SEM5A_HUMAN
ID SEM5A_HUMAN Reviewed; 1074 AA.
AC Q13591; D3DTC6; O60408; Q1RLL9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 3.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Semaphorin-5A;
DE AltName: Full=Semaphorin-F;
DE Short=Sema F;
DE Flags: Precursor;
GN Name=SEMA5A; Synonyms=SEMAF;
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].
RX PubMed=9464278; DOI=10.1006/bbrc.1997.8027;
RA Simmons A.D., Puschel A.W., McPherson J.D., Overhauser J., Lovett M.;
RT "Molecular cloning and mapping of human semaphorin F from the Cri-du-chat
RT candidate interval.";
RL Biochem. Biophys. Res. Commun. 242:685-691(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP FUNCTION, AND INTERACTION WITH PLXNB3.
RX PubMed=15218527; DOI=10.1038/sj.embor.7400189;
RA Artigiani S., Conrotto P., Fazzari P., Gilestro G.F., Barberis D.,
RA Giordano S., Comoglio P.M., Tamagnone L.;
RT "Plexin-B3 is a functional receptor for semaphorin 5A.";
RL EMBO Rep. 5:710-714(2004).
RN [6]
RP FUNCTION.
RX PubMed=20696765; DOI=10.1074/jbc.m110.120451;
RA Li X., Lee A.Y.;
RT "Semaphorin 5A and plexin-B3 inhibit human glioma cell motility through
RT RhoGDIalpha-mediated inactivation of Rac1 GTPase.";
RL J. Biol. Chem. 285:32436-32445(2010).
RN [7]
RP FUNCTION.
RX PubMed=19850054; DOI=10.1016/j.mvr.2009.10.005;
RA Sadanandam A., Rosenbaugh E.G., Singh S., Varney M., Singh R.K.;
RT "Semaphorin 5A promotes angiogenesis by increasing endothelial cell
RT proliferation, migration, and decreasing apoptosis.";
RL Microvasc. Res. 79:1-9(2010).
RN [8]
RP FUNCTION.
RX PubMed=21706053; DOI=10.1038/onc.2011.256;
RA Li X., Law J.W., Lee A.Y.;
RT "Semaphorin 5A and plexin-B3 regulate human glioma cell motility and
RT morphology through Rac1 and the actin cytoskeleton.";
RL Oncogene 31:595-610(2012).
RN [9]
RP VARIANT 196-ARG--TYR-1074 DEL.
RX PubMed=26637798; DOI=10.1016/j.neuron.2015.11.009;
RA D'Gama A.M., Pochareddy S., Li M., Jamuar S.S., Reiff R.E., Lam A.T.,
RA Sestan N., Walsh C.A.;
RT "Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates
RT Multiple Genetic Mechanisms.";
RL Neuron 88:910-917(2015).
CC -!- FUNCTION: Bifunctional axonal guidance cue regulated by sulfated
CC proteoglycans; attractive effects result from interactions with heparan
CC sulfate proteoglycans (HSPGs), while the inhibitory effects depend on
CC interactions with chondroitin sulfate proteoglycans (CSPGs) (By
CC similarity). Ligand for receptor PLXNB3. In glioma cells, SEMA5A
CC stimulation of PLXNB3 results in the disassembly of F-actin stress
CC fibers, disruption of focal adhesions and cellular collapse as well as
CC inhibition of cell migration and invasion through ARHGDIA-mediated
CC inactivation of RAC1. May promote angiogenesis by increasing
CC endothelial cell proliferation and migration and inhibiting apoptosis.
CC {ECO:0000250, ECO:0000269|PubMed:15218527, ECO:0000269|PubMed:19850054,
CC ECO:0000269|PubMed:20696765, ECO:0000269|PubMed:21706053}.
CC -!- SUBUNIT: Binds PLXNB3.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- SIMILARITY: Belongs to the semaphorin family. {ECO:0000305}.
