ID CELR1_HUMAN Reviewed; 3014 AA. AC Q9NYQ6; O95722; Q5TH47; Q9BWQ5; Q9Y506; Q9Y526; DT 02-AUG-2002, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 02-OCT-2024, entry version 216. DE RecName: Full=Cadherin EGF LAG seven-pass G-type receptor 1; DE AltName: Full=Cadherin family member 9; DE AltName: Full=Flamingo homolog 2; DE Short=hFmi2; DE Flags: Precursor; GN Name=CELSR1; Synonyms=CDHF9, FMI2; 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 1). RX PubMed=10716726; DOI=10.1073/pnas.97.7.3124; RA Wu Q., Maniatis T.; RT "Large exons encoding multiple ectodomains are a characteristic feature of RT protocadherin genes."; RL Proc. Natl. Acad. Sci. U.S.A. 97:3124-3129(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 627-3014 (ISOFORM 2), AND RP VARIANTS TRP-664 AND ARG-1126. RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2764, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [5] RP INVOLVEMENT IN LMPHM9, AND VARIANT LMPHM9 1957-TRP--PRO-3014 DEL. RX PubMed=26855770; DOI=10.1186/s13221-016-0035-5; RA Gonzalez-Garay M.L., Aldrich M.B., Rasmussen J.C., Guilliod R., RA Lapinski P.E., King P.D., Sevick-Muraca E.M.; RT "A novel mutation in CELSR1 is associated with hereditary lymphedema."; RL Vasc. Cell 8:1-1(2016). RN [6] RP VARIANTS NTD VAL-773; GLN-2438; LEU-2964 AND ALA-2983, VARIANTS PRO-2312 RP AND THR-2739, CHARACTERIZATION OF VARIANTS NTD VAL-773; GLN-2438; LEU-2964 RP AND ALA-2983, AND CHARACTERIZATION OF VARIANTS PRO-2312 AND THR-2739. RX PubMed=22095531; DOI=10.1002/humu.21662; RA Robinson A., Escuin S., Doudney K., Vekemans M., Stevenson R.E., RA Greene N.D., Copp A.J., Stanier P.; RT "Mutations in the planar cell polarity genes CELSR1 and SCRIB are RT associated with the severe neural tube defect craniorachischisis."; RL Hum. Mutat. 33:440-447(2012). RN [7] RP VARIANTS LMPHM9 290-GLU--PRO-3014 DEL; THR-1058; SER-1539; HIS-1883; RP VAL-2150; TRP-2425; GLY-2709 AND ARG-3001. RX PubMed=31215153; DOI=10.1002/ajmg.a.61269; RA Maltese P.E., Michelini S., Ricci M., Maitz S., Fiorentino A., Serrani R., RA Lazzerotti A., Bruson A., Paolacci S., Benedetti S., Bertelli M.; RT "Increasing evidence of hereditary lymphedema caused by CELSR1 loss-of- RT function variants."; RL Am. J. Med. Genet. A 179:1718-1724(2019). CC -!- FUNCTION: Receptor that may have an important role in cell/cell CC signaling during nervous system formation. CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NYQ6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NYQ6-2; Sequence=VSP_002011, VSP_002012; CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate CC and asparagine is (R) stereospecific within EGF domains. {ECO:0000250}. CC -!- DISEASE: Neural tube defects (NTD) [MIM:182940]: Congenital CC malformations of the central nervous system and adjacent structures CC related to defective neural tube closure during the first trimester of CC pregnancy. Failure of neural tube closure can occur at any level of the CC embryonic axis. Common NTD forms include anencephaly, myelomeningocele CC and spina bifida, which result from the failure of fusion in the CC cranial and spinal region of the neural tube. NTDs have a CC multifactorial etiology encompassing both genetic and environmental CC components. {ECO:0000269|PubMed:22095531}. Note=The disease may be CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Lymphatic malformation 9 (LMPHM9) [MIM:619319]: A form of CC