ID NELL2_BOVIN Reviewed; 816 AA. AC A6QR11; DT 25-NOV-2008, integrated into UniProtKB/Swiss-Prot. DT 21-AUG-2007, sequence version 1. DT 27-MAR-2024, entry version 101. DE RecName: Full=Protein kinase C-binding protein NELL2; DE AltName: Full=NEL-like protein 2; DE Flags: Precursor; GN Name=NELL2; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Hippocampus; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases. 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, functions as a repulsive CC guidance cue for commissural axons, helping to steer them across the CC spinal cord midline (By similarity). 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:Q61220, CC ECO:0000250|UniProtKB:Q62918}. CC -!- FUNCTION: Testicular luminal 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 (By similarity). Binds to PRKCB (By similarity). CC Interacts with NICOL1; this interaction triggers epididymal CC differentiation (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:Q61220, ECO:0000250|UniProtKB:Q62918}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q62918}. 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; BC150070; AAI50071.1; -; mRNA. DR RefSeq; NP_001095554.1; NM_001102084.1. DR RefSeq; XP_005206438.1; XM_005206381.3. DR RefSeq; XP_005206439.1; XM_005206382.3. DR AlphaFoldDB; A6QR11; -. DR SMR; A6QR11; -. DR STRING; 9913.ENSBTAP00000042993; -. DR GlyCosmos; A6QR11; 7 sites, No reported glycans. DR PaxDb; 9913-ENSBTAP00000042993; -. DR Ensembl; ENSBTAT00000045616.4; ENSBTAP00000042993.3; ENSBTAG00000032183.4. DR GeneID; 524622; -. DR KEGG; bta:524622; -. DR CTD; 4753; -. DR VEuPathDB; HostDB:ENSBTAG00000032183; -. DR VGNC; VGNC:32003; NELL2. DR eggNOG; KOG1217; Eukaryota. DR GeneTree; ENSGT00810000125439; -. DR HOGENOM; CLU_006887_0_0_1; -. DR InParanoid; A6QR11; -. DR OMA; TCGQFLE; -. DR OrthoDB; 5487at2759; -. DR TreeFam; TF323325; -. DR Proteomes; UP000009136; Chromosome 5. DR Bgee; ENSBTAG00000032183; Expressed in Ammon's horn and 82 other cell types or tissues. DR ExpressionAtlas; A6QR11; 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; ISS:UniProtKB. DR GO; GO:0008201; F:heparin binding; IBA:GO_Central. DR GO; GO:0005080; F:protein kinase C binding; IBA:GO_Central. DR GO; GO:0071679; P:commissural neuron axon guidance; ISS:UniProtKB. DR GO; GO:0009566; P:fertilization; 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. PE 2: Evidence at transcript level; KW Calcium; Disulfide bond; EGF-like domain; Glycoprotein; Metal-binding; KW Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..21 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT CHAIN 22..816 FT /note="Protein kinase C-binding protein NELL2" FT /id="PRO_0000354681" FT DOMAIN 30..258 FT /note="Laminin G-like" 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:0000250|UniProtKB:Q99435" FT BINDING 441 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 443 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 459 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 460 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 463 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 555 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 556 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 558 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 574 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 575 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 578 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 602 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 603 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 605 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 621 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 622 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" FT BINDING 625 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q99435" 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:0000250|UniProtKB:Q99435" FT CARBOHYD 548 FT /note="O-linked (GlcNAc...) threonine" FT /evidence="ECO:0000250|UniProtKB:Q99435" 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:0000250|UniProtKB:Q99435" FT DISULFID 407..422 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 424..438 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 444..457 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 451..466 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 468..480 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 486..499 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 493..508 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 510..521 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 525..535 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 529..541 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 543..552 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 559..572 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 566..581 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 583..600 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 606..619 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 613..628 FT /evidence="ECO:0000250|UniProtKB:Q99435" FT DISULFID 630..636 FT /evidence="ECO:0000250|UniProtKB:Q99435" SQ SEQUENCE 816 AA; 91270 MW; AA3407C610A18819 CRC64; MESRVLLRTF CLLFGLGAVW GLGVDPSLQI DVLTELELGE STTGVRQVPG LHNGTKAFLF QDTPRSIKAS TATAEQFFQK LRNKHEFTIL VTLKQTHLNS GVILSIHHLD HRYLELESSG HRNEVRLHYR SGSHHPHTEV FPYILADDKW HKLSLAISAS HLILHIDCNK IYERVVEKPS TDLPLGTSFW LGQRNNAHGY FKGIMQDVQL LVMPQGFIAQ CPDLNRTCPT CNDFHGLVQK IMELQDILAK TSAKLSRAEQ RMNRLDQCYC ERTCTMKGTT YREFESWTDG CKNCTCLNGT IQCETLICPN PDCPLKSAPA YVDGKCCKEC KSICQFQGRT YFEGQRNTVY SSSGVCVLYE CKDQSMKLVE SSGCPALDCA ESHQITLSHS CCKVCKGYDF CSERHNCMEN SVCRNLNDRA VCSCRDGFRA LREDNAYCED IDECAEGRHY CRENTMCVNT PGSFMCICKT GYIRIDDYSC TEHDECVTNQ HNCDENALCF NTVGGHNCVC KPGYTGNGTT CKAFCQDGCR NGGACIAANV CACPQGFTGH SCETDIDECS DGFVQCDSRA NCINLPGWYH CECRDGYHDN GMFSPSGESC EDIDECGTGR HSCANDTICF NLDGGYDCRC PHGKNCTGDC IHDGKIKHNG QIWVLENDRC SVCSCQNGFV MCRRMVCDCE NPTVDLFCCP ECDPRLSSQC LHQNGETLYN SGDTWVQNCQ QCRCLQGEVD CWPLPCPEVE CEFSVLPENE CCPRCVTDPC QADTIRNDIT KTCLDEMNVV RFTGSSWIKH GTECTLCQCK NGHICCSVDP QCLQEL //