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DR EMBL; U52840; AAC09473.1; -; mRNA.
DR EMBL; AC004615; AAC14668.1; -; Genomic_DNA.
DR EMBL; AC022446; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC027336; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091906; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471102; EAX08078.1; -; Genomic_DNA.
DR EMBL; CH471102; EAX08079.1; -; Genomic_DNA.
DR EMBL; BC115696; AAI15697.1; -; mRNA.
DR CCDS; CCDS3875.1; -.
DR PIR; JC5928; JC5928.
DR RefSeq; NP_003957.2; NM_003966.2.
DR RefSeq; XP_006714569.1; XM_006714506.2.
DR RefSeq; XP_006714570.1; XM_006714507.3.
DR RefSeq; XP_011512457.1; XM_011514155.2.
DR RefSeq; XP_011512458.1; XM_011514156.1.
DR RefSeq; XP_011512459.1; XM_011514157.1.
DR RefSeq; XP_011512460.1; XM_011514158.1.
DR AlphaFoldDB; Q13591; -.
DR SMR; Q13591; -.
DR IntAct; Q13591; 2.
DR STRING; 9606.ENSP00000371936; -.
DR GlyGen; Q13591; 11 sites.
DR iPTMnet; Q13591; -.
DR PhosphoSitePlus; Q13591; -.
DR BioMuta; SEMA5A; -.
DR DMDM; 109939725; -.
DR jPOST; Q13591; -.
DR MassIVE; Q13591; -.
DR PaxDb; Q13591; -.
DR PeptideAtlas; Q13591; -.
DR PRIDE; Q13591; -.
DR ProteomicsDB; 59586; -.
DR Antibodypedia; 960; 306 antibodies from 29 providers.
DR DNASU; 9037; -.
DR Ensembl; ENST00000382496.10; ENSP00000371936.5; ENSG00000112902.12.
DR Ensembl; ENST00000652226.1; ENSP00000499013.1; ENSG00000112902.12.
DR GeneID; 9037; -.
DR KEGG; hsa:9037; -.
DR MANE-Select; ENST00000382496.10; ENSP00000371936.5; NM_003966.3; NP_003957.2.
DR CTD; 9037; -.
DR DisGeNET; 9037; -.
DR GeneCards; SEMA5A; -.
DR HGNC; HGNC:10736; SEMA5A.
DR HPA; ENSG00000112902; Tissue enhanced (brain).
DR MalaCards; SEMA5A; -.
DR MIM; 609297; gene.
DR neXtProt; NX_Q13591; -.
DR OpenTargets; ENSG00000112902; -.
DR Orphanet; 281; Monosomy 5p.
DR PharmGKB; PA35658; -.
DR VEuPathDB; HostDB:ENSG00000112902; -.
DR eggNOG; KOG3611; Eukaryota.
DR GeneTree; ENSGT00940000158036; -.
DR HOGENOM; CLU_005410_1_0_1; -.
DR InParanoid; Q13591; -.
DR OMA; VEIANCS; -.
DR OrthoDB; 64683at2759; -.
DR PhylomeDB; Q13591; -.
DR TreeFam; TF329951; -.
DR PathwayCommons; Q13591; -.
DR Reactome; R-HSA-416700; Other semaphorin interactions.
DR Reactome; R-HSA-5083635; Defective B3GALTL causes PpS.
DR Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR SignaLink; Q13591; -.
DR SIGNOR; Q13591; -.
DR BioGRID-ORCS; 9037; 10 hits in 1060 CRISPR screens.
DR ChiTaRS; SEMA5A; human.
DR GeneWiki; SEMA5A; -.
DR GenomeRNAi; 9037; -.
DR Pharos; Q13591; Tbio.
DR PRO; PR:Q13591; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q13591; protein.
DR Bgee; ENSG00000112902; Expressed in metanephric glomerulus and 187 other tissues.
DR ExpressionAtlas; Q13591; baseline and differential.
