ID   CADM1_HUMAN             Reviewed;         442 AA.
AC   Q9BY67; Q86WB8; Q8N2F4;
DT   26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   26-JUN-2007, sequence version 2.
DT   04-NOV-2008, entry version 51.
DE   RecName: Full=Cell adhesion molecule 1;
DE   AltName: Full=Immunoglobulin superfamily member 4;
DE   AltName: Full=Nectin-like protein 2;
DE            Short=NECL-2;
DE   AltName: Full=Tumor suppressor in lung cancer 1;
DE            Short=TSLC-1;
DE   AltName: Full=Synaptic cell adhesion molecule;
DE   AltName: Full=Spermatogenic immunoglobulin superfamily;
DE            Short=SgIGSF;
DE   Flags: Precursor;
GN   Name=CADM1; Synonyms=IGSF4, NECL2, SYNCAM, TSLC1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=15893517; DOI=10.1016/j.bbamem.2005.01.013;
RA   Zhou Y., Du G., Hu X., Yu S., Liu Y., Xu Y., Huang X., Liu J., Yin B.,
RA   Fan M., Peng X., Qiang B., Yuan J.;
RT   "Nectin-like molecule 1 is a protein 4.1N associated protein and
RT   recruits protein 4.1N from cytoplasm to the plasma membrane.";
RL   Biochim. Biophys. Acta 1669:142-154(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Lung;
RA   Ito A., Koma Y., Nagano T.;
RT   "Cloning of a secretory isoform of SgIGSF/TSLC-1.";
RL   Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Embryo;
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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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   [4]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=11279526; DOI=10.1038/86934;
RA   Kuramochi M., Fukuhara H., Nobukuni T., Kanbe T., Maruyama T.,
RA   Ghosh H.P., Pletcher M., Isomura M., Onizuka M., Kitamura T.,
RA   Sekiya T., Reeves R.H., Murakami Y.;
RT   "TSLC1 is a tumor-suppressor gene in human non-small-cell lung
RT   cancer.";
RL   Nat. Genet. 27:427-430(2001).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH EPB41L3.
RX   PubMed=12234973;
RA   Yageta M., Kuramochi M., Masuda M., Fukami T., Fukuhara H.,
RA   Maruyama T., Shibuya M., Murakami Y.;
RT   "Direct association of TSLC1 and DAL-1, two distinct tumor suppressor
RT   proteins in lung cancer.";
RL   Cancer Res. 62:5129-5133(2002).
RN   [6]
RP   FUNCTION, SUBUNIT, AND GLYCOSYLATION.
RX   PubMed=12050160; DOI=10.1074/jbc.M203620200;
RA   Masuda M., Yageta M., Fukuhara H., Kuramochi M., Maruyama T.,
RA   Nomoto A., Murakami Y.;
RT   "The tumor suppressor protein TSLC1 is involved in cell-cell
RT   adhesion.";
RL   J. Biol. Chem. 277:31014-31019(2002).
RN   [7]
RP   DOMAIN.
RX   PubMed=14633730;
RA   Mao X., Seidlitz E., Ghosh K., Murakami Y., Ghosh H.P.;
RT   "The cytoplasmic domain is critical to the tumor suppressor activity
RT   of TSLC1 in non-small cell lung cancer.";
RL   Cancer Res. 63:7979-7985(2003).
RN   [8]
RP   DISEASE.
RX   PubMed=12925956; DOI=10.1002/ijc.11348;
RA   Fukami T., Fukuhara H., Kuramochi M., Maruyama T., Isogai K.,
RA   Sakamoto M., Takamoto S., Murakami Y.;
RT   "Promoter methylation of the TSLC1 gene in advanced lung tumors and
RT   various cancer cell lines.";
RL   Int. J. Cancer 107:53-59(2003).
RN   [9]
RP   FUNCTION.
RX   PubMed=12920246; DOI=10.1097/01.LAB.0000081391.28136.80;
RA   Ito A., Okada M., Uchino K., Wakayama T., Koma Y., Iseki S.,
RA   Tsubota N., Okita Y., Kitamura Y.;
RT   "Expression of the TSLC1 adhesion molecule in pulmonary epithelium and
RT   its down-regulation in pulmonary adenocarcinoma other than
RT   bronchioloalveolar carcinoma.";
RL   Lab. Invest. 83:1175-1183(2003).
RN   [10]
RP   INTERACTION WITH MPP3.
RX   PubMed=13679854; DOI=10.1038/sj.onc.1206744;
RA   Fukuhara H., Masuda M., Yageta M., Fukami T., Kuramochi M.,
RA   Maruyama T., Kitamura T., Murakami Y.;
RT   "Association of a lung tumor suppressor TSLC1 with MPP3, a human
RT   homologue of Drosophila tumor suppressor Dlg.";
RL   Oncogene 22:6160-6165(2003).
RN   [11]
RP   DOMAIN.
