ID DSCAM_HUMAN Reviewed; 2012 AA. AC O60469; O60468; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 2. DT 14-DEC-2011, entry version 113. DE RecName: Full=Down syndrome cell adhesion molecule; DE AltName: Full=CHD2; DE Flags: Precursor; GN Name=DSCAM; 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], AND ALTERNATIVE SPLICING. RC TISSUE=Brain; RX MEDLINE=98087574; PubMed=9426258; DOI=10.1093/hmg/7.2.227; RA Yamakawa K., Huot Y.-K., Haendelt M.A., Hubert R., Chen X.-N., RA Lyons G.E., Korenberg J.R.; RT "DSCAM: a novel member of the immunoglobulin superfamily maps in a RT Down syndrome region and is involved in the development of the nervous RT system."; RL Hum. Mol. Genet. 7:227-237(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RX MEDLINE=20384934; PubMed=10925149; DOI=10.1016/S0169-328X(00)00108-X; RA Agarwala K.L., Nakamura S., Tsutsumi Y., Yamakawa K.; RT "Down syndrome cell adhesion molecule DSCAM mediates homophilic RT intercellular adhesion."; RL Brain Res. Mol. Brain Res. 79:118-126(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=20289799; PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., RA Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [4] RP FUNCTION, AND INTERACTION WITH PAK1 AND RAC1. RX PubMed=15169762; DOI=10.1074/jbc.M401878200; RA Li W., Guan K.L.; RT "The Down syndrome cell adhesion molecule (DSCAM) interacts with and RT activates Pak."; RL J. Biol. Chem. 279:32824-32831(2004). RN [5] RP FUNCTION. RX PubMed=18585357; DOI=10.1016/j.cell.2008.05.030; RA Ly A., Nikolaev A., Suresh G., Zheng Y., Tessier-Lavigne M., Stein E.; RT "DSCAM is a netrin receptor that collaborates with DCC in mediating RT turning responses to netrin-1."; RL Cell 133:1241-1254(2008). RN [6] RP FUNCTION, INTERACTION WITH NTN1, AND PHOSPHORYLATION. RX PubMed=19196994; DOI=10.1073/pnas.0811083106; RA Liu G., Li W., Wang L., Kar A., Guan K.L., Rao Y., Wu J.Y.; RT "DSCAM functions as a netrin receptor in commissural axon RT pathfinding."; RL Proc. Natl. Acad. Sci. U.S.A. 106:2951-2956(2009). CC -!- FUNCTION: Cell adhesion molecule that plays a role in neuronal CC self-avoidance. Promotes repulsion between specific neuronal CC processes of either the same cell or the same subtype of cells. CC Mediates within retinal amacrine and ganglion cell subtypes both CC isoneuronal self-avoidance for creating an orderly dendritic CC arborization and heteroneuronal self-avoidance to maintain the CC mosaic spacing between amacrine and ganglion cell bodies. Receptor CC for netrin required for axon guidance independently of and in CC collaboration with the receptor DCC. In spinal chord development CC plays a role in guiding commissural axons projection and CC pathfinding across the ventral midline to reach the floor plate CC upon ligand binding. Enhances netrin-induced phosphorylation of CC PAK1 and FYN. Mediates intracellular signaling by stimulating the CC activation of MAPK8 and MAP kinase p38. CC -!