SEM6B_HUMAN
ID SEM6B_HUMAN Reviewed; 888 AA.
AC Q9H3T3; A5PKU4; F6IB19; Q9NRK9;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 4.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Semaphorin-6B;
DE AltName: Full=Semaphorin-Z;
DE Short=Sema Z;
DE Flags: Precursor;
GN Name=SEMA6B; Synonyms=SEMAN, SEMAZ; ORFNames=UNQ1907/PRO4353;
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;
RA Kimura T., Ishida H.;
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11350127; DOI=10.1006/geno.2001.6525;
RA Correa R.G., Sasahara R.M., Bengtson M.H., Katayama M.L.H., Salim A.C.M.,
RA Brentani M.M., Sogayar M.C., de Souza S.J., Simpson A.J.G.;
RT "Human semaphorin 6b [(HSA)SEMA6B], a novel human class 6 semaphorin gene:
RT alternative splicing and all-trans-retinoic acid-dependent downregulation
RT in glioblastoma cell lines.";
RL Genomics 73:343-348(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Mammary cancer;
RA D'Apice L., Costa V., Caivano A., Trovato M., Pagani A., Manera S.,
RA Zambelli A., Ciccodicola A., De Berardinis P.;
RT "Analysis of SEMA6B gene expression in breast cancer: identification of a
RT new isoform.";
RL Submitted (MAY-2011) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [8]
RP PROTEIN SEQUENCE OF 26-40.
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 [9]
RP INVOLVEMENT IN EPM11, AND TISSUE SPECIFICITY.
RX PubMed=32169168; DOI=10.1016/j.ajhg.2020.02.011;
RA Hamanaka K., Imagawa E., Koshimizu E., Miyatake S., Tohyama J.,
RA Yamagata T., Miyauchi A., Ekhilevitch N., Nakamura F., Kawashima T.,
RA Goshima Y., Mohamed A.R., Ch'ng G.S., Fujita A., Azuma Y., Yasuda K.,
RA Imamura S., Nakashima M., Saitsu H., Mitsuhashi S., Mizuguchi T.,
RA Takata A., Miyake N., Matsumoto N.;
RT "De novo truncating variants in the last exon of SEMA6B Cause progressive
RT myoclonic epilepsy.";
RL Am. J. Hum. Genet. 106:549-558(2020).
RN [10]
RP INTERACTION WITH P.SORDELLII PROTEIN TCSL (MICROBIAL INFECTION), FUNCTION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=32302524; DOI=10.1016/j.chom.2020.03.007;
RA Tian S., Liu Y., Wu H., Liu H., Zeng J., Choi M.Y., Chen H., Gerhard R.,
RA Dong M.;
RT "Genome-wide CRISPR screen identifies semaphorin 6A and 6B as receptors for
RT Paeniclostridium sordellii toxin TcsL.";
RL Cell Host Microbe 27:782-792(2020).
RN [11]
RP INTERACTION WITH P.SORDELLII PROTEIN TCSL (MICROBIAL INFECTION), AND
RP FUNCTION.
RX PubMed=32589945; DOI=10.1016/j.cell.2020.06.005;
RA Lee H., Beilhartz G.L., Kucharska I., Raman S., Cui H., Lam M.H.Y.,
RA Liang H., Rubinstein J.L., Schramek D., Julien J.P., Melnyk R.A.,
RA Taipale M.;
RT "Recognition of semaphorin proteins by P. sordellii lethal toxin reveals
RT principles of receptor specificity in clostridial toxins.";
RL Cell 0:0-0(2020).
CC -!- FUNCTION: Functions as a cell surface repellent for mossy fibers of
CC developping neurons in the hippocampus where it plays a role in axon
CC guidance. May function through the PLXNA4 receptor expressed by mossy
CC cell axons. {ECO:0000250|UniProtKB:O54951}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for P.sordellii
CC toxin TcsL in the in the vascular endothelium.
CC {ECO:0000269|PubMed:32302524, ECO:0000269|PubMed:32589945}.
CC -!- SUBUNIT: (Microbial infection) Interacts with P.sordellii toxin TcsL;
CC semaphorins SEMA6A and SEMA6B constitute the major host receptors for
CC TcsL in the vascular endothelium. {ECO:0000269|PubMed:32302524,
CC ECO:0000269|PubMed:32589945}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:32302524};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H3T3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H3T3-3; Sequence=VSP_047625, VSP_047626;
CC -!- TISSUE SPECIFICITY: Expressed in the brain in GABAergic neurons.
