ID   CADM4_HUMAN             Reviewed;         388 AA.
AC   Q8NFZ8; B2R7L5; Q9Y4A4;
DT   26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   27-MAR-2024, entry version 163.
DE   RecName: Full=Cell adhesion molecule 4;
DE   AltName: Full=Immunoglobulin superfamily member 4C;
DE            Short=IgSF4C;
DE   AltName: Full=Nectin-like protein 4;
DE            Short=NECL-4;
DE   AltName: Full=TSLC1-like protein 2;
DE   Flags: Precursor;
GN   Name=CADM4; Synonyms=IGSF4C, NECL4, TSLL2;
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], AND TISSUE SPECIFICITY.
RX   PubMed=11536053; DOI=10.1038/sj.onc.1204696;
RA   Fukuhara H., Kuramochi M., Nobukuni T., Fukami T., Saino M., Maruyama T.,
RA   Nomura S., Sekiya T., Murakami Y.;
RT   "Isolation of the TSLL1 and TSLL2 genes, members of the tumor suppressor
RT   TSLC1 gene family encoding transmembrane proteins.";
RL   Oncogene 20:5401-5407(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Amygdala;
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   [3]
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   [4]
RP   FUNCTION, SUBUNIT, AND TISSUE SPECIFICITY.
RX   PubMed=16261159; DOI=10.1038/sj.onc.1209192;
RA   Williams Y.N., Masuda M., Sakurai-Yageta M., Maruyama T., Shibuya M.,
RA   Murakami Y.;
RT   "Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an
RT   immunoglobulin superfamily molecule homologous to TSLC1/IGSF4.";
RL   Oncogene 25:1446-1453(2006).
CC   -!- FUNCTION: Involved in the cell-cell adhesion. Has calcium- and
CC       magnesium-independent cell-cell adhesion activity. May have tumor-
CC       suppressor activity. {ECO:0000269|PubMed:16261159}.
CC   -!- SUBUNIT: Monomer and homodimer. {ECO:0000269|PubMed:16261159}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC       membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in brain, prostate, brain, kidney and
CC       some other organs. {ECO:0000269|PubMed:11536053,
CC       ECO:0000269|PubMed:16261159}.
CC   -!- PTM: N-glycosylated. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the nectin family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC32740.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AF363368; AAM60750.1; -; mRNA.
DR   EMBL; AK313028; BAG35862.1; -; mRNA.
DR   EMBL; AC005525; AAC32740.1; ALT_SEQ; Genomic_DNA.
DR   CCDS; CCDS12627.1; -.
DR   RefSeq; NP_660339.1; NM_145296.1.
DR   AlphaFoldDB; Q8NFZ8; -.
DR   SMR; Q8NFZ8; -.
DR   BioGRID; 128268; 64.
DR   IntAct; Q8NFZ8; 9.
DR   MINT; Q8NFZ8; -.
DR   STRING; 9606.ENSP00000222374; -.
DR   GlyConnect; 1102; 2 N-Linked glycans (2 sites).
DR   GlyCosmos; Q8NFZ8; 3 sites, 2 glycans.
DR   GlyGen; Q8NFZ8; 6 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
DR   iPTMnet; Q8NFZ8; -.
DR   PhosphoSitePlus; Q8NFZ8; -.
DR   SwissPalm; Q8NFZ8; -.
DR   BioMuta; CADM4; -.
DR   DMDM; 74762572; -.
DR   EPD; Q8NFZ8; -.
DR   jPOST; Q8NFZ8; -.
DR   MassIVE; Q8NFZ8; -.
DR   MaxQB; Q8NFZ8; -.
DR   PaxDb; 9606-ENSP00000222374; -.
DR   PeptideAtlas; Q8NFZ8; -.
DR   ProteomicsDB; 73401; -.
DR   Pumba; Q8NFZ8; -.
DR   ABCD; Q8NFZ8; 1 sequenced antibody.
DR   Antibodypedia; 2174; 320 antibodies from 41 providers.
DR   DNASU; 199731; -.
DR   Ensembl; ENST00000222374.3; ENSP00000222374.1; ENSG00000105767.3.
DR   GeneID; 199731; -.
DR   KEGG; hsa:199731; -.
DR   MANE-Select; ENST00000222374.3; ENSP00000222374.1; NM_145296.2; NP_660339.1.
DR   UCSC; uc002oxc.2; human.
DR   AGR; HGNC:30825; -.
DR   CTD; 199731; -.
DR   DisGeNET; 199731; -.
DR   GeneCards; CADM4; -.
DR   HGNC; HGNC:30825; CADM4.
DR   HPA; ENSG00000105767; Tissue enhanced (brain).
