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   24-JAN-2024, entry version 193.
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. Required for localization of
CC       the potassium channel subunit proteins KCNA1/KV1.1 and KCNA2/KV1.2 at
CC       cerebellar cortex basket cell distal terminals, is thereby involved in
CC       ephaptic inhibitory synchronization of Purkinje cell firing and
CC       response to stress (By similarity). Plays a role in spatial learning
CC       and motor coordination (By similarity). Involved in the nociceptive
CC       pain response to chemical-derived stimulation (By similarity).
CC       {ECO:0000250|UniProtKB:Q9R1V4}.
CC   -!- SUBUNIT: Interacts with LGI1 and LGI4 (By similarity). Interacts with
CC       KCNA1/KV1.1, KCNA2/KV1.2, DLG4/PSD-95 and ADAM22 (By similarity).
CC       {ECO:0000250|UniProtKB:Q9R1V4}.
CC   -!- SUBCELLULAR LOCATION: Presynaptic cell membrane
CC       {ECO:0000250|UniProtKB:Q9R1V4}; Single-pass type I membrane protein.
CC       Perikaryon {ECO:0000250|UniProtKB:Q9R1V4}. Cell projection, axon
CC       {ECO:0000250|UniProtKB:Q9R1V4}. Note=Localizes to basket cell terminals
CC       and pinceaux. {ECO:0000250|UniProtKB:Q9R1V4}.
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   GlyCosmos; O75078; 4 sites, No reported glycans.
DR   GlyGen; O75078; 4 sites.
DR   iPTMnet; O75078; -.
DR   PhosphoSitePlus; O75078; -.
DR   BioMuta; ADAM11; -.
DR   MassIVE; O75078; -.
DR   PaxDb; 9606-ENSP00000200557; -.
DR   PeptideAtlas; O75078; -.
DR   ProteomicsDB; 49743; -. [O75078-1]
DR   ProteomicsDB; 49744; -. [O75078-2]
DR   Antibodypedia; 29870; 165 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   AGR; HGNC:189; -.
DR   CTD; 4185; -.
DR   DisGeNET; 4185; -.
DR   GeneCards; ADAM11; -.
DR   HGNC; HGNC:189; ADAM11.
DR   HPA; ENSG00000073670; Tissue enriched (brain).
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; WGYSAAD; -.
DR   OrthoDB; 5406290at2759; -.
DR   PhylomeDB; O75078; -.
DR   TreeFam; TF314733; -.
DR   PathwayCommons; O75078; -.
DR   Reactome; R-HSA-5682910; LGI-ADAM interactions.
DR   SignaLink; O75078; -.
DR   BioGRID-ORCS; 4185; 38 hits in 1145 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 139 other cell types or tissues.
DR   ExpressionAtlas; O75078; baseline and differential.
DR   GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR   GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005178; F:integrin binding; TAS:ProtInc.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR   GO; GO:0061367; P:behavioral response to acetic acid induced pain; ISS:UniProtKB.
DR   GO; GO:0061368; P:behavioral response to formalin induced pain; ISS:UniProtKB.
DR   GO; GO:0045184; P:establishment of protein localization; ISS:UniProtKB.
DR   GO; GO:0007229; P:integrin-mediated signaling pathway; TAS:ProtInc.
DR   GO; GO:0033555; P:multicellular organismal response to stress; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   CDD; cd04269; ZnMc_adamalysin_II_like; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 4.10.70.10; Disintegrin domain; 1.
DR   Gene3D; 2.10.25.10; Laminin; 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   PANTHER; PTHR11905; ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN; 1.
DR   PANTHER; PTHR11905:SF114; DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 11; 1.
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; Blood coagulation inhibitor (disintegrin); 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 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.
DR   Genevisible; O75078; HS.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Cell membrane; Cell projection;
KW   Cleavage on pair of basic residues; Disulfide bond; EGF-like domain;
KW   Glycoprotein; Membrane; Reference proteome; Signal; Synapse; Transmembrane;
KW   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   REGION          332..769
FT                   /note="Required for localization to cerebellar cortex
FT                   basket cell terminals. Also required for localization of
FT                   KCNA1, KCNA2, DLG4 and ADAM22 to cerebellar cortex basket
FT                   cell terminal perisomatic axons and pinceaux"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R1V4"
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
//