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Q13591

- SEM5A_HUMAN

UniProt

Q13591 - SEM5A_HUMAN

Protein

Semaphorin-5A

Gene

SEMA5A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 3 (30 May 2006)
      Previous versions | rss
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    Functioni

    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.By similarity4 Publications

    GO - Molecular functioni

    1. axon guidance receptor activity Source: Ensembl
    2. chondroitin sulfate proteoglycan binding Source: UniProtKB
    3. heparan sulfate proteoglycan binding Source: UniProtKB
    4. semaphorin receptor binding Source: UniProtKB
    5. syndecan binding Source: UniProtKB

    GO - Biological processi

    1. axonal fasciculation Source: UniProtKB
    2. axon guidance Source: Reactome
    3. blood vessel endothelial cell proliferation involved in sprouting angiogenesis Source: UniProtKB
    4. cell adhesion Source: ProtInc
    5. cell-cell signaling Source: ProtInc
    6. cell chemotaxis Source: UniProtKB
    7. diencephalon development Source: UniProtKB
    8. negative regulation of axon extension involved in axon guidance Source: UniProtKB
    9. negative regulation of cell adhesion Source: UniProtKB
    10. negative regulation of endothelial cell apoptotic process Source: UniProtKB
    11. nervous system development Source: ProtInc
    12. patterning of blood vessels Source: Ensembl
    13. positive chemotaxis Source: UniProtKB
    14. positive regulation of actin filament depolymerization Source: UniProtKB
    15. positive regulation of angiogenesis Source: UniProtKB
    16. positive regulation of axon extension involved in axon guidance Source: UniProtKB
    17. positive regulation of catenin import into nucleus Source: UniProtKB
    18. positive regulation of endothelial cell chemotaxis Source: UniProtKB
    19. positive regulation of endothelial cell proliferation Source: UniProtKB
    20. positive regulation of protein kinase B signaling Source: UniProtKB
    21. signal clustering Source: UniProtKB

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Biological processi

    Differentiation, Neurogenesis

    Enzyme and pathway databases

    ReactomeiREACT_19200. Other semaphorin interactions.
    REACT_200626. O-glycosylation of TSR domain-containing proteins.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Semaphorin-5A
    Alternative name(s):
    Semaphorin-F
    Short name:
    Sema F
    Gene namesi
    Name:SEMA5A
    Synonyms:SEMAF
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:10736. SEMA5A.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular vesicular exosome Source: UniProt
    2. integral component of membrane Source: UniProtKB-KW
    3. membrane Source: UniProtKB
    4. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    Orphaneti281. Monosomy 5p.
    PharmGKBiPA35658.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2222Sequence AnalysisAdd
    BLAST
    Chaini23 – 10741052Semaphorin-5APRO_0000032335Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi104 ↔ 114By similarity
    Disulfide bondi131 ↔ 140By similarity
    Glycosylationi142 – 1421N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi168 – 1681N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi227 – 2271N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi254 ↔ 357By similarity
    Glycosylationi277 – 2771N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi278 ↔ 320By similarity
    Glycosylationi323 – 3231N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi367 – 3671N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi437 – 4371N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi487 ↔ 504By similarity
    Disulfide bondi496 ↔ 513By similarity
    Glycosylationi536 – 5361N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi591 – 5911N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi607 ↔ 644By similarity
    Disulfide bondi611 ↔ 650By similarity
    Disulfide bondi622 ↔ 634By similarity
    Disulfide bondi665 ↔ 696By similarity
    Disulfide bondi669 ↔ 701By similarity
    Disulfide bondi680 ↔ 686By similarity
    Glycosylationi717 – 7171N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi796 ↔ 833By similarity
    Disulfide bondi800 ↔ 838By similarity
    Disulfide bondi811 ↔ 823By similarity
    Disulfide bondi853 ↔ 890By similarity
    Disulfide bondi857 ↔ 895By similarity
    Disulfide bondi868 ↔ 880By similarity
    Glycosylationi933 – 9331N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ13591.
    PRIDEiQ13591.

    PTM databases

    PhosphoSiteiQ13591.

    Expressioni

    Gene expression databases

    ArrayExpressiQ13591.
    BgeeiQ13591.
    CleanExiHS_SEMA5A.
    GenevestigatoriQ13591.

    Organism-specific databases

    HPAiHPA004632.

    Interactioni

    Subunit structurei

    Binds PLXNB3.

    Protein-protein interaction databases

    BioGridi114501. 1 interaction.
    IntActiQ13591. 1 interaction.
    STRINGi9606.ENSP00000371936.

