ID NELL2_HUMAN Reviewed; 816 AA. AC Q99435; B7Z2U7; B7Z5Q4; B7Z9J5; B7Z9U3; Q96JS2; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 27-MAR-2024, entry version 195. DE RecName: Full=Protein kinase C-binding protein NELL2; DE AltName: Full=NEL-like protein 2; DE AltName: Full=Nel-related protein 2; DE Flags: Precursor; GN Name=NELL2 {ECO:0000312|HGNC:HGNC:7751}; Synonyms=NRP2; 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). RC TISSUE=Brain; RX PubMed=8975702; DOI=10.1006/geno.1996.0628; RA Watanabe T.K., Katagiri T., Suzuki M., Shimizu F., Fujiwara T., RA Kanemoto N., Nakamura Y., Hirai Y., Maekawa H., Takahashi E.; RT "Cloning and characterization of two novel human cDNAs (NELL1 and NELL2) RT encoding proteins with six EGF-like repeats."; RL Genomics 38:273-276(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). RC TISSUE=Brain; RA Yoshimoto M., Yazaki M., Takayama K., Matsumoto K.; RT "Biological functions of a novel human gene, hucep-12, which is RT specifically expressed in the central nervous system."; RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4). RC TISSUE=Amygdala, Brain, and Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Duodenum; 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 [7] RP PROTEIN SEQUENCE OF 22-36 (ISOFORM 1). RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [8] {ECO:0007744|PDB:6POG} RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 397-638 IN COMPLEX WITH ROBO3, RP FUNCTION, SUBUNIT, DISULFIDE BOND, CALCIUM-BINDING, GLYCOSYLATION AT RP ASN-517 AND THR-548, AND MUTAGENESIS OF ARG-448; TYR-450; ARG-452; ASP-476; RP ASP-477; TYR-478; LEU-498; PHE-500 AND VAL-509. RX PubMed=32198364; DOI=10.1038/s41467-020-15211-1; RA Pak J.S., DeLoughery Z.J., Wang J., Acharya N., Park Y., Jaworski A., RA Ozkan E.; RT "NELL2-Robo3 complex structure reveals mechanisms of receptor activation RT for axon guidance."; RL Nat. Commun. 11:1489-1489(2020). CC -!- FUNCTION: Plays multiple roles in neural tissues, regulates neuronal CC proliferation, survival, differentiation, polarization, as well as axon CC guidance and synaptic functions. Plays an important role in axon CC development during neuronal differentiation through the MAPK CC intracellular signaling pathway (By similarity). Via binding to its CC receptor ROBO3, plays a role in axon guidance, functioning as a CC repulsive axon guidance cue that contributes to commissural axon CC guidance to the midline (PubMed:32198364). Required for neuron survival CC through the modulation of MAPK signaling pathways too. Involved in the CC regulation of hypothalamic GNRH secretion and the control of puberty CC (By similarity). {ECO:0000250|UniProtKB:Q62918, CC ECO:0000269|PubMed:32198364}. CC -!- FUNCTION: Epididymal-secreted protein that signals through a ROS1- CC pathway to regulate the epididymal initial segment (IS) maturation, CC sperm maturation and male fertility. {ECO:0000250|UniProtKB:Q61220}. CC -!- SUBUNIT: Homotrimer (PubMed:32198364). Binds to PRKCB (By similarity). CC Interacts with NICOL1; this interaction triggers epididymal CC differentiation (By similarity). Interacts (via the EGF domains) with CC ROBO3 (via Fibronectin type-III 1 domain) with a 3:3 stoichiometry; CC this interaction promotes oligomerization of ROBO3 resulting in the CC repulsion of commissural axons in the midline (PubMed:32198364). CC {ECO:0000250|UniProtKB:Q61220, ECO:0000250|UniProtKB:Q62918, CC ECO:0000269|PubMed:32198364}. CC -!