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Q14563 (SEM3A_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-3A
Alternative name(s):
Semaphorin III
Short name=Sema III
Gene names
Name:SEMA3A
Synonyms:SEMAD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length771 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the development of the olfactory system and in neuronal control of puberty. Induces the collapse and paralysis of neuronal growth cones. Could serve as a ligand that guides specific growth cones by a motility-inhibiting mechanism. Binds to the complex neuropilin-1/plexin-1. Ref.3

Subunit structure

Interacts with PLXND1 By similarity.

Subcellular location

Secreted By similarity.

Domain

Strong binding to neuropilin is mediated by the carboxy third of the protein.

Involvement in disease

Hypogonadotropic hypogonadism 16 with or without anosmia (HH16) [MIM:614897]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
Note: The disease may be caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Ref.3 Ref.6

Sequence similarities

Belongs to the semaphorin family.

Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

Contains 1 PSI domain.

Contains 1 Sema domain.

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Hypogonadotropic hypogonadism
Kallmann syndrome
   DomainImmunoglobulin domain
Signal
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: Ensembl

axon extension involved in axon guidance

Inferred from sequence or structural similarity. Source: BHF-UCL

axon guidance

Traceable author statement PubMed 19909241. Source: BHF-UCL

axonal fasciculation

Inferred from electronic annotation. Source: Ensembl

axonogenesis involved in innervation

Inferred from sequence or structural similarity. Source: BHF-UCL

dendrite morphogenesis

Inferred from electronic annotation. Source: Ensembl

dichotomous subdivision of terminal units involved in salivary gland branching

Inferred from electronic annotation. Source: Ensembl

negative regulation of axon extension involved in axon guidance

Inferred from electronic annotation. Source: Ensembl

negative regulation of epithelial cell migration

Inferred from electronic annotation. Source: Ensembl

nerve development

Inferred from sequence or structural similarity. Source: BHF-UCL

neuron migration

Inferred from sequence or structural similarity. Source: BHF-UCL

olfactory bulb development

Inferred from mutant phenotype Ref.3. Source: UniProtKB

positive regulation of neuron migration

Inferred from electronic annotation. Source: Ensembl

regulation of axon extension involved in axon guidance

Inferred from direct assay PubMed 18053124. Source: UniProtKB

regulation of heart rate

Inferred from electronic annotation. Source: Ensembl

semaphorin-plexin signaling pathway

Traceable author statement PubMed 19909241. Source: BHF-UCL

semaphorin-plexin signaling pathway involved in neuron projection guidance

Inferred from sequence or structural similarity. Source: BHF-UCL

sensory system development

Traceable author statement PubMed 19909241. Source: BHF-UCL

sympathetic ganglion development

Inferred from sequence or structural similarity. Source: BHF-UCL

sympathetic nervous system development

Traceable author statement PubMed 19909241. Source: BHF-UCL

sympathetic neuron projection extension

Inferred from sequence or structural similarity. Source: BHF-UCL

sympathetic neuron projection guidance

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentaxon

Inferred from electronic annotation. Source: Ensembl

dendrite

Inferred from electronic annotation. Source: Ensembl

extracellular region

Traceable author statement. Source: Reactome

membrane

Inferred from electronic annotation. Source: InterPro

   Molecular_functionchemorepellent activity

Traceable author statement PubMed 19909241. Source: BHF-UCL

receptor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Chain21 – 771751Semaphorin-3A
PRO_0000032303

Regions

Domain31 – 514484Sema
Domain580 – 66485Ig-like C2-type
Compositional bias727 – 76943Arg/Lys-rich (basic)

Amino acid modifications

Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation1251N-linked (GlcNAc...) Potential
Glycosylation5901N-linked (GlcNAc...) Potential
Disulfide bond103 ↔ 114 By similarity
Disulfide bond132 ↔ 141 By similarity
Disulfide bond269 ↔ 381 By similarity
Disulfide bond293 ↔ 341 By similarity
Disulfide bond517 ↔ 535 By similarity
Disulfide bond649 ↔ 722 By similarity

