ADA23_HUMAN
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 03-AUG-2022, entry version 166.
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 AlphaFoldDB; O75077; -.
DR SMR; O75077; -.
DR BioGRID; 114282; 3.
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; 244 antibodies from 29 providers.
DR DNASU; 8745; -.
DR Ensembl; ENST00000264377.8; ENSP00000264377.3; ENSG00000114948.13. [O75077-1]
DR GeneID; 8745; -.
DR KEGG; hsa:8745; -.
DR MANE-Select; ENST00000264377.8; ENSP00000264377.3; NM_003812.4; NP_003803.1.
DR UCSC; uc002vbq.6; human. [O75077-1]
DR CTD; 8745; -.
DR DisGeNET; 8745; -.
DR GeneCards; ADAM23; -.
DR HGNC; HGNC:202; ADAM23.
DR HPA; ENSG00000114948; Tissue enhanced (brain, parathyroid gland).
DR MIM; 603710; gene.
DR neXtProt; NX_O75077; -.
DR OpenTargets; ENSG00000114948; -.
DR PharmGKB; PA24519; -.
DR VEuPathDB; HostDB:ENSG00000114948; -.
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 SignaLink; O75077; -.
DR BioGRID-ORCS; 8745; 20 hits in 1070 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 Brodmann (1909) area 10 and 160 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 GO; GO:0006508; P:proteolysis; IEA:InterPro.
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 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 563..568
FT /note="May bind the integrin receptor"
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