CC {ECO:0000269|PubMed:32169168}.
CC -!- DISEASE: Epilepsy, progressive myoclonic 11 (EPM11) [MIM:618876]: A
CC form of progressive myoclonic epilepsy, a clinically and genetically
CC heterogeneous group of disorders defined by the combination of action
CC and reflex myoclonus, other types of epileptic seizures, and
CC progressive neurodegeneration and neurocognitive impairment. EPM11 is
CC an autosomal dominant form. Clinical features include normal or mildly
CC delayed early development, developmental regression after seizures
CC onset, inability to walk, severely impaired intellectual development,
CC poor or absent speech, spasticity, ataxia, and intention tremor. Brain
CC imaging shows cerebellar atrophy in some patients.
CC {ECO:0000269|PubMed:32169168}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the semaphorin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF87661.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; AB022433; BAB20669.1; -; mRNA.
DR EMBL; AF216389; AAF87661.1; ALT_SEQ; mRNA.
DR EMBL; FR839673; CCA61013.1; -; mRNA.
DR EMBL; AY358939; AAQ89298.1; -; mRNA.
DR EMBL; AC011498; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471139; EAW69208.1; -; Genomic_DNA.
DR EMBL; BC142617; AAI42618.1; -; mRNA.
DR CCDS; CCDS12131.1; -. [Q9H3T3-1]
DR RefSeq; NP_115484.2; NM_032108.3. [Q9H3T3-1]
DR AlphaFoldDB; Q9H3T3; -.
DR SMR; Q9H3T3; -.
DR BioGRID; 115763; 73.
DR STRING; 9606.ENSP00000467290; -.
DR GlyGen; Q9H3T3; 7 sites.
DR iPTMnet; Q9H3T3; -.
DR PhosphoSitePlus; Q9H3T3; -.
DR BioMuta; SEMA6B; -.
DR DMDM; 116242786; -.
DR EPD; Q9H3T3; -.
DR jPOST; Q9H3T3; -.
DR MassIVE; Q9H3T3; -.
DR MaxQB; Q9H3T3; -.
DR PaxDb; Q9H3T3; -.
DR PeptideAtlas; Q9H3T3; -.
DR PRIDE; Q9H3T3; -.
DR ProteomicsDB; 80754; -. [Q9H3T3-1]
DR Antibodypedia; 57701; 117 antibodies from 23 providers.
DR DNASU; 10501; -.
DR Ensembl; ENST00000586582.6; ENSP00000467290.1; ENSG00000167680.17. [Q9H3T3-1]
DR Ensembl; ENST00000586965.1; ENSP00000465722.1; ENSG00000167680.17. [Q9H3T3-3]
DR Ensembl; ENST00000676793.1; ENSP00000503414.1; ENSG00000167680.17. [Q9H3T3-1]
DR GeneID; 10501; -.
DR KEGG; hsa:10501; -.
DR MANE-Select; ENST00000586582.6; ENSP00000467290.1; NM_032108.4; NP_115484.2.
DR UCSC; uc010dud.3; human. [Q9H3T3-1]
DR CTD; 10501; -.
DR DisGeNET; 10501; -.
DR GeneCards; SEMA6B; -.
DR HGNC; HGNC:10739; SEMA6B.
DR HPA; ENSG00000167680; Tissue enhanced (brain).
DR MalaCards; SEMA6B; -.
DR MIM; 608873; gene.
DR MIM; 618876; phenotype.
DR neXtProt; NX_Q9H3T3; -.
DR OpenTargets; ENSG00000167680; -.
DR PharmGKB; PA35661; -.
DR VEuPathDB; HostDB:ENSG00000167680; -.
DR eggNOG; KOG3611; Eukaryota.
DR GeneTree; ENSGT00940000159170; -.
DR HOGENOM; CLU_009051_2_1_1; -.
DR InParanoid; Q9H3T3; -.
DR OMA; QKRVMRL; -.
DR OrthoDB; 119118at2759; -.
DR PhylomeDB; Q9H3T3; -.
DR TreeFam; TF316102; -.
DR PathwayCommons; Q9H3T3; -.
DR BioGRID-ORCS; 10501; 58 hits in 1076 CRISPR screens.
DR ChiTaRS; SEMA6B; human.
DR GenomeRNAi; 10501; -.