- SUBUNIT: Interacts with DCC; the interaction is abolished in CC response to NTN1 (By similarity). Probably found in a ternary CC complex composed of DSCAM, PAK1 and RAC1. Interacts (via CC extracellular domain) with NTN1. Interacts (via cytoplasmic CC domain) with PAK1; the interaction is direct and enhanced in CC presence of RAC1. Interacts with RAC1; the interaction requires CC PAK1. CC -!- SUBCELLULAR LOCATION: Isoform Long: Cell membrane; Single-pass CC type I membrane protein (Potential). Note=Localized in the soma, CC cell membrane, axon and growth cone of dissociated commissural CC axons (By similarity). CC -!- SUBCELLULAR LOCATION: Isoform Short: Secreted (Probable). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; Synonyms=CHD2-42; CC IsoId=O60469-1; Sequence=Displayed; CC Name=Short; Synonyms=CHD2-52; CC IsoId=O60469-2; Sequence=VSP_002502, VSP_002503; CC -!- TISSUE SPECIFICITY: Primarily expressed in brain. CC -!- DOMAIN: Ig-like C2-type domains 7 to 9 are sufficient for CC interaction with NTN1 and commissural axon outgrowth. The CC transmembrane domain is necessary for interaction with DCC (By CC similarity). CC -!- PTM: Phosphorylated at tyrosine residues. Phosphorylation is CC enhanced by netrin. CC -!- SIMILARITY: Contains 6 fibronectin type-III domains. CC -!- SIMILARITY: Contains 10 Ig-like C2-type (immunoglobulin-like) CC domains. 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; AF023450; AAC17967.1; -; mRNA. DR EMBL; AF023449; AAC17966.1; -; mRNA. DR EMBL; AF217525; AAF27525.1; -; mRNA. DR EMBL; AL163283; CAB90464.1; -; Genomic_DNA. DR EMBL; AL163282; CAB90436.1; -; Genomic_DNA. DR EMBL; AL163281; CAB90444.1; -; Genomic_DNA. DR IPI; IPI00029700; -. DR IPI; IPI00219339; -. DR RefSeq; NP_001380.2; NM_001389.3. DR UniGene; Hs.397800; -. DR ProteinModelPortal; O60469; -. DR SMR; O60469; 22-1560. DR STRING; O60469; -. DR PhosphoSite; O60469; -. DR PRIDE; O60469; -. DR Ensembl; ENST00000400454; ENSP00000383303; ENSG00000171587. DR GeneID; 1826; -. DR KEGG; hsa:1826; -. DR UCSC; uc002yyq.1; human. DR CTD; 1826; -. DR GeneCards; GC21M026864; -. DR H-InvDB; HIX0040859; -. DR HGNC; HGNC:3039; DSCAM. DR MIM; 602523; gene. DR neXtProt; NX_O60469; -. DR PharmGKB; PA27491; -. DR eggNOG; prNOG05860; -. DR HOVERGEN; HBG051409; -. DR InParanoid; O60469; -. DR OMA; IPMEAAS; -. DR OrthoDB; EOG4J9MXZ; -. DR PhylomeDB; O60469; -. DR Pathway_Interaction_DB; hnf3apathway; FOXA1 transcription factor network. DR Reactome; REACT_111155; Cell-Cell communication. DR NextBio; 7449; -. DR ArrayExpress; O60469; -. DR Bgee; O60469; -. DR CleanEx; HS_DSCAM; -. DR Genevestigator; O60469; -. DR GermOnline; ENSG00000171587; Homo sapiens. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0030426; C:growth cone; ISS:UniProtKB. DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc. DR GO; GO:0005624; C:membrane fraction; TAS:ProtInc. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0070593; P:dendrite self-avoidance; ISS:UniProtKB. DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB. DR GO; GO:0048842; P:positive regulation of axon extension involved in axon guidance; IDA:UniProtKB. DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:UniProtKB. DR InterPro; IPR003961; Fibronectin_type3. DR InterPro; IPR007110; Ig-like. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR Gene3D; G3DSA:2.60.40.10; Ig-like_fold; 16. DR KO; K06767; -. DR Pfam; PF00041; fn3; 6. DR Pfam; PF07679; I-set; 8. DR SMART; SM00060; FN3; 6. DR SMART; SM00409; IG; 2. DR SMART; SM00408; IGc2; 7. DR SUPFAM; SSF49265; FN_III-like; 6. DR PROSITE; PS50853; FN3; 6. DR PROSITE; PS50835; IG_LIKE; 9. PE 1: Evidence at protein level; KW Alternative splicing; Cell adhesion; Cell membrane; Complete proteome; KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane; KW Neurogenesis; Phosphoprotein; Polymorphism; Reference proteome; KW Repeat; Secreted; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1 17 Potential. FT CHAIN 18 2012 Down syndrome cell adhesion molecule. FT /FTId=PRO_0000014747. FT TOPO_DOM 18 1595 Extracellular (Potential). FT TRANSMEM 1596 1616 Helical; (Potential). FT TOPO_DOM 1617 2012 Cytoplasmic (Potential). FT DOMAIN 39 129 Ig-like C2-type 1. FT DOMAIN 125 216 Ig-like C2-type 2. FT DOMAIN 225 305 Ig-like C2-type 3. FT DOMAIN 313 401 Ig-like C2-type 4. FT DOMAIN 407 500 Ig-like C2-type 5. FT DOMAIN 504 592 Ig-like C2-type 6. FT DOMAIN 596 685 Ig-like C2-type 7. FT DOMAIN 690 783 Ig-like C2-type 8. FT DOMAIN 787 883 Ig-like C2-type 9. FT DOMAIN 885 978 Fibronectin type-III 1. FT DOMAIN 984 1082 Fibronectin type-III 2. FT DOMAIN 1088 1183 Fibronectin type-III 3. FT DOMAIN 1189 1279 Fibronectin type-III 4. FT DOMAIN 1285 1377 Ig-like C2-type 10. FT DOMAIN 1376 1470 Fibronectin type-III 5. FT DOMAIN 1476 1566 Fibronectin type-III 6. FT CARBOHYD 28 28 N-linked (GlcNAc...) (Potential). FT CARBOHYD 78 78 N-linked (GlcNAc...) (Potential). FT CARBOHYD 470 470 N-linked (GlcNAc...) (Potential). FT CARBOHYD 487 487 N-linked (GlcNAc...) (Potential). FT CARBOHYD 512 512 N-linked (GlcNAc...) (Potential). FT CARBOHYD 556 556 N-linked (GlcNAc...) (Potential). FT CARBOHYD 658 658 N-linked (GlcNAc...) (Potential). FT CARBOHYD 666 666 N-linked (GlcNAc...) (Potential). FT CARBOHYD 710 710 N-linked (GlcNAc...) (Potential). FT CARBOHYD 748 748 N-linked (GlcNAc...) (Potential). FT CARBOHYD 795 795 N-linked (GlcNAc...) (Potential). FT CARBOHYD 924 924 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1142 1142 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1160 1160 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1250 1250 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1271 1271 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1341 1341 N-linked (GlcNAc...) (Potential). FT CARBOHYD 1488 1488 N-linked (GlcNAc...) (Potential). FT DISULFID 46 102 By similarity. FT DISULFID 145 197 By similarity. FT DISULFID 246 293 By