Natural variations

Natural variant661R → W in HH16; phenotype consistent with Kallmann syndrome. Ref.6
Corresponds to variant rs199979628 [ dbSNP | Ensembl ].
VAR_069200
Natural variant1311A → T in a breast cancer sample; somatic mutation. Ref.4
VAR_036283
Natural variant1531N → S in HH16; phenotype consistent with Kallmann syndrome. Ref.6
Corresponds to variant rs139295139 [ dbSNP | Ensembl ].
VAR_069201
Natural variant3961P → S Found in a renal cell carcinoma sample; somatic mutation. Ref.5
VAR_064749
Natural variant4001I → V in HH16; phenotype consistent with Kallmann syndrome; digenic; found in a patient also carrying mutation Cys-268 in PROKR2. Ref.6
Corresponds to variant rs36026860 [ dbSNP | Ensembl ].
VAR_069202
Natural variant4351V → I in HH16; phenotype consistent with Kallmann syndrome; digenic; found in patients also carrying mutation Cys-268 in PROKR2 or mutation Arg-687 in FGFR1. Ref.6
Corresponds to variant rs147436181 [ dbSNP | Ensembl ].
VAR_069203
Natural variant6881T → A in HH16; phenotype consistent with Kallmann syndrome; digenic; found in a patient also carrying mutation Asp-217 in KAL1. Ref.6
Corresponds to variant rs318240751 [ dbSNP | Ensembl ].
VAR_069204
Natural variant7301R → Q in HH16; phenotype consistent with Kallmann syndrome. Ref.6
Corresponds to variant rs318240752 [ dbSNP | Ensembl ].
VAR_069205
Natural variant7331R → H in HH16; phenotype consistent with Kallmann syndrome. Ref.6
Corresponds to variant rs318240753 [ dbSNP | Ensembl ].
VAR_069206

Sequences

Sequence LengthMass (Da)Tools
Q14563 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 9985F8D3EAED8456

FASTA77188,889
        10         20         30         40         50         60 
MGWLTRIVCL FWGVLLTARA NYQNGKNNVP RLKLSYKEML ESNNVITFNG LANSSSYHTF 

        70         80         90        100        110        120 
LLDEERSRLY VGAKDHIFSF DLVNIKDFQK IVWPVSYTRR DECKWAGKDI LKECANFIKV 

       130        140        150        160        170        180 
LKAYNQTHLY ACGTGAFHPI CTYIEIGHHP EDNIFKLENS HFENGRGKSP YDPKLLTASL 

       190        200        210        220        230        240 
LIDGELYSGT AADFMGRDFA IFRTLGHHHP IRTEQHDSRW LNDPKFISAH LISESDNPED 

       250        260        270        280        290        300 
DKVYFFFREN AIDGEHSGKA THARIGQICK NDFGGHRSLV NKWTTFLKAR LICSVPGPNG 

       310        320        330        340        350        360 
IDTHFDELQD VFLMNFKDPK NPVVYGVFTT SSNIFKGSAV CMYSMSDVRR VFLGPYAHRD 

       370        380        390        400        410        420 
GPNYQWVPYQ GRVPYPRPGT CPSKTFGGFD STKDLPDDVI TFARSHPAMY NPVFPMNNRP 

       430        440        450        460        470        480 
IVIKTDVNYQ FTQIVVDRVD AEDGQYDVMF IGTDVGTVLK VVSIPKETWY DLEEVLLEEM 

       490        500        510        520        530        540 
TVFREPTAIS AMELSTKQQQ LYIGSTAGVA QLPLHRCDIY GKACAECCLA RDPYCAWDGS 

       550        560        570        580        590        600 
ACSRYFPTAK RRTRRQDIRN GDPLTHCSDL HHDNHHGHSP EERIIYGVEN SSTFLECSPK 

       610        620        630        640        650        660 
SQRALVYWQF QRRNEERKEE IRVDDHIIRT DQGLLLRSLQ QKDSGNYLCH AVEHGFIQTL 

       670        680        690        700        710        720 
LKVTLEVIDT EHLEELLHKD DDGDGSKTKE MSNSMTPSQK VWYRDFMQLI NHPNLNTMDE 

