ID   CADM2_HUMAN             Reviewed;         435 AA.
AC   Q8N3J6; G3XHN7; G3XHN8; Q3KQY9; Q658Q7; Q8IZP8;
DT   26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   27-MAR-2024, entry version 165.
DE   RecName: Full=Cell adhesion molecule 2;
DE   AltName: Full=Immunoglobulin superfamily member 4D;
DE            Short=IgSF4D;
DE   AltName: Full=Nectin-like protein 3;
DE            Short=NECL-3;
DE   AltName: Full=Synaptic cell adhesion molecule 2;
DE            Short=SynCAM 2;
DE   Flags: Precursor;
GN   Name=CADM2; Synonyms=IGSF4D, NECL3;
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] (ISOFORMS 5 AND 6), AND ALTERNATIVE SPLICING.
RX   PubMed=21864505; DOI=10.1016/j.bbrc.2011.08.013;
RA   Hiruma A., Ikeda I., Terui T., Ozawa M., Hashimoto T., Yasumoto S.,
RA   Nakayama J., Kubota Y., Iijima M., Sueki H., Matsumoto Y., Kato M.,
RA   Akasaka E., Ikoma N., Mabuchi T., Tamiya S., Matsuyama T., Ozawa A.,
RA   Inoko H., Oka A.;
RT   "A novel splicing variant of CADM2 as a protective transcript of
RT   psoriasis.";
RL   Biochem. Biophys. Res. Commun. 412:626-632(2011).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA   Gingrich J.R., D'Angelo A., Chang G.M., Greenberg N.M.;
RL   Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 105-435 (ISOFORM 2).
RC   TISSUE=Amygdala, and Stomach;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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   [5]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=17967169; DOI=10.1186/1471-2202-8-90;
RA   Pellissier F., Gerber A., Bauer C., Ballivet M., Ossipow V.;
RT   "The adhesion molecule Necl-3/SynCAM-2 localizes to myelinated axons, binds
RT   to oligodendrocytes and promotes cell adhesion.";
RL   BMC Neurosci. 8:90-90(2007).
CC   -!- FUNCTION: Adhesion molecule that engages in homo- and heterophilic
CC       interactions with the other nectin-like family members, leading to cell
CC       aggregation. Important for synapse organization, providing regulated
CC       trans-synaptic adhesion. Preferentially binds to oligodendrocytes.
CC       {ECO:0000269|PubMed:17967169}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17967169};
CC       Single-pass type I membrane protein {ECO:0000269|PubMed:17967169}.
CC       Synapse {ECO:0000269|PubMed:17967169}. Cell projection, axon
CC       {ECO:0000269|PubMed:17967169}. Note=Found in the axoplasm of myelinated
CC       axons.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1;
CC         IsoId=Q8N3J6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8N3J6-2; Sequence=VSP_026334, VSP_026335;
CC       Name=3;
CC         IsoId=Q8N3J6-3; Sequence=VSP_026333;
CC       Name=5; Synonyms=7;
CC         IsoId=Q8N3J6-4; Sequence=VSP_055355, VSP_055356;
CC       Name=6; Synonyms=8;
CC         IsoId=Q8N3J6-5; Sequence=VSP_055355;
CC   -!- SIMILARITY: Belongs to the nectin family. {ECO:0000305}.
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DR   EMBL; AB646740; BAK93303.1; -; mRNA.
DR   EMBL; AB646741; BAK93304.1; -; mRNA.
DR   EMBL; AB646742; BAK93305.1; -; mRNA.
DR   EMBL; AB646743; BAK93306.1; -; mRNA.
DR   EMBL; AF538973; AAN16368.1; -; mRNA.
DR   EMBL; AL833049; CAH56314.1; -; mRNA.
DR   EMBL; AL834270; CAD38945.1; -; mRNA.
DR   EMBL; BC105999; AAI06000.1; -; mRNA.
