ID   ADA11_HUMAN             Reviewed;         769 AA.
AC   O75078; Q14808; Q14809; Q14810;
DT   01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 3.
DT   13-FEB-2019, entry version 167.
DE   RecName: Full=Disintegrin and metalloproteinase domain-containing protein 11;
DE            Short=ADAM 11;
DE   AltName: Full=Metalloproteinase-like, disintegrin-like, and cysteine-rich protein;
DE            Short=MDC;
DE   Flags: Precursor;
GN   Name=ADAM11; Synonyms=MDC;
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 LONG).
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 SHORT).
RC   TISSUE=Cerebellum;
RX   PubMed=8252040; DOI=10.1038/ng1093-151;
RA   Emi M., Katagiri T., Harada Y., Saito H., Inazawa J., Ito I.,
RA   Kasumi F., Nakamura Y.;
RT   "A novel metalloprotease/disintegrin-like gene at 17q21.3 is
RT   somatically rearranged in two primary breast cancers.";
RL   Nat. Genet. 5:151-157(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 106-769 (ISOFORMS LONG AND
RP   SHORT).
RC   TISSUE=Brain, Mammary gland, Ovary, and Testis;
RX   PubMed=7956356;
RA   Katagiri T., Harada Y., Emi M., Nakamura Y.;
RT   "Human metalloprotease/disintegrin-like (MDC) gene: exon-intron
RT   organization and alternative splicing.";
RL   Cytogenet. Cell Genet. 68:39-44(1995).
RN   [4]
RP   SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX   PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA   Hillman R.T., Green R.E., Brenner S.E.;
RT   "An unappreciated role for RNA surveillance.";
RL   Genome Biol. 5:R8.1-R8.16(2004).
RN   [5]
RP   VARIANT [LARGE SCALE ANALYSIS] ARG-693.
RX   PubMed=18772397; DOI=10.1126/science.1164368;
RA   Jones S., Zhang X., Parsons D.W., Lin J.C., Leary R.J., Angenendt P.,
RA   Mankoo P., Carter H., Kamiyama H., Jimeno A., Hong S.M., Fu B.,
RA   Lin M.T., Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T.,
RA   Nikolsky Y., Hartigan J., Smith D.R., Hidalgo M., Leach S.D.,
RA   Klein A.P., Jaffee E.M., Goggins M., Maitra A., Iacobuzio-Donahue C.,
RA   Eshleman J.R., Kern S.E., Hruban R.H., Karchin R., Papadopoulos N.,
RA   Parmigiani G., Vogelstein B., Velculescu V.E., Kinzler K.W.;
RT   "Core signaling pathways in human pancreatic cancers revealed by
RT   global genomic analyses.";
RL   Science 321:1801-1806(2008).
CC   -!- FUNCTION: Probable ligand for integrin in the brain. This is a non
CC       catalytic metalloprotease-like protein.
CC   -!- SUBUNIT: Can bind to LGI1 and LGI4. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC       protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Long; Synonyms=MDC-769;
CC         IsoId=O75078-1; Sequence=Displayed;
CC       Name=Short; Synonyms=MDC-524;
CC         IsoId=O75078-2; Sequence=VSP_005472, VSP_005473, VSP_005474,
CC                                  VSP_005475;
CC         Note=May be produced at very low levels due to a premature stop
CC         codon in the mRNA, leading to nonsense-mediated mRNA decay.;
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in brain. Slightly
CC       detected or not at all in other tissues.
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   -!- PTM: The precursor is cleaved by a furin endopeptidase.
CC       {ECO:0000250}.
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DR   EMBL; AB009675; BAA32352.1; -; mRNA.
DR   EMBL; D17390; BAA04213.1; -; mRNA.
DR   EMBL; D31872; BAA06670.1; -; Genomic_DNA.
DR   EMBL; D31872; BAA06671.1; -; Genomic_DNA.
DR   CCDS; CCDS11486.1; -. [O75078-1]
DR   PIR; I65967; I65967.
DR   PIR; S38539; S38539.
DR   RefSeq; NP_002381.2; NM_002390.5. [O75078-1]
DR   UniGene; Hs.6088; -.
