ADA11_HUMAN
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 03-AUG-2022, entry version 185.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 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 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., Kasumi F.,
RA Nakamura Y.;
RT "A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically
RT 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 SHORT).
RC TISSUE=Brain, Mammary gland, Ovary, and Testis;
RX PubMed=7956356; DOI=10.1159/000133884;
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., Lin M.T.,
RA Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T., Nikolsky Y.,
RA Hartigan J., Smith D.R., Hidalgo M., Leach S.D., Klein A.P., Jaffee E.M.,
RA Goggins M., Maitra A., Iacobuzio-Donahue C., Eshleman J.R., Kern S.E.,
RA Hruban R.H., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B.,
RA Velculescu V.E., Kinzler K.W.;
RT "Core signaling pathways in human pancreatic cancers revealed by global
RT 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 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 -!- TISSUE SPECIFICITY: Expressed predominantly in brain. Slightly detected
CC 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. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform Short]: May be produced at very low levels due
CC to a premature stop codon in the mRNA, leading to nonsense-mediated
CC mRNA decay. {ECO:0000305}.
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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 AlphaFoldDB; O75078; -.
DR SMR; O75078; -.
DR BioGRID; 110351; 53.
DR IntAct; O75078; 3.
DR STRING; 9606.ENSP00000200557; -.
DR MEROPS; M12.976; -.
DR TCDB; 8.A.77.1.1; the sheddase (sheddase) family.
DR GlyGen; O75078; 4 sites.
DR iPTMnet; O75078; -.
DR PhosphoSitePlus; O75078; -.
DR BioMuta; ADAM11; -.
DR MassIVE; O75078; -.
DR PaxDb; O75078; -.
DR PeptideAtlas; O75078; -.
DR PRIDE; O75078; -.
DR ProteomicsDB; 49743; -. [O75078-1]
DR ProteomicsDB; 49744; -. [O75078-2]
DR Antibodypedia; 29870; 139 antibodies from 24 providers.
DR DNASU; 4185; -.
DR Ensembl; ENST00000200557.11; ENSP00000200557.6; ENSG00000073670.14. [O75078-1]
DR GeneID; 4185; -.
DR KEGG; hsa:4185; -.
DR MANE-Select; ENST00000200557.11; ENSP00000200557.6; NM_002390.6; NP_002381.2.
DR UCSC; uc002ihh.4; human. [O75078-1]
DR CTD; 4185; -.
DR DisGeNET; 4185; -.
DR GeneCards; ADAM11; -.
DR HGNC; HGNC:189; ADAM11.
DR HPA; ENSG00000073670; Group enriched (brain, heart muscle).
DR MIM; 155120; gene.
DR neXtProt; NX_O75078; -.
DR OpenTargets; ENSG00000073670; -.
DR PharmGKB; PA24506; -.
DR VEuPathDB; HostDB:ENSG00000073670; -.
DR eggNOG; KOG3607; Eukaryota.
DR GeneTree; ENSGT00940000159790; -.
DR InParanoid; O75078; -.
DR OMA; LWLGCIM; -.
DR OrthoDB; 162519at2759; -.
DR PhylomeDB; O75078; -.
DR TreeFam; TF314733; -.
DR PathwayCommons; O75078; -.
DR Reactome; R-HSA-5682910; LGI-ADAM interactions.
DR SignaLink; O75078; -.
DR BioGRID-ORCS; 4185; 36 hits in 1067 CRISPR screens.
DR ChiTaRS; ADAM11; human.
DR GeneWiki; ADAM11; -.
DR GenomeRNAi; 4185; -.
DR Pharos; O75078; Tbio.
DR PRO; PR:O75078; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O75078; protein.
DR Bgee; ENSG00000073670; Expressed in right hemisphere of cerebellum and 138 other tissues.
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 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; IPR018358; Disintegrin_CS.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
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; Disulfide bond;
KW EGF-like domain; Glycoprotein; Membrane; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..225
FT /evidence="ECO:0000250"
FT /id="PRO_0000029074"
FT CHAIN 226..769
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 11"
FT /id="PRO_0000029075"
FT TOPO_DOM 226..734
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 735..755
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 756..769
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 239..438
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 444..531
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DOMAIN 677..709
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 40..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..70
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 605
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 673
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 349..433
FT /evidence="ECO:0000250"
FT DISULFID 392..417
FT /evidence="ECO:0000250"
FT DISULFID 394..401
FT /evidence="ECO:0000250"
FT DISULFID 503..523
FT /evidence="ECO:0000250"
FT DISULFID 677..692
FT /evidence="ECO:0000250"
FT DISULFID 686..698
FT /evidence="ECO:0000250"
FT DISULFID 700..709
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..99
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:8252040"
FT /id="VSP_005472"
FT VAR_SEQ 100..104
FT /note="DLELN -> MCWLS (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:8252040"
FT /id="VSP_005473"
FT VAR_SEQ 595..623
FT /note="DVLCGFLLCVNISGAPRLGDLVGDISSVT -> PQQGRAVWLPPLCQHLWSS
FT SARGPGGRHQ (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:8252040"
FT /id="VSP_005474"
FT VAR_SEQ 624..769
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:8252040"
FT /id="VSP_005475"
FT VARIANT 693
FT /note="S -> R (in a pancreatic ductal adenocarcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:18772397"
FT /id="VAR_062669"
FT CONFLICT 106
FT /note="H -> Q (in Ref. 2; BAA06670 and 3; BAA06671)"
FT /evidence="ECO:0000305"
FT CONFLICT 325
FT /note="D -> N (in Ref. 2; BAA04213)"
FT /evidence="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