primary lymphedema, a disease characterized by swelling of body parts CC due to developmental anomalies and functional defects of the lymphatic CC system. Patients with lymphedema may suffer from recurrent local CC infections. Impaired lymphatic drainage in the fetus can develop into CC hydrops fetalis, a severe condition characterized by excessive fluid CC accumulation in more than two fetal extra-vascular compartments and CC body cavities, placental enlargement and edema, pericardial or pleural CC effusion, or ascites. LMPHM9 is an autosomal dominant form with CC variable expressivity and incomplete penetrance, characterized by the CC onset of lower-extremity lymphedema in the first decades of life. CC {ECO:0000269|PubMed:26855770, ECO:0000269|PubMed:31215153}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family. LN-TM7 CC subfamily. {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; AF231024; AAF61930.1; -; mRNA. DR EMBL; AL021392; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL031588; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL031597; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000059; AAH00059.2; -; mRNA. DR CCDS; CCDS14076.1; -. [Q9NYQ6-1] DR RefSeq; NP_055061.1; NM_014246.1. [Q9NYQ6-1] DR PDB; 7SZ8; X-ray; 2.34 A; A/B=556-996. DR PDB; 8D40; X-ray; 3.55 A; A/B=236-683. DR PDBsum; 7SZ8; -. DR PDBsum; 8D40; -. DR SASBDB; Q9NYQ6; -. DR SMR; Q9NYQ6; -. DR BioGRID; 114981; 116. DR IntAct; Q9NYQ6; 57. DR MINT; Q9NYQ6; -. DR STRING; 9606.ENSP00000262738; -. DR TCDB; 9.A.14.6.4; the g-protein-coupled receptor (gpcr) family. DR GlyConnect; 1054; 7 N-Linked glycans (7 sites). DR GlyCosmos; Q9NYQ6; 22 sites, 9 glycans. DR GlyGen; Q9NYQ6; 29 sites, 6 N-linked glycans (6 sites), 5 O-linked glycans (8 sites). DR iPTMnet; Q9NYQ6; -. DR PhosphoSitePlus; Q9NYQ6; -. DR SwissPalm; Q9NYQ6; -. DR BioMuta; CELSR1; -. DR DMDM; 22095551; -. DR CPTAC; CPTAC-1482; -. DR jPOST; Q9NYQ6; -. DR MassIVE; Q9NYQ6; -. DR PaxDb; 9606-ENSP00000262738; -. DR PeptideAtlas; Q9NYQ6; -. DR ProteomicsDB; 83263; -. [Q9NYQ6-1] DR ProteomicsDB; 83264; -. [Q9NYQ6-2] DR Pumba; Q9NYQ6; -. DR Antibodypedia; 13897; 220 antibodies from 30 providers. DR DNASU; 9620; -. DR Ensembl; ENST00000262738.9; ENSP00000262738.3; ENSG00000075275.18. [Q9NYQ6-1] DR Ensembl; ENST00000454637.2; ENSP00000414689.2; ENSG00000075275.18. [Q9NYQ6-2] DR GeneID; 9620; -. DR KEGG; hsa:9620; -. DR UCSC; uc003bhw.1; human. [Q9NYQ6-1] DR AGR; HGNC:1850; -. DR CTD; 9620; -. DR DisGeNET; 9620; -. DR GeneCards; CELSR1; -. DR HGNC; HGNC:1850; CELSR1. DR HPA; ENSG00000075275; Tissue enhanced (skin). DR MalaCards; CELSR1; -. DR MIM; 182940; phenotype. DR MIM; 604523; gene. DR MIM; 619319; phenotype. DR neXtProt; NX_Q9NYQ6; -. DR OpenTargets; ENSG00000075275; -. DR Orphanet; 569816; CELSR1-related late-onset primary lymphedema. DR PharmGKB; PA26393; -. DR VEuPathDB; HostDB:ENSG00000075275; -. DR eggNOG; KOG4289; Eukaryota. DR GeneTree; ENSGT00940000159839; -. DR HOGENOM; CLU_000158_1_0_1; -. DR InParanoid; Q9NYQ6; -. DR OrthoDB; 4006628at2759; -. DR PhylomeDB; Q9NYQ6; -. DR TreeFam; TF323983; -. DR PathwayCommons; Q9NYQ6; -. DR SignaLink; Q9NYQ6; -. DR BioGRID-ORCS; 9620; 16 hits in 1155 CRISPR screens. DR ChiTaRS; CELSR1; human. DR GeneWiki; CELSR1; -. DR GenomeRNAi; 9620; -. DR Pharos; Q9NYQ6; Tbio. DR PRO; PR:Q9NYQ6; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q9NYQ6; protein. DR Bgee; ENSG00000075275; Expressed