    Structurei

    3D structure databases

    ProteinModelPortaliQ13591.
    SMRiQ13591. Positions 68-506, 540-647, 656-723, 783-838, 840-940.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini23 – 968946ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini990 – 107485CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei969 – 98921HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini35 – 484450SemaPROSITE-ProRule annotationAdd
    BLAST
    Domaini540 – 59354TSP type-1 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini595 – 65157TSP type-1 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini653 – 70250TSP type-1 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini707 – 76559TSP type-1 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini784 – 83956TSP type-1 5PROSITE-ProRule annotationAdd
    BLAST
    Domaini841 – 89656TSP type-1 6PROSITE-ProRule annotationAdd
    BLAST
    Domaini897 – 94448TSP type-1 7PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the semaphorin family.Curated
    Contains 1 PSI domain.Curated
    Contains 1 Sema domain.PROSITE-ProRule annotation
    Contains 7 TSP type-1 domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG316291.
    HOGENOMiHOG000047106.
    HOVERGENiHBG062356.
    InParanoidiQ13591.
    KOiK06841.
    OMAiYSNAYFT.
    OrthoDBiEOG7SN8C0.
    PhylomeDBiQ13591.
    TreeFamiTF329951.

    Family and domain databases

    Gene3Di2.130.10.10. 1 hit.
    InterProiIPR016201. Plexin-like_fold.
    IPR002165. Plexin_repeat.
    IPR001627. Semap_dom.
    IPR027231. Semaphorin.
    IPR000884. Thrombospondin_1_rpt.
    IPR015943. WD40/YVTN_repeat-like_dom.
    [Graphical view]
    PANTHERiPTHR11036. PTHR11036. 1 hit.
    PfamiPF01437. PSI. 1 hit.
    PF01403. Sema. 1 hit.
    PF00090. TSP_1. 5 hits.
    [Graphical view]
    SMARTiSM00423. PSI. 1 hit.
    SM00630. Sema. 1 hit.
    SM00209. TSP1. 6 hits.
    [Graphical view]
    SUPFAMiSSF101912. SSF101912. 1 hit.
    SSF103575. SSF103575. 1 hit.
    SSF82895. SSF82895. 6 hits.
    PROSITEiPS51004. SEMA. 1 hit.
    PS50092. TSP1. 6 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q13591-1 [UniParc]FASTAAdd to Basket

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    MKGTCVIAWL FSSLGLWRLA HPEAQGTTQC QRTEHPVISY KEIGPWLREF     50
    RAKNAVDFSQ LTFDPGQKEL VVGARNYLFR LQLEDLSLIQ AVEWECDEAT 100
    KKACYSKGKS KEECQNYIRV LLVGGDRLFT CGTNAFTPVC TNRSLSNLTE 150
    IHDQISGMAR CPYSPQHNST ALLTAGGELY AATAMDFPGR DPAIYRSLGI 200
    LPPLRTAQYN SKWLNEPNFV SSYDIGNFTY FFFRENAVEH DCGKTVFSRA 250
    ARVCKNDIGG RFLLEDTWTT FMKARLNCSR PGEVPFYYNE LQSTFFLPEL 300
    DLIYGIFTTN VNSIAASAVC VFNLSAIAQA FSGPFKYQEN SRSAWLPYPN 350
    PNPHFQCGTV DQGLYVNLTE RNLQDAQKFI LMHEVVQPVT TVPSFMEDNS 400
    RFSHVAVDVV QGREALVHII YLATDYGTIK KVRVPLNQTS SSCLLEEIEL 450
    FPERRREPIR SLQILHSQSV LFVGLREHVV KIPLKRCQFY RTRSTCIGAQ 500
    DPYCGWDVVM KKCTSLEESL SMTQWEQSIS ACPTRNLTVD GHFGVWSPWT 550
    PCTHTDGSAV GSCLCRTRSC DSPAPQCGGW QCEGPGMEIA NCSRNGGWTP 600
    WTSWSPCSTT CGIGFQVRQR SCSNPTPRHG GRVCVGQNRE ERYCNEHLLC 650
    PPHMFWTGWG PWERCTAQCG GGIQARRRIC ENGPDCAGCN VEYQSCNTNP 700
    CPELKKTTPW TPWTPVNISD NGGHYEQRFR YTCKARLADP NLLEVGRQRI 750
    EMRYCSSDGT SGCSTDGLSG DFLRAGRYSA HTVNGAWSAW TSWSQCSRDC 800
    SRGIRNRKRV CNNPEPKYGG MPCLGPSLEY QECNILPCPV DGVWSCWSPW 850
    TKCSATCGGG HYMRTRSCSN PAPAYGGDIC LGLHTEEALC NTQPCPESWS 900
    EWSDWSECEA SGVQVRARQC ILLFPMGSQC SGNTTESRPC VFDSNFIPEV 950
    SVARSSSVEE KRCGEFNMFH MIAVGLSSSI LGCLLTLLVY TYCQRYQQQS 1000
    HDATVIHPVS PAPLNTSITN HINKLDKYDS VEAIKAFNKN NLILEERNKY 1050
    FNPHLTGKTY SNAYFTDLNN YDEY 1074
    Length:1,074
    Mass (Da):120,615
    Last modified:May 30, 2006 - v3
    Checksum:iAE073413AC974CCC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti56 – 561V → A in AAC09473. (PubMed:9464278)Curated
    Sequence conflicti149 – 1491T → A in AAC09473. (PubMed:9464278)Curated
    Sequence conflicti382 – 3821M → V in AAC09473. (PubMed:9464278)Curated
    Sequence conflicti494 – 4941S → R in AAC14668. (PubMed:15372022)Curated
    Sequence conflicti723 – 7231G → D in AAC09473. (PubMed:9464278)Curated
    Sequence conflicti835 – 8351I → T in AAC09473. (PubMed:9464278)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti246 – 2461V → L.
    Corresponds to variant rs1806079 [ dbSNP | Ensembl ].
    VAR_030294
    Natural varianti792 – 7921S → L.
    Corresponds to variant rs2290734 [ dbSNP | Ensembl ].
    VAR_030295

