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   10-FEB-2021, entry version 160.
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; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   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 and
RT   MDC3: novel human cellular disintegrins highly expressed in the 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-independent
RT   mechanism.";
RL   Mol. Biol. Cell 11:1457-1469(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA AND GAMMA), AND TISSUE
RP   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 of
RT   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., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., 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 project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: May play a role in cell-cell and cell-matrix interactions.
CC       This is a non-catalytic metalloprotease-like protein.
CC   -!- SUBUNIT: Can bind to LGI1 and LGI4 (By similarity). Ligand for integrin
CC       alpha-V/beta-3. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I
CC       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 expressed
CC       in the heart. In the brain, expressed prominently in the amygdala,
CC       caudate nucleus, hypothalamus, thalamus, cerebral cortex and occipital
CC       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 domain
CC       could be involved in the binding to the integrin receptor.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       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   SMR; O75077; -.
DR   BioGRID; 114282; 1.
DR   CORUM; O75077; -.
DR   IntAct; O75077; 2.
DR   MINT; O75077; -.
DR   STRING; 9606.ENSP00000264377; -.
DR   MEROPS; M12.979; -.
DR   GlyGen; O75077; 8 sites.
DR   iPTMnet; O75077; -.
DR   PhosphoSitePlus; O75077; -.
DR   SwissPalm; O75077; -.
DR   BioMuta; ADAM23; -.
DR   MassIVE; O75077; -.
DR   PaxDb; O75077; -.
DR   PeptideAtlas; O75077; -.
DR   PRIDE; O75077; -.
DR   ProteomicsDB; 49740; -. [O75077-1]
DR   ProteomicsDB; 49741; -. [O75077-2]
DR   ProteomicsDB; 49742; -. [O75077-3]
DR   Antibodypedia; 34180; 236 antibodies.
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   GeneCards; ADAM23; -.
DR   HGNC; HGNC:202; ADAM23.
DR   HPA; ENSG00000114948; Group enriched (brain, heart muscle, parathyroid gland).
DR   MIM; 603710; gene.
DR   neXtProt; NX_O75077; -.
DR   OpenTargets; ENSG00000114948; -.
DR   PharmGKB; PA24519; -.
DR   VEuPathDB; HostDB:ENSG00000114948.12; -.
DR   eggNOG; KOG3607; Eukaryota.
DR   GeneTree; ENSGT00940000158781; -.
DR   HOGENOM; CLU_012714_5_2_1; -.
DR   InParanoid; O75077; -.
DR   OMA; ECDCTES; -.
DR   OrthoDB; 162519at2759; -.
DR   PhylomeDB; O75077; -.
DR   TreeFam; TF314733; -.
DR   PathwayCommons; O75077; -.
DR   Reactome; R-HSA-5682910; LGI-ADAM interactions.
DR   BioGRID-ORCS; 8745; 12 hits in 871 CRISPR screens.
DR   ChiTaRS; ADAM23; human.
DR   GeneWiki; ADAM23; -.
DR   GenomeRNAi; 8745; -.
DR   Pharos; O75077; Tbio.
DR   PRO; PR:O75077; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; O75077; protein.
DR   Bgee; ENSG00000114948; Expressed in middle temporal gyrus and 186 other tissues.
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; IBA:GO_Central.
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; 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; Disulfide bond; EGF-like domain;
KW   Glycoprotein; Membrane; Reference proteome; Secreted; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..59
FT                   /evidence="ECO:0000255"
FT   PROPEP          60..286
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000029118"
FT   CHAIN           287..832
FT                   /note="Disintegrin and metalloproteinase domain-containing
FT                   protein 23"
FT                   /id="PRO_0000029119"
FT   TOPO_DOM        287..792
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        793..813
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        814..832
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          299..496
FT                   /note="Peptidase M12B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT   DOMAIN          502..588
FT                   /note="Disintegrin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT   DOMAIN          732..769
FT                   /note="EGF-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   REGION          563..568
FT                   /note="May bind the integrin receptor"
FT   COMPBIAS        589..611
FT                   /note="Cys-rich"
FT   CARBOHYD        76
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        96
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        100
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        263
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        547
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        548
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        664
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        732
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        408..491
FT                   /evidence="ECO:0000250"
FT   DISULFID        450..475
FT                   /evidence="ECO:0000250"
FT   DISULFID        452..459
FT                   /evidence="ECO:0000250"
FT   DISULFID        560..580
FT                   /evidence="ECO:0000250"
FT   DISULFID        736..751
FT                   /evidence="ECO:0000250"
FT   DISULFID        745..757
FT                   /evidence="ECO:0000250"
FT   DISULFID        759..768
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         787..832
FT                   /note="GPSATNLIIGSIAGAILVAAIVLGGTGWGFKNVKKRRFDPTQQGPI -> EM
FT                   SRREGSILLSKAPSESAALDGHRLALLDSGYDILAAVLLELLSL (in isoform
FT                   Gamma)"
FT                   /evidence="ECO:0000303|PubMed:14697522"
FT                   /id="VSP_012045"
FT   VAR_SEQ         787..817
FT                   /note="GPSATNLIIGSIAGAILVAAIVLGGTGWGFK -> VNMATSRLIGAVAGTLL
FT                   ALGVIFGGTGWGIE (in isoform Beta)"
FT                   /evidence="ECO:0000303|PubMed:14697522"
FT                   /id="VSP_012046"
FT   MUTAGEN         566
FT                   /note="E->A: Significantly lower of adhesion-promoting
FT                   activity."
FT                   /evidence="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
//