- INTERACTION: CC Q99435; Q5VTD9: GFI1B; NbExp=2; IntAct=EBI-946274, EBI-946212; CC Q99435; P49639: HOXA1; NbExp=2; IntAct=EBI-946274, EBI-740785; CC Q99435; Q9UIS9: MBD1; NbExp=2; IntAct=EBI-946274, EBI-867196; CC Q99435; Q7Z417: NUFIP2; NbExp=2; IntAct=EBI-946274, EBI-1210753; CC Q99435; Q9BYB0: SHANK3; NbExp=2; IntAct=EBI-946274, EBI-1752330; CC Q99435-1; Q96MS0: ROBO3; NbExp=3; IntAct=EBI-16185191, EBI-1220465; CC Q99435-2; P49639: HOXA1; NbExp=3; IntAct=EBI-17754404, EBI-740785; CC Q99435-2; P37173: TGFBR2; NbExp=3; IntAct=EBI-17754404, EBI-296151; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q62918}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q99435-1; Sequence=Displayed; CC Name=2; CC IsoId=Q99435-2; Sequence=VSP_043801; CC Name=3; CC IsoId=Q99435-3; Sequence=VSP_043802; CC Name=4; CC IsoId=Q99435-4; Sequence=VSP_043869; 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; D83018; BAA11681.1; -; mRNA. DR EMBL; D89629; BAB46925.1; -; mRNA. DR EMBL; AK295125; BAH11983.1; -; mRNA. DR EMBL; AK299277; BAH12990.1; -; mRNA. DR EMBL; AK315960; BAH14331.1; -; mRNA. DR EMBL; AK316058; BAH14429.1; -; mRNA. DR EMBL; AC018923; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC025253; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC079033; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC079825; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC090012; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471111; EAW57873.1; -; Genomic_DNA. DR EMBL; CH471111; EAW57874.1; -; Genomic_DNA. DR EMBL; CH471111; EAW57875.1; -; Genomic_DNA. DR EMBL; BC020544; AAH20544.1; -; mRNA. DR CCDS; CCDS44863.1; -. [Q99435-3] DR CCDS; CCDS44864.1; -. [Q99435-4] DR CCDS; CCDS53781.1; -. [Q99435-2] DR CCDS; CCDS8746.1; -. [Q99435-1] DR RefSeq; NP_001138579.1; NM_001145107.1. [Q99435-3] DR RefSeq; NP_001138580.1; NM_001145108.1. [Q99435-1] DR RefSeq; NP_001138581.1; NM_001145109.1. [Q99435-4] DR RefSeq; NP_001138582.1; NM_001145110.1. [Q99435-2] DR RefSeq; NP_006150.1; NM_006159.2. [Q99435-1] DR RefSeq; XP_005268962.1; XM_005268905.3. DR RefSeq; XP_011536698.1; XM_011538396.1. [Q99435-1] DR PDB; 6POG; X-ray; 2.75 A; B=397-638. DR PDBsum; 6POG; -. DR AlphaFoldDB; Q99435; -. DR SMR; Q99435; -. DR BioGRID; 110828; 54. DR DIP; DIP-49927N; -. DR IntAct; Q99435; 45. DR MINT; Q99435; -. DR STRING; 9606.ENSP00000416341; -. DR GlyCosmos; Q99435; 9 sites, 1 glycan. DR GlyGen; Q99435; 10 sites, 2 O-linked glycans (3 sites). DR iPTMnet; Q99435; -. DR PhosphoSitePlus; Q99435; -. DR BioMuta; NELL2; -. DR DMDM; 2494289; -. DR EPD; Q99435; -. DR MassIVE; Q99435; -. DR PaxDb; 9606-ENSP00000416341; -. DR PeptideAtlas; Q99435; -. DR ProteomicsDB; 78262; -. [Q99435-1] DR ProteomicsDB; 78263; -. [Q99435-2] DR ProteomicsDB; 78264; -. [Q99435-3] DR ProteomicsDB; 78265; -. [Q99435-4] DR Antibodypedia; 25202; 227 antibodies from 27 providers. DR DNASU; 4753; -. DR Ensembl; ENST00000333837.8; ENSP00000327988.4; ENSG00000184613.11. [Q99435-2] DR Ensembl; ENST00000395487.6; ENSP00000378866.2; ENSG00000184613.11. [Q99435-4] DR Ensembl; ENST00000429094.7; ENSP00000390680.2; ENSG00000184613.11. [Q99435-1] DR Ensembl; ENST00000437801.6; ENSP00000416341.2; ENSG00000184613.11. [Q99435-3] DR Ensembl; ENST00000452445.6; ENSP00000394612.2; ENSG00000184613.11. [Q99435-1] DR Ensembl; ENST00000549027.5; ENSP00000447927.1; ENSG00000184613.11. [Q99435-4] DR GeneID; 4753; -. DR KEGG; hsa:4753; -. DR MANE-Select; ENST00000429094.7; ENSP00000390680.2; NM_001145108.2; NP_001138580.1. DR UCSC; uc001rof.4; human. [Q99435-1] DR AGR; HGNC:7751; -. DR CTD; 4753; -. DR DisGeNET; 4753; -. DR GeneCards; NELL2; -. DR HGNC; HGNC:7751; NELL2. DR HPA; ENSG00000184613; Tissue enhanced (brain, choroid plexus, retina). DR MIM; 602320; gene. DR neXtProt; NX_Q99435; -. DR OpenTargets; ENSG00000184613; -. DR