       730        740        750        760        770 
FCEQVWKRDR KQRRQRPGHT PGNSNKWKHL QENKKGRNRR THEFERAPRS V 

« Hide

References

« Hide 'large scale' references
[1]"The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules."
Kolodkin A.L., Matthes D.J., Goodman C.S.
Cell 75:1389-1399(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[2]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"SEMA3A deletion in a family with Kallmann syndrome validates the role of semaphorin 3A in human puberty and olfactory system development."
Young J., Metay C., Bouligand J., Tou B., Francou B., Maione L., Tosca L., Sarfati J., Brioude F., Esteva B., Briand-Suleau A., Brisset S., Goossens M., Tachdjian G., Guiochon-Mantel A.
Hum. Reprod. 27:1460-1465(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN HH16, FUNCTION.
[4]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-131.
[5]"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma."
Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. expand/collapse author list , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.
Nature 469:539-542(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SER-396.
[6]"SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome."
Hanchate N.K., Giacobini P., Lhuillier P., Parkash J., Espy C., Fouveaut C., Leroy C., Baron S., Campagne C., Vanacker C., Collier F., Cruaud C., Meyer V., Garcia-Pinero A., Dewailly D., Cortet-Rudelli C., Gersak K., Metz C. expand/collapse author list , Chabrier G., Pugeat M., Young J., Hardelin J.P., Prevot V., Dode C.
PLoS Genet. 8:E1002896-E1002896(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HH16 TRP-66; SER-153; VAL-400; ILE-435; ALA-688; GLN-730 AND HIS-733, CHARACTERIZATION OF VARIANTS HH16 TRP-66; SER-153; VAL-400; ILE-435; ALA-688; GLN-730 AND HIS-733.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L26081 mRNA. Translation: AAA65938.1.
AC004451 Genomic DNA. Translation: AAS00353.1.
AC004848 Genomic DNA. Translation: AAC78622.1.
PIRD49423.
RefSeqNP_006071.1. NM_006080.2.
XP_005250167.1. XM_005250110.1.
XP_005250168.1. XM_005250111.2.
UniGeneHs.252451.

3D structure databases

ProteinModelPortalQ14563.
SMRQ14563. Positions 26-663.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-5744N.
STRING9606.ENSP00000265362.

PTM databases

PhosphoSiteQ14563.

Polymorphism databases

DMDM8134674.

Proteomic databases

PaxDbQ14563.
PRIDEQ14563.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265362; ENSP00000265362; ENSG00000075213.
ENST00000436949; ENSP00000415260; ENSG00000075213.
ENST00000448879; ENSP00000402093; ENSG00000075213.
GeneID10371.
KEGGhsa:10371.
UCSCuc003uhz.3. human.

Organism-specific databases

CTD10371.
GeneCardsGC07M083587.
HGNCHGNC:10723. SEMA3A.
HPAHPA029447.
HPA052235.
MIM603961. gene.
614897. phenotype.
neXtProtNX_Q14563.
Orphanet478. Kallmann syndrome.
PharmGKBPA35645.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG305380.
HOGENOMHOG000039964.
HOVERGENHBG055071.
InParanoidQ14563.
KOK06840.
OMAREPTTIS.
OrthoDBEOG7VMP4F.
PhylomeDBQ14563.
TreeFamTF316102.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.

Gene expression databases

ArrayExpressQ14563.
BgeeQ14563.
CleanExHS_SEMA3A.
GenevestigatorQ14563.

Family and domain databases

Gene3D2.130.10.10. 1 hit.
2.60.40.10. 1 hit.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR016201. Plexin-like_fold.
IPR001627. Semap_dom.
IPR027231. Semaphorin.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
PANTHERPTHR11036. PTHR11036. 1 hit.
PfamPF01403. Sema. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
[Graphical view]
SUPFAMSSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
PROSITEPS50835. IG_LIKE. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSEMA3A. human.
GeneWikiSEMA3A.
GenomeRNAi10371.
NextBio39311.
PROQ14563.
SOURCESearch...

Entry information

Entry nameSEM3A_HUMAN
AccessionPrimary (citable) accession number: Q14563
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 134 of the entry and version 1 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 7

Human chromosome 7: entries, gene names and cross-references to MIM