IGSF3_HUMAN
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 03-AUG-2022, entry version 161.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND VARIANT
RP 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-like
RT membrane protein: expression and mapping to chromosome band 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 from
RT 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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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 protein
RT 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. {ECO:0000269|PubMed:9790749}.
CC -!- DISEASE: Lacrimal duct defect (LCDD) [MIM:149700]: A condition
CC resulting in the imbalance between tear production and tear drainage.
CC Infants typically manifest persistent epiphora and/or recurrent
CC infections of the lacrimal pathway, such as conjunctivitis. LCDD is
CC caused by failure of the nasolacrimal duct to open into the inferior
CC meatus. {ECO:0000269|PubMed:24372406}. Note=The disease is caused by
CC variants affecting the gene 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 Alu
CC elements as well as in the 5' or 3' ends of them.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC72013.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA32311.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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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.
DR RefSeq; XP_011539617.1; XM_011541315.1. [O75054-2]
DR AlphaFoldDB; O75054; -.
DR BioGRID; 109553; 64.
DR IntAct; O75054; 17.
DR STRING; 9606.ENSP00000358495; -.
DR GlyConnect; 1392; 2 N-Linked glycans (2 sites).
DR GlyGen; O75054; 8 sites, 2 N-linked glycans (2 sites).
DR iPTMnet; O75054; -.
DR PhosphoSitePlus; O75054; -.
DR BioMuta; IGSF3; -.
DR EPD; O75054; -.
DR jPOST; O75054; -.
DR MassIVE; O75054; -.
DR MaxQB; O75054; -.
DR PaxDb; O75054; -.
DR PeptideAtlas; O75054; -.
DR PRIDE; O75054; -.
DR ProteomicsDB; 1365; -.
DR ProteomicsDB; 49728; -. [O75054-1]
DR ProteomicsDB; 49729; -. [O75054-2]
DR Antibodypedia; 46948; 183 antibodies from 27 providers.
DR DNASU; 3321; -.
DR Ensembl; ENST00000318837.6; ENSP00000321184.6; ENSG00000143061.18. [O75054-2]
DR Ensembl; ENST00000369483.5; ENSP00000358495.1; ENSG00000143061.18. [O75054-2]
DR Ensembl; ENST00000369486.8; ENSP00000358498.4; ENSG00000143061.18. [O75054-1]
DR GeneID; 3321; -.
DR KEGG; hsa:3321; -.
DR MANE-Select; ENST00000369486.8; ENSP00000358498.4; NM_001007237.3; NP_001007238.1.
DR UCSC; uc001egr.3; human. [O75054-1]
DR CTD; 3321; -.
DR DisGeNET; 3321; -.
DR GeneCards; IGSF3; -.
DR HGNC; HGNC:5950; IGSF3.
DR HPA; ENSG00000143061; Low tissue specificity.
DR MalaCards; IGSF3; -.
DR MIM; 149700; phenotype.
DR MIM; 603491; gene.
DR neXtProt; NX_O75054; -.
DR OpenTargets; ENSG00000143061; -.
DR Orphanet; 451612; Familial congenital nasolacrimal duct obstruction.
DR PharmGKB; PA29763; -.
DR VEuPathDB; HostDB:ENSG00000143061; -.
DR eggNOG; ENOG502QRRB; Eukaryota.
DR GeneTree; ENSGT00940000155177; -.
DR HOGENOM; CLU_005187_0_0_1; -.
DR InParanoid; O75054; -.
DR OMA; AYAVYSQ; -.
DR OrthoDB; 180654at2759; -.
DR PhylomeDB; O75054; -.
DR TreeFam; TF332702; -.
DR PathwayCommons; O75054; -.
DR SignaLink; O75054; -.
DR BioGRID-ORCS; 3321; 86 hits in 1080 CRISPR screens.
DR ChiTaRS; IGSF3; human.
DR GenomeRNAi; 3321; -.
DR Pharos; O75054; Tbio.
DR PRO; PR:O75054; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O75054; protein.
DR Bgee; ENSG00000143061; Expressed in cortical plate and 191 other tissues.
DR Genevisible; O75054; HS.
DR GO; GO:0009986; C:cell surface; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
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; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR Pfam; PF07686; V-set; 4.
DR SMART; SM00409; IG; 8.
DR SMART; SM00408; IGc2; 4.
DR SMART; SM00406; IGv; 4.
DR SUPFAM; SSF48726; SSF48726; 7.
DR PROSITE; PS50835; IG_LIKE; 7.
PE 2: Evidence at transcript level;
KW Alternative splicing; Chromosomal rearrangement; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Membrane; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1194
FT /note="Immunoglobulin superfamily member 3"
FT /id="PRO_0000320134"
FT TOPO_DOM 20..1124
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1125..1145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1146..1194
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 20..138
FT /note="Ig-like C2-type 1"
FT DOMAIN 143..262
FT /note="Ig-like C2-type 2"
FT DOMAIN 276..386
FT /note="Ig-like C2-type 3"
FT DOMAIN 401..539
FT /note="Ig-like C2-type 4"
FT DOMAIN 545..661
FT /note="Ig-like C2-type 5"
FT DOMAIN 676..803
FT /note="Ig-like C2-type 6"
FT DOMAIN 813..945
FT /note="Ig-like C2-type 7"
FT DOMAIN 949..1097
FT /note="Ig-like C2-type 8"
FT REGION 997..1033
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 250..252
FT /note="EWI motif"
FT COMPBIAS 1009..1028
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 418
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 655
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 842
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1077
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 42..120
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 167..246
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 302..376
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 432..511
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 566..645
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 701..782
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 838..918
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 974..1080
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 407..408
FT /note="LK -> LTDNWVVKVPQHHQLLSQGHLE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9790749"
FT /id="VSP_031609"
FT VARIANT 51
FT /note="S -> P (in dbSNP:rs3965246)"
FT /id="VAR_039134"
FT VARIANT 1020
FT /note="D -> E (in dbSNP:rs647711)"
FT /evidence="ECO:0000269|PubMed:9790749"
FT /id="VAR_039135"
FT VARIANT 1073
FT /note="Q -> R (in dbSNP:rs6703791)"
FT /id="VAR_039136"
FT CONFLICT 932
FT /note="Y -> S (in Ref. 1; AAC72013)"
FT /evidence="ECO:0000305"
FT CONFLICT 1013
FT /note="R -> RE (in Ref. 1; AAC72013)"
FT /evidence="ECO:0000305"
FT CONFLICT 1047
FT /note="S -> N (in Ref. 1; AAC72013)"
FT /evidence="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
