ID IGSF3_HUMAN Reviewed; 1194 AA. AC O75054; A6NJZ6; A6NMC7; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 26-FEB-2008, sequence version 3. DT 24-JUN-2015, entry version 111. DE RecName: Full=Immunoglobulin superfamily member 3; DE Short=IgSF3; DE AltName: Full=Glu-Trp-Ile EWI motif-containing protein 3; DE Short=EWI-3; DE Flags: Precursor; GN Name=IGSF3; Synonyms=EWI3, KIAA0466; 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] (ISOFORM 2), TISSUE SPECIFICITY, AND RP VARIANT GLU-1020. RX PubMed=9790749; DOI=10.1006/geno.1998.5439; RA Saupe S., Roizes G., Peter M., Boyle S., Gardiner K., De Sario A.; RT "Molecular cloning of a human cDNA IGSF3 encoding an immunoglobulin- RT like membrane protein: expression and mapping to chromosome band RT 1p13."; RL Genomics 52:305-311(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9455484; DOI=10.1093/dnares/4.5.345; RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., RA Nomura N., Ohara O.; RT "Characterization of cDNA clones in size-fractionated cDNA libraries RT from human brain."; RL DNA Res. 4:345-349(1997). RN [3] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP DOMAIN EWI MOTIF. RX PubMed=11504738; DOI=10.1074/jbc.M107338200; RA Stipp C.S., Kolesnikova T.V., Hemler M.E.; RT "EWI-2 is a major CD9 and CD81 partner and member of a novel Ig RT protein subfamily."; RL J. Biol. Chem. 276:40545-40554(2001). RN [6] RP BREAKPOINTS. RX PubMed=14656960; DOI=10.1101/gr.1549503; RA Babcock M., Pavlicek A., Spiteri E., Kashork C.D., Ioshikhes I., RA Shaffer L.G., Jurka J., Morrow B.E.; RT "Shuffling of genes within low-copy repeats on 22q11 (LCR22) by Alu- RT mediated recombination events during evolution."; RL Genome Res. 13:2519-2532(2003). RN [7] RP INVOLVEMENT IN LCDD. RX PubMed=24372406; DOI=10.1111/cge.12321; RA Foster J., Kapoor S., Diaz-Horta O., Singh A., Abad C., Rastogi A., RA Moharana R., Tekeli O., Walz K., Tekin M.; RT "Identification of an IGSF3 mutation in a family with congenital RT nasolacrimal duct obstruction."; RL Clin. Genet. 86:589-591(2014). CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I CC membrane protein {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O75054-1; Sequence=Displayed; CC Name=2; CC IsoId=O75054-2; Sequence=VSP_031609; CC -!- TISSUE SPECIFICITY: Expressed in a wide range of tissues with High CC expression in Placenta, kidney and lung. CC {ECO:0000269|PubMed:9790749}. CC -!- DISEASE: Lacrimal duct defect (LCDD) [MIM:149700]: A condition CC resulting in the imbalance between tear production and tear CC drainage. Infants typically manifest persistent epiphora and/or CC recurrent infections of the lacrimal pathway, such as CC conjunctivitis. LCDD is caused by failure of the nasolacrimal duct CC to open into the inferior meatus. {ECO:0000269|PubMed:24372406}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- MISCELLANEOUS: Likely interchromosomal Alu-mediated fusion between CC IGSF3 on 1p13.1 and GGT on 22q11.2. Breakpoints occurred inside CC Alu elements as well as in the 5' or 3' ends of them. CC -!