RX   PubMed=15184878; DOI=10.1038/sj.onc.1207756;
RA   Mao X., Seidlitz E., Truant R., Hitt M., Ghosh H.P.;
RT   "Re-expression of TSLC1 in a non-small-cell lung cancer cell line
RT   induces apoptosis and inhibits tumor growth.";
RL   Oncogene 23:5632-5642(2004).
RN   [12]
RP   FUNCTION, AND INTERACTION WITH CRTAM.
RX   PubMed=15811952; DOI=10.1182/blood-2005-02-0817;
RA   Boles K.S., Barchet W., Diacovo T., Cella M., Colonna M.;
RT   "The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell
RT   responses through the cell-surface receptor CRTAM.";
RL   Blood 106:779-786(2005).
RN   [13]
RP   INTERACTION WITH CRTAM.
RX   PubMed=15781451; DOI=10.1074/jbc.M502095200;
RA   Galibert L., Diemer G.S., Liu Z., Johnson R.S., Smith J.L., Walzer T.,
RA   Comeau M.R., Rauch C.T., Wolfson M.F., Sorensen R.A.,
RA   Van der Vuurst de Vries A.-R., Branstetter D.G., Koelling R.M.,
RA   Scholler J., Fanslow W.C., Baum P.R., Derry J.M., Yan W.;
RT   "Nectin-like protein 2 defines a subset of T-cell zone dendritic cells
RT   and is a ligand for class-I-restricted T-cell-associated molecule.";
RL   J. Biol. Chem. 280:21955-21964(2005).
RN   [14]
RP   FUNCTION.
RX   PubMed=15905536;
RA   Furuno T., Ito A., Koma Y., Watabe K., Yokozaki H., Bienenstock J.,
RA   Nakanishi M., Kitamura Y.;
RT   "The spermatogenic Ig superfamily/synaptic cell adhesion molecule
RT   mast-cell adhesion molecule promotes interaction with nerves.";
RL   J. Immunol. 174:6934-6942(2005).
RN   [15]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-101 AND ASN-113, AND MASS
RP   SPECTROMETRY.
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.,
RA   Moore R.J., 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).
CC   -!- FUNCTION: Mediates homophilic cell-cell adhesion in a Ca(2+)-
CC       independent manner. Also mediates heterophilic cell-cell adhesion
CC       with CADM3 and PVRL3 in a Ca(2+)-independent manner. Acts as a
CC       tumor suppressor in non-small-cell lung cancer (NSCLC) cells.
CC       Interaction with CRTAM promotes natural killer (NK) cell
CC       cytotoxicity and interferon-gamma (IFN-gamma) secretion by CD8+
CC       cells in vitro as well as NK cell-mediated rejection of tumors
CC       expressing CADM3 in vivo. May contribute to the less invasive
CC       phenotypes of lepidic growth tumor cells. In mast cells, may
CC       mediate attachment to and promote communication with nerves.
CC       CADM1, together with MITF, is essential for development and
CC       survival of mast cells in vivo. May act as a synaptic cell
CC       adhesion molecule that drives synapse assembly. May be involved in
CC       neuronal migration, axon growth, pathfinding, and fasciculation on
CC       the axons of differentiating neurons. May play diverse roles in
CC       the spermatogenesis including in the adhesion of spermatocytes and
CC       spermatids to Sertoli cells and for their normal differentiation
CC       into mature spermatozoa.
CC   -!- SUBUNIT: Homodimer. Interacts with CRTAM and EPB41L3/DAL1. The
CC       interaction with EPB41L3/DAL1 may act to anchor CADM1 to the actin
CC       cytoskeleton. Interacts via its C-terminus with the PDZ domain of
CC       MPP3 and the PDZ domain of MPP6.
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC       protein. Note=Associates with perinuclear and plasma membranes in
CC       vivo. Localized to the basolateral plasma membrane of epithelial
CC       cells in gall bladder.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9BY67-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9BY67-2; Sequence=VSP_052461, VSP_052462;
CC   -!- DOMAIN: The cytoplasmic domain appears to play a critical role in
CC       proapoptosis and tumor suppressor activity in NSCLC.
CC   -!- DISEASE: Absent or down-regulated in many advanced cases of NSCLC
CC       as well as in many other human cancers, due to gene silencing by
CC       promoter methylation.
CC   -!- SIMILARITY: Belongs to the nectin family.
CC   -!- SIMILARITY: Contains 2 Ig-like C2-type (immunoglobulin-like)
CC       domains.
CC   -!- SIMILARITY: Contains 1 Ig-like V-type (immunoglobulin-like)
CC       domain.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF132811; AAF69029.1; -; mRNA.
DR   EMBL; AB094146; BAC66178.1; -; mRNA.
DR   EMBL; AK075502; BAC11657.1; -; mRNA.
DR   RefSeq; NP_001091987.1; -.
DR   RefSeq; NP_055148.3; -.
DR   UniGene; Hs.370510; -.
DR   PDB; 3BIN; X-ray; 2.30 A; B=400-411.