in ventricular zone and 147 other cell types or tissues. DR ExpressionAtlas; Q9NYQ6; baseline and differential. DR GO; GO:0016020; C:membrane; TAS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW. DR GO; GO:0045176; P:apical protein localization; ISS:UniProtKB. DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central. DR GO; GO:0007417; P:central nervous system development; TAS:UniProtKB. DR GO; GO:0048105; P:establishment of body hair planar orientation; ISS:UniProtKB. DR GO; GO:0001736; P:establishment of planar polarity; ISS:UniProtKB. DR GO; GO:0042249; P:establishment of planar polarity of embryonic epithelium; ISS:UniProtKB. DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro. DR GO; GO:0060490; P:lateral sprouting involved in lung morphogenesis; ISS:UniProtKB. DR GO; GO:0001843; P:neural tube closure; ISS:UniProtKB. DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB. DR GO; GO:0060488; P:orthogonal dichotomous subdivision of terminal units involved in lung branching morphogenesis; ISS:UniProtKB. DR GO; GO:0060489; P:planar dichotomous subdivision of terminal units involved in lung branching morphogenesis; ISS:UniProtKB. DR GO; GO:0090251; P:protein localization involved in establishment of planar polarity; ISS:UniProtKB. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0007266; P:Rho protein signal transduction; ISS:UniProtKB. DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; NAS:ParkinsonsUK-UCL. DR CDD; cd11304; Cadherin_repeat; 9. DR CDD; cd00054; EGF_CA; 4. DR CDD; cd00055; EGF_Lam; 1. DR CDD; cd00110; LamG; 2. DR Gene3D; 1.25.40.610; -; 1. DR Gene3D; 2.60.120.200; -; 2. DR Gene3D; 2.60.220.50; -; 1. DR Gene3D; 2.60.40.60; Cadherins; 9. DR Gene3D; 4.10.1240.10; GPCR, family 2, extracellular hormone receptor domain; 1. DR Gene3D; 2.10.25.10; Laminin; 6. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR Gene3D; 2.170.300.10; Tie2 ligand-binding domain superfamily; 1. DR InterPro; IPR002126; Cadherin-like_dom. DR InterPro; IPR015919; Cadherin-like_sf. DR InterPro; IPR020894; Cadherin_CS. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR032471; GAIN_dom_N. DR InterPro; IPR046338; GAIN_dom_sf. DR InterPro; IPR017981; GPCR_2-like_7TM. DR InterPro; IPR036445; GPCR_2_extracell_dom_sf. DR InterPro; IPR001879; GPCR_2_extracellular_dom. DR InterPro; IPR000832; GPCR_2_secretin-like. DR InterPro; IPR000203; GPS. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR001791; Laminin_G. DR InterPro; IPR002049; LE_dom. DR PANTHER; PTHR24026:SF36; CADHERIN EGF LAG SEVEN-PASS G-TYPE RECEPTOR 1; 1. DR PANTHER; PTHR24026; FAT ATYPICAL CADHERIN-RELATED; 1. DR Pfam; PF00002; 7tm_2; 1. DR Pfam; PF00028; Cadherin; 8. DR Pfam; PF00008; EGF; 1. DR Pfam; PF16489; GAIN; 1. DR Pfam; PF01825; GPS; 1. DR Pfam; PF02793; HRM; 1. DR Pfam; PF00053; Laminin_EGF; 1. DR Pfam; PF02210; Laminin_G_2; 2. DR PRINTS; PR00205; CADHERIN. DR PRINTS; PR00249; GPCRSECRETIN. DR SMART; SM00112; CA; 9. DR SMART; SM00181; EGF; 6. DR SMART; SM00179; EGF_CA; 4. DR SMART; SM00180; EGF_Lam; 1. DR SMART; SM00303; GPS; 1. DR SMART; SM00008; HormR; 1. DR SMART; SM00282; LamG; 2. DR SUPFAM; SSF49313; Cadherin-like; 9. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 2. DR SUPFAM; SSF57196; EGF/Laminin; 3. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR PROSITE; PS00010; ASX_HYDROXYL; 2. DR PROSITE; PS00232; CADHERIN_1; 7. DR PROSITE; PS50268; CADHERIN_2; 9. DR PROSITE; PS00022; EGF_1; 6. DR PROSITE; PS01186; EGF_2; 2. DR PROSITE; PS50026; EGF_3; 6. DR PROSITE; PS01248; EGF_LAM_1; 1. DR PROSITE; PS50027; EGF_LAM_2; 1. DR PROSITE; PS50227; G_PROTEIN_RECEP_F2_3; 1. DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1. DR PROSITE; PS50221; GAIN_B; 1. DR PROSITE; PS50025; LAM_G_DOMAIN; 2. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cell membrane; KW Developmental protein; Disease variant; Disulfide bond; EGF-like domain; KW G-protein coupled receptor; Glycoprotein; Hydroxylation; KW Laminin EGF-like domain; Membrane; Phosphoprotein; KW Proteomics identification; Receptor; Reference proteome; Repeat; Signal; KW Transducer; Transmembrane; Transmembrane helix. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT CHAIN 21..3014 FT /note="Cadherin EGF LAG seven-pass G-type receptor 1" FT /id="PRO_0000012914" FT TOPO_DOM 22..2469 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 2470..2490 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 2491..2501 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2502..2522 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 2523..2527 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 2528..2548 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 2549..2572 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2573..2593 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 2594..2611 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 2612..2632 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 2633..2655 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2656..2676 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 2677..2683 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 2684..2704 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 2705..3014 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 246..353 FT /note="Cadherin 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 354..459 FT /note="Cadherin 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 460..565 FT /note="Cadherin 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 566..687 FT /note="Cadherin 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 688..789 FT /note="Cadherin 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 790..892 FT /note="Cadherin 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 893..999 FT /note="Cadherin 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 1000..1101 FT /note="Cadherin 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 1106..1224 FT /note="Cadherin 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 1303..1361 FT /note="EGF-like 1; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1363..1399 FT /note="EGF-like 2; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1403..1441 FT /note="EGF-like 3; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1442..1646 FT /note="Laminin G-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT DOMAIN 1649..1685 FT /note="EGF-like 4; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1689..1870 FT /note="Laminin G-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT DOMAIN 1872..1907 FT /note="EGF-like 5; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1908..1946 FT /note="EGF-like 6; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1947..1979 FT /note="EGF-like 7; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 1981..2016 FT /note="EGF-like 8; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 2003..2050 FT /note="Laminin EGF-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460" FT DOMAIN 2297..2461 FT /note="GAIN-B" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098" FT REGION 204..242 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2291..2328 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2411..2461 FT /note="GPS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098" FT REGION 2777..2939 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2954..3014 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 210..224 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2812..2828 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2829..2844 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2872..2903 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2959..2973 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1666 FT /note="(3R)-3-hydroxyasparagine" FT /evidence="ECO:0000255" FT MOD_RES 1889 FT /note="(3R)-3-hydroxyaspartate" FT /evidence="ECO:0000255" FT MOD_RES 2761 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O35161" FT MOD_RES 2764 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 2871 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O35161" FT MOD_RES 2873 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O35161" FT CARBOHYD 403 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 546 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 634 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 778 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1114 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1139 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1213 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1249 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1259 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1287 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1576 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1623 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1640 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1979 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2103 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2122 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2257 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2415 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2437 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2523 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 1307..1318 FT /evidence="ECO:0000250" FT DISULFID 1312..1349 FT /evidence="ECO:0000250" FT DISULFID 1351..1360 FT /evidence="ECO:0000250" FT DISULFID 1367..1378 FT /evidence="ECO:0000250" FT DISULFID 1372..1387 FT /evidence="ECO:0000250" FT DISULFID 1389..1398 FT /evidence="ECO:0000250" FT DISULFID 1407..1418 FT /evidence="ECO:0000250" FT DISULFID 1412..1428 FT /evidence="ECO:0000250" FT DISULFID 1430..1440 FT /evidence="ECO:0000250" FT DISULFID 1620..1646 FT /evidence="ECO:0000250" FT DISULFID 1653..1664 FT /evidence="ECO:0000250" FT DISULFID 1658..1673 FT /evidence="ECO:0000250" FT DISULFID 1675..1684 FT /evidence="ECO:0000250" FT DISULFID 1840..1870 FT /evidence="ECO:0000250" FT DISULFID 1876..1887 FT /evidence="ECO:0000250" FT DISULFID 1881..1896 FT /evidence="ECO:0000250" FT DISULFID 1898..1907 FT /evidence="ECO:0000250" FT DISULFID 1911..1922 FT /evidence="ECO:0000250" FT DISULFID 1916..1934 