ID SEM4D_HUMAN Reviewed; 862 AA. AC Q92854; B2RPM6; Q7Z5S4; Q8N8B0; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 27-MAR-2024, entry version 224. DE RecName: Full=Semaphorin-4D; DE AltName: Full=A8; DE AltName: Full=BB18; DE AltName: Full=GR3; DE AltName: CD_antigen=CD100; DE Flags: Precursor; GN Name=SEMA4D; Synonyms=C9orf164, CD100, SEMAJ; 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), FUNCTION, SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RC TISSUE=T-cell; RX PubMed=8876214; DOI=10.1073/pnas.93.21.11780; RA Hall K.T., Boumsell L., Schultze J.L., Boussiotis V.A., Dorfman D.M., RA Cardoso A.A., Bensussan A., Nadler L.M., Freeman G.J.; RT "Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation RT and differentiation."; RL Proc. Natl. Acad. Sci. U.S.A. 93:11780-11785(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND PARTIAL NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain, and Eye; 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 PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Small intestine; 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 [5] RP INTERACTION WITH PLXNB1. RX PubMed=10520995; DOI=10.1016/s0092-8674(00)80063-x; RA Tamagnone L., Artigiani S., Chen H., He Z., Ming G.-L., Song H.-L., RA Chedotal A., Winberg M.L., Goodman C.S., Poo M.-M., Tessier-Lavigne M., RA Comoglio P.M.; RT "Plexins are a large family of receptors for transmembrane, secreted and RT GPI-anchored semaphorins in vertebrates."; RL Cell 99:71-80(1999). RN [6] RP FUNCTION. RX PubMed=16055703; DOI=10.1128/mcb.25.16.6889-6898.2005; RA Basile J.R., Afkhami T., Gutkind J.S.; RT "Semaphorin 4D/plexin-B1 induces endothelial cell migration through the RT activation of PYK2, Src, and the phosphatidylinositol 3-kinase-Akt RT pathway."; RL Mol. Cell. Biol. 25:6889-6898(2005). RN [7] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-419. RC TISSUE=Platelet; RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200; RA Lewandrowski U., Moebius J., Walter U., Sickmann A.; RT "Elucidation of N-glycosylation sites on human platelet proteins: a RT glycoproteomic approach."; RL Mol. Cell. Proteomics 5:226-233(2006). RN [8] RP FUNCTION. RX PubMed=19788569; DOI=10.1111/j.1460-9568.2009.06934.x; RA Vodrazka P., Korostylev A., Hirschberg A., Swiercz J.M., Worzfeld T., RA Deng S., Fazzari P., Tamagnone L., Offermanns S., Kuner R.; RT "The semaphorin 4D-plexin-B signalling complex regulates dendritic and RT axonal complexity in developing neurons via diverse pathways."; RL Eur. J. Neurosci. 30:1193-1208(2009). RN [9] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-49; ASN-77; ASN-379 AND RP ASN-419. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-833, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 24-684, AND DISULFIDE BONDS. RX PubMed=12958590; DOI=10.1038/nsb977; RA Love C.A., Harlos K., Mavaddat N., Davis S.J., Stuart D.I., Jones E.Y., RA Esnouf R.M.; RT "The ligand-binding face of the semaphorins revealed by the high-resolution RT crystal structure of SEMA4D."; RL Nat. Struct. Biol. 10:843-848(2003). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.99 ANGSTROMS) OF 22-677 IN COMPLEX WITH PLXNB1, RP SUBUNIT, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF 100-LYS-GLY-101; RP 181-PHE-LEU-182; PHE-244; PHE-246 AND LYS-395, GLYCOSYLATION AT ASN-49; RP ASN-77; ASN-139; ASN-191; ASN-329 AND ASN-419, AND DISULFIDE BONDS. RX PubMed=20877282; DOI=10.1038/nature09468; RA Janssen B.J., Robinson R.A., Perez-Branguli F., Bell C.H., Mitchell K.J., RA Siebold C., Jones E.Y.; RT "Structural basis of semaphorin-plexin signalling."; RL Nature 467:1118-1122(2010). CC -!