ID ADA22_HUMAN Reviewed; 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 22-JAN-2014, entry version 128. DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 22; DE Short=ADAM 22; DE AltName: Full=Metalloproteinase-disintegrin ADAM22-3; DE AltName: Full=Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 2; DE Flags: Precursor; 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 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 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 [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 40-906 (ISOFORM 1), AND VARIANT ARG-81. RC TISSUE=Cerebellum; RX 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 [6] 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 [7] 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 [8] 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 [9] 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). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-834, AND MASS RP SPECTROMETRY. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.36 ANGSTROMS) OF 233-736, GLYCOSYLATION AT RP ASN-519; ASN-634 AND ASN-675, AND DISULFIDE BONDS. RX PubMed=19692335; DOI=10.1074/jbc.M109.014258; RA Liu H., Shim A.H., He X.; RT "Structural characterization of the ectodomain of a disintegrin and RT metalloproteinase-22 (ADAM22), a neural adhesion receptor instead of RT metalloproteinase: insights on ADAM function."; RL J. Biol. Chem. 284:29077-29086(2009). 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. Neuronal receptor for LGI1. CC -!- SUBUNIT: Interacts with LGI1 and can bind to LGI4 (By similarity). CC Interacts through its C-terminal region with YWHAB/14-3-3 beta and CC YWHAZ/14-3-3 zeta but not with YWHAE/14-3-3 epsilon or YWHAH/14-3- CC 3 eta. CC -!- INTERACTION: CC P31946:YWHAB; NbExp=2; IntAct=EBI-1567267, EBI-359815; CC P27348:YWHAQ; NbExp=2; IntAct=EBI-1567267, EBI-359854; CC P63104:YWHAZ; NbExp=3; IntAct=EBI-1567236, EBI-347088; 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 Ref.2 (AAF73288) sequence is in conflict in position: 848:G->E; 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; AC005075; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF158637; AAD55251.1; -; mRNA. DR RefSeq; NP_004185.1; NM_004194.3. DR RefSeq; NP_068367.1; NM_021721.3. DR RefSeq; NP_068368.2; NM_021722.4. DR RefSeq; NP_068369.1; NM_021723.3. DR UniGene; Hs.256398; -. DR PDB; 3G5C; X-ray; 2.36 A; A/B=233-736. DR PDBsum; 3G5C; -. DR ProteinModelPortal; Q9P0K1; -. DR SMR; Q9P0K1; 233-718. DR IntAct; Q9P0K1; 11. DR MINT; MINT-252818; -. DR STRING; 9606.ENSP00000265727; -. DR MEROPS; M12.978; -. DR PhosphoSite; Q9P0K1; -. DR DMDM; 14423634; -. DR PaxDb; Q9P0K1; -. DR PRIDE; Q9P0K1; -. DR Ensembl; ENST00000265727; ENSP00000265727; ENSG00000008277. DR Ensembl; ENST00000398201; ENSP00000381260; ENSG00000008277. DR Ensembl; ENST00000398204; ENSP00000381262; ENSG00000008277. DR Ensembl; ENST00000398209; ENSP00000381267; ENSG00000008277. DR GeneID; 53616; -. DR KEGG; hsa:53616; -. DR UCSC; uc003ujk.2; human. DR CTD; 53616; -. DR GeneCards; GC07P087563; -. DR HGNC; HGNC:201; ADAM22. DR HPA; HPA045282; -. DR MIM; 603709; gene. DR neXtProt; NX_Q9P0K1; -. DR PharmGKB; PA24518; -. DR eggNOG; NOG256419; -. DR HOGENOM; HOG000231962; -. DR HOVERGEN; HBG050456; -. DR InParanoid; Q9P0K1; -. DR KO; K16068; -. DR OMA; FSGSQFE; -. DR OrthoDB; EOG7B31M6; -. DR ChiTaRS; ADAM22; human. DR EvolutionaryTrace; Q9P0K1; -. DR GeneWiki; ADAM22; -. DR GenomeRNAi; 53616; -. DR NextBio; 56096; -. DR PRO; PR:Q9P0K1; -. DR ArrayExpress; Q9P0K1; -. DR