FT /evidence="ECO:0000250" FT DISULFID 1936..1945 FT /evidence="ECO:0000250" FT DISULFID 1953..1966 FT /evidence="ECO:0000250" FT DISULFID 1968..1978 FT /evidence="ECO:0000250" FT DISULFID 1985..2000 FT /evidence="ECO:0000250" FT DISULFID 1987..2003 FT /evidence="ECO:0000250" FT DISULFID 2005..2015 FT /evidence="ECO:0000250" FT DISULFID 2024..2033 FT /evidence="ECO:0000250" FT DISULFID 2036..2048 FT /evidence="ECO:0000250" FT DISULFID 2411..2443 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098" FT DISULFID 2431..2445 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098" FT VAR_SEQ 1395..1397 FT /note="GEH -> EIS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_002011" FT VAR_SEQ 1398..3014 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_002012" FT VARIANT 290..3014 FT /note="Missing (in LMPHM9)" FT /evidence="ECO:0000269|PubMed:26855770" FT /id="VAR_085932" FT VARIANT 587 FT /note="I -> V (in dbSNP:rs34141466)" FT /id="VAR_049464" FT VARIANT 664 FT /note="S -> W (in dbSNP:rs4823850)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_016094" FT VARIANT 773 FT /note="A -> V (in NTD; shows significantly reduced protein FT localization to the cell membrane; dbSNP:rs12170597)" FT /evidence="ECO:0000269|PubMed:22095531" FT /id="VAR_067213" FT VARIANT 1058 FT /note="A -> T (in LMPHM9; uncertain significance; FT dbSNP:rs146657902)" FT /evidence="ECO:0000269|PubMed:31215153" FT /id="VAR_085933" FT VARIANT 1126 FT /note="C -> R (in dbSNP:rs4823561)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_016095" FT VARIANT 1242 FT /note="V -> I (in dbSNP:rs6008842)" FT /id="VAR_049465" FT VARIANT 1539 FT /note="N -> S (in LMPHM9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:31215153" FT /id="VAR_085934" FT VARIANT 1883 FT /note="P -> H (in LMPHM9; uncertain significance; FT dbSNP:rs369237672)" FT /evidence="ECO:0000269|PubMed:31215153" FT /id="VAR_085935" FT VARIANT 1894 FT /note="Y -> H (in dbSNP:rs34467708)" FT /id="VAR_049466" FT VARIANT 1957..3014 FT /note="Missing (in LMPHM9)" FT /evidence="ECO:0000269|PubMed:26855770" FT /id="VAR_085936" FT VARIANT 1994 FT /note="L -> P (in dbSNP:rs6008795)" FT /id="VAR_049467" FT VARIANT 1995 FT /note="L -> P (in dbSNP:rs6008794)" FT /id="VAR_049468" FT VARIANT 2045 FT /note="T -> M (in dbSNP:rs12169391)" FT /id="VAR_049469" FT VARIANT 2107 FT /note="I -> V (in dbSNP:rs4044210)" FT /id="VAR_024479" FT VARIANT 2150 FT /note="G -> V (in LMPHM9; uncertain significance; FT dbSNP:rs1167228557)" FT /evidence="ECO:0000269|PubMed:31215153" FT /id="VAR_085937" FT VARIANT 2219 FT /note="R -> H (in dbSNP:rs34267201)" FT /id="VAR_049470" FT VARIANT 2268 FT /note="T -> A (in dbSNP:rs6007897)" FT /id="VAR_024480" FT VARIANT 2312 FT /note="R -> P (does not affect protein localization to the FT cell membrane; dbSNP:rs7287089)" FT /evidence="ECO:0000269|PubMed:22095531" FT /id="VAR_067214" FT VARIANT 2425 FT /note="G -> W (in LMPHM9; uncertain significance; FT dbSNP:rs774311996)" FT /evidence="ECO:0000269|PubMed:31215153" FT /id="VAR_085938" FT VARIANT 2438 FT /note="R -> Q (in NTD; shows reduced protein localization FT to the cell membrane; dbSNP:rs199688538)" FT /evidence="ECO:0000269|PubMed:22095531" FT /id="VAR_067215" FT VARIANT 2709 FT /note="R -> G (in LMPHM9; uncertain significance; FT dbSNP:rs138303327)" FT /evidence="ECO:0000269|PubMed:31215153" FT /id="VAR_085939" FT VARIANT 2739 FT /note="N -> T (does