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Q13591 (SEM5A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Semaphorin-5A
Alternative name(s):
Semaphorin-F
Short name=Sema F
Gene names
Name:SEMA5A
Synonyms:SEMAF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1074 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Bifunctional axonal guidance cue regulated by sulfated proteoglycans; attractive effects result from interactions with heparan sulfate proteoglycans (HSPGs), while the inhibitory effects depend on interactions with chondroitin sulfate proteoglycans (CSPGs) By similarity. Ligand for receptor PLXNB3. In glioma cells, SEMA5A stimulation of PLXNB3 results in the disassembly of F-actin stress fibers, disruption of focal adhesions and cellular collapse as well as inhibition of cell migration and invasion through ARHGDIA-mediated inactivation of RAC1. May promote angiogenesis by increasing endothelial cell proliferation and migration and inhibiting apoptosis. Ref.5 Ref.6 Ref.7 Ref.8

Subunit structure

Binds PLXNB3.

Subcellular location

Membrane; Single-pass type I membrane protein.

Sequence similarities

Belongs to the semaphorin family.

Contains 1 PSI domain.

Contains 1 Sema domain.

Contains 7 TSP type-1 domains.

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaxon guidance

Traceable author statement. Source: Reactome

blood vessel endothelial cell proliferation involved in sprouting angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cell adhesion

Traceable author statement PubMed 9049630. Source: ProtInc

cell chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

cell-cell signaling

Traceable author statement Ref.1. Source: ProtInc

diencephalon development

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of GTPase activity

Inferred from mutant phenotype Ref.6. Source: UniProtKB

negative regulation of axon extension involved in axon guidance

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of endothelial cell apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

nervous system development

Traceable author statement Ref.1. Source: ProtInc

patterning of blood vessels

Inferred from electronic annotation. Source: Ensembl

positive regulation of actin filament depolymerization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of axon extension involved in axon guidance

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of catenin import into nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of endothelial cell chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of endothelial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionaxon guidance receptor activity

Inferred from electronic annotation. Source: Ensembl

chondroitin sulfate proteoglycan binding

Inferred from sequence or structural similarity. Source: UniProtKB

heparan sulfate proteoglycan binding

Inferred from sequence or structural similarity. Source: UniProtKB

semaphorin receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

syndecan binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 10741052Semaphorin-5A
PRO_0000032335

Regions

Topological domain23 – 968946Extracellular Potential
Transmembrane969 – 98921Helical; Potential
Topological domain990 – 107485Cytoplasmic Potential
Domain35 – 484450Sema
Domain540 – 59354TSP type-1 1
Domain595 – 65157TSP type-1 2
Domain653 – 70250TSP type-1 3
Domain707 – 76559TSP type-1 4
Domain784 – 83956TSP type-1 5
Domain841 – 89656TSP type-1 6
Domain897 – 94448TSP type-1 7

Amino acid modifications

Glycosylation1421N-linked (GlcNAc...) Potential
Glycosylation1681N-linked (GlcNAc...) Potential
Glycosylation2271N-linked (GlcNAc...) Potential
Glycosylation2771N-linked (GlcNAc...) Potential
Glycosylation3231N-linked (GlcNAc...) Potential
Glycosylation3671N-linked (GlcNAc...) Potential
Glycosylation4371N-linked (GlcNAc...) Potential
Glycosylation5361N-linked (GlcNAc...) Potential
Glycosylation5911N-linked (GlcNAc...) Potential
Glycosylation7171N-linked (GlcNAc...) Potential
Glycosylation9331N-linked (GlcNAc...) Potential
Disulfide bond104 ↔ 114 By similarity
Disulfide bond131 ↔ 140 By similarity
Disulfide bond254 ↔ 357 By similarity
Disulfide bond278 ↔ 320 By similarity
Disulfide bond487 ↔ 504 By similarity
Disulfide bond496 ↔ 513 By similarity
Disulfide bond607 ↔ 644 By similarity
Disulfide bond611 ↔ 650 By similarity
Disulfide bond622 ↔ 634 By similarity
Disulfide bond665 ↔ 696 By similarity
Disulfide bond669 ↔ 701 By similarity
Disulfide bond680 ↔ 686 By similarity
Disulfide bond796 ↔ 833 By similarity
Disulfide bond800 ↔ 838 By similarity
Disulfide bond811 ↔ 823 By similarity
Disulfide bond853 ↔ 890 By similarity
Disulfide bond857 ↔ 895 By similarity
Disulfide bond868 ↔ 880 By similarity

