Q64151 (SEM4C_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Semaphorin-4C

Alternative name(s):
M-Sema F
Semaphorin-C-like 1
Short name=Sema I
Short name=Semaphorin I

Gene names

Name:	Sema4c
Synonyms:	S4c, Semacl1, Semai

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	834 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 PLXNB2 that plays an important role in cell-cell signaling. PLXNB2 binding promotes downstream activation of RHOA and phosphorylation of ERBB2 at 'Tyr-1248'. Required for normal brain development, axon guidance and cell migration. Probable signaling receptor which may play a role in myogenic differentiation through activation of the stress-activated MAPK cascade. Ref.5 Ref.6 Ref.7 Ref.8
Subunit structure	Interacts (via the PDZ-binding motif) with GIPC (via the PDZ domain). Interacts with NCDN. Interacts (via the PDZ-binding motif) with DLG4. Interacts with PLXNB2. Ref.2 Ref.3 Ref.4 Ref.7 Ref.8
Subcellular location	Cell junction › synapse › postsynaptic cell membrane › postsynaptic density; Single-pass type I membrane protein. Cytoplasmic vesicle › secretory vesicle › synaptic vesicle membrane; Single-pass type I membrane protein Ref.4.
Tissue specificity	Predominantly expressed in brain (at protein level). Ref.4
Developmental stage	First detected at E14, levels increase by birth and remain strong in the adult brain (at protein level). Expressed widely in the nervous tissues during development. Ref.4
Induction	Up-regulated in differentiating myoblasts and upon muscle regeneration (at protein level). Ref.5 Ref.6
Disruption phenotype	Partial neonate lethality, due to defects in brain and neural tube development. In about one third of the embryos cranial neural folds fail to converge, leading to an open neural tube and exencephaly. Mice without exencephaly are viable and fertile. Ref.8
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	Cell junction Cell membrane Cytoplasmic vesicle Membrane Postsynaptic cell membrane Synapse
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell migration in hindbrain Inferred from mutant phenotype Ref.8. Source: UniProtKB cerebellum development Inferred from mutant phenotype Ref.8. Source: UniProtKB muscle cell differentiation Inferred from mutant phenotype Ref.5Ref.6. Source: UniProtKB neural tube closure Inferred from mutant phenotype Ref.8. Source: UniProtKB positive regulation of stress-activated MAPK cascade Inferred from sequence or structural similarity. Source: UniProtKB semaphorin-plexin signaling pathway Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW postsynaptic density Inferred from direct assay Ref.4. Source: UniProtKB postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW synaptic vesicle membrane Inferred from direct assay Ref.4. Source: UniProtKB
Molecular_function	receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Gipc1	Q9Z0G0	8	EBI-987075,EBI-300855
Gipc2	Q9Z2H7	3	EBI-987075,EBI-987119

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 834	814	Semaphorin-4C		PRO_0000032326
Regions
	Topological domain	21 – 664	644	Extracellular Potential
	Transmembrane	665 – 685	21	Helical; Potential
	Topological domain	686 – 834	149	Cytoplasmic Potential
	Domain	30 – 497	468	Sema
	Domain	499 – 552	54	PSI
	Domain	557 – 645	89	Ig-like C2-type
	Region	46 – 489	444	Dominant negative effect on myogenic differentiation
	Motif	831 – 834	4	PDZ-binding
	Compositional bias	678 – 687	10	Poly-Leu
	Compositional bias	709 – 774	66	Pro-rich
Amino acid modifications
	Glycosylation	106	1	N-linked (GlcNAc...) Potential
	Glycosylation	121	1	N-linked (GlcNAc...) Potential
	Glycosylation	310	1	N-linked (GlcNAc...) Potential
	Glycosylation	419	1	N-linked (GlcNAc...) Potential
	Glycosylation	522	1	N-linked (GlcNAc...) Potential
	Glycosylation	565	1	N-linked (GlcNAc...) Potential
	Disulfide bond	99 ↔ 110		By similarity
	Disulfide bond	128 ↔ 137		By similarity
	Disulfide bond	261 ↔ 370		By similarity
	Disulfide bond	285 ↔ 330		By similarity
	Disulfide bond	500 ↔ 517		By similarity
	Disulfide bond	509 ↔ 526		By similarity
	Disulfide bond	578 ↔ 628		By similarity
Experimental info
	Mutagenesis	832	1	S → A: Loss of the effect on myogenic differentiation; when associated with A-834. Loss of interaction with DLG4; when associated with A-833 and A-834. Ref.4 Ref.5
	Mutagenesis	833	1	S → A: Loss of interaction with DLG4; when associated with A-832 and A-834. Ref.4
	Mutagenesis	834	1	V → A: Loss of the effect on myogenic differentiation; when associated with A-832. Loss of interaction with DLG4; when associated with A-832 and A-833. Ref.4 Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q64151 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 6868BB5BF571482D	FASTA	834	92,557
	10 20 30 40 50 60 MAPHWAVWLL AAGLWGLGIG AEMWWNLVPR KTVSSGELVT VVRRFSQTGI QDFLTLTLTE 70 80 90 100 110 120 HSGLLYVGAR EALFAFSVEA LELQGAISWE APAEKKIECT QKGKSNQTEC FNFIRFLQPY 130 140 150 160 170 180 NSSHLYVCGT YAFQPKCTYI NMLTFTLDRA EFEDGKGKCP YDPAKGHTGL LVDGELYSAT 190 200 210 220 230 240 LNNFLGTEPV ILRYMGTHHS IKTEYLAFWL NEPHFVGSAF VPESVGSFTG DDDKIYFFFS 250 260 270 280 290 300 ERAVEYDCYS EQVVARVARV CKGDMGGART LQKKWTTFLK ARLVCSAPDW KVYFNQLKAV 310 320 330 340 350 360 HTLRGASWHN TTFFGVFQAR WGDMDLSAVC EYQLEQIQQV FEGPYKEYSE QAQKWARYTD 370 380 390 400 410 420 PVPSPRPGSC INNWHRDNGY TSSLELPDNT LNFIKKHPLM EDQVKPRLGR PLLVKKNTNF 430 440 450 460 470 480 THVVADRVPG LDGATYTVLF IGTGDGWLLK AVSLGPWIHM VEELQVFDQE PVESLVLSQS 490 500 510 520 530 540 KKVLFAGSRS QLVQLSLADC TKYRFCVDCV LARDPYCAWN VNTSRCVATT SGRSGSFLVQ 550 560 570 580 590 600 HVANLDTSKM CNQYGIKKVR SIPKNITVVS GTDLVLPCHL SSNLAHAHWT FGSQDLPAEQ 610 620 630 640 650 660 PGSFLYDTGL QALVVMAAQS RHSGPYRCYS EEQGTRLAAE SYLVAVVAGS SVTLEARAPL 670 680 690 700 710 720 ENLGLVWLAV VALGAVCLVL LLLVLSLRRR LREELEKGAK ASERTLVYPL ELPKEPASPP 730 740 750 760 770 780 FRPGPETDEK LWDPVGYYYS DGSLKIVPGH ARCQPGGGPP SPPPGIPGQP LPSPTRLHLG 790 800 810 820 830 GGRNSNANGY VRLQLGGEDR GGSGHPLPEL ADELRRKLQQ RQPLPDSNPE ESSV