- FUNCTION: Cell surface receptor for PLXNB1 and PLXNB2 that plays an CC important role in cell-cell signaling (PubMed:20877282). Regulates CC GABAergic synapse development (By similarity). Promotes the development CC of inhibitory synapses in a PLXNB1-dependent manner (By similarity). CC Modulates the complexity and arborization of developing neurites in CC hippocampal neurons by activating PLXNB1 and interaction with PLXNB1 CC mediates activation of RHOA (PubMed:19788569). Promotes the migration CC of cerebellar granule cells (PubMed:16055703). Plays a role in the CC immune system; induces B-cells to aggregate and improves their CC viability (in vitro) (PubMed:8876214). Induces endothelial cell CC migration through the activation of PTK2B/PYK2, SRC, and the CC phosphatidylinositol 3-kinase-AKT pathway (PubMed:16055703). CC {ECO:0000250|UniProtKB:O09126, ECO:0000269|PubMed:16055703, CC ECO:0000269|PubMed:19788569, ECO:0000269|PubMed:20877282, CC ECO:0000269|PubMed:8876214}. CC -!- SUBUNIT: Homodimer (PubMed:20877282). Interacts with PLXNB2 (By CC similarity). Interacts with PLXNB1 (PubMed:10520995). CC {ECO:0000250|UniProtKB:O09126, ECO:0000269|PubMed:10520995, CC ECO:0000269|PubMed:20877282}. CC -!- INTERACTION: CC Q92854-1; O43157-1: PLXNB1; NbExp=3; IntAct=EBI-15880903, EBI-15880891; CC Q92854-1; Q92854-1: SEMA4D; NbExp=3; IntAct=EBI-15880903, EBI-15880903; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20877282, CC ECO:0000269|PubMed:8876214}; Single-pass type I membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q92854-1; Sequence=Displayed; CC Name=2; CC IsoId=Q92854-2; Sequence=VSP_039483, VSP_039484; CC -!- TISSUE SPECIFICITY: Strongly expressed in skeletal muscle, peripheral CC blood lymphocytes, spleen, and thymus and also expressed at lower CC levels in testes, brain, kidney, small intestine, prostate, heart, CC placenta, lung and pancreas, but not in colon and liver. CC {ECO:0000269|PubMed:8876214}. CC -!- SIMILARITY: Belongs to the semaphorin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAI37516.1; Type=Miscellaneous discrepancy; Note=Cloning artifact.; Evidence={ECO:0000305}; CC Sequence=AAI37519.1; Type=Miscellaneous discrepancy; Note=Cloning artifact.; Evidence={ECO:0000305}; CC Sequence=BAC04938.1; Type=Miscellaneous discrepancy; Note=Cloning artifact.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42255/SEMA4D"; 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; U60800; AAC50810.1; -; mRNA. DR EMBL; AL590233; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL929575; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC054500; AAH54500.1; -; mRNA. DR EMBL; BC137515; AAI37516.1; ALT_SEQ; mRNA. DR EMBL; BC137518; AAI37519.1; ALT_SEQ; mRNA. DR EMBL; AK097056; BAC04938.1; ALT_SEQ; mRNA. DR CCDS; CCDS47991.1; -. [Q92854-2] DR CCDS; CCDS6685.1; -. [Q92854-1] DR RefSeq; NP_001135759.1; NM_001142287.1. [Q92854-2] DR RefSeq; NP_006369.3; NM_006378.3. [Q92854-1] DR RefSeq; XP_005251711.1; XM_005251654.3. DR RefSeq; XP_011516425.1; XM_011518123.2. [Q92854-1] DR RefSeq; XP_011516426.1; XM_011518124.2. [Q92854-1] DR RefSeq; XP_011516427.1; XM_011518125.1. [Q92854-1] DR RefSeq; XP_011516429.1; XM_011518127.2. [Q92854-1] DR RefSeq; XP_011516430.1; XM_011518128.2. [Q92854-1] DR RefSeq; XP_011516431.1; XM_011518129.1. [Q92854-1] DR RefSeq; XP_011516432.1; XM_011518130.2. [Q92854-1] DR RefSeq; XP_011516433.1; XM_011518131.2. [Q92854-1] DR RefSeq; XP_011516435.1; XM_011518133.2. [Q92854-1] DR RefSeq; XP_011516436.1; XM_011518134.2. [Q92854-1] DR RefSeq; XP_016869682.1; XM_017014193.1. [Q92854-1] DR RefSeq; XP_016869683.1; XM_017014194.1. [Q92854-1] DR