Natural variations

Natural variant2461V → L.
Corresponds to variant rs1806079 [ dbSNP | Ensembl ].
VAR_030294
Natural variant7921S → L.
Corresponds to variant rs2290734 [ dbSNP | Ensembl ].
VAR_030295

Experimental info

Sequence conflict561V → A in AAC09473. Ref.1
Sequence conflict1491T → A in AAC09473. Ref.1
Sequence conflict3821M → V in AAC09473. Ref.1
Sequence conflict4941S → R in AAC14668. Ref.2
Sequence conflict7231G → D in AAC09473. Ref.1
Sequence conflict8351I → T in AAC09473. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q13591 [UniParc].

Last modified May 30, 2006. Version 3.
Checksum: AE073413AC974CCC

FASTA1,074120,615
        10         20         30         40         50         60 
MKGTCVIAWL FSSLGLWRLA HPEAQGTTQC QRTEHPVISY KEIGPWLREF RAKNAVDFSQ 

        70         80         90        100        110        120 
LTFDPGQKEL VVGARNYLFR LQLEDLSLIQ AVEWECDEAT KKACYSKGKS KEECQNYIRV 

       130        140        150        160        170        180 
LLVGGDRLFT CGTNAFTPVC TNRSLSNLTE IHDQISGMAR CPYSPQHNST ALLTAGGELY 

       190        200        210        220        230        240 
AATAMDFPGR DPAIYRSLGI LPPLRTAQYN SKWLNEPNFV SSYDIGNFTY FFFRENAVEH 

       250        260        270        280        290        300 
DCGKTVFSRA ARVCKNDIGG RFLLEDTWTT FMKARLNCSR PGEVPFYYNE LQSTFFLPEL 

       310        320        330        340        350        360 
DLIYGIFTTN VNSIAASAVC VFNLSAIAQA FSGPFKYQEN SRSAWLPYPN PNPHFQCGTV 

       370        380        390        400        410        420 
DQGLYVNLTE RNLQDAQKFI LMHEVVQPVT TVPSFMEDNS RFSHVAVDVV QGREALVHII 

       430        440        450        460        470        480 
YLATDYGTIK KVRVPLNQTS SSCLLEEIEL FPERRREPIR SLQILHSQSV LFVGLREHVV 

       490        500        510        520        530        540 
KIPLKRCQFY RTRSTCIGAQ DPYCGWDVVM KKCTSLEESL SMTQWEQSIS ACPTRNLTVD 

       550        560        570        580        590        600 
GHFGVWSPWT PCTHTDGSAV GSCLCRTRSC DSPAPQCGGW QCEGPGMEIA NCSRNGGWTP 

       610        620        630        640        650        660 
WTSWSPCSTT CGIGFQVRQR SCSNPTPRHG GRVCVGQNRE ERYCNEHLLC PPHMFWTGWG 

       670        680        690        700        710        720 
PWERCTAQCG GGIQARRRIC ENGPDCAGCN VEYQSCNTNP CPELKKTTPW TPWTPVNISD 

       730        740        750        760        770        780 
NGGHYEQRFR YTCKARLADP NLLEVGRQRI EMRYCSSDGT SGCSTDGLSG DFLRAGRYSA 

       790        800        810        820        830        840 
HTVNGAWSAW TSWSQCSRDC SRGIRNRKRV CNNPEPKYGG MPCLGPSLEY QECNILPCPV 

       850        860        870        880        890        900 
DGVWSCWSPW TKCSATCGGG HYMRTRSCSN PAPAYGGDIC LGLHTEEALC NTQPCPESWS 

       910        920        930        940        950        960 
EWSDWSECEA SGVQVRARQC ILLFPMGSQC SGNTTESRPC VFDSNFIPEV SVARSSSVEE 

       970        980        990       1000       1010       1020 
KRCGEFNMFH MIAVGLSSSI LGCLLTLLVY TYCQRYQQQS HDATVIHPVS PAPLNTSITN 

