RA Chitteti B.R., Kobayashi M., Cheng Y., Zhang H., Poteat B.A.,
RA Broxmeyer H.E., Pelus L.M., Hanenberg H., Zollman A., Kamocka M.M.,
RA Carlesso N., Cardoso A.A., Kacena M.A., Srour E.F.;
RT "CD166 regulates human and murine hematopoietic stem cells and the
RT hematopoietic niche.";
RL Blood 124:519-529(2014).
RN [20]
RP INTERACTION WITH CD6; LGALS1 AND LGALS3, GLYCOSYLATION, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=24945728; DOI=10.1016/j.febslet.2014.05.064;
RA Escoda-Ferran C., Carrasco E., Caballero-Banos M., Miro-Julia C.,
RA Martinez-Florensa M., Consuegra-Fernandez M., Martinez V.G., Liu F.T.,
RA Lozano F.;
RT "Modulation of CD6 function through interaction with galectin-1 and -3.";
RL FEBS Lett. 588:2805-2813(2014).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [23]
RP FUNCTION.
RX PubMed=29263213; DOI=10.4049/jimmunol.1700553;
RA Xu Z., Chang C.C., Li M., Zhang Q.Y., Vasilescu E.M., D'Agati V.,
RA Floratos A., Vlad G., Suciu-Foca N.;
RT "ILT3.Fc-CD166 Interaction Induces Inactivation of p70 S6 Kinase and
RT Inhibits Tumor Cell Growth.";
RL J. Immunol. 200:1207-1219(2018).
RN [24]
RP 3D-STRUCTURE MODELING OF 28-133.
RX PubMed=8520490; DOI=10.1002/pro.5560040822;
RA Bajorath J., Bowen M.A., Aruffo A.;
RT "Molecular model of the N-terminal receptor-binding domain of the human CD6
RT ligand ALCAM.";
RL Protein Sci. 4:1644-1647(1995).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS), DISULFIDE BONDS, INTERACTION WITH
RP CD6, AND SUBUNIT.
RX PubMed=26146185; DOI=10.1016/j.str.2015.05.019;
RA Chappell P.E., Garner L.I., Yan J., Metcalfe C., Hatherley D., Johnson S.,
RA Robinson C.V., Lea S.M., Brown M.H.;
RT "Structures of CD6 and its ligand CD166 give insight into their
RT interaction.";
RL Structure 23:1426-1436(2015).
CC -!- FUNCTION: Cell adhesion molecule that mediates both heterotypic cell-
CC cell contacts via its interaction with CD6, as well as homotypic cell-
CC cell contacts (PubMed:7760007, PubMed:15496415, PubMed:15048703,
CC PubMed:16352806, PubMed:23169771, PubMed:24945728). Promotes T-cell
CC activation and proliferation via its interactions with CD6
CC (PubMed:15048703, PubMed:16352806, PubMed:24945728). Contributes to the
CC formation and maturation of the immunological synapse via its
CC interactions with CD6 (PubMed:15294938, PubMed:16352806). Mediates
CC homotypic interactions with cells that express ALCAM (PubMed:15496415,
CC PubMed:16352806). Acts as a ligand for the LILRB4 receptor, enhancing
CC LILRB4-mediated inhibition of T cell proliferation (PubMed:29263213).
CC Required for normal hematopoietic stem cell engraftment in the bone
CC marrow (PubMed:24740813). Mediates attachment of dendritic cells onto
CC endothelial cells via homotypic interaction (PubMed:23169771). Inhibits
CC endothelial cell migration and promotes endothelial tube formation via
CC homotypic interactions (PubMed:15496415, PubMed:23169771). Required for
CC normal organization of the lymph vessel network. Required for normal
CC hematopoietic stem cell engraftment in the bone marrow. Plays a role in
CC hematopoiesis; required for normal numbers of hematopoietic stem cells
CC in bone marrow. Promotes in vitro osteoblast proliferation and
CC differentiation (By similarity). Promotes neurite extension, axon
CC growth and axon guidance; axons grow preferentially on surfaces that
CC contain ALCAM. Mediates outgrowth and pathfinding for retinal ganglion
CC cell axons (By similarity). {ECO:0000250|UniProtKB:P42292,
CC ECO:0000269|PubMed:15048703, ECO:0000269|PubMed:15294938,
CC ECO:0000269|PubMed:15496415, ECO:0000269|PubMed:16352806,
CC ECO:0000269|PubMed:24945728, ECO:0000269|PubMed:29263213,
CC ECO:0000269|PubMed:7760007}.
CC -!- FUNCTION: [Isoform 3]: Inhibits activities of membrane-bound isoforms
CC by competing for the same interaction partners. Inhibits cell
CC attachment via homotypic interactions. Promotes endothelial cell
CC migration. Inhibits endothelial cell tube formation.