DR   ProteinModelPortal; O75078; -.
DR   SMR; O75078; -.
DR   BioGrid; 110351; 4.
DR   IntAct; O75078; 1.
DR   STRING; 9606.ENSP00000200557; -.
DR   MEROPS; M12.976; -.
DR   TCDB; 8.A.77.1.1; the sheddase (sheddase) family.
DR   iPTMnet; O75078; -.
DR   PhosphoSitePlus; O75078; -.
DR   BioMuta; ADAM11; -.
DR   jPOST; O75078; -.
DR   PaxDb; O75078; -.
DR   PeptideAtlas; O75078; -.
DR   PRIDE; O75078; -.
DR   ProteomicsDB; 49743; -.
DR   ProteomicsDB; 49744; -. [O75078-2]
DR   DNASU; 4185; -.
DR   Ensembl; ENST00000200557; ENSP00000200557; ENSG00000073670. [O75078-1]
DR   GeneID; 4185; -.
DR   KEGG; hsa:4185; -.
DR   UCSC; uc002ihh.4; human. [O75078-1]
DR   CTD; 4185; -.
DR   DisGeNET; 4185; -.
DR   EuPathDB; HostDB:ENSG00000073670.13; -.
DR   GeneCards; ADAM11; -.
DR   HGNC; HGNC:189; ADAM11.
DR   HPA; HPA074550; -.
DR   MIM; 155120; gene.
DR   neXtProt; NX_O75078; -.
DR   OpenTargets; ENSG00000073670; -.
DR   PharmGKB; PA24506; -.
DR   eggNOG; KOG3607; Eukaryota.
DR   eggNOG; ENOG410XX2M; LUCA.
DR   GeneTree; ENSGT00940000159790; -.
DR   HOGENOM; HOG000231962; -.
DR   HOVERGEN; HBG050456; -.
DR   InParanoid; O75078; -.
DR   KO; K16067; -.
DR   OMA; DNMGAMA; -.
DR   OrthoDB; 162519at2759; -.
DR   PhylomeDB; O75078; -.
DR   TreeFam; TF314733; -.
DR   Reactome; R-HSA-5682910; LGI-ADAM interactions.
DR   ChiTaRS; ADAM11; human.
DR   GeneWiki; ADAM11; -.
DR   GenomeRNAi; 4185; -.
DR   PRO; PR:O75078; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   Bgee; ENSG00000073670; Expressed in 157 organ(s), highest expression level in right hemisphere of cerebellum.
DR   ExpressionAtlas; O75078; baseline and differential.
DR   Genevisible; O75078; HS.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0007229; P:integrin-mediated signaling pathway; 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; IPR018358; Disintegrin_CS.
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; IPR013111; EGF_extracell.
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; PF07974; EGF_2; 1.
DR   Pfam; PF01562; Pep_M12B_propep; 1.
DR   Pfam; PF01421; Reprolysin; 1.
DR   PRINTS; PR00289; DISINTEGRIN.
DR   SMART; SM00608; ACR; 1.
DR   SMART; SM00050; DISIN; 1.
DR   SUPFAM; SSF57552; SSF57552; 1.
DR   PROSITE; PS50215; ADAM_MEPRO; 1.
DR   PROSITE; PS00427; DISINTEGRIN_1; 1.
DR   PROSITE; PS50214; DISINTEGRIN_2; 1.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS50026; EGF_3; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Cleavage on pair of basic residues;
KW   Complete proteome; Disulfide bond; EGF-like domain; Glycoprotein;
KW   Membrane; Polymorphism; Reference proteome; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   PROPEP       24    225       {ECO:0000250}.
FT                                /FTId=PRO_0000029074.
FT   CHAIN       226    769       Disintegrin and metalloproteinase domain-
FT                                containing protein 11.
FT                                /FTId=PRO_0000029075.
FT   TOPO_DOM    226    734       Extracellular. {ECO:0000255}.
FT   TRANSMEM    735    755       Helical. {ECO:0000255}.
FT   TOPO_DOM    756    769       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN      239    438       Peptidase M12B. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00276}.