DR Pharos; Q9H3T3; Tbio.
DR PRO; PR:Q9H3T3; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9H3T3; protein.
DR Bgee; ENSG00000167680; Expressed in right frontal lobe and 109 other tissues.
DR Genevisible; Q9H3T3; HS.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045499; F:chemorepellent activity; IBA:GO_Central.
DR GO; GO:0030215; F:semaphorin receptor binding; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IMP:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; ISS:UniProtKB.
DR GO; GO:0050919; P:negative chemotaxis; IBA:GO_Central.
DR GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; IBA:GO_Central.
DR GO; GO:0001755; P:neural crest cell migration; IBA:GO_Central.
DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central.
DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; IBA:GO_Central.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR002165; Plexin_repeat.
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; PF01437; PSI; 1.
DR Pfam; PF01403; Sema; 1.
DR SMART; SM00630; Sema; 1.
DR SUPFAM; SSF101912; SSF101912; 1.
DR PROSITE; PS51004; SEMA; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Developmental protein;
KW Differentiation; Direct protein sequencing; Disulfide bond; Epilepsy;
KW Glycoprotein; Membrane; Methylation; Neurodegeneration; Neurogenesis;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 26..888
FT /note="Semaphorin-6B"
FT /id="PRO_0000032341"
FT TOPO_DOM 26..603
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 604..624
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 625..888
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 31..523
FT /note="Sema"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT REGION 651..679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 695..742
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 757..888
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 714..728
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 817..832
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 851..867
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 665
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O54951"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 291
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 386
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 441
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 462
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 116..126
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 144..153
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 267..378
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 292..337
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 486..517
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 526..544
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 532..578
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DISULFID 536..552
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT VAR_SEQ 620..677
FT /note="WFVGLRERRELARRKDKEAILAHGAGEAVLSVSRLGERRAQGPGGRGGGGGG
FT GAGVPP -> VCVRASEGCCGRVCQVGHACRVCVHERRSWWPQRPGRWLSRRWGFQKAR
FT GSPRCRLGV (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_047625"
FT VAR_SEQ 678..888
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_047626"
FT CONFLICT 30
FT /note="E -> D (in Ref. 1; BAB20669)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 888 AA; 95285 MW; EF34843A4A7A4E1C CRC64;
MQTPRASPPR PALLLLLLLL GGAHGLFPEE PPPLSVAPRD YLNHYPVFVG SGPGRLTPAE
GADDLNIQRV LRVNRTLFIG DRDNLYRVEL EPPTSTELRY QRKLTWRSNP SDINVCRMKG
KQEGECRNFV KVLLLRDEST LFVCGSNAFN PVCANYSIDT LQPVGDNISG MARCPYDPKH
ANVALFSDGM LFTATVTDFL AIDAVIYRSL GDRPTLRTVK HDSKWFKEPY FVHAVEWGSH
VYFFFREIAM EFNYLEKVVV SRVARVCKND VGGSPRVLEK QWTSFLKARL NCSVPGDSHF
YFNVLQAVTG VVSLGGRPVV LAVFSTPSNS IPGSAVCAFD LTQVAAVFEG RFREQKSPES
IWTPVPEDQV PRPRPGCCAA PGMQYNASSA LPDDILNFVK THPLMDEAVP SLGHAPWILR
TLMRHQLTRV AVDVGAGPWG NQTVVFLGSE AGTVLKFLVR PNASTSGTSG LSVFLEEFET
YRPDRCGRPG GGETGQRLLS LELDAASGGL LAAFPRCVVR VPVARCQQYS GCMKNCIGSQ
DPYCGWAPDG SCIFLSPGTR AAFEQDVSGA STSGLGDCTG LLRASLSEDR AGLVSVNLLV
TSSVAAFVVG AVVSGFSVGW FVGLRERREL ARRKDKEAIL AHGAGEAVLS VSRLGERRAQ
GPGGRGGGGG GGAGVPPEAL LAPLMQNGWA KATLLQGGPH DLDSGLLPTP EQTPLPQKRL
PTPHPHPHAL GPRAWDHGHP LLPASASSSL LLLAPARAPE QPPAPGEPTP DGRLYAARPG
RASHGDFPLT PHASPDRRRV VSAPTGPLDP ASAADGLPRP WSPPPTGSLR RPLGPHAPPA
ATLRRTHTFN SGEARPGDRH RGCHARPGTD LAHLLPYGGA DRTAPPVP
