ID   ADA23_HUMAN             Reviewed;         832 AA.
AC   O75077; A2RU59;
DT   07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   13-FEB-2019, entry version 147.
DE   RecName: Full=Disintegrin and metalloproteinase domain-containing protein 23;
DE            Short=ADAM 23;
DE   AltName: Full=Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 3;
DE            Short=MDC-3;
DE   Flags: Precursor;
GN   Name=ADAM23; Synonyms=MDC3;
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 ALPHA).
RC   TISSUE=Brain;
RX   PubMed=9693107; DOI=10.1042/bj3340093;
RA   Sagane K., Ohya Y., Hasegawa Y., Tanaka I.;
RT   "Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2
RT   and MDC3: novel human cellular disintegrins highly expressed in the
RT   brain.";
RL   Biochem. J. 334:93-98(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), INTERACTION WITH INTEGRIN
RP   ALPHA-V/BETA-3, AND MUTAGENESIS OF GLU-566.
RC   TISSUE=Brain;
RX   PubMed=10749942; DOI=10.1091/mbc.11.4.1457;
RA   Cal S., Freije J.M.P., Lopez J.M., Takada Y., Lopez-Otin C.;
RT   "ADAM 23/MDC3, a human disintegrin that promotes cell adhesion via
RT   interaction with the alpha v beta 3 integrin through an RGD-
RT   independent mechanism.";
RL   Mol. Biol. Cell 11:1457-1469(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA AND GAMMA), AND
RP   TISSUE SPECIFICITY.
RC   TISSUE=Fetal brain;
RX   PubMed=14697522; DOI=10.1016/j.gene.2003.10.012;
RA   Sun Y.P., Deng K.J., Wang F., Zhang J., Huang X., Qiao S., Zhao S.;
RT   "Two novel isoforms of Adam23 expressed in the developmental process
RT   of mouse and human brains.";
RL   Gene 325:171-178(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: May play a role in cell-cell and cell-matrix
CC       interactions. This is a non-catalytic metalloprotease-like
CC       protein.
CC   -!- SUBUNIT: Can bind to LGI1 and LGI4 (By similarity). Ligand for
CC       integrin alpha-V/beta-3. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass
CC       type I membrane protein {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Isoform Gamma: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=Alpha;
CC         IsoId=O75077-1; Sequence=Displayed;
CC       Name=Beta;
CC         IsoId=O75077-2; Sequence=VSP_012046;
CC       Name=Gamma;
CC         IsoId=O75077-3; Sequence=VSP_012045;
CC   -!- TISSUE SPECIFICITY: Highly expressed in the brain and weakly
CC       expressed in the heart. In the brain, expressed prominently in the
CC       amygdala, caudate nucleus, hypothalamus, thalamus, cerebral cortex
CC       and occipital pole. {ECO:0000269|PubMed:14697522}.
CC   -!- DEVELOPMENTAL STAGE: Highly expressed in the fetal brain.
CC   -!- DOMAIN: A conserved motif AVN[ED]CD within the disintegrin-like
CC       domain could be involved in the binding to the integrin receptor.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/ADAM23ID44041ch2q33.html";
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DR   EMBL; AB009672; BAA32351.1; -; mRNA.
DR   EMBL; AJ005580; CAC20565.1; -; mRNA.
DR   EMBL; CH471063; EAW70386.1; -; Genomic_DNA.
DR   EMBL; BC132763; AAI32764.1; -; mRNA.
DR   EMBL; BC132765; AAI32766.1; -; mRNA.
DR   CCDS; CCDS2369.1; -. [O75077-1]
DR   RefSeq; NP_003803.1; NM_003812.3. [O75077-1]
DR   RefSeq; XP_005246989.1; XM_005246932.3. [O75077-3]
DR   UniGene; Hs.370287; -.
DR   UniGene; Hs.591643; -.
DR   ProteinModelPortal; O75077; -.
DR   SMR; O75077; -.
DR   BioGrid; 114282; 1.
DR   CORUM; O75077; -.
DR   IntAct; O75077; 1.
DR   MINT; O75077; -.
DR   STRING; 9606.ENSP00000264377; -.