RefSeq; XP_016869684.1; XM_017014195.1. [Q92854-1] DR RefSeq; XP_016869685.1; XM_017014196.1. DR RefSeq; XP_016869686.1; XM_017014197.1. DR RefSeq; XP_016869687.1; XM_017014198.1. [Q92854-1] DR PDB; 1OLZ; X-ray; 2.00 A; A/B=22-677. DR PDB; 3OL2; X-ray; 2.99 A; A=22-677. DR PDBsum; 1OLZ; -. DR PDBsum; 3OL2; -. DR AlphaFoldDB; Q92854; -. DR SMR; Q92854; -. DR BioGRID; 115766; 31. DR CORUM; Q92854; -. DR DIP; DIP-59221N; -. DR IntAct; Q92854; 11. DR MINT; Q92854; -. DR STRING; 9606.ENSP00000416523; -. DR ChEMBL; CHEMBL4630887; -. DR GuidetoPHARMACOLOGY; 2883; -. DR GlyConnect; 1734; 13 N-Linked glycans (4 sites). DR GlyCosmos; Q92854; 11 sites, 14 glycans. DR GlyGen; Q92854; 19 sites, 13 N-linked glycans (4 sites), 3 O-linked glycans (9 sites). DR iPTMnet; Q92854; -. DR PhosphoSitePlus; Q92854; -. DR SwissPalm; Q92854; -. DR BioMuta; SEMA4D; -. DR DMDM; 8134701; -. DR EPD; Q92854; -. DR jPOST; Q92854; -. DR MassIVE; Q92854; -. DR MaxQB; Q92854; -. DR PaxDb; 9606-ENSP00000416523; -. DR PeptideAtlas; Q92854; -. DR ProteomicsDB; 75549; -. [Q92854-1] DR ProteomicsDB; 75550; -. [Q92854-2] DR ABCD; Q92854; 20 sequenced antibodies. DR Antibodypedia; 3064; 1055 antibodies from 39 providers. DR DNASU; 10507; -. DR Ensembl; ENST00000339861.8; ENSP00000344923.4; ENSG00000187764.12. [Q92854-2] DR Ensembl; ENST00000356444.6; ENSP00000348822.2; ENSG00000187764.12. [Q92854-1] DR Ensembl; ENST00000420987.5; ENSP00000391733.1; ENSG00000187764.12. [Q92854-2] DR Ensembl; ENST00000422704.7; ENSP00000388768.2; ENSG00000187764.12. [Q92854-1] DR Ensembl; ENST00000438547.6; ENSP00000405102.2; ENSG00000187764.12. [Q92854-1] DR Ensembl; ENST00000450295.5; ENSP00000416523.1; ENSG00000187764.12. [Q92854-1] DR Ensembl; ENST00000455551.6; ENSP00000411981.2; ENSG00000187764.12. [Q92854-2] DR GeneID; 10507; -. DR KEGG; hsa:10507; -. DR MANE-Select; ENST00000422704.7; ENSP00000388768.2; NM_001371194.2; NP_001358123.1. DR UCSC; uc004aqo.2; human. [Q92854-1] DR AGR; HGNC:10732; -. DR CTD; 10507; -. DR DisGeNET; 10507; -. DR GeneCards; SEMA4D; -. DR HGNC; HGNC:10732; SEMA4D. DR HPA; ENSG00000187764; Tissue enhanced (brain). DR MalaCards; SEMA4D; -. DR MIM; 601866; gene. DR neXtProt; NX_Q92854; -. DR OpenTargets; ENSG00000187764; -. DR Orphanet; 171; Primary sclerosing cholangitis. DR PharmGKB; PA35654; -. DR VEuPathDB; HostDB:ENSG00000187764; -. DR eggNOG; KOG3611; Eukaryota. DR GeneTree; ENSGT00940000159594; -. DR HOGENOM; CLU_009051_4_0_1; -. DR InParanoid; Q92854; -. DR OMA; PCLKFRS; -. DR OrthoDB; 5342713at2759; -. DR PhylomeDB; Q92854; -. DR TreeFam; TF316102; -. DR PathwayCommons; Q92854; -. DR Reactome; R-HSA-416550; Sema4D mediated inhibition of cell attachment and migration. DR Reactome; R-HSA-416572; Sema4D induced cell migration and growth-cone collapse. DR Reactome; R-HSA-416700; Other semaphorin interactions. DR SignaLink; Q92854; -. DR SIGNOR; Q92854; -. DR BioGRID-ORCS; 10507; 10 hits in 1149 CRISPR screens. DR ChiTaRS; SEMA4D; human. DR EvolutionaryTrace; Q92854; -. DR GeneWiki; SEMA4D; -. DR GenomeRNAi; 10507; -. DR Pharos; Q92854; Tbio. DR PRO; PR:Q92854; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q92854; Protein. DR Bgee; ENSG00000187764; Expressed in C1 segment of cervical spinal cord and 182 other cell types or tissues. DR ExpressionAtlas; Q92854; baseline and differential. DR GO; GO:0005615; C:extracellular space; ISS:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0002116; C:semaphorin receptor complex; ISS:BHF-UCL. DR GO; GO:0045499; F:chemorepellent activity; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0048018; F:receptor ligand activity; ISS:BHF-UCL. DR GO; GO:0030215; F:semaphorin