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Protein

Semaphorin-4A

Gene

SEMA4A

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

Functioni

Cell surface receptor for PLXNB1, PLXNB2, PLXNB3 and PLXND1 that plays an important role in cell-cell signaling. Plays a role in priming antigen-specific T-cells, promotes differentiation of Th1 T-helper cells, and thereby contributes to adaptive immunity. Promotes phosphorylation of TIMD2. Inhibits angiogenesis. Promotes axon growth cone collapse. Inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons (By similarity).By similarity

Caution

Variant Gln-713 was originally reported as mutation causing retinitis pigmentosa (PubMed:16199541). Subsequently, it has been shown to be a likely benign variant (PubMed:22956603, PubMed:28805479).3 Publications

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processAdaptive immunity, Angiogenesis, Differentiation, Immunity, Neurogenesis

Enzyme and pathway databases

ReactomeiR-HSA-416700 Other semaphorin interactions

Names & Taxonomyi

Protein namesi
Recommended name:
Semaphorin-4A
Alternative name(s):
Semaphorin-B
Short name:
Sema B
Gene namesi
Name:SEMA4A
Synonyms:SEMAB, SEMB
ORF Names:UNQ783/PRO1317
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000196189.12
HGNCiHGNC:10729 SEMA4A
MIMi607292 gene
neXtProtiNX_Q9H3S1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini33 – 683ExtracellularSequence analysisAdd BLAST651
Transmembranei684 – 704HelicalSequence analysisAdd BLAST21
Topological domaini705 – 761CytoplasmicSequence analysisAdd BLAST57

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Retinitis pigmentosa 35 (RP35)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
See also OMIM:610282
Cone-rod dystrophy 10 (CORD10)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors.
See also OMIM:610283

Keywords - Diseasei

Cone-rod dystrophy, Disease mutation, Retinitis pigmentosa

Organism-specific databases

DisGeNETi64218
GeneReviewsiSEMA4A
MalaCardsiSEMA4A
MIMi610282 phenotype
610283 phenotype
OpenTargetsiENSG00000196189
Orphaneti1872 Cone rod dystrophy
791 Retinitis pigmentosa
PharmGKBiPA35651

Polymorphism and mutation databases

BioMutaiSEMA4A
DMDMi29840871

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Sequence analysisAdd BLAST32
ChainiPRO_000003232233 – 761Semaphorin-4AAdd BLAST729

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi113 ↔ 124PROSITE-ProRule annotation
Glycosylationi120N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi135N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi142 ↔ 151PROSITE-ProRule annotation
Disulfide bondi269 ↔ 379PROSITE-ProRule annotation
Disulfide bondi293 ↔ 339PROSITE-ProRule annotation
Glycosylationi496N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi497 ↔ 514PROSITE-ProRule annotation
Disulfide bondi506 ↔ 523PROSITE-ProRule annotation
Disulfide bondi580 ↔ 624PROSITE-ProRule annotation
Glycosylationi607N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9H3S1
MaxQBiQ9H3S1
PaxDbiQ9H3S1
PeptideAtlasiQ9H3S1
PRIDEiQ9H3S1

PTM databases

iPTMnetiQ9H3S1
PhosphoSitePlusiQ9H3S1

Expressioni

Gene expression databases

BgeeiENSG00000196189
CleanExiHS_SEMA4A
ExpressionAtlasiQ9H3S1 baseline and differential
GenevisibleiQ9H3S1 HS

Organism-specific databases

HPAiHPA053726
HPA066006
HPA069136

Interactioni

Subunit structurei

Interacts with PLXNB1, PLXNB2, PLXNB3 and PLXND1. Probable ligand for TIMD2 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
PLXND1Q9Y4D72EBI-3924922,EBI-310731

Protein-protein interaction databases

BioGridi1221087 interactors.
CORUMiQ9H3S1
IntActiQ9H3S1 5 interactors.
MINTiQ9H3S1
STRINGi9606.ENSP00000347117

Structurei

3D structure databases

ProteinModelPortaliQ9H3S1
SMRiQ9H3S1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini36 – 494SemaPROSITE-ProRule annotationAdd BLAST459
Domaini496 – 548PSIAdd BLAST53
Domaini573 – 631Ig-like C2-typeAdd BLAST59

Sequence similaritiesi

Belongs to the semaphorin family.Curated

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3611 Eukaryota
ENOG410XQZC LUCA
GeneTreeiENSGT00760000118854
HOGENOMiHOG000116087
HOVERGENiHBG061165
InParanoidiQ9H3S1
KOiK06521
OMAiFAFSPAC
OrthoDBiEOG091G01W0
PhylomeDBiQ9H3S1
TreeFamiTF316102

Family and domain databases

Gene3Di2.130.10.101 hit
InterProiView protein in InterPro
IPR002165 Plexin_repeat
IPR016201 PSI
IPR001627 Semap_dom
IPR036352 Semap_dom_sf
IPR027231 Semaphorin
IPR015943 WD40/YVTN_repeat-like_dom_sf
PANTHERiPTHR11036 PTHR11036, 1 hit
PfamiView protein in Pfam
PF01437 PSI, 1 hit
PF01403 Sema, 1 hit
SMARTiView protein in SMART
SM00423 PSI, 1 hit
SM00630 Sema, 1 hit
SUPFAMiSSF101912 SSF101912, 1 hit
PROSITEiView protein in PROSITE
PS51004 SEMA, 1 hit

