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Protein

Semaphorin-6A

Gene

SEMA6A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation (By similarity).By similarity

GO - Molecular functioni

  1. receptor activity Source: InterPro

GO - Biological processi

  1. apoptotic process Source: UniProtKB
  2. axon guidance Source: UniProtKB
  3. cell surface receptor signaling pathway Source: UniProtKB
  4. cytoskeleton organization Source: UniProtKB
  5. nervous system development Source: UniProtKB
  6. organ morphogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis

Enzyme and pathway databases

ReactomeiREACT_19200. Other semaphorin interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Semaphorin-6A
Alternative name(s):
Semaphorin VIA
Short name:
Sema VIA
Semaphorin-6A-1
Short name:
SEMA6A-1
Gene namesi
Name:SEMA6A
Synonyms:KIAA1368, SEMAQ
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:10738. SEMA6A.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 649631ExtracellularSequence AnalysisAdd
BLAST
Transmembranei650 – 67021HelicalSequence AnalysisAdd
BLAST
Topological domaini671 – 1030360CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. axon Source: UniProtKB
  2. integral component of membrane Source: UniProtKB
  3. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35660.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence AnalysisAdd
BLAST
Chaini19 – 10301012Semaphorin-6APRO_0000032339Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi33 – 331N-linked (GlcNAc...)Sequence Analysis
Glycosylationi49 – 491N-linked (GlcNAc...)Sequence Analysis
Glycosylationi65 – 651N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi107 ↔ 117PROSITE-ProRule annotation
Disulfide bondi135 ↔ 144PROSITE-ProRule annotation
Disulfide bondi258 ↔ 369PROSITE-ProRule annotation
Glycosylationi282 – 2821N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi283 ↔ 328PROSITE-ProRule annotation
Glycosylationi434 – 4341N-linked (GlcNAc...)Sequence Analysis
Glycosylationi461 – 4611N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi477 ↔ 506PROSITE-ProRule annotation
Disulfide bondi515 ↔ 533PROSITE-ProRule annotation
Disulfide bondi521 ↔ 568PROSITE-ProRule annotation
Disulfide bondi525 ↔ 542PROSITE-ProRule annotation
Modified residuei698 – 6981Phosphoserine1 Publication
Modified residuei952 – 9521Phosphoserine1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ9H2E6.
PaxDbiQ9H2E6.
PRIDEiQ9H2E6.

PTM databases

PhosphoSiteiQ9H2E6.

Expressioni

Gene expression databases

BgeeiQ9H2E6.
CleanExiHS_SEMA6A.
ExpressionAtlasiQ9H2E6. baseline and differential.
GenevestigatoriQ9H2E6.

Organism-specific databases

HPAiHPA031265.

Interactioni

Subunit structurei

Active as a homodimer or oligomer. The SEMA6A homodimer interacts with a PLXNA2 homodimer, giving rise to a heterotetramer (By similarity). Interacts with EVL.By similarity1 Publication

Protein-protein interaction databases

BioGridi121612. 9 interactions.
IntActiQ9H2E6. 5 interactions.
STRINGi9606.ENSP00000345512.

Structurei

3D structure databases

SMRiQ9H2E6. Positions 20-568.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 512489SemaPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi792 – 81928Pro-richAdd
BLAST