DR   MIM; 609744; gene.
DR   neXtProt; NX_Q8NFZ8; -.
DR   OpenTargets; ENSG00000105767; -.
DR   PharmGKB; PA162380931; -.
DR   VEuPathDB; HostDB:ENSG00000105767; -.
DR   eggNOG; ENOG502RFJZ; Eukaryota.
DR   GeneTree; ENSGT00940000161223; -.
DR   HOGENOM; CLU_047574_2_0_1; -.
DR   InParanoid; Q8NFZ8; -.
DR   OMA; CITPRCQ; -.
DR   OrthoDB; 3039994at2759; -.
DR   PhylomeDB; Q8NFZ8; -.
DR   TreeFam; TF338300; -.
DR   PathwayCommons; Q8NFZ8; -.
DR   SignaLink; Q8NFZ8; -.
DR   BioGRID-ORCS; 199731; 190 hits in 1159 CRISPR screens.
DR   ChiTaRS; CADM4; human.
DR   GenomeRNAi; 199731; -.
DR   Pharos; Q8NFZ8; Tbio.
DR   PRO; PR:Q8NFZ8; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q8NFZ8; Protein.
DR   Bgee; ENSG00000105767; Expressed in cortical plate and 145 other cell types or tissues.
DR   GO; GO:0031252; C:cell leading edge; IDA:UniProtKB.
DR   GO; GO:0044291; C:cell-cell contact zone; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR   GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:Ensembl.
DR   GO; GO:0043183; F:vascular endothelial growth factor receptor 1 binding; IEA:Ensembl.
DR   GO; GO:0043184; F:vascular endothelial growth factor receptor 2 binding; IPI:UniProtKB.
DR   GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IBA:GO_Central.
DR   GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IMP:UniProtKB.
DR   GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IMP:UniProtKB.
DR   GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:UniProtKB.
DR   GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; ISS:UniProtKB.
DR   GO; GO:2000145; P:regulation of cell motility; IMP:UniProtKB.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB.
DR   GO; GO:0001932; P:regulation of protein phosphorylation; IMP:UniProtKB.
DR   GO; GO:0035020; P:regulation of Rac protein signal transduction; IMP:UniProtKB.
DR   GO; GO:0061041; P:regulation of wound healing; IMP:UniProtKB.
DR   CDD; cd05885; IgI_2_Necl-4; 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:SF3; CELL ADHESION MOLECULE 4; 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; 3.
DR   SMART; SM00408; IGc2; 2.
DR   SUPFAM; SSF48726; Immunoglobulin; 3.
DR   PROSITE; PS50835; IG_LIKE; 2.
DR   Genevisible; Q8NFZ8; HS.
PE   1: Evidence at protein level;
KW   Cell adhesion; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW   Membrane; Phosphoprotein; Reference proteome; Repeat; Signal;
KW   Transmembrane; Transmembrane helix; Tumor suppressor.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..388
FT                   /note="Cell adhesion molecule 4"
FT                   /id="PRO_0000291980"
FT   TOPO_DOM        21..324
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        325..345
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        346..388
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          21..119
FT                   /note="Ig-like V-type"
FT   DOMAIN          124..219
FT                   /note="Ig-like C2-type 1"
FT   DOMAIN          224..307
FT                   /note="Ig-like C2-type 2"
FT   MOD_RES         361
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8R464"
FT   CARBOHYD        31
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        67
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        286
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        44..104
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        145..199
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        245..291
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   VARIANT         225
FT                   /note="T -> A (in dbSNP:rs34246023)"
FT                   /id="VAR_032906"
SQ   SEQUENCE   388 AA;  42785 MW;  B22301C9E21A9339 CRC64;
     MGRARRFQWP LLLLWAAAAG PGAGQEVQTE NVTVAEGGVA EITCRLHQYD GSIVVIQNPA
     RQTLFFNGTR ALKDERFQLE EFSPRRVRIR LSDARLEDEG GYFCQLYTED THHQIATLTV
     LVAPENPVVE VREQAVEGGE VELSCLVPRS RPAATLRWYR DRKELKGVSS SQENGKVWSV
     ASTVRFRVDR KDDGGIIICE AQNQALPSGH SKQTQYVLDV QYSPTARIHA SQAVVREGDT
     LVLTCAVTGN PRPNQIRWNR GNESLPERAE AVGETLTLPG LVSADNGTYT CEASNKHGHA
     RALYVLVVYD PGAVVEAQTS VPYAIVGGIL ALLVFLIICV LVGMVWCSVR QKGSYLTHEA
     SGLDEQGEAR EAFLNGSDGH KRKEEFFI
//