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Protein

Semaphorin-4C

Gene

Sema4c

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.4 Publications

GO - Molecular functioni

  1. receptor activity Source: InterPro

GO - Biological processi

  1. cell migration in hindbrain Source: UniProtKB
  2. cerebellum development Source: UniProtKB
  3. muscle cell differentiation Source: UniProtKB
  4. neural tube closure Source: UniProtKB
  5. positive regulation of stress-activated MAPK cascade Source: UniProtKB
  6. semaphorin-plexin signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Semaphorin-4C
Alternative name(s):
M-Sema F
Semaphorin-C-like 1
Short name:
Sema I
Short name:
Semaphorin I
Gene namesi
Name:Sema4c
Synonyms:S4c, Semacl1, Semai
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:109252. Sema4c.

Subcellular locationi

Cell junctionsynapsepostsynaptic cell membranepostsynaptic density 1 Publication; Single-pass type I membrane protein 1 Publication. Cytoplasmic vesiclesecretory vesiclesynaptic vesicle membrane 1 Publication; Single-pass type I membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 664644ExtracellularSequence AnalysisAdd
BLAST
Transmembranei665 – 68521HelicalSequence AnalysisAdd
BLAST
Topological domaini686 – 834149CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. extracellular space Source: MGI
  3. integral component of membrane Source: UniProtKB-KW
  4. postsynaptic density Source: UniProtKB
  5. postsynaptic membrane Source: UniProtKB-KW
  6. synaptic vesicle membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasmic vesicle, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi832 – 8321S → 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. 2 Publications
Mutagenesisi833 – 8331S → A: Loss of interaction with DLG4; when associated with A-832 and A-834. 1 Publication
Mutagenesisi834 – 8341V → 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. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence AnalysisAdd
BLAST
Chaini21 – 834814Semaphorin-4CPRO_0000032326Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi99 ↔ 110By similarity
Glycosylationi106 – 1061N-linked (GlcNAc...)Sequence Analysis
Glycosylationi121 – 1211N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi128 ↔ 137By similarity
Disulfide bondi261 ↔ 370By similarity
Disulfide bondi285 ↔ 330By similarity
Glycosylationi310 – 3101N-linked (GlcNAc...)Sequence Analysis
Glycosylationi419 – 4191N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi500 ↔ 517By similarity
Disulfide bondi509 ↔ 526By similarity
Glycosylationi522 – 5221N-linked (GlcNAc...)Sequence Analysis
Glycosylationi565 – 5651N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi578 ↔ 628By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ64151.
PRIDEiQ64151.

PTM databases

PhosphoSiteiQ64151.

Expressioni

Tissue specificityi

Predominantly expressed in brain (at protein level).1 Publication

Developmental stagei

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.1 Publication

Inductioni

Up-regulated in differentiating myoblasts and upon muscle regeneration (at protein level).2 Publications

Gene expression databases

BgeeiQ64151.
GenevestigatoriQ64151.

Interactioni

Subunit structurei

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 PLXNB2.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Gipc1Q9Z0G08EBI-987075,EBI-300855
Gipc2Q9Z2H73EBI-987075,EBI-987119

Protein-protein interaction databases

IntActiQ64151. 2 interactions.
MINTiMINT-91862.
STRINGi10090.ENSMUSP00000027295.

Structurei

3D structure databases

ProteinModelPortaliQ64151.
SMRiQ64151. Positions 28-633.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 497468SemaPROSITE-ProRule annotationAdd
BLAST
Domaini499 – 55254PSIAdd
BLAST
Domaini557 – 64589Ig-like C2-typeAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni46 – 489444Dominant negative effect on myogenic differentiationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi831 – 8344PDZ-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi678 – 68710Poly-Leu
Compositional biasi709 – 77466Pro-richAdd
BLAST