- SIMILARITY: Contains 8 Ig-like C2-type (immunoglobulin-like) CC domains. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC72013.1; Type=Frameshift; Positions=829, 861; Evidence={ECO:0000305}; CC Sequence=BAA32311.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={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; AF031174; AAC72013.1; ALT_FRAME; mRNA. DR EMBL; AB007935; BAA32311.2; ALT_INIT; mRNA. DR EMBL; AL355794; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL356748; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS30813.1; -. [O75054-1] DR CCDS; CCDS30814.1; -. [O75054-2] DR RefSeq; NP_001007238.1; NM_001007237.2. [O75054-1] DR RefSeq; NP_001533.2; NM_001542.3. [O75054-2] DR RefSeq; XP_005270850.1; XM_005270793.2. [O75054-2] DR UniGene; Hs.171057; -. DR ProteinModelPortal; O75054; -. DR SMR; O75054; 25-250. DR BioGrid; 109553; 5. DR STRING; 9606.ENSP00000321184; -. DR PhosphoSite; O75054; -. DR MaxQB; O75054; -. DR PaxDb; O75054; -. DR PRIDE; O75054; -. DR DNASU; 3321; -. DR Ensembl; ENST00000318837; ENSP00000321184; ENSG00000143061. [O75054-2] DR Ensembl; ENST00000369483; ENSP00000358495; ENSG00000143061. [O75054-2] DR Ensembl; ENST00000369486; ENSP00000358498; ENSG00000143061. [O75054-1] DR GeneID; 3321; -. DR KEGG; hsa:3321; -. DR UCSC; uc001egr.2; human. [O75054-1] DR UCSC; uc031pnr.1; human. DR CTD; 3321; -. DR GeneCards; GC01M117117; -. DR H-InvDB; HIX0000930; -. DR HGNC; HGNC:5950; IGSF3. DR HPA; HPA036305; -. DR HPA; HPA036306; -. DR MIM; 149700; phenotype. DR MIM; 603491; gene. DR neXtProt; NX_O75054; -. DR PharmGKB; PA29763; -. DR eggNOG; NOG41502; -. DR GeneTree; ENSGT00390000010278; -. DR HOGENOM; HOG000293322; -. DR HOVERGEN; HBG107998; -. DR InParanoid; O75054; -. DR KO; K06522; -. DR OMA; VEEWLLN; -. DR OrthoDB; EOG7ZKS99; -. DR PhylomeDB; O75054; -. DR TreeFam; TF332702; -. DR ChiTaRS; IGSF3; human. DR GenomeRNAi; 3321; -. DR NextBio; 13168; -. DR PRO; PR:O75054; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; O75054; -. DR CleanEx; HS_IGSF3; -. DR Genevisible; O75054; HS. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0032808; P:lacrimal gland development; IMP:UniProtKB. DR Gene3D; 2.60.40.10; -; 8. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR013106; Ig_V-set. DR Pfam; PF07686; V-set; 6. DR SMART; SM00409; IG; 8. DR PROSITE; PS50835; IG_LIKE; 7. PE 2: Evidence at transcript level; KW Alternative splicing; Chromosomal rearrangement; Complete proteome; KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane; KW Polymorphism; Reference proteome; Repeat; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1 19 {ECO:0000255}. FT CHAIN 20 1194 Immunoglobulin superfamily member 3. FT /FTId=PRO_0000320134. FT TOPO_DOM 20 1124 Extracellular. {ECO:0000255}. FT TRANSMEM 1125 1145 Helical. {ECO:0000255}. FT TOPO_DOM 1146 1194 Cytoplasmic. {ECO:0000255}. FT DOMAIN 20 138 Ig-like C2-type 1. FT DOMAIN 143 262 Ig-like C2-type 2. FT