ID ADA22_HUMAN STANDARD; PRT; 906 AA. AC Q9P0K1; O75075; O75076; Q9P0K2; Q9UIA1; Q9UKK2; DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 30-MAY-2006, entry version 52. DE ADAM 22 precursor (A disintegrin and metalloproteinase domain 22) DE (Metalloproteinase-like, disintegrin-like, and cysteine-rich protein DE 2) (Metalloproteinase-disintegrin ADAM22-3). GN Name=ADAM22; Synonyms=MDC2; 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] (ISOFORMS 3 AND 4). RC TISSUE=Brain; RX MEDLINE=98359734; PubMed=9693107; 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] (ISOFORMS 1 AND 2). RX MEDLINE=20504287; PubMed=11050470; RA Harada T., Nishie A., Torigoe K., Ikezaki K., Shono T., Maehara Y., RA Kuwano M., Wada M.; RT "The specific expression of three novel splice variant forms of human RT metalloprotease-like disintegrin-like cysteine-rich protein 2 gene in RT brain tissues and gliomas."; RL Jpn. J. Cancer Res. 91:1001-1006(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND VARIANT ARG-81. RC TISSUE=Brain; RA Wada M., Torigoe K., Harada T., Kuwano M.; RT "Isolation and tissue specific expression of novel ADAM family from RT 7q21.1 region."; RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 40-906 (ISOFORM 1), AND VARIANT ARG-81. RC TISSUE=Cerebellum; RX MEDLINE=99453762; PubMed=10524237; DOI=10.1016/S0378-1119(99)00302-9; RA Poindexter K., Nelson N., DuBose R.F., Black R.A., Cerretti D.P.; RT "The identification of seven metalloproteinase-disintegrin (ADAM) RT genes from genomic libraries."; RL Gene 237:61-70(1999). RN [5] RP FUNCTION, INTERACTION WITH YWHAZ, AND MUTAGENESIS OF SER-834 AND RP SER-857. RX PubMed=12589811; DOI=10.1016/S0006-291X(03)00056-1; RA Zhu P., Sun Y., Xu R., Sang Y., Zhao J., Liu G., Cai L., Li C., RA Zhao S.; RT "The interaction between ADAM 22 and 14-3-3zeta: regulation of cell RT adhesion and spreading."; RL Biochem. Biophys. Res. Commun. 301:991-999(2003). RN [6] 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:RESEARCH008.1-RESEARCH008.16(2004). RN [7] RP FUNCTION, INTERACTION WITH YWHAB, AND MUTAGENESIS OF SER-834 AND RP SER-857. RX PubMed=15882968; DOI=10.1016/j.bbrc.2005.03.229; RA Zhu P., Sang Y., Xu H., Zhao J., Xu R., Sun Y., Xu T., Wang X., RA Chen L., Feng H., Li C., Zhao S.; RT "ADAM22 plays an important role in cell adhesion and spreading with RT the assistance of 14-3-3."; RL Biochem. Biophys. Res. Commun. 331:938-946(2005). RN [8] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=16385342; DOI=10.1227/01.NEU.0000192363.84287.8B; RA D'Abaco G.M., Ng K., Paradiso L., Godde N.J., Kaye A., Novak U.; RT "ADAM22, expressed in normal brain but not in high-grade gliomas, RT inhibits cellular proliferation via the disintegrin domain."; RL Neurosurgery 58:179-186(2006). CC -!- FUNCTION: Probable ligand for integrin in the brain. This is a non CC catalytic metalloprotease-like protein. Involved in regulation of CC cell adhesion and spreading and in inhibition of cell CC proliferation. CC -!- SUBUNIT: Interacts through its C-terminal region with YWHAB/14-3-3 CC beta and YWHAZ/14-3-3 zeta but not with YWHAE/14-3-3 epsilon or CC YWHAH/14-3-3 eta. CC -!- SUBCELLULAR LOCATION: Membrane; single-pass type I membrane CC protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=Epsilon; CC IsoId=Q9P0K1-1; Sequence=Displayed; CC Name=2; Synonyms=Delta; CC IsoId=Q9P0K1-2; Sequence=VSP_005482, VSP_005484; 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 Name=3; Synonyms=Alpha; CC IsoId=Q9P0K1-3; Sequence=VSP_005483; CC Name=4; Synonyms=Beta; CC IsoId=Q9P0K1-4; Sequence=VSP_005482, VSP_005483; CC Name=5; CC IsoId=Q9P0K1-5; Sequence=VSP_005482; CC -!- TISSUE SPECIFICITY: Highly expressed in the brain and in some CC high-grade but not low-grade gliomas. Detected slightly or not at CC all in other tissues. CC -!- PTM: The precursor is cleaved by a furin endopeptidase (By CC similarity). CC -!- SIMILARITY: Contains 1 disintegrin domain. CC -!