References

[1]	"Identification of a member of mouse semaphorin family." Inagaki S., Furuyama T., Iwahashi Y. FEBS Lett. 370:269-272(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Neonatal brain.
[2]	"A PDZ protein regulates the distribution of the transmembrane semaphorin, M-SemF." Wang L.-H., Kalb R.G., Strittmatter S.M. J. Biol. Chem. 274:14137-14146(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GIPC.
[3]	"Semaphorin 4C, a transmembrane semaphorin, associates with a neurite-outgrowth-related protein, SFAP75." Ohoka Y., Hirotani M., Sugimoto H., Fujioka S., Furuyama T., Inagaki S. Biochem. Biophys. Res. Commun. 280:237-243(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NCDN.
[4]	"Sema4c, a transmembrane semaphorin, interacts with a post-synaptic density protein, PSD-95." Inagaki S., Ohoka Y., Sugimoto H., Fujioka S., Amazaki M., Kurinami H., Miyazaki N., Tohyama M., Furuyama T. J. Biol. Chem. 276:9174-9181(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH DLG4, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, MUTAGENESIS OF SER-832; SER-833 AND VAL-834.
[5]	"Requirement of the transmembrane semaphorin Sema4C for myogenic differentiation." Ko J.-A., Gondo T., Inagaki S., Inui M. FEBS Lett. 579:2236-2242(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF SER-832 AND VAL-834, INDUCTION.
[6]	"Sema4C participates in myogenic differentiation in vivo and in vitro through the p38 MAPK pathway." Wu H., Wang X., Liu S., Wu Y., Zhao T., Chen X., Zhu L., Wu Y., Ding X., Peng X., Yuan J., Wang X., Fan W., Fan M. Eur. J. Cell Biol. 86:331-344(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION.
[7]	"Plexin-B2, but not Plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo." Deng S., Hirschberg A., Worzfeld T., Penachioni J.Y., Korostylev A., Swiercz J.M., Vodrazka P., Mauti O., Stoeckli E.T., Tamagnone L., Offermanns S., Kuner R. J. Neurosci. 27:6333-6347(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PLXNB2.
[8]	"Semaphorin 4C and 4G are ligands of Plexin-B2 required in cerebellar development." Maier V., Jolicoeur C., Rayburn H., Takegahara N., Kumanogoh A., Kikutani H., Tessier-Lavigne M., Wurst W., Friedel R.H. Mol. Cell. Neurosci. 46:419-431(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PLXNB2, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S79463 mRNA. Translation: AAB35184.1.
IPI	IPI00890869.
PIR	S66498.
RefSeq	NP_001119519.1. NM_001126047.1.
UniGene	Mm.29558.
3D structure databases
ProteinModelPortal	Q64151.
SMR	Q64151. Positions 28-633.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q64151. 2 interactions.
MINT	MINT-91862.
STRING	10090.ENSMUSP00000027295.
PTM databases
PhosphoSite	Q64151.
Proteomic databases
PRIDE	Q64151.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000027295; ENSMUSP00000027295; ENSMUSG00000026121. ENSMUST00000114990; ENSMUSP00000110641; ENSMUSG00000026121. ENSMUST00000114991; ENSMUSP00000110643; ENSMUSG00000026121. ENSMUST00000114992; ENSMUSP00000110644; ENSMUSG00000026121.
GeneID	20353.
KEGG	mmu:20353.
UCSC	uc007aqq.2. mouse.
Organism-specific databases
CTD	54910.
MGI	MGI:109252. Sema4c.
Phylogenomic databases
eggNOG	NOG293968.
GeneTree	ENSGT00560000076864.
HOGENOM	HOG000116087.
HOVERGEN	HBG061165.
InParanoid	Q64151.
KO	K06521.
OMA	YNASHLY.
OrthoDB	EOG4WH8K5.
Gene expression databases
ArrayExpress	Q64151.
Bgee	Q64151.
Genevestigator	Q64151.
GermOnline	ENSMUSG00000026121. Mus musculus.
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. 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	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	SEMA4C. mouse.
NextBio	298215.
SOURCE	Search...

Entry information

Entry name

SEM4C_MOUSE

Accession

Primary (citable) accession number: Q64151

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program