DOMAIN 276 386 Ig-like C2-type 3. FT DOMAIN 401 539 Ig-like C2-type 4. FT DOMAIN 545 661 Ig-like C2-type 5. FT DOMAIN 676 803 Ig-like C2-type 6. FT DOMAIN 813 945 Ig-like C2-type 7. FT DOMAIN 949 1097 Ig-like C2-type 8. FT MOTIF 250 252 EWI motif. FT CARBOHYD 43 43 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 418 418 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 655 655 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 842 842 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1077 1077 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 42 120 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 167 246 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 302 376 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 432 511 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 566 645 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 701 782 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 838 918 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 974 1080 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT VAR_SEQ 407 408 LK -> LTDNWVVKVPQHHQLLSQGHLE (in isoform FT 2). {ECO:0000303|PubMed:9790749}. FT /FTId=VSP_031609. FT VARIANT 51 51 S -> P (in dbSNP:rs3965246). FT /FTId=VAR_039134. FT VARIANT 1020 1020 D -> E (in dbSNP:rs647711). FT {ECO:0000269|PubMed:9790749}. FT /FTId=VAR_039135. FT VARIANT 1073 1073 Q -> R (in dbSNP:rs6703791). FT /FTId=VAR_039136. FT CONFLICT 932 932 Y -> S (in Ref. 1; AAC72013). FT {ECO:0000305}. FT CONFLICT 1013 1013 R -> RE (in Ref. 1; AAC72013). FT {ECO:0000305}. FT CONFLICT 1047 1047 S -> N (in Ref. 1; AAC72013). FT {ECO:0000305}. SQ SEQUENCE 1194 AA; 135196 MW; C5E22EDBC81714DD CRC64; MKCFFPVLSC LAVLGVVSAQ RQVTVQEGPL YRTEGSHITI WCNVSGYQGP SEQNFQWSIY LPSSPEREVQ IVSTMDSSFP YAIYTQRVRG GKIFIERVQG NSTLLHITDL QARDAGEYEC HTPSTDKQYF GSYSAKMNLV VIPDSLQTTA MPQTLHRVEQ DPLELTCEVA SETIQHSHLS VAWLRQKVGE KPVEVISLSR DFMLHSSSEY AQRQSLGEVR LDKLGRTTFR LTIFHLQPSD QGEFYCEAAE WIQDPDGSWY AMTRKRSEGA VVNVQPTDKE FTVRLETEKR LHTVGEPVEF RCILEAQNVP DRYFAVSWAF NSSLIATMGP NAVPVLNSEF AHREARGQLK VAKESDSVFV LKIYHLRQED SGKYNCRVTE REKTVTGEFI DKESKRPKNI PIIVLPLKSS ISVEVASNAS VILEGEDLRF SCSVRTAGRP QGRFSVIWQL VDRQNRRSNI MWLDRDGTVQ PGSSYWERSS FGGVQMEQVQ PNSFSLGIFN SRKEDEGQYE CHVTEWVRAV DGEWQIVGER RASTPISITA LEMGFAVTAI SRTPGVTYSD SFDLQCIIKP HYPAWVPVSV TWRFQPVGTV EFHDLVTFTR DGGVQWGDRS SSFRTRTAIE KAESSNNVRL SISRASDTEA GKYQCVAELW RKNYNNTWTR LAERTSNLLE IRVLQPVTKL QVSKSKRTLT LVENKPIQLN CSVKSQTSQN SHFAVLWYVH KPSDADGKLI LKTTHNSAFE YGTYAEEEGL RARLQFERHV SGGLFSLTVQ RAEVSDSGSY YCHVEEWLLS PNYAWYKLAE EVSGRTEVTV KQPDSRLRLS QAQGNLSVLE TRQVQLECVV LNRTSITSQL MVEWFVWKPN HPERETVARL SRDATFHYGE QAAKNNLKGR LHLESPSPGV YRLFIQNVAV QDSGTYSCHV EEWLPSPSGM WYKRAEDTAG QTALTVMRPD ASLQVDTVVP NATVSEKAAF QLDCSIVSRS SQDSRFAVAW YSLRTKAGGK RSSPGLEEQE EEREEEEEED DDDDDDPTER TALLSVGPDA VFGPEGSPWE GRLRFQRLSP VLYRLTVLQA SPQDTGNYSC HVEEWLPSPQ KEWYRLTEEE SAPIGIRVLD TSPTLQSIIC SNDALFYFVF FYPFPIFGIL IITILLVRFK SRNSSKNSDG KNGVPLLWIK EPHLNYSPTC LEPPVLSIHP GAID //