PharmGKB; PA31553; -. DR VEuPathDB; HostDB:ENSG00000184613; -. DR eggNOG; KOG1217; Eukaryota. DR GeneTree; ENSGT00810000125439; -. DR HOGENOM; CLU_006887_0_0_1; -. DR InParanoid; Q99435; -. DR OMA; TCGQFLE; -. DR OrthoDB; 5487at2759; -. DR PhylomeDB; Q99435; -. DR TreeFam; TF323325; -. DR PathwayCommons; Q99435; -. DR Reactome; R-HSA-428542; Regulation of commissural axon pathfinding by SLIT and ROBO. DR SignaLink; Q99435; -. DR BioGRID-ORCS; 4753; 10 hits in 1145 CRISPR screens. DR ChiTaRS; NELL2; human. DR GeneWiki; NELL2; -. DR GenomeRNAi; 4753; -. DR Pharos; Q99435; Tbio. DR PRO; PR:Q99435; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q99435; Protein. DR Bgee; ENSG00000184613; Expressed in middle temporal gyrus and 184 other cell types or tissues. DR ExpressionAtlas; Q99435; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0008201; F:heparin binding; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0005080; F:protein kinase C binding; IBA:GO_Central. DR GO; GO:0071679; P:commissural neuron axon guidance; IMP:UniProtKB. DR GO; GO:0009566; P:fertilization; ISS:UniProtKB. DR GO; GO:0070050; P:neuron cellular homeostasis; ISS:UniProtKB. DR CDD; cd00054; EGF_CA; 3. DR CDD; cd00110; LamG; 1. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 6.20.200.20; -; 2. DR Gene3D; 2.10.70.10; Complement Module, domain 1; 1. DR Gene3D; 2.10.25.10; Laminin; 6. 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; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR024731; EGF_dom. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR001791; Laminin_G. DR InterPro; IPR048287; TSPN-like_N. DR InterPro; IPR001007; VWF_dom. DR PANTHER; PTHR24042; NEL HOMOLOG; 1. DR PANTHER; PTHR24042:SF0; PROTEIN KINASE C-BINDING PROTEIN NELL2; 1. DR Pfam; PF12947; EGF_3; 1. DR Pfam; PF07645; EGF_CA; 3. DR Pfam; PF02210; Laminin_G_2; 1. DR Pfam; PF00093; VWC; 2. DR SMART; SM00181; EGF; 6. DR SMART; SM00179; EGF_CA; 5. DR SMART; SM00282; LamG; 1. DR SMART; SM00210; TSPN; 1. DR SMART; SM00214; VWC; 3. DR SMART; SM00215; VWC_out; 2. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF57196; EGF/Laminin; 2. DR SUPFAM; SSF57603; FnI-like domain; 2. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR PROSITE; PS00010; ASX_HYDROXYL; 3. DR PROSITE; PS00022; EGF_1; 1. DR PROSITE; PS01186; EGF_2; 4. DR PROSITE; PS50026; EGF_3; 6. DR PROSITE; PS01187; EGF_CA; 3. DR PROSITE; PS01208; VWFC_1; 2. DR PROSITE; PS50184; VWFC_2; 3. DR Genevisible; Q99435; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Direct protein sequencing; KW Disulfide bond; EGF-like domain; Glycoprotein; Neurogenesis; KW Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..21 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 22..816 FT /note="Protein kinase C-binding protein NELL2" FT /id="PRO_0000007666" FT DOMAIN 64..228 FT /note="Laminin G-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT DOMAIN 272..331 FT /note="VWFC 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220" FT DOMAIN 397..439 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 440..481 FT /note="EGF-like 2; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 482..522 FT /note="EGF-like 3; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 523..553 FT /note="EGF-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 555..601 FT /note="EGF-like 5; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 602..637 FT /note="EGF-like 6; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 638..693 FT /note="VWFC 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220" FT DOMAIN 698..756 FT /note="VWFC 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220" FT