DR Genevisible; Q13591; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045499; F:chemorepellent activity; IBA:GO_Central.
DR GO; GO:0035373; F:chondroitin sulfate proteoglycan binding; ISS:UniProtKB.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; ISS:UniProtKB.
DR GO; GO:0030215; F:semaphorin receptor binding; ISS:UniProtKB.
DR GO; GO:0045545; F:syndecan binding; ISS:UniProtKB.
DR GO; GO:0048675; P:axon extension; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007413; P:axonal fasciculation; ISS:UniProtKB.
DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0060326; P:cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0021536; P:diencephalon development; ISS:UniProtKB.
DR GO; GO:0048843; P:negative regulation of axon extension involved in axon guidance; ISS:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0001755; P:neural crest cell migration; IBA:GO_Central.
DR GO; GO:0050918; P:positive chemotaxis; ISS:UniProtKB.
DR GO; GO:0030836; P:positive regulation of actin filament depolymerization; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0048842; P:positive regulation of axon extension involved in axon guidance; ISS:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central.
DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; IBA:GO_Central.
DR GO; GO:1990256; P:signal clustering; ISS:UniProtKB.
DR CDD; cd11263; Sema_5A; 1.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.20.100.10; -; 6.
DR InterPro; IPR016201; PSI.
DR InterPro; IPR042821; Sema5A_sema.
DR InterPro; IPR001627; Semap_dom.
DR InterPro; IPR036352; Semap_dom_sf.
DR InterPro; IPR027231; Semaphorin.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR PANTHER; PTHR11036; PTHR11036; 1.
DR Pfam; PF01403; Sema; 1.
DR Pfam; PF00090; TSP_1; 5.
DR SMART; SM00423; PSI; 1.
DR SMART; SM00630; Sema; 1.
DR SMART; SM00209; TSP1; 6.
DR SUPFAM; SSF101912; SSF101912; 1.
DR SUPFAM; SSF82895; SSF82895; 6.
DR PROSITE; PS51004; SEMA; 1.
DR PROSITE; PS50092; TSP1; 6.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; Disulfide bond; Glycoprotein;
KW Membrane; Neurogenesis; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1074
FT /note="Semaphorin-5A"
FT /id="PRO_0000032335"
FT TOPO_DOM 23..968
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 969..989
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 990..1074
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 35..484
FT /note="Sema"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
FT DOMAIN 540..593
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 595..651
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 653..702
FT /note="TSP type-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 707..765
FT /note="TSP type-1 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 784..839
FT /note="TSP type-1 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 841..896
FT /note="TSP type-1 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 897..944
FT /note="TSP type-1 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 437
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 536
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 591
