SEM4D_HUMAN
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 03-AUG-2022, entry version 215.
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="http://atlasgeneticsoncology.org/Genes/SEMA4DID42255ch9q22.html";
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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; 29.
DR CORUM; Q92854; -.
DR DIP; DIP-59221N; -.
DR IntAct; Q92854; 10.
DR MINT; Q92854; -.
DR STRING; 9606.ENSP00000416523; -.
DR ChEMBL; CHEMBL4630887; -.
DR GuidetoPHARMACOLOGY; 2883; -.
DR GlyConnect; 1734; 13 N-Linked glycans (4 sites).
DR GlyGen; Q92854; 12 sites, 13 N-linked glycans (4 sites), 1 O-linked glycan (2 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; Q92854; -.
DR PeptideAtlas; Q92854; -.
DR PRIDE; Q92854; -.
DR ProteomicsDB; 75549; -. [Q92854-1]
DR ProteomicsDB; 75550; -. [Q92854-2]
DR ABCD; Q92854; 20 sequenced antibodies.
DR Antibodypedia; 3064; 911 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 CTD; 10507; -.
DR DisGeNET; 10507; -.
DR GeneCards; SEMA4D; -.
DR HGNC; HGNC:10732; SEMA4D.
DR HPA; ENSG00000187764; Tissue enhanced (brain).
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; FRQHFFK; -.
DR OrthoDB; 64683at2759; -.
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; 9 hits in 1069 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 181 other tissues.
DR ExpressionAtlas; Q92854; baseline and differential.
DR Genevisible; Q92854; HS.
DR GO; GO:0005615; C:extracellular space; ISS:BHF-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045499; F:chemorepellent activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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: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:0010693; P:negative regulation of alkaline phosphatase activity; IMP:BHF-UCL.
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; ISS:BHF-UCL.
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; ISS:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
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 GO; GO:1900220; P:semaphorin-plexin signaling pathway involved in bone trabecula morphogenesis; ISS:BHF-UCL.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 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; PTHR11036; 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; SSF101912; SSF101912; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51004; SEMA; 1.
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