receptor binding; IPI:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; IDA:HGNC-UCL. DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IMP:UniProtKB. DR GO; GO:0007411; P:axon guidance; IBA:GO_Central. DR GO; GO:0061430; P:bone trabecula morphogenesis; ISS:BHF-UCL. DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0070486; P:leukocyte aggregation; IMP:UniProtKB. DR GO; GO:0050919; P:negative chemotaxis; IBA:GO_Central. DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc. DR GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IBA:GO_Central. DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISS:BHF-UCL. DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0001755; P:neural crest cell migration; IBA:GO_Central. DR GO; GO:0043931; P:ossification involved in bone maturation; IMP:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB. DR GO; GO:0048672; P:positive regulation of collateral sprouting; IMP:UniProtKB. DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:UniProtKB. DR GO; GO:1905704; P:positive regulation of inhibitory synapse assembly; ISS:UniProtKB. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; ISS:BHF-UCL. DR GO; GO:0031344; P:regulation of cell projection organization; IMP:UniProtKB. DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB. DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IMP:UniProtKB. DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; IDA:UniProtKB. DR CDD; cd05873; Ig_Sema4D_like; 1. DR CDD; cd11259; Sema_4D; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR Gene3D; 3.30.1680.10; ligand-binding face of the semaphorins, domain 2; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. 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; IPR013151; Immunoglobulin. DR InterPro; IPR002165; Plexin_repeat. DR InterPro; IPR016201; PSI. DR InterPro; IPR001627; Semap_dom. DR InterPro; IPR036352; Semap_dom_sf. DR InterPro; IPR027231; Semaphorin. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR PANTHER; PTHR11036; SEMAPHORIN; 1. DR PANTHER; PTHR11036:SF18; SEMAPHORIN-4D; 1. DR Pfam; PF00047; ig; 1. DR Pfam; PF01437; PSI; 1. DR Pfam; PF01403; Sema; 1. DR SMART; SM00409; IG; 1. DR SMART; SM00408; IGc2; 1. DR SMART; SM00423; PSI; 1. DR SMART; SM00630; Sema; 1. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR SUPFAM; SSF103575; Plexin repeat; 1. DR SUPFAM; SSF101912; Sema domain; 1. DR PROSITE; PS50835; IG_LIKE; 1. DR PROSITE; PS51004; SEMA; 1. DR Genevisible; Q92854; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Developmental protein; KW Differentiation; Disulfide bond; Glycoprotein; Immunoglobulin domain; KW Membrane; Neurogenesis; Phosphoprotein; Receptor; Reference proteome; KW Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..862 FT /note="Semaphorin-4D" FT /id="PRO_0000032327" FT TOPO_DOM 22..734 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 735..755 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 756..862 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 22..500 FT /note="Sema" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DOMAIN 502..551 FT /note="PSI" FT DOMAIN 554..636 FT /note="Ig-like C2-type" FT REGION 794..837 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 823..837 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 833 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CARBOHYD 49 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973, FT ECO:0000269|PubMed:20877282" FT CARBOHYD 77 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973, FT ECO:0000269|PubMed:20877282" FT CARBOHYD 139 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20877282" FT