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 717
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 933
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 104..114
FT /evidence="ECO:0000250"
FT DISULFID 131..140
FT /evidence="ECO:0000250"
FT DISULFID 254..357
FT /evidence="ECO:0000250"
FT DISULFID 278..320
FT /evidence="ECO:0000250"
FT DISULFID 487..504
FT /evidence="ECO:0000250"
FT DISULFID 496..513
FT /evidence="ECO:0000250"
FT DISULFID 607..644
FT /evidence="ECO:0000250"
FT DISULFID 611..650
FT /evidence="ECO:0000250"
FT DISULFID 622..634
FT /evidence="ECO:0000250"
FT DISULFID 665..696
FT /evidence="ECO:0000250"
FT DISULFID 669..701
FT /evidence="ECO:0000250"
FT DISULFID 680..686
FT /evidence="ECO:0000250"
FT DISULFID 796..833
FT /evidence="ECO:0000250"
FT DISULFID 800..838
FT /evidence="ECO:0000250"
FT DISULFID 811..823
FT /evidence="ECO:0000250"
FT DISULFID 853..890
FT /evidence="ECO:0000250"
FT DISULFID 857..895
FT /evidence="ECO:0000250"
FT DISULFID 868..880
FT /evidence="ECO:0000250"
FT VARIANT 196..1074
FT /note="Missing (probable disease-associated variant found
FT in a patient with autism spectrum disorder)"
FT /evidence="ECO:0000269|PubMed:26637798"
FT /id="VAR_078706"
FT VARIANT 246
FT /note="V -> L (in dbSNP:rs1806079)"
FT /id="VAR_030294"
FT VARIANT 792
FT /note="S -> L (in dbSNP:rs2290734)"
FT /id="VAR_030295"
FT CONFLICT 56
FT /note="V -> A (in Ref. 1; AAC09473)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="T -> A (in Ref. 1; AAC09473)"
FT /evidence="ECO:0000305"
FT CONFLICT 382
FT /note="M -> V (in Ref. 1; AAC09473)"
FT /evidence="ECO:0000305"
FT CONFLICT 494
FT /note="S -> R (in Ref. 2; AAC14668)"
FT /evidence="ECO:0000305"
FT CONFLICT 723
FT /note="G -> D (in Ref. 1; AAC09473)"
FT /evidence="ECO:0000305"
FT CONFLICT 835
FT /note="I -> T (in Ref. 1; AAC09473)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1074 AA; 120615 MW; AE073413AC974CCC CRC64;
MKGTCVIAWL FSSLGLWRLA HPEAQGTTQC QRTEHPVISY KEIGPWLREF RAKNAVDFSQ
LTFDPGQKEL VVGARNYLFR LQLEDLSLIQ AVEWECDEAT KKACYSKGKS KEECQNYIRV
LLVGGDRLFT CGTNAFTPVC TNRSLSNLTE IHDQISGMAR CPYSPQHNST ALLTAGGELY
AATAMDFPGR DPAIYRSLGI LPPLRTAQYN SKWLNEPNFV SSYDIGNFTY FFFRENAVEH
DCGKTVFSRA ARVCKNDIGG RFLLEDTWTT FMKARLNCSR PGEVPFYYNE LQSTFFLPEL
DLIYGIFTTN VNSIAASAVC VFNLSAIAQA FSGPFKYQEN SRSAWLPYPN PNPHFQCGTV
DQGLYVNLTE RNLQDAQKFI LMHEVVQPVT TVPSFMEDNS RFSHVAVDVV QGREALVHII
YLATDYGTIK KVRVPLNQTS SSCLLEEIEL FPERRREPIR SLQILHSQSV LFVGLREHVV
KIPLKRCQFY RTRSTCIGAQ DPYCGWDVVM KKCTSLEESL SMTQWEQSIS ACPTRNLTVD
GHFGVWSPWT PCTHTDGSAV GSCLCRTRSC DSPAPQCGGW QCEGPGMEIA NCSRNGGWTP
WTSWSPCSTT CGIGFQVRQR SCSNPTPRHG GRVCVGQNRE ERYCNEHLLC PPHMFWTGWG
PWERCTAQCG GGIQARRRIC ENGPDCAGCN VEYQSCNTNP CPELKKTTPW TPWTPVNISD
NGGHYEQRFR YTCKARLADP NLLEVGRQRI EMRYCSSDGT SGCSTDGLSG DFLRAGRYSA
HTVNGAWSAW TSWSQCSRDC SRGIRNRKRV CNNPEPKYGG MPCLGPSLEY QECNILPCPV
DGVWSCWSPW TKCSATCGGG HYMRTRSCSN PAPAYGGDIC LGLHTEEALC NTQPCPESWS
EWSDWSECEA SGVQVRARQC ILLFPMGSQC SGNTTESRPC VFDSNFIPEV SVARSSSVEE
KRCGEFNMFH MIAVGLSSSI LGCLLTLLVY TYCQRYQQQS HDATVIHPVS PAPLNTSITN
HINKLDKYDS VEAIKAFNKN NLILEERNKY FNPHLTGKTY SNAYFTDLNN YDEY
