SEM5A_MOUSE
ID SEM5A_MOUSE Reviewed; 1077 AA.
AC Q62217;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 146.
DE RecName: Full=Semaphorin-5A;
DE AltName: Full=Semaphorin-F;
DE Short=Sema F;
DE Flags: Precursor;
GN Name=Sema5a; Synonyms=Semaf, SemF;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=NMRI;
RX PubMed=8817451; DOI=10.1016/0925-4773(96)00525-4;
RA Adams R.H., Betz H., Pueschel A.W.;
RT "A novel class of murine semaphorins with homology to thrombospondin is
RT differentially expressed during early embryogenesis.";
RL Mech. Dev. 57:33-45(1996).
RN [2]
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=15743826; DOI=10.1128/mcb.25.6.2310-2319.2005;
RA Fiore R., Rahim B., Christoffels V.M., Moorman A.F., Puschel A.W.;
RT "Inactivation of the Sema5a gene results in embryonic lethality and
RT defective remodeling of the cranial vascular system.";
RL Mol. Cell. Biol. 25:2310-2319(2005).
RN [3]
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 [4]
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=21835343; DOI=10.1016/j.neuron.2011.06.009;
RA Matsuoka R.L., Chivatakarn O., Badea T.C., Samuels I.S., Cahill H.,
RA Katayama K., Kumar S.R., Suto F., Chedotal A., Peachey N.S., Nathans J.,
RA Yoshida Y., Giger R.J., Kolodkin A.L.;
RT "Class 5 transmembrane semaphorins control selective Mammalian retinal
RT lamination and function.";
RL Neuron 71:460-473(2011).
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). Ligand for
CC receptor PLXNB3. In glioma cells, SEMA5A stimulation of PLXNB3 results
CC in the disassembly of F-actin stress fibers, disruption of focal
CC adhesions and cellular collapse as well as inhibition of cell migration
CC and invasion through ARHGDIA-mediated inactivation of RAC1 (By
CC similarity). May promote angiogenesis by increasing endothelial cell
CC proliferation and migration and inhibiting apoptosis. {ECO:0000250,
CC ECO:0000269|PubMed:19850054}.
CC -!- SUBUNIT: Binds PLXNB3. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: In adult, detected in liver, brain, kidney, heart,
CC lung and spleen.
CC -!- DEVELOPMENTAL STAGE: Differentially expressed in embryonic and adult
CC tissues. Its abundance decreases from 10 dpc to birth. At 10.5 dpc,
CC detected in the atrial septum and endocardial cushions, and at lower
CC levels in the atrial and ventricular endocardium. Strong expression
CC detected in embryonic and postnatal retina. At P0 and P3, expression
CC detected in the outer neuroblastic layer. After P7, the expression
CC becomes more restricted and is observed in the middle to outer part of
CC inner nuclear layer, and is not detectable at P21 when retinal
CC development is almost complete. {ECO:0000269|PubMed:15743826,
CC ECO:0000269|PubMed:21835343}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice die between 11.5 and 12.5 dpc. At
CC this stage, no defects are detected in the development of
CC extraembryonic tissues, cardiovascular system, axonal trajectories and
CC peripheral nervous system. Mutants display decreased complexity of the
CC hierarchically organized branches of the cranial blood vessels
CC (PubMed:15743826). Mutant mice are viable and fertile
CC (PubMed:21835343). {ECO:0000269|PubMed:15743826,
CC ECO:0000269|PubMed:21835343}.
CC -!- SIMILARITY: Belongs to the semaphorin family. {ECO:0000305}.
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DR EMBL; X97817; CAA66397.1; -; mRNA.
DR AlphaFoldDB; Q62217; -.
DR SMR; Q62217; -.
DR STRING; 10090.ENSMUSP00000069024; -.
DR GlyGen; Q62217; 10 sites.
DR iPTMnet; Q62217; -.
DR PhosphoSitePlus; Q62217; -.
DR MaxQB; Q62217; -.
DR PaxDb; Q62217; -.
DR PeptideAtlas; Q62217; -.
DR PRIDE; Q62217; -.
DR ProteomicsDB; 256944; -.
DR MGI; MGI:107556; Sema5a.
DR eggNOG; KOG3611; Eukaryota.
DR InParanoid; Q62217; -.
DR PhylomeDB; Q62217; -.
DR Reactome; R-MMU-416700; Other semaphorin interactions.
DR Reactome; R-MMU-5173214; O-glycosylation of TSR domain-containing proteins.
DR ChiTaRS; Sema5a; mouse.
DR PRO; PR:Q62217; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q62217; protein.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0008046; F:axon guidance receptor activity; IDA:MGI.
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; IPI:UniProtKB.
DR GO; GO:0045545; F:syndecan binding; ISS:UniProtKB.
DR GO; GO:0048675; P:axon extension; IGI:MGI.
DR GO; GO:0007411; P:axon guidance; IMP:MGI.
DR GO; GO:0007413; P:axonal fasciculation; ISS:UniProtKB.
DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IDA:UniProtKB.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:MGI.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:MGI.
DR GO; GO:0060326; P:cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IGI:MGI.
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; IDA:UniProtKB.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0001755; P:neural crest cell migration; IBA:GO_Central.
DR GO; GO:1990138; P:neuron projection extension; IDA:MGI.
DR GO; GO:0097485; P:neuron projection guidance; IGI:MGI.
DR GO; GO:0050918; P:positive chemotaxis; IDA:UniProtKB.
DR GO; GO:0030836; P:positive regulation of actin filament depolymerization; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA: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; IDA: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; IDA:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0090091; P:positive regulation of extracellular matrix disassembly; NAS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; IDA:UniProtKB.
DR GO; GO:1990256; P:signal clustering; IDA: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 2: Evidence at transcript level;
KW Developmental protein; Differentiation; Disulfide bond; Glycoprotein;
KW Membrane; Neurogenesis; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1077
FT /note="Semaphorin-5A"
FT /id="PRO_0000032336"
FT TOPO_DOM 22..971
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 972..992
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 993..1077
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 147
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 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"
SQ SEQUENCE 1077 AA; 120826 MW; EDAB0DDDA42789FF CRC64;
MKGACILAWL FSSLGVWRLA RPETQDPAKC QRAEHPVVSY KEIGPWLREF RAENAVDFSR
LTFDPGQKEL VVGARNYLFR LELEDLSLIQ AVEWECDEAT KKACYSKGKS KEECQNYIRV
LLVGGDRLFT CGTNAFTPVC TIRSLSNLTE IHDQISGMAR CPYSPQHNST ALLTASGELY
AATAMDFPGR DPAIYRSLGT LPPLRTAQYN SKWLNEPNFV SSYDIGNFTY FFFRENAVEH
DCGKTVFSRP ARVCKNDIGG RFLLEDTWTT FMKARLNCSR PGEVPFYYNE LQGTFFLPEL
DLIYGIFTTN VNSIASSAVC VFNLSAISQA FNGPFKYQEN SRSAWLPYPN PNPNFQCGTM
DQGLYVNLTE RNLQDAQKFI LMHEVVQPVT TVPSFMEDNS RFSHLAVDVV QGRETLVHII
YLGTDYGTIK KVRAPLSQSS GSCLLEEIEL FPERRSEPIR SLQILHSQSV LFVGLQEHVA
KIPLKRCHFH QTRSACIGAQ DPYCGWDAVM KKCTSLEESL SMTQWDQSIP TCPTRNLTVD
GSFGPWSPWT PCTHTDGTAV GSCLCRSRSC DRPAPQCGGW QCEGPRMEIT NCSRNGGWTP
WTSWSPCSTT CGIGFQVRQR SCSNPTPRHG GRVCVGQNRE ERYCNEHLLC PPHVFWTGWG
PWERCTAQCG GGIQARRRTC ENGPDCAGSN VEYHPCNTNA CPELKKTTPW TPWTPVNISD
NGGHYEQRFR YTCKARLPDP NLLEVGRQRI EMRYCSSDGT SGCSTDGLSG DFLRAGRYSA
HTVNGAWSAW TSWSQCSRDC SRGIRNRKRV CNNPEPKFGG MPCLGPSLEF QECNILPCPV
DGVWSCWSSW SKCSATCGGG HYMRTRSCSN PAPAYGGDIC LGLHTEEALC NTQTCPESWS
EWSDWSVCDA SGTQVRARQC ILLFPVGSQC SGNTTESRPC VFDSNFIPEV SVARSSSVEE
KRCGEFNMFH MFHMMAVGLS SSILGCLLTL LVYTYCQRYQ QQSHDATVIH PVSPAALNSS
ITNHINKLDK YDSVEAIKAF NKNNLILEER NKYFNPHLTG KTYSNAYFTD LNNYDEY