CC {ECO:0000269|PubMed:15496415}.
CC -!- SUBUNIT: Homodimer (PubMed:7760007, PubMed:16352806, PubMed:15048703,
CC PubMed:26146185). Interacts (via extracellular domain) with CD6 (via
CC extracellular domain) (PubMed:7760007, PubMed:8823162, PubMed:15048703,
CC PubMed:16914752, PubMed:24945728, PubMed:26146185). Homodimerization
CC and interaction with CD6 involve the same region and cannot occur
CC simultaneously. The affinity for CD6 is much higher than the affinity
CC for self-association (PubMed:15048703). Interacts (via glycosylated
CC extracellular domain) with LGALS1 and LGALS3 (PubMed:24945728).
CC Interaction with LGALS1 or LGALS3 inhibits interaction with CD6
CC (PubMed:24945728). {ECO:0000269|PubMed:15048703,
CC ECO:0000269|PubMed:16352806, ECO:0000269|PubMed:16914752,
CC ECO:0000269|PubMed:24945728, ECO:0000269|PubMed:26146185,
CC ECO:0000269|PubMed:7760007, ECO:0000269|PubMed:8823162}.
CC -!- INTERACTION:
CC Q13740; Q13740: ALCAM; NbExp=3; IntAct=EBI-1188108, EBI-1188108;
CC Q13740; P30203: CD6; NbExp=5; IntAct=EBI-1188108, EBI-2873748;
CC Q13740; P09382: LGALS1; NbExp=3; IntAct=EBI-1188108, EBI-1048875;
CC Q13740; P17931: LGALS3; NbExp=3; IntAct=EBI-1188108, EBI-1170392;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15048703,
CC ECO:0000269|PubMed:15294938, ECO:0000269|PubMed:16352806,
CC ECO:0000269|PubMed:23169771, ECO:0000269|PubMed:24740813,
CC ECO:0000269|PubMed:24945728, ECO:0000269|PubMed:7760007}; Single-pass
CC type I membrane protein {ECO:0000305}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q61490}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q61490}. Note=Detected at the immunological
CC synapse, i.e, at the contact zone between antigen-presenting dendritic
CC cells and T-cells (PubMed:15294938, PubMed:16352806). Colocalizes with
CC CD6 and the TCR/CD3 complex at the immunological synapse
CC (PubMed:15294938). {ECO:0000269|PubMed:15294938,
CC ECO:0000269|PubMed:16352806}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted
CC {ECO:0000269|PubMed:15496415}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q13740-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13740-2; Sequence=VSP_021797;
CC Name=3; Synonyms=sALCAM;
CC IsoId=Q13740-3; Sequence=VSP_053530, VSP_053531;
CC Name=4;
CC IsoId=Q13740-4; Sequence=VSP_053529, VSP_053532;
CC -!- TISSUE SPECIFICITY: Detected on hematopoietic stem cells derived from
CC umbilical cord blood (PubMed:24740813). Detected on lymph vessel
CC endothelial cells, skin and tonsil (PubMed:23169771). Detected on
CC peripheral blood monocytes (PubMed:15048703). Detected on monocyte-
CC derived dendritic cells (at protein level) (PubMed:16352806). Detected
CC at low levels in spleen, placenta, liver (PubMed:9502422). Expressed by
CC activated T-cells, B-cells, monocytes and thymic epithelial cells
CC (PubMed:7760007). Isoform 1 and isoform 3 are detected in vein and
CC artery endothelial cells, astrocytes, keratinocytes and artery smooth
CC muscle cells (PubMed:15496415). Expressed by neurons in the brain.
CC Restricted expression in tumor cell lines. Detected in highly
CC metastasizing melanoma cell lines (PubMed:9502422).
CC {ECO:0000269|PubMed:15048703, ECO:0000269|PubMed:24740813,
CC ECO:0000269|PubMed:7760007, ECO:0000269|PubMed:9502422}.
CC -!- INDUCTION: Up-regulated by TNF and IFNG (at protein level).
CC {ECO:0000269|PubMed:23169771}.
CC -!- DOMAIN: The CD6 binding site is located in the N-terminal Ig-like
CC domain. {ECO:0000269|PubMed:8823162}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:15496415,
CC ECO:0000305|PubMed:24945728}.
CC -!- MISCELLANEOUS: [Isoform 3]: Secreted form, inhibits isoform 1
CC homophilic interaction. {ECO:0000305}.
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DR EMBL; L38608; AAB59499.1; -; mRNA.
DR EMBL; AY644765; AAV28819.1; -; mRNA.
DR EMBL; DQ486139; ABF48405.1; -; mRNA.
DR EMBL; DQ486140; ABF48406.1; -; mRNA.
DR EMBL; AK127617; BAC87059.1; -; mRNA.
DR EMBL; AK300362; BAG62102.1; -; mRNA.