CARBOHYD 191 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20877282" FT CARBOHYD 329 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20877282" FT CARBOHYD 379 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973" FT CARBOHYD 419 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16263699, FT ECO:0000269|PubMed:19349973, ECO:0000269|PubMed:20877282" FT CARBOHYD 613 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 632 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 97..108 FT DISULFID 126..135 FT DISULFID 257..370 FT DISULFID 281..326 FT DISULFID 503..520 FT DISULFID 509..553 FT DISULFID 512..529 FT DISULFID 576..624 FT VAR_SEQ 555..738 FT /note="DKSKGSYRQHFFKHGGTAELKCSQKSNLARVFWKFQNGVLKAESPKYGLMGR FT KNLLIFNLSEGDSGVYQCLSEERVKNKTVFQVVAKHVLEVKVVPKPVVAPTLSVVQTEG FT SRIATKVLVASTQGSSPPTPAVQATSSGAITLPPKPAPTGTSCEPKIVINTVPQLHSEK FT TMYLKSSDNRLLMS -> ASSPKPLPPPGSSSLSCLGHVGDRRLSSPWTPWPASGAGPD FT SSSRVSLLPPFLSDQAQHVHALGNFYLFCQATGPADIRFVWEKNGRALETCVPVQTHAL FT PDGRAHALSWLQDAIRESAEYRCSVLSSAGNKTSKVQVAVMRPEVTHQERWTRELSAWR FT AVAGEHDRMMQSWRKAWESCSKDTL (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_039483" FT VAR_SEQ 739..862 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_039484" FT VARIANT 72 FT /note="A -> T (in dbSNP:rs13284404)" FT /id="VAR_030293" FT VARIANT 327 FT /note="A -> T (in dbSNP:rs11526468)" FT /id="VAR_057175" FT MUTAGEN 100..101 FT /note="KG->DT: Abolishes PLXNB1 binding." FT /evidence="ECO:0000269|PubMed:20877282" FT MUTAGEN 181..182 FT /note="FL->ER: Abolishes PLXNB1 binding." FT /evidence="ECO:0000269|PubMed:20877282" FT MUTAGEN 244 FT /note="F->N: Abolishes homodimerization, abolishes collapse FT of growth cones and reduces PLXNB1 binding; when associated FT with S-246." FT /evidence="ECO:0000269|PubMed:20877282" FT MUTAGEN 246 FT /note="F->S: Abolishes homodimerization, abolishes collapse FT of growth cones and reduces PLXNB1 binding; when associated FT with N-244." FT /evidence="ECO:0000269|PubMed:20877282" FT MUTAGEN 395 FT /note="K->E: Strongly reduces PLXNB1 binding." FT /evidence="ECO:0000269|PubMed:20877282" FT CONFLICT 592 FT /note="G -> D (in Ref. 3; AAH54500)" FT /evidence="ECO:0000305" FT STRAND 29..32 FT /evidence="ECO:0007829|PDB:1OLZ" FT TURN 34..36 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 40..42 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 52..55 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 59..65 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 67..74 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 77..86 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 91..99 FT /evidence="ECO:0007829|PDB:1OLZ" FT TURN 104..107 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 111..117 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 119..127 FT /evidence="ECO:0007829|PDB:1OLZ" FT TURN 129..131 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 134..139 FT /evidence="ECO:0007829|PDB:1OLZ" FT TURN 140..143 FT /evidence="ECO:0007829|PDB:1OLZ" FT TURN 153..155 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 164..169 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 172..180 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 185..191 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 193..195 FT /evidence="ECO:0007829|PDB:3OL2" FT TURN 203..205 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 210..217 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 230..238 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 249..257 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 264..267 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 275..279 