DR   CCDS; CCDS33792.1; -. [Q8N3J6-3]
DR   CCDS; CCDS54613.1; -. [Q8N3J6-2]
DR   CCDS; CCDS54614.1; -. [Q8N3J6-1]
DR   RefSeq; NP_001161146.1; NM_001167674.1. [Q8N3J6-1]
DR   RefSeq; NP_001161147.1; NM_001167675.1. [Q8N3J6-2]
DR   RefSeq; NP_001243431.1; NM_001256502.1. [Q8N3J6-5]
DR   RefSeq; NP_001243432.1; NM_001256503.1. [Q8N3J6-5]
DR   RefSeq; NP_001243433.1; NM_001256504.1. [Q8N3J6-4]
DR   RefSeq; NP_001243434.1; NM_001256505.1. [Q8N3J6-4]
DR   RefSeq; NP_694854.2; NM_153184.3. [Q8N3J6-3]
DR   RefSeq; XP_006713144.1; XM_006713081.3.
DR   AlphaFoldDB; Q8N3J6; -.
DR   SMR; Q8N3J6; -.
DR   BioGRID; 128973; 4.
DR   IntAct; Q8N3J6; 2.
DR   STRING; 9606.ENSP00000384193; -.
DR   GlyCosmos; Q8N3J6; 3 sites, No reported glycans.
DR   GlyGen; Q8N3J6; 3 sites.
DR   iPTMnet; Q8N3J6; -.
DR   PhosphoSitePlus; Q8N3J6; -.
DR   BioMuta; CADM2; -.
DR   DMDM; 74759850; -.
DR   EPD; Q8N3J6; -.
DR   jPOST; Q8N3J6; -.
DR   MassIVE; Q8N3J6; -.
DR   PaxDb; 9606-ENSP00000384193; -.
DR   PeptideAtlas; Q8N3J6; -.
DR   ProteomicsDB; 71814; -. [Q8N3J6-1]
DR   ProteomicsDB; 71815; -. [Q8N3J6-2]
DR   ProteomicsDB; 71816; -. [Q8N3J6-3]
DR   TopDownProteomics; Q8N3J6-3; -. [Q8N3J6-3]
DR   Antibodypedia; 2209; 237 antibodies from 26 providers.
DR   DNASU; 253559; -.
DR   Ensembl; ENST00000383699.8; ENSP00000373200.3; ENSG00000175161.14. [Q8N3J6-2]
DR   Ensembl; ENST00000405615.2; ENSP00000384193.2; ENSG00000175161.14. [Q8N3J6-3]
DR   Ensembl; ENST00000407528.6; ENSP00000384575.2; ENSG00000175161.14. [Q8N3J6-1]
DR   GeneID; 253559; -.
DR   KEGG; hsa:253559; -.
DR   MANE-Select; ENST00000383699.8; ENSP00000373200.3; NM_001167675.2; NP_001161147.1. [Q8N3J6-2]
DR   UCSC; uc003dqj.4; human. [Q8N3J6-1]
DR   AGR; HGNC:29849; -.
DR   CTD; 253559; -.
DR   DisGeNET; 253559; -.
DR   GeneCards; CADM2; -.
DR   HGNC; HGNC:29849; CADM2.
DR   HPA; ENSG00000175161; Group enriched (brain, retina).
DR   MIM; 609938; gene.
DR   neXtProt; NX_Q8N3J6; -.
DR   OpenTargets; ENSG00000175161; -.
DR   PharmGKB; PA162380882; -.
DR   VEuPathDB; HostDB:ENSG00000175161; -.
DR   eggNOG; ENOG502QV9X; Eukaryota.
DR   GeneTree; ENSGT00940000155947; -.
DR   HOGENOM; CLU_047574_2_1_1; -.
DR   InParanoid; Q8N3J6; -.
DR   OMA; CEVFHET; -.
DR   OrthoDB; 3039994at2759; -.
DR   PhylomeDB; Q8N3J6; -.
DR   TreeFam; TF326804; -.
DR   PathwayCommons; Q8N3J6; -.
DR   Reactome; R-HSA-418990; Adherens junctions interactions.
DR   SignaLink; Q8N3J6; -.
DR   SIGNOR; Q8N3J6; -.
DR   BioGRID-ORCS; 253559; 20 hits in 1151 CRISPR screens.
DR   ChiTaRS; CADM2; human.
DR   GenomeRNAi; 253559; -.
DR   Pharos; Q8N3J6; Tbio.
