Q14563 (SEM3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Semaphorin-3A

Alternative name(s):
Semaphorin III
Short name=Sema III

Gene names

Name:	SEMA3A
Synonyms:	SEMAD

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	771 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	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 process	Differentiation Neurogenesis
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hypogonadotropic hypogonadism Kallmann syndrome
Domain	Immunoglobulin domain Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: Compara axon guidance Traceable author statement PubMed 19909241. Source: BHF-UCL axonal fasciculation Inferred from electronic annotation. Source: Compara dendrite morphogenesis Inferred from electronic annotation. Source: Compara dichotomous subdivision of terminal units involved in salivary gland branching Inferred from electronic annotation. Source: Compara negative regulation of axon extension involved in axon guidance Inferred from electronic annotation. Source: Compara negative regulation of epithelial cell migration Inferred from electronic annotation. Source: Compara olfactory bulb development Inferred from mutant phenotype Ref.3. Source: UniProtKB 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: Compara semaphorin-plexin signaling pathway Traceable author statement PubMed 19909241. Source: BHF-UCL sensory system development Traceable author statement PubMed 19909241. Source: BHF-UCL sympathetic nervous system development Traceable author statement PubMed 19909241. Source: BHF-UCL
Cellular_component	axon Inferred from electronic annotation. Source: Compara dendrite Inferred from electronic annotation. Source: Compara extracellular region Traceable author statement. Source: Reactome membrane Inferred from electronic annotation. Source: InterPro
Molecular_function	chemorepellent activity Traceable author statement PubMed 19909241. Source: BHF-UCL receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 771	751	Semaphorin-3A		PRO_0000032303
Regions
	Domain	31 – 514	484	Sema
	Domain	580 – 664	85	Ig-like C2-type
	Compositional bias	727 – 769	43	Arg/Lys-rich (basic)
Amino acid modifications
	Glycosylation	53	1	N-linked (GlcNAc...) Potential
	Glycosylation	125	1	N-linked (GlcNAc...) Potential
	Glycosylation	590	1	N-linked (GlcNAc...) Potential
	Disulfide bond	103 ↔ 114		By similarity
	Disulfide bond	132 ↔ 141		By similarity
	Disulfide bond	269 ↔ 381		By similarity
	Disulfide bond	293 ↔ 341		By similarity
	Disulfide bond	517 ↔ 535		By similarity
	Disulfide bond	649 ↔ 722		By similarity
Natural variations
	Natural variant	66	1	R → W in HH16; phenotype consistent with Kallmann syndrome. Ref.6		VAR_069200
	Natural variant	131	1	A → T in a breast cancer sample; somatic mutation. Ref.4		VAR_036283
	Natural variant	153	1	N → S in HH16; phenotype consistent with Kallmann syndrome. Ref.6		VAR_069201
	Natural variant	396	1	P → S Found in a renal cell carcinoma sample; somatic mutation. Ref.5		VAR_064749
	Natural variant	400	1	I → V in HH16; phenotype consistent with Kallmann syndrome; digenic; found in a patient also carrying mutation Cys-268 in PROKR2. Ref.6		VAR_069202
	Natural variant	435	1	V → 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		VAR_069203
	Natural variant	688	1	T → A in HH16; phenotype consistent with Kallmann syndrome; digenic; found in a patient also carrying mutation Asp-217 in KAL1. Ref.6		VAR_069204
	Natural variant	730	1	R → Q in HH16; phenotype consistent with Kallmann syndrome. Ref.6		VAR_069205
	Natural variant	733	1	R → H in HH16; phenotype consistent with Kallmann syndrome. Ref.6		VAR_069206

Sequences

	Sequence		Length	Mass (Da)
	Q14563 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 9985F8D3EAED8456	FASTA	771	88,889
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.
IPI	IPI00031510.
PIR	D49423.
RefSeq	NP_006071.1. NM_006080.2.
UniGene	Hs.252451.
3D structure databases
ProteinModelPortal	Q14563.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-5744N.
STRING	9606.ENSP00000265362.
PTM databases
PhosphoSite	Q14563.
Polymorphism databases
DMDM	8134674.
Proteomic databases
PaxDb	Q14563.
PRIDE	Q14563.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265362; ENSP00000265362; ENSG00000075213. ENST00000436949; ENSP00000415260; ENSG00000075213. ENST00000448879; ENSP00000402093; ENSG00000075213.
GeneID	10371.
KEGG	hsa:10371.
UCSC	uc003uhz.3. human.
Organism-specific databases
CTD	10371.
GeneCards	GC07M083587.
HGNC	HGNC:10723. SEMA3A.
HPA	HPA029447.
MIM	603961. gene. 614897. phenotype.
neXtProt	NX_Q14563.
Orphanet	478. Kallmann syndrome.
PharmGKB	PA35645.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG305380.
HOGENOM	HOG000039964.
HOVERGEN	HBG055071.
InParanoid	Q14563.
KO	K06840.
OMA	CTYIEVG.
OrthoDB	EOG4ZPDTM.
PhylomeDB	Q14563.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
ArrayExpress	Q14563.
Bgee	Q14563.
CleanEx	HS_SEMA3A.
Genevestigator	Q14563.
GermOnline	ENSG00000075213. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.10. 1 hit. 2.60.40.10. 1 hit.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR003659. Plexin-like. IPR016201. Plexin-like_fold. IPR027231. Semaphorin. IPR001627. Semaphorin/CD100_Ag. IPR015943. WD40/YVTN_repeat-like_dom. [Graphical view]
PANTHER	PTHR11036. PTHR11036. 1 hit.
Pfam	PF01403. Sema. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. SM00423. PSI. 1 hit. SM00630. Sema. 1 hit. [Graphical view]
SUPFAM	SSF103575. Plexin-like_fold. 1 hit. SSF101912. Sema. 1 hit.
PROSITE	PS50835. IG_LIKE. 1 hit. PS51004. SEMA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SEMA3A. human.
GenomeRNAi	10371.
NextBio	39311.
SOURCE	Search...

Entry information

Entry name

SEM3A_HUMAN

Accession

Primary (citable) accession number: Q14563

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 126 of the entry and version 1 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.