not affect protein localization to the FT cell membrane; dbSNP:rs148905592)" FT /evidence="ECO:0000269|PubMed:22095531" FT /id="VAR_067216" FT VARIANT 2797 FT /note="C -> S (in dbSNP:rs12165943)" FT /id="VAR_049471" FT VARIANT 2903 FT /note="E -> Q (in dbSNP:rs9615351)" FT /id="VAR_049472" FT VARIANT 2948 FT /note="G -> S (in dbSNP:rs35364389)" FT /id="VAR_049473" FT VARIANT 2964 FT /note="S -> L (in NTD; shows reduced protein localization FT to the cell membrane; dbSNP:rs6008777)" FT /evidence="ECO:0000269|PubMed:22095531" FT /id="VAR_067217" FT VARIANT 2983 FT /note="P -> A (in NTD; shows reduced protein localization FT to the cell membrane; dbSNP:rs61741871)" FT /evidence="ECO:0000269|PubMed:22095531" FT /id="VAR_067218" FT VARIANT 3001 FT /note="T -> R (in LMPHM9; uncertain significance)" FT /evidence="ECO:0000269|PubMed:31215153" FT /id="VAR_085940" FT CONFLICT 651 FT /note="E -> D (in Ref. 3; AAH00059)" FT /evidence="ECO:0000305" FT STRAND 564..575 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 583..586 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 600..605 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 630..632 FT /evidence="ECO:0007829|PDB:7SZ8" FT TURN 634..636 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 638..641 FT /evidence="ECO:0007829|PDB:7SZ8" FT TURN 647..649 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 651..661 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 668..678 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 686..690 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 692..697 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 705..709 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 721..726 FT /evidence="ECO:0007829|PDB:7SZ8" FT HELIX 729..731 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 733..737 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 742..746 FT /evidence="ECO:0007829|PDB:7SZ8" FT TURN 752..754 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 756..768 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 770..780 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 788..790 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 792..799 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 807..810 FT /evidence="ECO:0007829|PDB:7SZ8" FT HELIX 819..822 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 825..830 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 835..837 FT /evidence="ECO:0007829|PDB:7SZ8" FT TURN 839..841 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 843..846 FT /evidence="ECO:0007829|PDB:7SZ8" FT TURN 852..854 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 856..865 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 873..883 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 891..902 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 910..913 FT /evidence="ECO:0007829|PDB:7SZ8" FT HELIX 922..924 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 927..935 FT /evidence="ECO:0007829|PDB:7SZ8" FT TURN 937..940 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 941..943 FT /evidence="ECO:0007829|PDB:7SZ8" FT TURN 945..947 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 949..952 FT /evidence="ECO:0007829|PDB:7SZ8" FT TURN 958..960 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 962..972 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 975..977 FT /evidence="ECO:0007829|PDB:7SZ8" FT