FT   DOMAIN      444    531       Disintegrin. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00068}.
FT   DOMAIN      677    709       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   COMPBIAS    532    676       Cys-rich.
FT   CARBOHYD     96     96       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    163    163       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    605    605       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    673    673       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    349    433       {ECO:0000250}.
FT   DISULFID    392    417       {ECO:0000250}.
FT   DISULFID    394    401       {ECO:0000250}.
FT   DISULFID    503    523       {ECO:0000250}.
FT   DISULFID    677    692       {ECO:0000250}.
FT   DISULFID    686    698       {ECO:0000250}.
FT   DISULFID    700    709       {ECO:0000250}.
FT   VAR_SEQ       1     99       Missing (in isoform Short).
FT                                {ECO:0000303|PubMed:8252040}.
FT                                /FTId=VSP_005472.
FT   VAR_SEQ     100    104       DLELN -> MCWLS (in isoform Short).
FT                                {ECO:0000303|PubMed:8252040}.
FT                                /FTId=VSP_005473.
FT   VAR_SEQ     595    623       DVLCGFLLCVNISGAPRLGDLVGDISSVT -> PQQGRAVW
FT                                LPPLCQHLWSSSARGPGGRHQ (in isoform Short).
FT                                {ECO:0000303|PubMed:8252040}.
FT                                /FTId=VSP_005474.
FT   VAR_SEQ     624    769       Missing (in isoform Short).
FT                                {ECO:0000303|PubMed:8252040}.
FT                                /FTId=VSP_005475.
FT   VARIANT     693    693       S -> R (in a pancreatic ductal
FT                                adenocarcinoma sample; somatic mutation).
FT                                {ECO:0000269|PubMed:18772397}.
FT                                /FTId=VAR_062669.
FT   CONFLICT    106    106       H -> Q (in Ref. 2; BAA06670 and 3;
FT                                BAA06671). {ECO:0000305}.
FT   CONFLICT    325    325       D -> N (in Ref. 2; BAA04213).
FT                                {ECO:0000305}.
SQ   SEQUENCE   769 AA;  83418 MW;  EEB091EB6730AC36 CRC64;
     MRLLRRWAFA ALLLSLLPTP GLGTQGPAGA LRWGGLPQLG GPGAPEVTEP SRLVRESSGG
     EVRKQQLDTR VRQEPPGGPP VHLAQVSFVI PAFNSNFTLD LELNHHLLSS QYVERHFSRE
     GTTQHSTGAG DHCYYQGKLR GNPHSFAALS TCQGLHGVFS DGNLTYIVEP QEVAGPWGAP
     QGPLPHLIYR TPLLPDPLGC REPGCLFAVP AQSAPPNRPR LRRKRQVRRG HPTVHSETKY
     VELIVINDHQ LFEQMRQSVV LTSNFAKSVV NLADVIYKEQ LNTRIVLVAM ETWADGDKIQ
     VQDDLLETLA RLMVYRREGL PEPSDATHLF SGRTFQSTSS GAAYVGGICS LSHGGGVNEY
     GNMGAMAVTL AQTLGQNLGM MWNKHRSSAG DCKCPDIWLG CIMEDTGFYL PRKFSRCSID
     EYNQFLQEGG GSCLFNKPLK LLDPPECGNG FVEAGEECDC GSVQECSRAG GNCCKKCTLT
     HDAMCSDGLC CRRCKYEPRG VSCREAVNEC DIAETCTGDS SQCPPNLHKL DGYYCDHEQG
     RCYGGRCKTR DRQCQVLWGH AAADRFCYEK LNVEGTERGS CGRKGSGWVQ CSKQDVLCGF
     LLCVNISGAP RLGDLVGDIS SVTFYHQGKE LDCRGGHVQL ADGSDLSYVE DGTACGPNML
     CLDHRCLPAS AFNFSTCPGS GERRICSHHG VCSNEGKCIC QPDWTGKDCS IHNPLPTSPP
     TGETERYKGP SGTNIIIGSI AGAVLVAAIV LGGTGWGFKN IRRGRSGGA
//