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-OCT-2015, entry version 149. 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 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 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 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 CC (PubMed:10925149). Receptor for netrin required for axon guidance CC independently of and in collaboration with the receptor DCC. In CC spinal chord development plays a role in guiding commissural axons CC projection and pathfinding across the ventral midline to reach the CC floor plate upon ligand binding (PubMed:18585357, CC PubMed:19196994). Enhances netrin-induced phosphorylation of PAK1 CC and FYN (PubMed:15169762). Mediates intracellular signaling by CC stimulating the activation of MAPK8 and MAP kinase p38 CC (PubMed:18585357, PubMed:19196994). Adhesion molecule that CC promotes lamina-specific synaptic connections in the retina: CC expressed in specific subsets of interneurons and retinal ganglion CC cells (RGCs) and promotes synaptic connectivity via homophilic CC interactions (By similarity). {ECO:0000250|UniProtKB:F1NY98, CC ECO:0000269|PubMed:10925149, ECO:0000269|PubMed:15169762, CC ECO:0000269|PubMed:18585357, ECO:0000269|PubMed:19196994}. CC -!- SUBUNIT: Homodimer; mediates homophilic interactions to promote CC cell adhesion (By similarity). Interacts with DCC; the interaction CC is abolished in response to NTN1 (By similarity). Probably found CC in a ternary complex composed of DSCAM, PAK1 and RAC1 CC (PubMed:15169762). Interacts (via extracellular domain) with NTN1 CC (PubMed:19196994). Interacts (via cytoplasmic domain) with PAK1; CC the interaction is direct and enhanced in presence of RAC1. CC Interacts with RAC1; the interaction requires PAK1. CC {ECO:0000250|UniProtKB:F1NY98, ECO:0000250|UniProtKB:Q9ERC8, CC ECO:0000269|PubMed:15169762, ECO:0000269|PubMed:19196994}. CC -!- SUBCELLULAR LOCATION: Isoform Short: Secreted {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Isoform Long: Cell membrane CC {ECO:0000250|UniProtKB:Q9ERC8}; Single-pass type I membrane CC protein {ECO:0000250|UniProtKB:Q9ERC8}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q9ERC8}. Cell junction, synapse CC {ECO:0000250|UniProtKB:F1NY98}. Note=Localized in the soma, cell CC membrane, axon and growth cone of dissociated commissural axons. CC {ECO:0000250|UniProtKB:Q9ERC8}. 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). {ECO:0000250}. CC -!- PTM: Phosphorylated at tyrosine residues. Phosphorylation is CC enhanced by netrin. {ECO:0000269|PubMed:19196994}. CC -!- SIMILARITY: Contains 6 fibronectin type-III domains. CC {ECO:0000255|PROSITE-ProRule:PRU00316}. CC -!- SIMILARITY: Contains 10 Ig-like C2-type (immunoglobulin-like) CC domains. {ECO:0000305}. 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 CCDS; CCDS42929.1; -. [O60469-1] DR RefSeq; NP_001258463.1; NM_001271534.1. DR RefSeq; NP_001380.2; NM_001389.3. [O60469-1] DR UniGene; Hs.397800; -. DR ProteinModelPortal; O60469; -. DR SMR; O60469; 980-1089. DR BioGrid; 108160; 1. DR STRING; 9606.ENSP00000383303; -. DR PhosphoSite; O60469; -. DR BioMuta; DSCAM; -. DR PaxDb; O60469; -. DR PRIDE; O60469; -. DR Ensembl; ENST00000400454; ENSP00000383303; ENSG00000171587. [O60469-1] DR GeneID; 1826; -. DR KEGG; hsa:1826; -. DR UCSC; uc002yyq.1; human. [O60469-1] DR CTD; 1826; -. DR GeneCards; DSCAM; -. DR HGNC; HGNC:3039; DSCAM. DR HPA; HPA019324; -. DR MIM; 602523; gene. DR neXtProt; NX_O60469; -. DR PharmGKB; PA27491; -. DR eggNOG; NOG12793; -. DR GeneTree; ENSGT00810000125365; -. DR HOVERGEN; HBG051409; -. DR InParanoid; O60469; -. DR KO; K06767; -. DR OMA; NSVRMTG; -. DR OrthoDB; EOG7R830M; -. DR PhylomeDB; O60469; -. DR TreeFam; TF316846; -. DR Reactome; R-HSA-376172; DSCAM interactions. DR ChiTaRS; DSCAM; human. DR GenomeRNAi; 1826; -. DR NextBio; 7449; -. DR PRO; PR:O60469; -. DR Proteomes; UP000005640; Chromosome 21. DR Bgee; O60469; -. DR CleanEx; HS_DSCAM; -. DR ExpressionAtlas; O60469; baseline and differential. DR Genevisible; O60469; HS. 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 component of plasma membrane; TAS:ProtInc. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl. DR GO; GO:0070593; P:dendrite self-avoidance; ISS:UniProtKB. DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl. DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. 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 GO; GO:0060060; P:post-embryonic retina morphogenesis in camera-type eye; IEA:Ensembl. DR Gene3D; 2.60.40.10; -; 16. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR Pfam; PF00041; fn3; 5. DR Pfam; PF07679; I-set; 8. DR SMART; SM00060; FN3; 6. DR SMART; SM00409; IG; 2. DR SMART; SM00408; IGc2; 7. DR SUPFAM; SSF48726; SSF48726; 10. DR SUPFAM; SSF49265; SSF49265; 3. DR PROSITE; PS50853; FN3; 6. DR PROSITE; PS50835; IG_LIKE; 8. PE 1: Evidence at protein level; KW Alternative splicing; Cell adhesion; Cell junction; Cell membrane; KW Cell projection; Complete proteome; Disulfide bond; Glycoprotein; KW Immunoglobulin domain; Membrane; Neurogenesis; Phosphoprotein; KW Polymorphism; Reference proteome; Repeat; Secreted; Signal; Synapse; KW Transmembrane; Transmembrane helix. FT SIGNAL 1 17 {ECO:0000255}. FT CHAIN 18 2012 Down syndrome cell adhesion molecule. FT /FTId=PRO_0000014747. FT TOPO_DOM 18 1595 Extracellular. {ECO:0000255}. FT TRANSMEM 1596 1616 Helical. {ECO:0000255}. FT TOPO_DOM 1617 2012 Cytoplasmic. {ECO:0000255}. 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 885 982 Fibronectin type-III 1. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 987 1086 Fibronectin type-III 2. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 1091 1187 Fibronectin type-III 3. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 1191 1285 Fibronectin type-III 4. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 1285 1377 Ig-like C2-type 10. FT DOMAIN 1379 1473 Fibronectin type-III 5. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 1474 1575 Fibronectin type-III 6. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT CARBOHYD 28 28 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 78 78 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 470 470 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 487 487 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 512 512 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 556 556 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 658 658 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 666 666 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 710 710 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 748 748 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 795 795 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 924 924 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1142 1142 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1160 1160 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1250 1250 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1271 1271 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1341 1341 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1488 1488 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 46 102 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 145 197 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 246 293 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 335 385 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 428 484 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 525 575 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 617 669 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 711 766 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 809 865 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 1307 1359 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT VAR_SEQ 1562 1571 NFATLNYDGS -> KEAARCKEFS (in isoform FT Short). {ECO:0000305}. FT /FTId=VSP_002502. FT VAR_SEQ 1572 2012 Missing (in isoform Short). FT {ECO:0000305}. 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). FT {ECO:0000305}. 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 //