STRAND 980..990 FT /evidence="ECO:0007829|PDB:7SZ8" SQ SEQUENCE 3014 AA; 329486 MW; C34691AD3A1DFF3A CRC64; MAPPPPPVLP VLLLLAAAAA LPAMGLRAAA WEPRVPGGTR AFALRPGCTY AVGAACTPRA PRELLDVGRD GRLAGRRRVS GAGRPLPLQV RLVARSAPTA LSRRLRARTH LPGCGARARL CGTGARLCGA LCFPVPGGCA AAQHSALAAP TTLPACRCPP RPRPRCPGRP ICLPPGGSVR LRLLCALRRA AGAVRVGLAL EAATAGTPSA SPSPSPPLPP NLPEARAGPA RRARRGTSGR GSLKFPMPNY QVALFENEPA GTLILQLHAH YTIEGEEERV SYYMEGLFDE RSRGYFRIDS ATGAVSTDSV LDRETKETHV LRVKAVDYST PPRSATTYIT VLVKDTNDHS PVFEQSEYRE RVRENLEVGY EVLTIRASDR DSPINANLRY RVLGGAWDVF QLNESSGVVS TRAVLDREEA AEYQLLVEAN DQGRNPGPLS ATATVYIEVE DENDNYPQFS EQNYVVQVPE DVGLNTAVLR VQATDRDQGQ NAAIHYSILS GNVAGQFYLH SLSGILDVIN PLDFEDVQKY SLSIKAQDGG RPPLINSSGV VSVQVLDVND NEPIFVSSPF QATVLENVPL GYPVVHIQAV DADSGENARL HYRLVDTAST FLGGGSAGPK NPAPTPDFPF QIHNSSGWIT VCAELDREEV EHYSFGVEAV DHGSPPMSSS TSVSITVLDV NDNDPVFTQP TYELRLNEDA AVGSSVLTLQ ARDRDANSVI TYQLTGGNTR NRFALSSQRG GGLITLALPL DYKQEQQYVL AVTASDGTRS HTAHVLINVT DANTHRPVFQ SSHYTVSVSE DRPVGTSIAT LSANDEDTGE NARITYVIQD PVPQFRIDPD SGTMYTMMEL DYENQVAYTL TIMAQDNGIP QKSDTTTLEI LILDANDNAP QFLWDFYQGS IFEDAPPSTS ILQVSATDRD SGPNGRLLYT FQGGDDGDGD FYIEPTSGVI RTQRRLDREN VAVYNLWALA VDRGSPTPLS ASVEIQVTIL DINDNAPMFE KDELELFVEE NNPVGSVVAK IRANDPDEGP NAQIMYQIVE GDMRHFFQLD LLNGDLRAMV ELDFEVRREY VLVVQATSAP LVSRATVHIL LVDQNDNPPV LPDFQILFNN YVTNKSNSFP TGVIGCIPAH DPDVSDSLNY TFVQGNELRL LLLDPATGEL QLSRDLDNNR PLEALMEVSV SDGIHSVTAF CTLRVTIITD DMLTNSITVR LENMSQEKFL SPLLALFVEG VAAVLSTTKD DVFVFNVQND TDVSSNILNV TFSALLPGGV RGQFFPSEDL QEQIYLNRTL LTTISTQRVL PFDDNICLRE PCENYMKCVS VLRFDSSAPF LSSTTVLFRP IHPINGLRCR CPPGFTGDYC ETEIDLCYSD PCGANGRCRS REGGYTCECF EDFTGEHCEV DARSGRCANG VCKNGGTCVN LLIGGFHCVC PPGEYERPYC EVTTRSFPPQ SFVTFRGLRQ RFHFTISLTF ATQERNGLLL YNGRFNEKHD FIALEIVDEQ VQLTFSAGET TTTVAPKVPS GVSDGRWHSV QVQYYNKPNI GHLGLPHGPS GEKMAVVTVD DCDTTMAVRF GKDIGNYSCA AQGTQTGSKK SLDLTGPLLL GGVPNLPEDF PVHNRQFVGC MRNLSVDGKN VDMAGFIANN GTREGCAARR NFCDGRRCQN GGTCVNRWNM YLCECPLRFG GKNCEQAMPH PQLFSGESVV SWSDLNIIIS VPWYLGLMFR TRKEDSVLME ATSGGPTSFR LQILNNYLQF EVSHGPSDVE SVMLSGLRVT DGEWHHLLIE LKNVKEDSEM KHLVTMTLDY GMDQNKADIG GMLPGLTVRS VVVGGASEDK VSVRRGFRGC MQGVRMGGTP TNVATLNMNN ALKVRVKDGC DVDDPCTSSP CPPNSRCHDA WEDYSCVCDK GYLGINCVDA CHLNPCENMG ACVRSPGSPQ GYVCECGPSH YGPYCENKLD LPCPRGWWGN PVCGPCHCAV SKGFDPDCNK TNGQCQCKEN YYKLLAQDTC LPCDCFPHGS HSRTCDMATG QCACKPGVIG RQCNRCDNPF AEVTTLGCEV IYNGCPKAFE AGIWWPQTKF GQPAAVPCPK GSVGNAVRHC SGEKGWLPPE LFNCTTISFV DLRAMNEKLS RNETQVDGAR ALQLVRALRS ATQHTGTLFG NDVRTAYQLL GHVLQHESWQ QGFDLAATQD ADFHEDVIHS GSALLAPATR AAWEQIQRSE GGTAQLLRRL EGYFSNVARN VRRTYLRPFV IVTANMILAV DIFDKFNFTG ARVPRFDTIH EEFPRELESS VSFPADFFRP PEEKEGPLLR PAGRRTTPQT TRPGPGTERE APISRRRRHP DDAGQFAVAL VIIYRTLGQL LPERYDPDRR SLRLPHRPII NTPMVSTLVY SEGAPLPRPL ERPVLVEFAL LEVEERTKPV CVFWNHSLAV GGTGGWSARG CELLSRNRTH VACQCSHTAS FAVLMDISRR ENGEVLPLKI VTYAAVSLSL AALLVAFVLL SLVRMLRSNL HSIHKHLAVA LFLSQLVFVI GINQTENPFL CTVVAILLHY IYMSTFAWTL VESLHVYRML TEVRNIDTGP MRFYYVVGWG IPAIVTGLAV GLDPQGYGNP DFCWLSLQDT LIWSFAGPIG AVIIINTVTS VLSAKVSCQR KHHYYGKKGI VSLLRTAFLL LLLISATWLL GLLAVNRDAL SFHYLFAIFS GLQGPFVLLF HCVLNQEVRK HLKGVLGGRK LHLEDSATTR ATLLTRSLNC NTTFGDGPDM LRTDLGESTA SLDSIVRDEG IQKLGVSSGL VRGSHGEPDA SLMPRSCKDP PGHDSDSDSE LSLDEQSSSY ASSHSSDSED DGVGAEEKWD PARGAVHSTP KGDAVANHVP AGWPDQSLAE SDSEDPSGKP RLKVETKVSV ELHREEQGSH RGEYPPDQES GGAARLASSQ PPEQRKGILK NKVTYPPPLT LTEQTLKGRL REKLADCEQS PTSSRTSSLG SGGPDCAITV KSPGREPGRD HLNGVAMNVR TGSAQADGSD SEKP //