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: Q9H3S1-1) [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
MALPALGLDP WSLLGLFLFQ LLQLLLPTTT AGGGGQGPMP RVRYYAGDER
60 70 80 90 100
RALSFFHQKG LQDFDTLLLS GDGNTLYVGA REAILALDIQ DPGVPRLKNM
110 120 130 140 150
IPWPASDRKK SECAFKKKSN ETQCFNFIRV LVSYNVTHLY TCGTFAFSPA
160 170 180 190 200
CTFIELQDSY LLPISEDKVM EGKGQSPFDP AHKHTAVLVD GMLYSGTMNN
210 220 230 240 250
FLGSEPILMR TLGSQPVLKT DNFLRWLHHD ASFVAAIPST QVVYFFFEET
260 270 280 290 300
ASEFDFFERL HTSRVARVCK NDVGGEKLLQ KKWTTFLKAQ LLCTQPGQLP
310 320 330 340 350
FNVIRHAVLL PADSPTAPHI YAVFTSQWQV GGTRSSAVCA FSLLDIERVF
360 370 380 390 400
KGKYKELNKE TSRWTTYRGP ETNPRPGSCS VGPSSDKALT FMKDHFLMDE
410 420 430 440 450
QVVGTPLLVK SGVEYTRLAV ETAQGLDGHS HLVMYLGTTT GSLHKAVVSG
460 470 480 490 500
DSSAHLVEEI QLFPDPEPVR NLQLAPTQGA VFVGFSGGVW RVPRANCSVY
510 520 530 540 550
ESCVDCVLAR DPHCAWDPES RTCCLLSAPN LNSWKQDMER GNPEWACASG
560 570 580 590 600
PMSRSLRPQS RPQIIKEVLA VPNSILELPC PHLSALASYY WSHGPAAVPE
610 620 630 640 650
ASSTVYNGSL LLIVQDGVGG LYQCWATENG FSYPVISYWV DSQDQTLALD
660 670 680 690 700
PELAGIPREH VKVPLTRVSG GAALAAQQSY WPHFVTVTVL FALVLSGALI
710 720 730 740 750
ILVASPLRAL RARGKVQGCE TLRPGEKAPL SREQHLQSPK ECRTSASDVD
760
ADNNCLGTEV A
Length:761
Mass (Da):83,574
Last modified:April 11, 2003 - v2
Checksum:i5BCB889AA32A2BB3
GO
Isoform 2 (identifier: Q9H3S1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-99: Missing.
     122-154: Missing.

Note: No experimental confirmation available.
Show »
Length:629
Mass (Da):69,104
Checksum:i3B97BA202D33502B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti293 – 328CTQPG…FTSQW → SAPSRGSCPSTSSATRSCSP PILPQLPTSTQSSPPSG (Ref. 1) CuratedAdd BLAST36
Sequence conflicti354Y → F in BAB20087 (Ref. 1) Curated1
Sequence conflicti641D → G in BAG52288 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028322345D → H in RP35 and CORD10; heterozygous compound with C-350; loss of localization to cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs267607033Ensembl.1
Natural variantiVAR_028323350F → C in RP35 and CORD10; heterozygous compound with H-345; loss of localization to cell membrane. 2 PublicationsCorresponds to variant dbSNP:rs267607034Ensembl.1
Natural variantiVAR_028324510R → Q. Corresponds to variant dbSNP:rs2075164Ensembl.1
Natural variantiVAR_028325713R → Q Polymorphism; originally reported as mutation causing retinitis pigmentosa; no effect on localization to cell membrane. 3 PublicationsCorresponds to variant dbSNP:rs41265017Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0463811 – 99Missing in isoform 2. 1 PublicationAdd BLAST99
Alternative sequenceiVSP_046382122 – 154Missing in isoform 2. 1 PublicationAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB029394 mRNA Translation: BAB20087.1
AY358531 mRNA Translation: AAQ88895.1
AK091127 mRNA Translation: BAG52288.1
AK315547 mRNA Translation: BAG37925.1
AL135927 Genomic DNA No translation available.
BC020974 mRNA Translation: AAH20974.1
CCDSiCCDS1132.1 [Q9H3S1-1]
CCDS53378.1 [Q9H3S1-2]
RefSeqiNP_001180229.1, NM_001193300.1 [Q9H3S1-1]
NP_001180230.1, NM_001193301.1 [Q9H3S1-1]
NP_001180231.1, NM_001193302.1 [Q9H3S1-2]
NP_071762.2, NM_022367.3 [Q9H3S1-1]
XP_011508174.1, XM_011509872.2 [Q9H3S1-1]
XP_011508175.1, XM_011509873.2 [Q9H3S1-1]
XP_016857545.1, XM_017002056.1 [Q9H3S1-1]
UniGeneiHs.408846

Genome annotation databases

EnsembliENST00000355014; ENSP00000347117; ENSG00000196189 [Q9H3S1-1]
ENST00000368282; ENSP00000357265; ENSG00000196189 [Q9H3S1-1]
ENST00000368284; ENSP00000357267; ENSG00000196189 [Q9H3S1-2]
ENST00000368285; ENSP00000357268; ENSG00000196189 [Q9H3S1-1]
GeneIDi64218
KEGGihsa:64218
UCSCiuc001fnl.4 human [Q9H3S1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSEM4A_HUMAN
AccessioniPrimary (citable) accession number: Q9H3S1
Secondary accession number(s): B2RDH8
, B3KR76, Q5TCI5, Q5TCJ6, Q8WUA9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: April 11, 2003
Last modified: February 28, 2018
This is version 161 of the entry and version 2 of the sequence. See 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