DR EMBL; AK316113; BAH14484.1; -; mRNA.
DR EMBL; AC023602; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC078806; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC133476; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC057809; AAH57809.1; -; mRNA.
DR EMBL; BC137096; AAI37097.1; -; mRNA.
DR EMBL; BC137097; AAI37098.1; -; mRNA.
DR EMBL; Y10183; CAA71256.1; -; mRNA.
DR CCDS; CCDS33810.1; -. [Q13740-1]
DR CCDS; CCDS58841.1; -. [Q13740-2]
DR PIR; I39428; I39428.
DR RefSeq; NP_001230209.1; NM_001243280.1. [Q13740-2]
DR RefSeq; NP_001230212.1; NM_001243283.1. [Q13740-3]
DR RefSeq; NP_001618.2; NM_001627.3. [Q13740-1]
DR PDB; 5A2F; X-ray; 1.86 A; A=1-583.
DR PDBsum; 5A2F; -.
DR AlphaFoldDB; Q13740; -.
DR SMR; Q13740; -.
DR BioGRID; 106716; 100.
DR DIP; DIP-39093N; -.
DR IntAct; Q13740; 19.
DR MINT; Q13740; -.
DR STRING; 9606.ENSP00000305988; -.
DR ChEMBL; CHEMBL4665584; -.
DR TCDB; 8.A.23.1.10; the basigin (basigin) family.
DR GlyConnect; 1085; 66 N-Linked glycans (8 sites).
DR GlyGen; Q13740; 11 sites, 73 N-linked glycans (7 sites), 1 O-linked glycan (1 site).
DR iPTMnet; Q13740; -.
DR MetOSite; Q13740; -.
DR PhosphoSitePlus; Q13740; -.
DR SwissPalm; Q13740; -.
DR BioMuta; ALCAM; -.
DR DMDM; 118572629; -.
DR CPTAC; CPTAC-1502; -.
DR CPTAC; CPTAC-1503; -.
DR EPD; Q13740; -.
DR jPOST; Q13740; -.
DR MassIVE; Q13740; -.
DR MaxQB; Q13740; -.
DR PaxDb; Q13740; -.
DR PeptideAtlas; Q13740; -.
DR PRIDE; Q13740; -.
DR ProteomicsDB; 5128; -.
DR ProteomicsDB; 59670; -. [Q13740-1]
DR ProteomicsDB; 59671; -. [Q13740-2]
DR ProteomicsDB; 68208; -.
DR ABCD; Q13740; 25 sequenced antibodies.
DR Antibodypedia; 2625; 844 antibodies from 40 providers.
DR CPTC; Q13740; 2 antibodies.
DR DNASU; 214; -.
DR Ensembl; ENST00000306107.9; ENSP00000305988.5; ENSG00000170017.12. [Q13740-1]
DR Ensembl; ENST00000472644.6; ENSP00000419236.2; ENSG00000170017.12. [Q13740-2]
DR GeneID; 214; -.
DR KEGG; hsa:214; -.
DR MANE-Select; ENST00000306107.9; ENSP00000305988.5; NM_001627.4; NP_001618.2.
DR UCSC; uc003dvx.4; human. [Q13740-1]
DR CTD; 214; -.
DR DisGeNET; 214; -.
DR GeneCards; ALCAM; -.
DR HGNC; HGNC:400; ALCAM.
DR HPA; ENSG00000170017; Tissue enriched (parathyroid).
DR MIM; 601662; gene.
DR neXtProt; NX_Q13740; -.
DR OpenTargets; ENSG00000170017; -.
DR PharmGKB; PA24691; -.
DR VEuPathDB; HostDB:ENSG00000170017; -.
DR eggNOG; ENOG502RMQM; Eukaryota.
DR GeneTree; ENSGT00940000156881; -.
DR InParanoid; Q13740; -.
DR OMA; GIVYWLY; -.
DR OrthoDB; 536204at2759; -.
DR PhylomeDB; Q13740; -.
DR TreeFam; TF321859; -.
DR PathwayCommons; Q13740; -.
DR Reactome; R-HSA-373760; L1CAM interactions.
DR SignaLink; Q13740; -.
DR SIGNOR; Q13740; -.
DR BioGRID-ORCS; 214; 11 hits in 1082 CRISPR screens.
DR ChiTaRS; ALCAM; human.
DR GeneWiki; ALCAM; -.
DR GenomeRNAi; 214; -.
DR Pharos; Q13740; Tbio.
DR PRO; PR:Q13740; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q13740; protein.
DR Bgee; ENSG00000170017; Expressed in bronchial epithelial cell and 203 other tissues.
DR ExpressionAtlas; Q13740; baseline and differential.
DR Genevisible; Q13740; HS.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0048846; P:axon extension involved in axon guidance; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IMP:UniProtKB.