DR   PDBsum; 3BIN; -.
DR   Ensembl; ENSG00000182985; Homo sapiens.
DR   GeneID; 23705; -.
DR   KEGG; hsa:23705; -.
DR   HGNC; HGNC:5951; CADM1.
DR   MIM; 605686; gene.
DR   HOVERGEN; Q9BY67; -.
DR   NextBio; 46597; -.
DR   ArrayExpress; Q9BY67; -.
DR   CleanEx; HS_CADM1; -.
DR   GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR   GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
DR   GO; GO:0008022; F:protein C-terminus binding; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0005102; F:receptor binding; IPI:UniProtKB.
DR   GO; GO:0008037; P:cell recognition; IDA:UniProtKB.
DR   GO; GO:0051606; P:detection of stimulus; IDA:UniProtKB.
DR   GO; GO:0007157; P:heterophilic cell adhesion; ISS:UniProtKB.
DR   GO; GO:0007156; P:homophilic cell adhesion; ISS:UniProtKB.
DR   GO; GO:0050715; P:positive regulation of cytokine secretion; IDA:UniProtKB.
DR   GO; GO:0042271; P:susceptibility to natural killer cell media...; IDA:UniProtKB.
DR   InterPro; IPR013162; CD80_C2-set.
DR   InterPro; IPR013151; Ig.
DR   InterPro; IPR007110; Ig-like.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR003598; Ig_sub2.
DR   InterPro; IPR013106; Ig_V-set.
DR   InterPro; IPR003585; Neurexin-like.
DR   Gene3D; G3DSA:2.60.40.10; Ig-like_fold; 2.
DR   Pfam; PF08205; C2-set_2; 1.
DR   Pfam; PF00047; ig; 1.
DR   Pfam; PF07686; V-set; 1.
DR   SMART; SM00294; 4.1m; 1.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00408; IGc2; 1.
DR   PROSITE; PS50835; IG_LIKE; 3.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Anti-oncogene; Apoptosis;
KW   Cell adhesion; Cell cycle; Cell membrane; Developmental protein;
KW   Differentiation; Glycoprotein; Immune response; Immunoglobulin domain;
KW   Membrane; Repeat; Signal; Spermatogenesis; Transmembrane.
FT   SIGNAL        1     44       Potential.
FT   CHAIN        45    442       Cell adhesion molecule 1.
FT                                /FTId=PRO_0000291968.
FT   TOPO_DOM     45    374       Extracellular (Potential).
FT   TRANSMEM    375    395       Potential.
FT   TOPO_DOM    396    442       Cytoplasmic (Potential).
FT   DOMAIN       45    139       Ig-like V-type.
FT   DOMAIN      144    238       Ig-like C2-type 1.
FT   DOMAIN      243    329       Ig-like C2-type 2.
FT   CARBOHYD    101    101       N-linked (GlcNAc...).
FT   CARBOHYD    113    113       N-linked (GlcNAc...).
FT   CARBOHYD    165    165       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    308    308       N-linked (GlcNAc...) (Potential).
FT   DISULFID     64    124       By similarity.
FT   DISULFID    166    220       By similarity.
FT   DISULFID    267    313       By similarity.
FT   VAR_SEQ     332    333       DP -> GT (in isoform 2).
FT                                /FTId=VSP_052461.
FT   VAR_SEQ     334    442       Missing (in isoform 2).
FT                                /FTId=VSP_052462.
FT   CONFLICT    153    153       K -> R (in Ref. 1; AAF69029).
FT   CONFLICT    333    359       PPTTIPPPTTTTTTTTTTTTTILTIIT -> TTATTEPAVH
FT                                GLTQLPNSAEELDSEDLS (in Ref. 3; BAC11657).
SQ   SEQUENCE   442 AA;  48509 MW;  CDEDE1E0C08BDD3A CRC64;
     MASVVLPSGS QCAAAAAAAA PPGLRLRLLL LLFSAAALIP TGDGQNLFTK DVTVIEGEVA
     TISCQVNKSD DSVIQLLNPN RQTIYFRDFR PLKDSRFQLL NFSSSELKVS LTNVSISDEG
     RYFCQLYTDP PQESYTTITV LVPPRNLMID IQKDTAVEGE EIEVNCTAMA SKPATTIRWF
     KGNTELKGKS EVEEWSDMYT VTSQLMLKVH KEDDGVPVIC QVEHPAVTGN LQTQRYLEVQ
     YKPQVHIQMT YPLQGLTREG DALELTCEAI GKPQPVMVTW VRVDDEMPQH AVLSGPNLFI
     NNLNKTDNGT YRCEASNIVG KAHSDYMLYV YDPPTTIPPP TTTTTTTTTT TTTILTIITD
     SRAGEEGSIR AVDHAVIGGV VAVVVFAMLC LLIILGRYFA RHKGTYFTHE AKGADDAADA
     DTAIINAEGG QNNSEEKKEY FI
//