similarity. FT DISULFID 335 385 By similarity. FT DISULFID 428 484 By similarity. FT DISULFID 525 575 By similarity. FT DISULFID 617 669 By similarity. FT DISULFID 711 766 By similarity. FT DISULFID 809 865 By similarity. FT DISULFID 1307 1359 By similarity. FT VAR_SEQ 1562 1571 NFATLNYDGS -> KEAARCKEFS (in isoform FT Short). FT /FTId=VSP_002502. FT VAR_SEQ 1572 2012 Missing (in isoform Short). FT /FTId=VSP_002503. FT VARIANT 232 232 D -> E (in dbSNP:rs2297270). FT /FTId=VAR_020080. FT CONFLICT 1893 2012 HRPGDLIHLPPYLRMDFLLNRGGPGTSRDLSLGQACLEPQK FT SRTLKRPTVLEPIPMEAASSASSTREGQSWQPGAVATLPQR FT EGAELGQAAKMSSSQESLLDSRGHLKGNNPYAKSYTLV -> FT IGQVTSYICLHTLEWTFC (in Ref. 1; AAC17966). SQ SEQUENCE 2012 AA; 222260 MW; 0E33CFB781A08334 CRC64; MWILALSLFQ SFANVFSEDL HSSLYFVNAS LQEVVFASTT GTLVPCPAAG IPPVTLRWYL ATGEEIYDVP GIRHVHPNGT LQIFPFPPSS FSTLIHDNTY YCTAENPSGK IRSQDVHIKA VLREPYTVRV EDQKTMRGNV AVFKCIIPSS VEAYITVVSW EKDTVSLVSG SRFLITSTGA LYIKDVQNED GLYNYRCITR HRYTGETRQS NSARLFVSDP ANSAPSILDG FDHRKAMAGQ RVELPCKALG HPEPDYRWLK DNMPLELSGR FQKTVTGLLI ENIRPSDSGS YVCEVSNRYG TAKVIGRLYV KQPLKATISP RKVKSSVGSQ VSLSCSVTGT EDQELSWYRN GEILNPGKNV RITGINHENL IMDHMVKSDG GAYQCFVRKD KLSAQDYVQV VLEDGTPKII SAFSEKVVSP AEPVSLMCNV KGTPLPTITW TLDDDPILKG GSHRISQMIT SEGNVVSYLN ISSSQVRDGG VYRCTANNSA GVVLYQARIN VRGPASIRPM KNITAIAGRD TYIHCRVIGY PYYSIKWYKN SNLLPFNHRQ VAFENNGTLK LSDVQKEVDE GEYTCNVLVQ PQLSTSQSVH VTVKVPPFIQ PFEFPRFSIG QRVFIPCVVV SGDLPITITW QKDGRPIPGS LGVTIDNIDF TSSLRISNLS LMHNGNYTCI ARNEAAAVEH QSQLIVRVPP KFVVQPRDQD GIYGKAVILN CSAEGYPVPT IVWKFSKGAG VPQFQPIALN GRIQVLSNGS LLIKHVVEED SGYYLCKVSN DVGADVSKSM YLTVKIPAMI TSYPNTTLAT QGQKKEMSCT AHGEKPIIVR WEKEDRIINP EMARYLVSTK EVGEEVISTL QILPTVREDS GFFSCHAINS YGEDRGIIQL TVQEPPDPPE IEIKDVKART ITLRWTMGFD GNSPITGYDI ECKNKSDSWD SAQRTKDVSP QLNSATIIDI HPSSTYSIRM YAKNRIGKSE PSNELTITAD EAAPDGPPQE VHLEPISSQS IRVTWKAPKK HLQNGIIRGY QIGYREYSTG GNFQFNIISV DTSGDSEVYT LDNLNKFTQY GLVVQACNRA GTGPSSQEII TTTLEDVPSY PPENVQAIAT SPESISISWS TLSKEALNGI LQGFRVIYWA NLMDGELGEI KNITTTQPSL ELDGLEKYTN YSIQVLAFTR AGDGVRSEQI FTRTKEDVPG PPAGVKAAAA SASMVFVSWL PPLKLNGIIR KYTVFCSHPY PTVISEFEAS PDSFSYRIPN LSRNRQYSVW VVAVTSAGRG NSSEIITVEP LAKAPARILT FSGTVTTPWM KDIVLPCKAV GDPSPAVKWM KDSNGTPSLV TIDGRRSIFS NGSFIIRTVK AEDSGYYSCI ANNNWGSDEI ILNLQVQVPP DQPRLTVSKT TSSSITLSWL PGDNGGSSIR GYILQYSEDN SEQWGSFPIS PSERSYRLEN LKCGTWYKFT LTAQNGVGPG RISEIIEAKT LGKEPQFSKE QELFASINTT RVRLNLIGWN DGGCPITSFT LEYRPFGTTV WTTAQRTSLS KSYILYDLQE ATWYELQMRV CNSAGCAEKQ ANFATLNYDG STIPPLIKSV VQNEEGLTTN EGLKMLVTIS CILVGVLLLF VLLLVVRRRR REQRLKRLRD AKSLAEMLMS KNTRTSDTLS KQQQTLRMHI DIPRAQLLIE ERDTMETIDD RSTVLLTDAD FGEAAKQKSL TVTHTVHYQS VSQATGPLVD VSDARPGTNP TTRRNAKAGP TARNRYASQW TLNRPHPTIS AHTLTTDWRL PTPRAAGSVD KESDSYSVSP SQDTDRARSS MVSTESASST YEELARAYEH AKMEEQLRHA KFTITECFIS DTSSEQLTAG TNEYTDSLTS STPSESGICR FTASPPKPQD GGRVMNMAVP KAHRPGDLIH LPPYLRMDFL LNRGGPGTSR DLSLGQACLE PQKSRTLKRP TVLEPIPMEA ASSASSTREG QSWQPGAVAT LPQREGAELG QAAKMSSSQE SLLDSRGHLK GNNPYAKSYT LV //