Bgee; Q9P0K1; -. DR CleanEx; HS_ADAM22; -. DR Genevestigator; Q9P0K1; -. DR GO; GO:0016021; C:integral to membrane; NAS:UniProtKB. DR GO; GO:0005178; F:integrin binding; NAS:UniProtKB. DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc. DR GO; GO:0022011; P:myelination in peripheral nervous system; IEA:Ensembl. DR GO; GO:0007162; P:negative regulation of cell adhesion; NAS:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:InterPro. DR Gene3D; 3.40.390.10; -; 1. DR Gene3D; 4.10.70.10; -; 1. DR InterPro; IPR006586; ADAM_Cys-rich. DR InterPro; IPR001762; Blood-coag_inhib_Disintegrin. DR InterPro; IPR018358; Disintegrin_CS. DR InterPro; IPR000742; EG-like_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR024079; MetalloPept_cat_dom. DR InterPro; IPR001590; Peptidase_M12B. DR InterPro; IPR002870; Peptidase_M12B_N. DR Pfam; PF08516; ADAM_CR; 1. DR Pfam; PF00200; Disintegrin; 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 SMART; SM00181; EGF; 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; PS01186; EGF_2; FALSE_NEG. DR PROSITE; PS50026; EGF_3; FALSE_NEG. DR PROSITE; PS00142; ZINC_PROTEASE; FALSE_NEG. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell adhesion; KW Cleavage on pair of basic residues; Complete proteome; Disulfide bond; KW EGF-like domain; Glycoprotein; Membrane; Phosphoprotein; Polymorphism; KW Receptor; Reference proteome; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1 25 Potential. FT PROPEP 26 222 By similarity. FT /FTId=PRO_0000029112. FT CHAIN 223 906 Disintegrin and metalloproteinase domain- FT containing protein 22. FT /FTId=PRO_0000029113. FT TOPO_DOM 223 736 Extracellular (Potential). FT TRANSMEM 737 757 Helical; (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 MOD_RES 834 834 Phosphoserine. FT CARBOHYD 175 175 N-linked (GlcNAc...) (Potential). FT CARBOHYD 519 519 N-linked (GlcNAc...). FT CARBOHYD 634 634 N-linked (GlcNAc...). FT CARBOHYD 675 675 N-linked (GlcNAc...). FT DISULFID 349 433 FT DISULFID 392 417 FT DISULFID 394 401 FT DISULFID 447 477 FT DISULFID 458 474 FT DISULFID 460 466 FT DISULFID 473 494 FT DISULFID 485 491 FT DISULFID 490 516 FT DISULFID 503 523 FT DISULFID 510 542 FT DISULFID 535 547 FT DISULFID 554 605 FT DISULFID 569 635 FT DISULFID 583 593 FT DISULFID 600 663 FT DISULFID 657 668 FT DISULFID 679 694 FT DISULFID 688 700 FT DISULFID 702 711 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 -> EYLNPWFKRDYNVAKWVEDVNKNTEGPYFR (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:rs2279542). FT /FTId=VAR_020057. FT VARIANT 119 119 H -> Y (in dbSNP:rs4728730). FT /FTId=VAR_051589. FT VARIANT 207 207 V -> I (in dbSNP:rs17255978). FT /FTId=VAR_051590. 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. FT STRAND 235 237 FT STRAND 239 247 FT HELIX 249 253 FT TURN 254 257 FT HELIX 259 280 FT STRAND 281 292 FT HELIX 305 318 FT STRAND 325 333 FT STRAND 336 338 FT STRAND 341 343 FT TURN 351 353 FT STRAND 354 359 FT HELIX 363 378 FT HELIX 384 389 FT HELIX 416 427 FT HELIX 432 435 FT HELIX 463 466 FT TURN 467 473 FT STRAND 486 488 FT STRAND 491 496 FT STRAND 502 504 FT TURN 536 539 FT STRAND 540 543 FT STRAND 546 548 FT HELIX 550 558 FT HELIX 567 573 FT TURN 574 576 FT STRAND 585 590 FT HELIX 595 597 FT STRAND 600 602 FT STRAND 605 607 FT STRAND 613 617 FT STRAND 622 628 FT STRAND 631 637 FT STRAND 640 645 FT STRAND 656 658 FT STRAND 661 666 FT STRAND 668 670 FT HELIX 671 674 FT HELIX 688 690 FT STRAND 692 695 FT STRAND 700 702 FT STRAND 706 708 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 //