DR   PRO; PR:Q8N3J6; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q8N3J6; Protein.
DR   Bgee; ENSG00000175161; Expressed in endothelial cell and 138 other cell types or tissues.
DR   ExpressionAtlas; Q8N3J6; baseline and differential.
DR   GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR   GO; GO:0032809; C:neuronal cell body membrane; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR   GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IBA:GO_Central.
DR   CDD; cd05884; IgI_2_Necl-3; 1.
DR   CDD; cd07701; IgV_1_Necl-3; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 3.
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   InterPro; IPR003585; Neurexin-like.
DR   PANTHER; PTHR45889:SF1; CELL ADHESION MOLECULE 2; 1.
DR   PANTHER; PTHR45889; IG-LIKE DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF08205; C2-set_2; 1.
DR   Pfam; PF13927; Ig_3; 1.
DR   Pfam; PF07686; V-set; 1.
DR   SMART; SM00294; 4.1m; 1.
DR   SMART; SM00409; IG; 2.
DR   SMART; SM00408; IGc2; 2.
DR   SUPFAM; SSF48726; Immunoglobulin; 3.
DR   PROSITE; PS50835; IG_LIKE; 3.
DR   Genevisible; Q8N3J6; HS.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Cell adhesion; Cell membrane; Cell projection;
KW   Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
KW   Phosphoprotein; Reference proteome; Repeat; Signal; Synapse; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..435
FT                   /note="Cell adhesion molecule 2"
FT                   /id="PRO_0000291970"
FT   TOPO_DOM        25..367
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        368..388
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        389..435
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          27..119
FT                   /note="Ig-like V-type"
FT   DOMAIN          127..219
FT                   /note="Ig-like C2-type 1"
FT   DOMAIN          227..312
FT                   /note="Ig-like C2-type 2"
FT   MOD_RES         423
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q1WIM2"
FT   CARBOHYD        31
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        51
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        291
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        44..104
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        146..203
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        248..296
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   VAR_SEQ         1..108
FT                   /note="Missing (in isoform 5 and isoform 6)"
FT                   /evidence="ECO:0000303|PubMed:21864505"
FT                   /id="VSP_055355"
FT   VAR_SEQ         1..20
FT                   /note="MIWKRSAVLRFYSVCGLLLQ -> MFVLFLCNLSLVPAAASKNKVK (in
FT                   isoform 3)"
FT                   /evidence="ECO:0000303|Ref.2"
FT                   /id="VSP_026333"
FT   VAR_SEQ         20
FT                   /note="Q -> QAAASKNKVK (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:17974005"
FT                   /id="VSP_026334"
FT   VAR_SEQ         315..354
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:21864505"
FT                   /id="VSP_055356"
FT   VAR_SEQ         316..355
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:17974005"
FT                   /id="VSP_026335"
FT   CONFLICT        174
FT                   /note="E -> K (in Ref. 2; AAN16368)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        212
FT                   /note="A -> T (in Ref. 2; AAN16368)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   435 AA;  47554 MW;  59DDD41B7F34D446 CRC64;
     MIWKRSAVLR FYSVCGLLLQ GSQGQFPLTQ NVTVVEGGTA ILTCRVDQND NTSLQWSNPA
     QQTLYFDDKK ALRDNRIELV RASWHELSIS VSDVSLSDEG QYTCSLFTMP VKTSKAYLTV
     LGVPEKPQIS GFSSPVMEGD LMQLTCKTSG SKPAADIRWF KNDKEIKDVK YLKEEDANRK
     TFTVSSTLDF RVDRSDDGVA VICRVDHESL NATPQVAMQV LEIHYTPSVK IIPSTPFPQE
     GQPLILTCES KGKPLPEPVL WTKDGGELPD PDRMVVSGRE LNILFLNKTD NGTYRCEATN
     TIGQSSAEYV LIVHDVPNTL LPTTIIPSLT TATVTTTVAI TTSPTTSATT SSIRDPNALA
     GQNGPDHALI GGIVAVVVFV TLCSIFLLGR YLARHKGTYL TNEAKGAEDA PDADTAIINA
     EGSQVNAEEK KEYFI
//