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 284..286 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 292..299 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 308..314 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 316..318 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 320..329 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 330..339 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 342..346 FT /evidence="ECO:0007829|PDB:1OLZ" FT TURN 349..351 FT /evidence="ECO:0007829|PDB:3OL2" FT STRAND 354..357 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 373..376 FT /evidence="ECO:0007829|PDB:1OLZ" FT TURN 377..379 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 383..385 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 388..396 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 399..404 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 407..409 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 412..417 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 420..429 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 431..433 FT /evidence="ECO:0007829|PDB:3OL2" FT STRAND 435..443 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 446..453 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 455..465 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 475..478 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 481..484 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 486..490 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 495..500 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 503..505 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 509..514 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 520..523 FT /evidence="ECO:0007829|PDB:1OLZ" FT TURN 524..527 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 528..531 FT /evidence="ECO:0007829|PDB:1OLZ" FT TURN 532..534 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 539..541 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 550..552 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 553..555 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 560..567 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 572..574 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 584..593 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 598..602 FT /evidence="ECO:0007829|PDB:1OLZ" FT TURN 604..607 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 609..611 FT /evidence="ECO:0007829|PDB:1OLZ" FT HELIX 616..618 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 620..629 FT /evidence="ECO:0007829|PDB:1OLZ" FT STRAND 631..647 FT /evidence="ECO:0007829|PDB:1OLZ" SQ SEQUENCE 862 AA; 96150 MW; 7B18EFEA98789371 CRC64; MRMCTPIRGL LMALAVMFGT AMAFAPIPRI TWEHREVHLV QFHEPDIYNY SALLLSEDKD TLYIGAREAV FAVNALNISE KQHEVYWKVS EDKKAKCAEK GKSKQTECLN YIRVLQPLSA TSLYVCGTNA FQPACDHLNL TSFKFLGKNE DGKGRCPFDP AHSYTSVMVD GELYSGTSYN FLGSEPIISR NSSHSPLRTE YAIPWLNEPS FVFADVIRKS PDSPDGEDDR VYFFFTEVSV EYEFVFRVLI PRIARVCKGD QGGLRTLQKK WTSFLKARLI CSRPDSGLVF NVLRDVFVLR SPGLKVPVFY ALFTPQLNNV GLSAVCAYNL STAEEVFSHG KYMQSTTVEQ SHTKWVRYNG PVPKPRPGAC IDSEARAANY TSSLNLPDKT LQFVKDHPLM DDSVTPIDNR PRLIKKDVNY TQIVVDRTQA LDGTVYDVMF VSTDRGALHK AISLEHAVHI IEETQLFQDF EPVQTLLLSS KKGNRFVYAG SNSGVVQAPL AFCGKHGTCE DCVLARDPYC AWSPPTATCV ALHQTESPSR GLIQEMSGDA SVCPDKSKGS YRQHFFKHGG TAELKCSQKS NLARVFWKFQ NGVLKAESPK YGLMGRKNLL IFNLSEGDSG VYQCLSEERV KNKTVFQVVA KHVLEVKVVP KPVVAPTLSV VQTEGSRIAT KVLVASTQGS SPPTPAVQAT SSGAITLPPK PAPTGTSCEP KIVINTVPQL HSEKTMYLKS SDNRLLMSLF LFFFVLFLCL FFYNCYKGYL PRQCLKFRSA LLIGKKKPKS DFCDREQSLK ETLVEPGSFS QQNGEHPKPA LDTGYETEQD TITSKVPTDR EDSQRIDDLS ARDKPFDVKC ELKFADSDAD GD //