- SIMILARITY: Contains 1 EGF-like domain. CC -!- SIMILARITY: Contains 1 peptidase M12B domain. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB009671; BAA32349.1; -; mRNA. DR EMBL; AB009671; BAA32350.1; -; mRNA. DR EMBL; AF155381; AAF73288.1; -; mRNA. DR EMBL; AF155382; AAF73289.1; -; mRNA. DR EMBL; AF073291; AAF22476.2; -; mRNA. DR EMBL; AF158637; AAD55251.1; -; mRNA. DR UniGene; Hs.592282; -. DR HSSP; P18619; 1FVL. DR MEROPS; M12.978; -. DR Ensembl; ENSG00000008277; Homo sapiens. DR HGNC; HGNC:201; ADAM22. DR MIM; 603709; gene. DR GO; GO:0016021; C:integral to membrane; NAS. DR GO; GO:0005178; F:integrin binding; NAS. DR GO; GO:0007417; P:central nervous system development; TAS. DR GO; GO:0007162; P:negative regulation of cell adhesion; NAS. DR InterPro; IPR006586; ADAM_cysteine. DR InterPro; IPR001762; Disintegrin. DR InterPro; IPR000742; EGF_3. DR InterPro; IPR013111; EGF_extracell. DR InterPro; IPR013032; EGF_like_reg. DR InterPro; IPR006025; Pept_M_Zn_BS. DR InterPro; IPR001590; Peptidase_M12B. DR InterPro; IPR002870; Peptidase_M12B_N. 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 ProDom; PD000664; Disintegrin; 1. DR SMART; SM00608; ACR; 1. DR SMART; SM00050; DISIN; 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; PS01186; EGF_2; FALSE_NEG. DR PROSITE; PS50026; EGF_3; FALSE_NEG. DR PROSITE; PS00142; ZINC_PROTEASE; FALSE_NEG. KW Alternative splicing; Cell adhesion; EGF-like domain; Glycoprotein; KW Membrane; Polymorphism; Signal; Transmembrane. FT SIGNAL 1 25 Potential. FT PROPEP 26 222 By similarity. FT /FTId=PRO_0000029112. FT CHAIN 223 906 ADAM 22. FT /FTId=PRO_0000029113. FT TOPO_DOM 223 736 Extracellular (Potential). FT TRANSMEM 737 757 Potential. FT TOPO_DOM 758 906 Cytoplasmic (Potential). FT DOMAIN 239 438 Peptidase M12B. FT DOMAIN 444 531 Disintegrin. FT DOMAIN 675 712 EGF-like. FT COMPBIAS 532 678 Cys-rich. FT CARBOHYD 175 175 N-linked (GlcNAc...) (Potential). FT CARBOHYD 519 519 N-linked (GlcNAc...) (Potential). FT CARBOHYD 634 634 N-linked (GlcNAc...) (Potential). FT CARBOHYD 675 675 N-linked (GlcNAc...) (Potential). FT DISULFID 349 433 By similarity. FT DISULFID 392 417 By similarity. FT DISULFID 394 401 By similarity. FT DISULFID 503 523 By similarity. FT DISULFID 679 694 By similarity. FT DISULFID 688 700 By similarity. FT DISULFID 702 711 By similarity. FT VAR_SEQ 768 803 Missing (in isoform 2, isoform 4 and FT isoform 5). FT /FTId=VSP_005482. FT VAR_SEQ 859 859 E -> EYLNPWFKRDYNVAKWVEDVNKNTEEPYFR (in FT isoform 2). FT /FTId=VSP_005484. FT VAR_SEQ 860 906 Missing (in isoform 3 and isoform 4). FT /FTId=VSP_005483. FT VARIANT 81 81 P -> R (in dbSNP:2279542). FT /FTId=VAR_020057. FT MUTAGEN 834 834 S->A: Abolishes interactions with YWHAB FT and YWHAZ; when associated with A-857. FT MUTAGEN 857 857 S->A: Abolishes interactions with YWHAB FT and YWHAZ; when associated with A-834. SQ SEQUENCE 906 AA; 100433 MW; 265ECCD0FA6C088B CRC64; MQAAVAVSVP FLLLCVLGTC PPARCGQAGD ASLMELEKRK ENRFVERQSI VPLRLIYRSG GEDESRHDAL DTRVRGDLGG PQLTHVDQAS FQVDAFGTSF ILDVVLNHDL LSSEYIERHI EHGGKTVEVK GGEHCYYQGH IRGNPDSFVA LSTCHGLHGM FYDGNHTYLI EPEENDTTQE DFHFHSVYKS RLFEFSLDDL PSEFQQVNIT PSKFILKPRP KRSKRQLRRY PRNVEEETKY IELMIVNDHL MFKKHRLSVV HTNTYAKSVV NMADLIYKDQ LKTRIVLVAM ETWATDNKFA ISENPLITLR EFMKYRRDFI KEKSDAVHLF SGSQFESSRS GAAYIGGICS LLKGGGVNEF GKTDLMAVTL AQSLAHNIGI ISDKRKLASG ECKCEDTWSG CIMGDTGYYL PKKFTQCNIE EYHDFLNSGG GACLFNKPSK LLDPPECGNG FIETGEECDC GTPAECVLEG AECCKKCTLT QDSQCSDGLC CKKCKFQPMG TVCREAVNDC DIRETCSGNS SQCAPNIHKM DGYSCDGVQG ICFGGRCKTR DRQCKYIWGQ KVTASDKYCY EKLNIEGTEK GNCGKDKDTW IQCNKRDVLC GYLLCTNIGN IPRLGELDGE ITSTLVVQQG RTLNCSGGHV KLEEDVDLGY VEDGTPCGPQ MMCLEHRCLP VASFNFSTCL SSKEGTICSG NGVCSNELKC VCNRHWIGSD CNTYFPHNDD AKTGITLSGN GVAGTNIIIG IIAGTILVLA LILGITAWGY KNYREQRQLP QGDYVKKPGD GDSFYSDIPP GVSTNSASSS KKRSNGLSHS WSERIPDTKH ISDICENGRP RSNSWQGNLG GNKKKIRGKR FRPRSNSTET LSPAKSPSSS TGSIASSRKY PYPMPPLPDE DKKVNRQSAR LWETSI //