Sequence similaritiesi

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG293968.
HOGENOMiHOG000232047.
HOVERGENiHBG072910.
InParanoidiQ9H2E6.
KOiK06842.
OMAiLMHNGKL.
OrthoDBiEOG7SV0TJ.
PhylomeDBiQ9H2E6.
TreeFamiTF316102.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR016201. Plexin-like_fold.
IPR002165. Plexin_repeat.
IPR001627. Semap_dom.
IPR027231. Semaphorin.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
PANTHERiPTHR11036. PTHR11036. 1 hit.
PfamiPF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
[Graphical view]
SMARTiSM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
[Graphical view]
SUPFAMiSSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
PROSITEiPS51004. SEMA. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H2E6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRSEALLLYF TLLHFAGAGF PEDSEPISIS HGNYTKQYPV FVGHKPGRNT
60 70 80 90 100
TQRHRLDIQM IMIMNGTLYI AARDHIYTVD IDTSHTEEIY CSKKLTWKSR
110 120 130 140 150
QADVDTCRMK GKHKDECHNF IKVLLKKNDD ALFVCGTNAF NPSCRNYKMD
160 170 180 190 200
TLEPFGDEFS GMARCPYDAK HANVALFADG KLYSATVTDF LAIDAVIYRS
210 220 230 240 250
LGESPTLRTV KHDSKWLKEP YFVQAVDYGD YIYFFFREIA VEYNTMGKVV
260 270 280 290 300
FPRVAQVCKN DMGGSQRVLE KQWTSFLKAR LNCSVPGDSH FYFNILQAVT
310 320 330 340 350
DVIRINGRDV VLATFSTPYN SIPGSAVCAY DMLDIASVFT GRFKEQKSPD
360 370 380 390 400
STWTPVPDER VPKPRPGCCA GSSSLERYAT SNEFPDDTLN FIKTHPLMDE
410 420 430 440 450
AVPSIFNRPW FLRTMVRYRL TKIAVDTAAG PYQNHTVVFL GSEKGIILKF
460 470 480 490 500
LARIGNSGFL NDSLFLEEMS VYNSEKCSYD GVEDKRIMGM QLDRASSSLY
510 520 530 540 550
VAFSTCVIKV PLGRCERYGK CKKTCIASRD PYCGWIKEGG ACSHLSPNSR
560 570 580 590 600
LTFEQDIERG NTDGLGDCHN SFVALNGHSS SLLPSTTTSD STAQEGYESR
610 620 630 640 650
GGMLDWKHLL DSPDSTDPLG AVSSHNHQDK KGVIRESYLK GHDQLVPVTL
660 670 680 690 700
LAIAVILAFV MGAVFSGITV YCVCDHRRKD VAVVQRKEKE LTHSRRGSMS
710 720 730 740 750
SVTKLSGLFG DTQSKDPKPE AILTPLMHNG KLATPGNTAK MLIKADQHHL
760 770 780 790 800
DLTALPTPES TPTLQQKRKP SRGSREWERN QNLINACTKD MPPMGSPVIP
810 820 830 840 850
TDLPLRASPS HIPSVVVLPI TQQGYQHEYV DQPKMSEVAQ MALEDQAATL
860 870 880 890 900
EYKTIKEHLS SKSPNHGVNL VENLDSLPPK VPQREASLGP PGASLSQTGL
910 920 930 940 950
SKRLEMHHSS SYGVDYKRSY PTNSLTRSHQ ATTLKRNNTN SSNSSHLSRN
960 970 980 990 1000
QSFGRGDNPP PAPQRVDSIQ VHSSQPSGQA VTVSRQPSLN AYNSLTRSGL
1010 1020 1030
KRTPSLKPDV PPKPSFAPLS TSMKPNDACT
Length:1,030
Mass (Da):114,395
Last modified:May 17, 2010 - v2
Checksum:iA1D5C9710AEC4B34
GO
Isoform 2 (identifier: Q9H2E6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     576-576: N → NDISTPLPDNEMSYNTVY

Note: No experimental confirmation available.

Show »
Length:1,047
Mass (Da):116,336
Checksum:i76D04113274B9EED
GO

Sequence cautioni

The sequence BAA92606.1 differs from that shown. Reason: Erroneous initiation. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti518 – 5181Y → H.2 Publications
Corresponds to variant rs34966 [ dbSNP | Ensembl ].
VAR_030296
Natural varianti559 – 5591R → H.
Corresponds to variant rs17432496 [ dbSNP | Ensembl ].
VAR_030297
Natural varianti567 – 5671D → E.
Corresponds to variant rs12516652 [ dbSNP | Ensembl ].
VAR_030298

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei576 – 5761N → NDISTPLPDNEMSYNTVY in isoform 2. CuratedVSP_007113

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF279656 mRNA. Translation: AAG29378.1.
AB037789 mRNA. Translation: BAA92606.1. Different initiation.
AC008524 Genomic DNA. No translation available.
AC010296 Genomic DNA. No translation available.
AC027304 Genomic DNA. No translation available.
CCDSiCCDS47256.1. [Q9H2E6-1]
CCDS75288.1. [Q9H2E6-2]
RefSeqiNP_001287709.1. NM_001300780.1.
NP_065847.1. NM_020796.4.
UniGeneiHs.156967.