BINDING 440 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 441 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 443 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 459 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 460 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 463 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 555 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 556 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 558 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 574 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 575 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 578 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 602 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 603 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 605 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 621 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 622 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT BINDING 625 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT CARBOHYD 53 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 225 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 293 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 298 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 517 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT CARBOHYD 548 FT /note="O-linked (GlcNAc...) threonine" FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT CARBOHYD 615 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 635 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 401..413 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 407..422 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 424..438 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 444..457 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 451..466 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 468..480 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 486..499 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 493..508 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 510..521 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 525..535 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 529..541 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 543..552 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 559..572 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 566..581 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 583..600 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 606..619 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 613..628 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT DISULFID 630..636 FT /evidence="ECO:0000269|PubMed:32198364, FT ECO:0007744|PDB:6POG" FT VAR_SEQ 1..18 FT /note="MESRVLLRTFCLIFGLGA -> METGLGAPLFKAWLLIS (in isoform FT 4)" FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.2" FT /id="VSP_043869" FT VAR_SEQ 1 FT /note="M -> MSIRRLLILILKIGRRWTELIRTM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043801" FT VAR_SEQ 1 FT /note="M -> MGFPPLLKGQASATRSSLASCSWVVFFLSCLSRHAPEIEGGRRWTEL FT IRTM (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043802" FT VARIANT 5 FT /note="V -> I (in dbSNP:rs2658973)" FT /id="VAR_048987" FT VARIANT 347 FT /note="N -> D (in dbSNP:rs17574839)" FT /id="VAR_048988" FT VARIANT 631 FT /note="P -> L (in dbSNP:rs1050710)" FT /id="VAR_048989" FT MUTAGEN 448 FT /note="R->A: Diminished binding to ROBO3; when associated FT with A-450." FT /evidence="ECO:0000269|PubMed:32198364" FT MUTAGEN 450 FT /note="Y->A: Diminished binding to ROBO3; when associated FT with A-448." FT /evidence="ECO:0000269|PubMed:32198364" FT MUTAGEN 452 FT /note="R->A: Diminished binding to ROBO3." FT /evidence="ECO:0000269|PubMed:32198364" FT MUTAGEN 476 FT /note="D->A: Abolished binding to ROBO3." FT /evidence="ECO:0000269|PubMed:32198364" FT MUTAGEN 477 FT /note="D->A: Abolished binding to ROBO3; when associated FT with A-478." FT /evidence="ECO:0000269|PubMed:32198364" FT MUTAGEN 478 FT /note="Y->A: Abolished binding to ROBO3; when associated FT with A-477." FT /evidence="ECO:0000269|PubMed:32198364" FT MUTAGEN 498 FT /note="L->A: Abolished binding to ROBO3; when associated FT with A-500." FT /evidence="ECO:0000269|PubMed:32198364" FT MUTAGEN 500 FT /note="F->A: Abolished binding to ROBO3; when associated FT with A-498." FT /evidence="ECO:0000269|PubMed:32198364" FT MUTAGEN 509 FT /note="V->A: Diminished binding to ROBO3." FT /evidence="ECO:0000269|PubMed:32198364" FT CONFLICT 353 FT /note="S -> P (in Ref. 3; BAH12990)" FT /evidence="ECO:0000305" FT CONFLICT 454 FT /note="N -> D (in Ref. 3; BAH12990)" FT /evidence="ECO:0000305" FT CONFLICT 489 FT /note="N -> D (in Ref. 3; BAH14331)" FT /evidence="ECO:0000305" FT CONFLICT 636 FT /note="C -> S (in Ref. 3; BAH14331)" FT /evidence="ECO:0000305" FT HELIX 400..403 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 411..415 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 420..424 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 428..430 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 432..440 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 449..451 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 455..460 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 463..468 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 473..476 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 479..483 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 497..502 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 505..510 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 514..516 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 518..523 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 534..537 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 540..542 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 547..549 FT /evidence="ECO:0007829|PDB:6POG" FT TURN 558..560 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 568..575 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 578..583 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 587..589 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 599..602 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 618..621 FT /evidence="ECO:0007829|PDB:6POG" FT STRAND 626..629 FT /evidence="ECO:0007829|PDB:6POG" SQ SEQUENCE 816 AA; 91346 MW; 89370B987DC7A324 CRC64; MESRVLLRTF CLIFGLGAVW GLGVDPSLQI DVLTELELGE STTGVRQVPG LHNGTKAFLF QDTPRSIKAS TATAEQFFQK LRNKHEFTIL VTLKQTHLNS GVILSIHHLD HRYLELESSG HRNEVRLHYR SGSHRPHTEV FPYILADDKW HKLSLAISAS HLILHIDCNK IYERVVEKPS TDLPLGTTFW LGQRNNAHGY FKGIMQDVQL LVMPQGFIAQ CPDLNRTCPT CNDFHGLVQK IMELQDILAK TSAKLSRAEQ RMNRLDQCYC ERTCTMKGTT YREFESWIDG CKNCTCLNGT IQCETLICPN PDCPLKSALA YVDGKCCKEC KSICQFQGRT YFEGERNTVY SSSGVCVLYE CKDQTMKLVE SSGCPALDCP ESHQITLSHS CCKVCKGYDF CSERHNCMEN SICRNLNDRA VCSCRDGFRA LREDNAYCED IDECAEGRHY CRENTMCVNT PGSFMCICKT GYIRIDDYSC TEHDECITNQ HNCDENALCF NTVGGHNCVC KPGYTGNGTT CKAFCKDGCR NGGACIAANV CACPQGFTGP SCETDIDECS DGFVQCDSRA NCINLPGWYH CECRDGYHDN GMFSPSGESC EDIDECGTGR HSCANDTICF NLDGGYDCRC PHGKNCTGDC IHDGKVKHNG QIWVLENDRC SVCSCQNGFV MCRRMVCDCE NPTVDLFCCP ECDPRLSSQC LHQNGETLYN SGDTWVQNCQ QCRCLQGEVD CWPLPCPDVE CEFSILPENE CCPRCVTDPC QADTIRNDIT KTCLDEMNVV RFTGSSWIKH GTECTLCQCK NGHICCSVDP QCLQEL //