DR   MEROPS; M12.979; -.
DR   iPTMnet; O75077; -.
DR   PhosphoSitePlus; O75077; -.
DR   SwissPalm; O75077; -.
DR   BioMuta; ADAM23; -.
DR   PaxDb; O75077; -.
DR   PeptideAtlas; O75077; -.
DR   PRIDE; O75077; -.
DR   ProteomicsDB; 49740; -.
DR   ProteomicsDB; 49741; -. [O75077-2]
DR   ProteomicsDB; 49742; -. [O75077-3]
DR   Ensembl; ENST00000264377; ENSP00000264377; ENSG00000114948. [O75077-1]
DR   GeneID; 8745; -.
DR   KEGG; hsa:8745; -.
DR   UCSC; uc002vbq.6; human. [O75077-1]
DR   CTD; 8745; -.
DR   DisGeNET; 8745; -.
DR   EuPathDB; HostDB:ENSG00000114948.12; -.
DR   GeneCards; ADAM23; -.
DR   HGNC; HGNC:202; ADAM23.
DR   HPA; CAB033276; -.
DR   HPA; HPA012130; -.
DR   MIM; 603710; gene.
DR   neXtProt; NX_O75077; -.
DR   OpenTargets; ENSG00000114948; -.
DR   PharmGKB; PA24519; -.
DR   eggNOG; KOG3607; Eukaryota.
DR   eggNOG; ENOG410XX2M; LUCA.
DR   GeneTree; ENSGT00940000158781; -.
DR   HOGENOM; HOG000231962; -.
DR   HOVERGEN; HBG050456; -.
DR   InParanoid; O75077; -.
DR   KO; K06837; -.
DR   OMA; SSDQWPF; -.
DR   OrthoDB; 162519at2759; -.
DR   PhylomeDB; O75077; -.
DR   TreeFam; TF314733; -.
DR   Reactome; R-HSA-5682910; LGI-ADAM interactions.
DR   ChiTaRS; ADAM23; human.
DR   GeneWiki; ADAM23; -.
DR   GenomeRNAi; 8745; -.
DR   PRO; PR:O75077; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   Bgee; ENSG00000114948; Expressed in 166 organ(s), highest expression level in middle temporal gyrus.
DR   ExpressionAtlas; O75077; baseline and differential.
DR   Genevisible; O75077; HS.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR   GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0005178; F:integrin binding; TAS:ProtInc.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR   GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR   GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR   GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR   GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR   CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR   Gene3D; 3.40.390.10; -; 1.
DR   Gene3D; 4.10.70.10; -; 1.
DR   InterPro; IPR006586; ADAM_Cys-rich.
DR   InterPro; IPR001762; Disintegrin_dom.
DR   InterPro; IPR036436; Disintegrin_dom_sf.
DR   InterPro; IPR013032; EGF-like_CS.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR001590; Peptidase_M12B.
DR   InterPro; IPR002870; Peptidase_M12B_N.
DR   InterPro; IPR034027; Reprolysin_adamalysin.
DR   Pfam; PF08516; ADAM_CR; 1.
DR   Pfam; PF00200; Disintegrin; 1.
DR   Pfam; PF01562; Pep_M12B_propep; 1.
DR   Pfam; PF01421; Reprolysin; 1.
DR   SMART; SM00608; ACR; 1.
DR   SMART; SM00050; DISIN; 1.
DR   SUPFAM; SSF57552; SSF57552; 1.
DR   PROSITE; PS50215; ADAM_MEPRO; 1.
DR   PROSITE; PS50214; DISINTEGRIN_2; 1.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS50026; EGF_3; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell adhesion; Cell membrane;
KW   Cleavage on pair of basic residues; Complete proteome; Disulfide bond;
KW   EGF-like domain; Glycoprotein; Membrane; Reference proteome; Secreted;
KW   Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL        1     59       {ECO:0000255}.
FT   PROPEP       60    286       {ECO:0000255}.
FT                                /FTId=PRO_0000029118.
FT   CHAIN       287    832       Disintegrin and metalloproteinase domain-
FT                                containing protein 23.
FT                                /FTId=PRO_0000029119.