Sequence similaritiesi

Belongs to the semaphorin family.Curated
Contains 1 PSI domain.Curated
Contains 1 Sema domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG293968.
GeneTreeiENSGT00760000118854.
HOGENOMiHOG000116087.
HOVERGENiHBG061165.
InParanoidiQ64151.
KOiK06521.
OMAiASHLYVC.
OrthoDBiEOG712TVJ.
PhylomeDBiQ64151.
TreeFamiTF316102.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR016201. Plexin-like_fold.
IPR002165. Plexin_repeat.
IPR001627. Semap_dom.
IPR027231. Semaphorin.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
PANTHERiPTHR11036. PTHR11036. 1 hit.
PfamiPF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
[Graphical view]
SUPFAMiSSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q64151-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPHWAVWLL AAGLWGLGIG AEMWWNLVPR KTVSSGELVT VVRRFSQTGI
60 70 80 90 100
QDFLTLTLTE HSGLLYVGAR EALFAFSVEA LELQGAISWE APAEKKIECT
110 120 130 140 150
QKGKSNQTEC FNFIRFLQPY NSSHLYVCGT YAFQPKCTYI NMLTFTLDRA
160 170 180 190 200
EFEDGKGKCP YDPAKGHTGL LVDGELYSAT LNNFLGTEPV ILRYMGTHHS
210 220 230 240 250
IKTEYLAFWL NEPHFVGSAF VPESVGSFTG DDDKIYFFFS ERAVEYDCYS
260 270 280 290 300
EQVVARVARV CKGDMGGART LQKKWTTFLK ARLVCSAPDW KVYFNQLKAV
310 320 330 340 350
HTLRGASWHN TTFFGVFQAR WGDMDLSAVC EYQLEQIQQV FEGPYKEYSE
360 370 380 390 400
QAQKWARYTD PVPSPRPGSC INNWHRDNGY TSSLELPDNT LNFIKKHPLM
410 420 430 440 450
EDQVKPRLGR PLLVKKNTNF THVVADRVPG LDGATYTVLF IGTGDGWLLK
460 470 480 490 500
AVSLGPWIHM VEELQVFDQE PVESLVLSQS KKVLFAGSRS QLVQLSLADC
510 520 530 540 550
TKYRFCVDCV LARDPYCAWN VNTSRCVATT SGRSGSFLVQ HVANLDTSKM
560 570 580 590 600
CNQYGIKKVR SIPKNITVVS GTDLVLPCHL SSNLAHAHWT FGSQDLPAEQ
610 620 630 640 650
PGSFLYDTGL QALVVMAAQS RHSGPYRCYS EEQGTRLAAE SYLVAVVAGS
660 670 680 690 700
SVTLEARAPL ENLGLVWLAV VALGAVCLVL LLLVLSLRRR LREELEKGAK
710 720 730 740 750
ASERTLVYPL ELPKEPASPP FRPGPETDEK LWDPVGYYYS DGSLKIVPGH
760 770 780 790 800
ARCQPGGGPP SPPPGIPGQP LPSPTRLHLG GGRNSNANGY VRLQLGGEDR
810 820 830
GGSGHPLPEL ADELRRKLQQ RQPLPDSNPE ESSV
Length:834
Mass (Da):92,557
Last modified:November 1, 1996 - v1
Checksum:i6868BB5BF571482D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S79463 mRNA. Translation: AAB35184.1.
CCDSiCCDS48240.1.
PIRiS66498.
RefSeqiNP_001119519.1. NM_001126047.3.
XP_006495868.1. XM_006495805.1.
XP_006495870.1. XM_006495807.1.
XP_006495871.1. XM_006495808.1.
XP_006495872.1. XM_006495809.2.
XP_006495873.1. XM_006495810.2.
UniGeneiMm.29558.

Genome annotation databases

EnsembliENSMUST00000114991; ENSMUSP00000110643; ENSMUSG00000026121.
ENSMUST00000191642; ENSMUSP00000142284; ENSMUSG00000026121.
ENSMUST00000191677; ENSMUSP00000141263; ENSMUSG00000026121.
ENSMUST00000195620; ENSMUSP00000141527; ENSMUSG00000026121.
GeneIDi20353.
KEGGimmu:20353.
UCSCiuc007aqq.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S79463 mRNA. Translation: AAB35184.1.
CCDSiCCDS48240.1.
PIRiS66498.
RefSeqiNP_001119519.1. NM_001126047.3.
XP_006495868.1. XM_006495805.1.
XP_006495870.1. XM_006495807.1.
XP_006495871.1. XM_006495808.1.
XP_006495872.1. XM_006495809.2.
XP_006495873.1. XM_006495810.2.
UniGeneiMm.29558.

3D structure databases

ProteinModelPortaliQ64151.
SMRiQ64151. Positions 28-633.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ64151. 2 interactions.
MINTiMINT-91862.
STRINGi10090.ENSMUSP00000027295.

PTM databases

PhosphoSiteiQ64151.

Proteomic databases

MaxQBiQ64151.
PRIDEiQ64151.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000114991; ENSMUSP00000110643; ENSMUSG00000026121.
ENSMUST00000191642; ENSMUSP00000142284; ENSMUSG00000026121.
ENSMUST00000191677; ENSMUSP00000141263; ENSMUSG00000026121.
ENSMUST00000195620; ENSMUSP00000141527; ENSMUSG00000026121.
GeneIDi20353.
KEGGimmu:20353.
UCSCiuc007aqq.2. mouse.

Organism-specific databases

CTDi54910.
MGIiMGI:109252. Sema4c.

Phylogenomic databases

eggNOGiNOG293968.
GeneTreeiENSGT00760000118854.
HOGENOMiHOG000116087.
HOVERGENiHBG061165.
InParanoidiQ64151.
KOiK06521.
OMAiASHLYVC.
OrthoDBiEOG712TVJ.
PhylomeDBiQ64151.
TreeFamiTF316102.

Miscellaneous databases

ChiTaRSiSema4c. mouse.
NextBioi298215.
PROiQ64151.
SOURCEiSearch...

Gene expression databases

BgeeiQ64151.
GenevestigatoriQ64151.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR016201. Plexin-like_fold.
IPR002165. Plexin_repeat.
IPR001627. Semap_dom.
IPR027231. Semaphorin.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
PANTHERiPTHR11036. PTHR11036. 1 hit.
PfamiPF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
[Graphical view]
SUPFAMiSSF101912. SSF101912. 1 hit.
SSF103575. SSF103575. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Identification of a member of mouse semaphorin family."
    Inagaki S., Furuyama T., Iwahashi Y.
    FEBS Lett. 370:269-272(1994) [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(1998) [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(2000) [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(2000) [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(2004) [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(2006) [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(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PLXNB2.
  8. Cited for: FUNCTION, INTERACTION WITH PLXNB2, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiSEM4C_MOUSE
AccessioniPrimary (citable) accession number: Q64151
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: April 1, 2015
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.