Genome annotation databases

EnsembliENST00000343348; ENSP00000345512; ENSG00000092421.
ENST00000510263; ENSP00000424388; ENSG00000092421.
GeneIDi57556.
KEGGihsa:57556.
UCSCiuc003krx.4. human. [Q9H2E6-2]
uc010jcj.3. human. [Q9H2E6-1]

Polymorphism databases

DMDMi296452903.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF279656 mRNA. Translation: AAG29378.1.
AB037789 mRNA. Translation: BAA92606.1. Different initiation.
AC008524 Genomic DNA. No translation available.
AC010296 Genomic DNA. No translation available.
AC027304 Genomic DNA. No translation available.
CCDSiCCDS47256.1. [Q9H2E6-1]
CCDS75288.1. [Q9H2E6-2]
RefSeqiNP_001287709.1. NM_001300780.1.
NP_065847.1. NM_020796.4.
UniGeneiHs.156967.

3D structure databases

SMRiQ9H2E6. Positions 20-568.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121612. 9 interactions.
IntActiQ9H2E6. 5 interactions.
STRINGi9606.ENSP00000345512.

PTM databases

PhosphoSiteiQ9H2E6.

Polymorphism databases

DMDMi296452903.

Proteomic databases

MaxQBiQ9H2E6.
PaxDbiQ9H2E6.
PRIDEiQ9H2E6.

Protocols and materials databases

DNASUi57556.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000343348; ENSP00000345512; ENSG00000092421.
ENST00000510263; ENSP00000424388; ENSG00000092421.
GeneIDi57556.
KEGGihsa:57556.
UCSCiuc003krx.4. human. [Q9H2E6-2]
uc010jcj.3. human. [Q9H2E6-1]

Organism-specific databases

CTDi57556.
GeneCardsiGC05M115807.
H-InvDBHIX0120999.
HIX0164350.
HGNCiHGNC:10738. SEMA6A.
HPAiHPA031265.
MIMi605885. gene.
neXtProtiNX_Q9H2E6.
PharmGKBiPA35660.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG293968.
HOGENOMiHOG000232047.
HOVERGENiHBG072910.
InParanoidiQ9H2E6.
KOiK06842.
OMAiLMHNGKL.
OrthoDBiEOG7SV0TJ.
PhylomeDBiQ9H2E6.
TreeFamiTF316102.

Enzyme and pathway databases

ReactomeiREACT_19200. Other semaphorin interactions.

Miscellaneous databases

ChiTaRSiSEMA6A. human.
GeneWikiiSEMA6A.
GenomeRNAii57556.
NextBioi64038.
PROiQ9H2E6.
SOURCEiSearch...

Gene expression databases

BgeeiQ9H2E6.
CleanExiHS_SEMA6A.
ExpressionAtlasiQ9H2E6. baseline and differential.
GenevestigatoriQ9H2E6.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR016201. Plexin-like_fold.
IPR002165. Plexin_repeat.
IPR001627. Semap_dom.
IPR027231. Semaphorin.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
PANTHERiPTHR11036. PTHR11036. 1 hit.
PfamiPF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
[Graphical view]
SMARTiSM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
[Graphical view]
SUPFAMiSSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
PROSITEiPS51004. SEMA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The orthologous human and murine semaphorin 6A-1 proteins (SEMA6A-1/Sema6A-1) bind to the enabled/vasodilator-stimulated phosphoprotein-like protein (EVL) via a novel carboxyl-terminal zyxin-like domain."
    Klostermann A., Lutz B., Gertler F., Behl C.
    J. Biol. Chem. 275:39647-39653(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH EVL, VARIANT HIS-518.
  2. "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro."
    Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
    DNA Res. 7:65-73(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT HIS-518.
    Tissue: Brain.
  3. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-698 AND SER-952, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiSEM6A_HUMAN
AccessioniPrimary (citable) accession number: Q9H2E6
Secondary accession number(s): Q9P2H9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 10, 2003
Last sequence update: May 17, 2010
Last modified: March 31, 2015
This is version 121 of the entry and version 2 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.