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS3875.1.
    PIRiJC5928.
    RefSeqiNP_003957.2. NM_003966.2.
    XP_006714569.1. XM_006714506.1.
    XP_006714570.1. XM_006714507.1.
    UniGeneiHs.27621.

    Genome annotation databases

    EnsembliENST00000382496; ENSP00000371936; ENSG00000112902.
    GeneIDi9037.
    KEGGihsa:9037.
    UCSCiuc003jek.2. human.

    Polymorphism databases

    DMDMi109939725.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS3875.1.
    PIRi JC5928.
    RefSeqi NP_003957.2. NM_003966.2.
    XP_006714569.1. XM_006714506.1.
    XP_006714570.1. XM_006714507.1.
    UniGenei Hs.27621.

    3D structure databases

    ProteinModelPortali Q13591.
    SMRi Q13591. Positions 68-506, 540-647, 656-723, 783-838, 840-940.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114501. 1 interaction.
    IntActi Q13591. 1 interaction.
    STRINGi 9606.ENSP00000371936.

    PTM databases

    PhosphoSitei Q13591.

    Polymorphism databases

    DMDMi 109939725.

    Proteomic databases

    PaxDbi Q13591.
    PRIDEi Q13591.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000382496 ; ENSP00000371936 ; ENSG00000112902 .
    GeneIDi 9037.
    KEGGi hsa:9037.
    UCSCi uc003jek.2. human.

    Organism-specific databases

    CTDi 9037.
    GeneCardsi GC05M009036.
    HGNCi HGNC:10736. SEMA5A.
    HPAi HPA004632.
    MIMi 609297. gene.
    neXtProti NX_Q13591.
    Orphaneti 281. Monosomy 5p.
    PharmGKBi PA35658.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG316291.
    HOGENOMi HOG000047106.
    HOVERGENi HBG062356.
    InParanoidi Q13591.
    KOi K06841.
    OMAi YSNAYFT.
    OrthoDBi EOG7SN8C0.
    PhylomeDBi Q13591.
    TreeFami TF329951.

    Enzyme and pathway databases

    Reactomei REACT_19200. Other semaphorin interactions.
    REACT_200626. O-glycosylation of TSR domain-containing proteins.

    Miscellaneous databases

    GeneWikii SEMA5A.
    GenomeRNAii 9037.
    NextBioi 33851.
    PROi Q13591.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q13591.
    Bgeei Q13591.
    CleanExi HS_SEMA5A.
    Genevestigatori Q13591.

    Family and domain databases

    Gene3Di 2.130.10.10. 1 hit.
    InterProi IPR016201. Plexin-like_fold.
    IPR002165. Plexin_repeat.
    IPR001627. Semap_dom.
    IPR027231. Semaphorin.
    IPR000884. Thrombospondin_1_rpt.
    IPR015943. WD40/YVTN_repeat-like_dom.
    [Graphical view ]
    PANTHERi PTHR11036. PTHR11036. 1 hit.
    Pfami PF01437. PSI. 1 hit.
    PF01403. Sema. 1 hit.
    PF00090. TSP_1. 5 hits.
    [Graphical view ]
    SMARTi SM00423. PSI. 1 hit.
    SM00630. Sema. 1 hit.
    SM00209. TSP1. 6 hits.
    [Graphical view ]
    SUPFAMi SSF101912. SSF101912. 1 hit.
    SSF103575. SSF103575. 1 hit.
    SSF82895. SSF82895. 6 hits.
    PROSITEi PS51004. SEMA. 1 hit.
    PS50092. TSP1. 6 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. 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.

    Entry informationi

    Entry nameiSEM5A_HUMAN
    AccessioniPrimary (citable) accession number: Q13591
    Secondary accession number(s): D3DTC6, O60408, Q1RLL9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: May 30, 2006
    Last modified: October 1, 2014
    This is version 139 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3