DR GO; GO:0008045; P:motor neuron axon guidance; IEA:Ensembl.
DR GO; GO:1990138; P:neuron projection extension; ISS:UniProtKB.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR DisProt; DP02515; -.
DR Gene3D; 2.60.40.10; -; 5.
DR InterPro; IPR039810; CD166_antigen.
DR InterPro; IPR013162; CD80_C2-set.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR PANTHER; PTHR11973:SF2; PTHR11973:SF2; 1.
DR Pfam; PF08205; C2-set_2; 1.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 5.
DR PROSITE; PS50835; IG_LIKE; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell adhesion;
KW Cell membrane; Cell projection; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Membrane;
KW Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..583
FT /note="CD166 antigen"
FT /id="PRO_0000014659"
FT TOPO_DOM 28..527
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 528..549
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 550..583
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..120
FT /note="Ig-like V-type 1"
FT DOMAIN 125..234
FT /note="Ig-like V-type 2"
FT DOMAIN 245..328
FT /note="Ig-like C2-type 1"
FT DOMAIN 333..409
FT /note="Ig-like C2-type 2"
FT DOMAIN 416..501
FT /note="Ig-like C2-type 3"
FT REGION 562..583
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519"
FT CARBOHYD 265
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 361
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 457
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:19349973"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 499
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:16335952"
FT DISULFID 43..113
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0007744|PDB:5A2F"
FT DISULFID 157..220
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0007744|PDB:5A2F"
FT DISULFID 270..313
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 354..392
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 435..485
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1..191
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053529"
FT VAR_SEQ 132..133
FT /note="KQ -> SK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15496415"
FT /id="VSP_053530"
FT VAR_SEQ 134..583
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15496415"
FT /id="VSP_053531"
FT VAR_SEQ 244..330
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053532"
FT VAR_SEQ 503..516
FT /note="ISIPEHDEADEISD -> N (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_021797"
FT VARIANT 229
FT /note="G -> D (in dbSNP:rs10933819)"
FT /id="VAR_029514"
FT VARIANT 258
FT /note="N -> S (in dbSNP:rs1044240)"
FT /id="VAR_003907"
FT VARIANT 301
FT /note="T -> M (in dbSNP:rs1044243)"
FT /evidence="ECO:0000269|PubMed:7760007"
FT /id="VAR_003908"
FT VARIANT 315
FT /note="L -> M (in dbSNP:rs12629872)"
FT /id="VAR_029515"
FT VARIANT 352
FT /note="V -> M (in dbSNP:rs2291375)"
FT /id="VAR_029516"
FT VARIANT 367
FT /note="M -> I (in dbSNP:rs34926152)"
FT /id="VAR_049856"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 51..59
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 65..72
FT /evidence="ECO:0007829|PDB:5A2F"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:5A2F"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:5A2F"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 98..102
FT /evidence="ECO:0007829|PDB:5A2F"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 109..117
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 120..132
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 144..148
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 152..164
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 167..172
FT /evidence="ECO:0007829|PDB:5A2F"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 184..192
FT /evidence="ECO:0007829|PDB:5A2F"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 199..207
FT /evidence="ECO:0007829|PDB:5A2F"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 218..226
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 229..234
FT /evidence="ECO:0007829|PDB:5A2F"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:5A2F"
SQ SEQUENCE 583 AA; 65102 MW; 68FEFD67C14B0C57 CRC64;
MESKGASSCR LLFCLLISAT VFRPGLGWYT VNSAYGDTII IPCRLDVPQN LMFGKWKYEK
PDGSPVFIAF RSSTKKSVQY DDVPEYKDRL NLSENYTLSI SNARISDEKR FVCMLVTEDN
VFEAPTIVKV FKQPSKPEIV SKALFLETEQ LKKLGDCISE DSYPDGNITW YRNGKVLHPL
EGAVVIIFKK EMDPVTQLYT MTSTLEYKTT KADIQMPFTC SVTYYGPSGQ KTIHSEQAVF
DIYYPTEQVT IQVLPPKNAI KEGDNITLKC LGNGNPPPEE FLFYLPGQPE GIRSSNTYTL
TDVRRNATGD YKCSLIDKKS MIASTAITVH YLDLSLNPSG EVTRQIGDAL PVSCTISASR
NATVVWMKDN IRLRSSPSFS SLHYQDAGNY VCETALQEVE GLKKRESLTL IVEGKPQIKM
TKKTDPSGLS KTIICHVEGF PKPAIQWTIT GSGSVINQTE ESPYINGRYY SKIIISPEEN
VTLTCTAENQ LERTVNSLNV SAISIPEHDE ADEISDENRE KVNDQAKLIV GIVVGLLLAA
LVAGVVYWLY MKKSKTASKH VNKDLGNMEE NKKLEENNHK TEA