      1030       1040       1050       1060       1070 
HINKLDKYDS VEAIKAFNKN NLILEERNKY FNPHLTGKTY SNAYFTDLNN YDEY 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and mapping of human semaphorin F from the Cri-du-chat candidate interval."
Simmons A.D., Puschel A.W., McPherson J.D., Overhauser J., Lovett M.
Biochem. Biophys. Res. Commun. 242:685-691(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Plexin-B3 is a functional receptor for semaphorin 5A."
Artigiani S., Conrotto P., Fazzari P., Gilestro G.F., Barberis D., Giordano S., Comoglio P.M., Tamagnone L.
EMBO Rep. 5:710-714(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PLXNB3.
[6]"Semaphorin 5A and plexin-B3 inhibit human glioma cell motility through RhoGDIalpha-mediated inactivation of Rac1 GTPase."
Li X., Lee A.Y.
J. Biol. Chem. 285:32436-32445(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Semaphorin 5A promotes angiogenesis by increasing endothelial cell proliferation, migration, and decreasing apoptosis."
Sadanandam A., Rosenbaugh E.G., Singh S., Varney M., Singh R.K.
Microvasc. Res. 79:1-9(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Semaphorin 5A and plexin-B3 regulate human glioma cell motility and morphology through Rac1 and the actin cytoskeleton."
Li X., Law J.W., Lee A.Y.
Oncogene 31:595-610(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U52840 mRNA. Translation: AAC09473.1.
AC004615 Genomic DNA. Translation: AAC14668.1.
AC022446 Genomic DNA. No translation available.
AC027336 Genomic DNA. No translation available.
AC091906 Genomic DNA. No translation available.
CH471102 Genomic DNA. Translation: EAX08078.1.
CH471102 Genomic DNA. Translation: EAX08079.1.
BC115696 mRNA. Translation: AAI15697.1.
PIRJC5928.
RefSeqNP_003957.2. NM_003966.2.
UniGeneHs.27621.

3D structure databases

ProteinModelPortalQ13591.
SMRQ13591. Positions 68-506, 540-723, 783-967.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114501. 1 interaction.
IntActQ13591. 1 interaction.
STRING9606.ENSP00000371936.

PTM databases

PhosphoSiteQ13591.

Polymorphism databases

DMDM109939725.

Proteomic databases

PaxDbQ13591.
PRIDEQ13591.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000382496; ENSP00000371936; ENSG00000112902.
GeneID9037.
KEGGhsa:9037.
UCSCuc003jek.2. human.

Organism-specific databases

CTD9037.
GeneCardsGC05M009036.
HGNCHGNC:10736. SEMA5A.
HPAHPA004632.
MIM609297. gene.
neXtProtNX_Q13591.
Orphanet281. Monosomy 5p.
PharmGKBPA35658.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG316291.
HOGENOMHOG000047106.
HOVERGENHBG062356.
InParanoidQ13591.
KOK06841.
OMAYSNAYFT.
OrthoDBEOG7SN8C0.
PhylomeDBQ13591.
TreeFamTF329951.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.

Gene expression databases

ArrayExpressQ13591.
BgeeQ13591.
CleanExHS_SEMA5A.
GenevestigatorQ13591.

Family and domain databases

Gene3D2.130.10.10. 1 hit.
InterProIPR016201. Plexin-like_fold.
IPR002165. Plexin_repeat.
IPR001627. Semap_dom.
IPR027231. Semaphorin.
IPR000884. Thrombospondin_1_rpt.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
PANTHERPTHR11036. PTHR11036. 1 hit.
PfamPF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
PF00090. TSP_1. 5 hits.
[Graphical view]
SMARTSM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00209. TSP1. 6 hits.
[Graphical view]
SUPFAMSSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
SSF82895. SSF82895. 6 hits.
PROSITEPS51004. SEMA. 1 hit.
PS50092. TSP1. 6 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSEMA5A.
GenomeRNAi9037.
NextBio33851.
PROQ13591.
SOURCESearch...

Entry information

Entry nameSEM5A_HUMAN
AccessionPrimary (citable) accession number: Q13591
Secondary accession number(s): D3DTC6, O60408, Q1RLL9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2006
Last modified: April 16, 2014
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM