Q9H2E6 (SEM6A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Semaphorin-6A

Alternative name(s):
Semaphorin VIA
Short name=Sema VIA
Semaphorin-6A-1
Short name=SEMA6A-1

Gene names

Name:	SEMA6A
Synonyms:	KIAA1368, SEMAQ

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1030 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	Active as a homodimer or oligomer. The SEMA6A homodimer interacts with a PLXNA2 homodimer, giving rise to a heterotetramer By similarity. Interacts with EVL. Ref.1
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Sequence similarities	Belongs to the semaphorin family. Contains 1 PSI domain. Contains 1 Sema domain.
Sequence caution	The sequence BAA92606.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Non-traceable author statement Ref.1. Source: UniProtKB axon guidance Non-traceable author statement Ref.1. Source: UniProtKB cell surface receptor signaling pathway Non-traceable author statement Ref.1. Source: UniProtKB centrosome localization Inferred from electronic annotation. Source: Compara cytoskeleton organization Non-traceable author statement Ref.1. Source: UniProtKB neuron migration Inferred from electronic annotation. Source: Compara organ morphogenesis Non-traceable author statement Ref.1. Source: UniProtKB positive regulation of neuron migration Inferred from electronic annotation. Source: Compara semaphorin-plexin signaling pathway Inferred from electronic annotation. Source: Compara
Cellular_component	axon Non-traceable author statement Ref.1. Source: UniProtKB integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB integral to plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	transmembrane signaling receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9H2E6-1)

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.

Isoform 2 (identifier: Q9H2E6-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 1030	1012	Semaphorin-6A		PRO_0000032339
Regions
	Topological domain	19 – 649	631	Extracellular Potential
	Transmembrane	650 – 670	21	Helical; Potential
	Topological domain	671 – 1030	360	Cytoplasmic Potential
	Domain	24 – 512	489	Sema
	Compositional bias	792 – 819	28	Pro-rich
Amino acid modifications
	Modified residue	698	1	Phosphoserine Ref.4
	Modified residue	952	1	Phosphoserine Ref.4
	Modified residue	988	1	Phosphoserine Ref.4
	Glycosylation	33	1	N-linked (GlcNAc...) Potential
	Glycosylation	49	1	N-linked (GlcNAc...) Potential
	Glycosylation	65	1	N-linked (GlcNAc...) Potential
	Glycosylation	282	1	N-linked (GlcNAc...) Potential
	Glycosylation	434	1	N-linked (GlcNAc...) Potential
	Glycosylation	461	1	N-linked (GlcNAc...) Potential
	Disulfide bond	107 ↔ 117		By similarity
	Disulfide bond	135 ↔ 144		By similarity
	Disulfide bond	258 ↔ 369		By similarity
	Disulfide bond	283 ↔ 328		By similarity
	Disulfide bond	477 ↔ 506		By similarity
	Disulfide bond	515 ↔ 533		By similarity
	Disulfide bond	521 ↔ 568		By similarity
	Disulfide bond	525 ↔ 542		By similarity
Natural variations
	Alternative sequence	576	1	N → NDISTPLPDNEMSYNTVY in isoform 2.		VSP_007113
	Natural variant	518	1	Y → H. Ref.1 Ref.2 Corresponds to variant rs34966 [ dbSNP | Ensembl ].		VAR_030296
	Natural variant	559	1	R → H. Corresponds to variant rs17432496 [ dbSNP | Ensembl ].		VAR_030297
	Natural variant	567	1	D → E. Corresponds to variant rs12516652 [ dbSNP | Ensembl ].		VAR_030298

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: A1D5C9710AEC4B34	FASTA	1,030	114,395
	10 20 30 40 50 60 MRSEALLLYF TLLHFAGAGF PEDSEPISIS HGNYTKQYPV FVGHKPGRNT TQRHRLDIQM 70 80 90 100 110 120 IMIMNGTLYI AARDHIYTVD IDTSHTEEIY CSKKLTWKSR QADVDTCRMK GKHKDECHNF 130 140 150 160 170 180 IKVLLKKNDD ALFVCGTNAF NPSCRNYKMD TLEPFGDEFS GMARCPYDAK HANVALFADG 190 200 210 220 230 240 KLYSATVTDF LAIDAVIYRS LGESPTLRTV KHDSKWLKEP YFVQAVDYGD YIYFFFREIA 250 260 270 280 290 300 VEYNTMGKVV FPRVAQVCKN DMGGSQRVLE KQWTSFLKAR LNCSVPGDSH FYFNILQAVT 310 320 330 340 350 360 DVIRINGRDV VLATFSTPYN SIPGSAVCAY DMLDIASVFT GRFKEQKSPD STWTPVPDER 370 380 390 400 410 420 VPKPRPGCCA GSSSLERYAT SNEFPDDTLN FIKTHPLMDE AVPSIFNRPW FLRTMVRYRL 430 440 450 460 470 480 TKIAVDTAAG PYQNHTVVFL GSEKGIILKF LARIGNSGFL NDSLFLEEMS VYNSEKCSYD 490 500 510 520 530 540 GVEDKRIMGM QLDRASSSLY VAFSTCVIKV PLGRCERYGK CKKTCIASRD PYCGWIKEGG 550 560 570 580 590 600 ACSHLSPNSR LTFEQDIERG NTDGLGDCHN SFVALNGHSS SLLPSTTTSD STAQEGYESR 610 620 630 640 650 660 GGMLDWKHLL DSPDSTDPLG AVSSHNHQDK KGVIRESYLK GHDQLVPVTL LAIAVILAFV 670 680 690 700 710 720 MGAVFSGITV YCVCDHRRKD VAVVQRKEKE LTHSRRGSMS SVTKLSGLFG DTQSKDPKPE 730 740 750 760 770 780 AILTPLMHNG KLATPGNTAK MLIKADQHHL DLTALPTPES TPTLQQKRKP SRGSREWERN 790 800 810 820 830 840 QNLINACTKD MPPMGSPVIP TDLPLRASPS HIPSVVVLPI TQQGYQHEYV DQPKMSEVAQ 850 860 870 880 890 900 MALEDQAATL EYKTIKEHLS SKSPNHGVNL VENLDSLPPK VPQREASLGP PGASLSQTGL 910 920 930 940 950 960 SKRLEMHHSS SYGVDYKRSY PTNSLTRSHQ ATTLKRNNTN SSNSSHLSRN QSFGRGDNPP 970 980 990 1000 1010 1020 PAPQRVDSIQ VHSSQPSGQA VTVSRQPSLN AYNSLTRSGL KRTPSLKPDV PPKPSFAPLS 1030 TSMKPNDACT
	Isoform 2 [UniParc]. Checksum: 76D04113274B9EED	FASTA	1,047	116,336
	10 20 30 40 50 60 MRSEALLLYF TLLHFAGAGF PEDSEPISIS HGNYTKQYPV FVGHKPGRNT TQRHRLDIQM 70 80 90 100 110 120 IMIMNGTLYI AARDHIYTVD IDTSHTEEIY CSKKLTWKSR QADVDTCRMK GKHKDECHNF 130 140 150 160 170 180 IKVLLKKNDD ALFVCGTNAF NPSCRNYKMD TLEPFGDEFS GMARCPYDAK HANVALFADG 190 200 210 220 230 240 KLYSATVTDF LAIDAVIYRS LGESPTLRTV KHDSKWLKEP YFVQAVDYGD YIYFFFREIA 250 260 270 280 290 300 VEYNTMGKVV FPRVAQVCKN DMGGSQRVLE KQWTSFLKAR LNCSVPGDSH FYFNILQAVT 310 320 330 340 350 360 DVIRINGRDV VLATFSTPYN SIPGSAVCAY DMLDIASVFT GRFKEQKSPD STWTPVPDER 370 380 390 400 410 420 VPKPRPGCCA GSSSLERYAT SNEFPDDTLN FIKTHPLMDE AVPSIFNRPW FLRTMVRYRL 430 440 450 460 470 480 TKIAVDTAAG PYQNHTVVFL GSEKGIILKF LARIGNSGFL NDSLFLEEMS VYNSEKCSYD 490 500 510 520 530 540 GVEDKRIMGM QLDRASSSLY VAFSTCVIKV PLGRCERYGK CKKTCIASRD PYCGWIKEGG 550 560 570 580 590 600 ACSHLSPNSR LTFEQDIERG NTDGLGDCHN SFVALNDIST PLPDNEMSYN TVYGHSSSLL 610 620 630 640 650 660 PSTTTSDSTA QEGYESRGGM LDWKHLLDSP DSTDPLGAVS SHNHQDKKGV IRESYLKGHD 670 680 690 700 710 720 QLVPVTLLAI AVILAFVMGA VFSGITVYCV CDHRRKDVAV VQRKEKELTH SRRGSMSSVT 730 740 750 760 770 780 KLSGLFGDTQ SKDPKPEAIL TPLMHNGKLA TPGNTAKMLI KADQHHLDLT ALPTPESTPT 790 800 810 820 830 840 LQQKRKPSRG SREWERNQNL INACTKDMPP MGSPVIPTDL PLRASPSHIP SVVVLPITQQ 850 860 870 880 890 900 GYQHEYVDQP KMSEVAQMAL EDQAATLEYK TIKEHLSSKS PNHGVNLVEN LDSLPPKVPQ 910 920 930 940 950 960 REASLGPPGA SLSQTGLSKR LEMHHSSSYG VDYKRSYPTN SLTRSHQATT LKRNNTNSSN 970 980 990 1000 1010 1020 SSHLSRNQSF GRGDNPPPAP QRVDSIQVHS SQPSGQAVTV SRQPSLNAYN SLTRSGLKRT 1030 1040 PSLKPDVPPK PSFAPLSTSM KPNDACT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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(2000) [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(2000) [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(2004) [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(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-698; SER-952 AND SER-988, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00002211. IPI00240598.
RefSeq	NP_065847.1. NM_020796.3.
UniGene	Hs.156967.
3D structure databases
ProteinModelPortal	Q9H2E6.
SMR	Q9H2E6. Positions 20-568.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H2E6. 5 interactions.
STRING	9606.ENSP00000345512.
PTM databases
PhosphoSite	Q9H2E6.
Polymorphism databases
DMDM	296452903.
Proteomic databases
PaxDb	Q9H2E6.
PRIDE	Q9H2E6.
Protocols and materials databases
DNASU	57556.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257414; ENSP00000257414; ENSG00000092421. ENST00000343348; ENSP00000345512; ENSG00000092421. ENST00000510263; ENSP00000424388; ENSG00000092421.
GeneID	57556.
KEGG	hsa:57556.
UCSC	uc003krx.4. human. uc010jcj.3. human.
Organism-specific databases
CTD	57556.
GeneCards	GC05M115807.
H-InvDB	HIX0120999. HIX0164350.
HGNC	HGNC:10738. SEMA6A.
HPA	HPA031265.
MIM	605885. gene.
neXtProt	NX_Q9H2E6.
PharmGKB	PA35660.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG293968.
HOGENOM	HOG000232047.
HOVERGEN	HBG072910.
KO	K06842.
OMA	DQPKMSE.
OrthoDB	EOG46WZ7N.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
ArrayExpress	Q9H2E6.
Bgee	Q9H2E6.
CleanEx	HS_SEMA6A.
Genevestigator	Q9H2E6.
GermOnline	ENSG00000092421. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.10. 1 hit.
InterPro	IPR003659. Plexin-like. IPR016201. Plexin-like_fold. IPR002165. Plexin_repeat. IPR027231. Semaphorin. IPR001627. Semaphorin/CD100_Ag. IPR015943. WD40/YVTN_repeat-like_dom. [Graphical view]
PANTHER	PTHR11036. PTHR11036. 1 hit.
Pfam	PF01437. PSI. 1 hit. PF01403. Sema. 1 hit. [Graphical view]
SMART	SM00423. PSI. 1 hit. SM00630. Sema. 1 hit. [Graphical view]
SUPFAM	SSF103575. Plexin-like_fold. 1 hit. SSF101912. Sema. 1 hit.
PROSITE	PS51004. SEMA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SEMA6A. human.
GenomeRNAi	57556.
NextBio	64038.
SOURCE	Search...

Entry information

Entry name

SEM6A_HUMAN

Accession

Primary (citable) accession number: Q9H2E6
Secondary accession number(s): Q9P2H9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 11, 2003
Last sequence update:	May 18, 2010
Last modified:	April 3, 2013
This is version 104 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.