FT   TOPO_DOM    287    792       Extracellular. {ECO:0000255}.
FT   TRANSMEM    793    813       Helical. {ECO:0000255}.
FT   TOPO_DOM    814    832       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN      299    496       Peptidase M12B. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00276}.
FT   DOMAIN      502    588       Disintegrin. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00068}.
FT   DOMAIN      732    769       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   REGION      563    568       May bind the integrin receptor.
FT   COMPBIAS    589    611       Cys-rich.
FT   CARBOHYD     76     76       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD     96     96       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    100    100       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    263    263       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    547    547       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    548    548       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    664    664       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    732    732       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    408    491       {ECO:0000250}.
FT   DISULFID    450    475       {ECO:0000250}.
FT   DISULFID    452    459       {ECO:0000250}.
FT   DISULFID    560    580       {ECO:0000250}.
FT   DISULFID    736    751       {ECO:0000250}.
FT   DISULFID    745    757       {ECO:0000250}.
FT   DISULFID    759    768       {ECO:0000250}.
FT   VAR_SEQ     787    832       GPSATNLIIGSIAGAILVAAIVLGGTGWGFKNVKKRRFDPT
FT                                QQGPI -> EMSRREGSILLSKAPSESAALDGHRLALLDSG
FT                                YDILAAVLLELLSL (in isoform Gamma).
FT                                {ECO:0000303|PubMed:14697522}.
FT                                /FTId=VSP_012045.
FT   VAR_SEQ     787    817       GPSATNLIIGSIAGAILVAAIVLGGTGWGFK -> VNMATS
FT                                RLIGAVAGTLLALGVIFGGTGWGIE (in isoform
FT                                Beta). {ECO:0000303|PubMed:14697522}.
FT                                /FTId=VSP_012046.
FT   MUTAGEN     566    566       E->A: Significantly lower of adhesion-
FT                                promoting activity.
FT                                {ECO:0000269|PubMed:10749942}.
SQ   SEQUENCE   832 AA;  91926 MW;  7841A9670E1C24EF CRC64;
     MKPPGSSSRQ PPLAGCSLAG ASCGPQRGPA GSVPASAPAR TPPCRLLLVL LLLPPLAASS
     RPRAWGAAAP SAPHWNETAE KNLGVLADED NTLQQNSSSN ISYSNAMQKE ITLPSRLIYY
     INQDSESPYH VLDTKARHQQ KHNKAVHLAQ ASFQIEAFGS KFILDLILNN GLLSSDYVEI
     HYENGKPQYS KGGEHCYYHG SIRGVKDSKV ALSTCNGLHG MFEDDTFVYM IEPLELVHDE
     KSTGRPHIIQ KTLAGQYSKQ MKNLTMERGD QWPFLSELQW LKRRKRAVNP SRGIFEEMKY
     LELMIVNDHK TYKKHRSSHA HTNNFAKSVV NLVDSIYKEQ LNTRVVLVAV ETWTEKDQID
     ITTNPVQMLH EFSKYRQRIK QHADAVHLIS RVTFHYKRSS LSYFGGVCSR TRGVGVNEYG
     LPMAVAQVLS QSLAQNLGIQ WEPSSRKPKC DCTESWGGCI MEETGVSHSR KFSKCSILEY
     RDFLQRGGGA CLFNRPTKLF EPTECGNGYV EAGEECDCGF HVECYGLCCK KCSLSNGAHC
     SDGPCCNNTS CLFQPRGYEC RDAVNECDIT EYCTGDSGQC PPNLHKQDGY ACNQNQGRCY
     NGECKTRDNQ CQYIWGTKAA GSDKFCYEKL NTEGTEKGNC GKDGDRWIQC SKHDVFCGFL
     LCTNLTRAPR IGQLQGEIIP TSFYHQGRVI DCSGAHVVLD DDTDVGYVED GTPCGPSMMC
     LDRKCLQIQA LNMSSCPLDS KGKVCSGHGV CSNEATCICD FTWAGTDCSI RDPVRNLHPP
     KDEGPKGPSA TNLIIGSIAG AILVAAIVLG GTGWGFKNVK KRRFDPTQQG PI
//