rndsy-lu-2945 periodic table of neurotrophic and ... · rndsy-lu-2945 periodic table of...

RnDSy-lu-2945

Periodic Table of Neurotrophic and Neurotactic Factors1* 35KG/ G 95

CNTN1Contactin-1

GP135; F3; MYPCN

Notch-1; PTPRZ; NrCAM; Neurofascin 155; L1CAM; Caspr1; TNC

2* 150K1 90

Sema4FSemaphorin 4F

SEMAM; SEMAW; M-SEMA-M; S4F

ligand unknown

3* 130–140KG/ G 90

CNTN2Contactin-2

TAG1; Axonin-1; AXT; TAX1; FAME5

NCAM; NrCAM; PTPRZ; Neurocan; APP; L1CAM; Caspr2

4* 100–120K1 97

APPAmyloid b

Precursor ProteinABPP; CVAP

CNTN2, 3, 4; DR6 (CD358); APLP-1, -2; ITM2B, 2C; Integrin b1; Reelin;

Laminin; Slit2

5* 90–110K1 95

Nectin-1Poliovirus Receptor

Related 1CD111; PVRL1; PRR1;

PVRR1; HVEC; HIgR

Nectin-3; FGF R1c; SynCAM3

6* 200–250K1 83

SYND3Syndecan-3

N-Syndecan; SDC3; SDCN

Pleiotrophin; GDNF; NRTN; ARTN; Sema5A

7* 18–22KS 93

GDNFGlial Cell Line-Derived Neurotrophic Factor

ATF1; ATF2; HFB1-GDNF; HSCR3

GFRa-1, -2; SYND3

8* 250K1▲ 96

PLXNA1Plexin A1

NOV; NOVP; PLXN1

Sema3A, 3C, 3E, 3F, 5A, 5B, 6D; PLXNB1; NRP1, 2

9* 200–210K1▲ 91

PLXND1Plexin D1

PLEXD1

Sema3A, 3C, 3E, 4A; NRP1; VEGF R2

10* 100–110K1 90

Sema4GSemaphorin 4G

PLXNB2, B3

11 145–155KG/ G 91

CNTN3Contactin-3

BIG-1; PANG; PCS

PTPRG; APP; APLP-1

12* 100–120K1 89

APLP-1Amyloid b Precursor-like

Protein 1C30

CNTN3, 4, 5; APP; APLP-2

13* 80–95K1 93

Nectin-3Poliovirus Receptor

Related 3CD113; PVRL3; PRR3; PVRR3

Nectin-1, -2; SynCAM1, 3

14 200–205KS▲ 94

Slit1SLIT Homolog 1

SLIL1; MEGF4

Glypican 1; GREM1; ROBO1, 2; EVA1C

15* 12–14KS 86

NRTNNeurturin

NTN

GFRa-1, -2; SYND3

16 250K1 97

PLXNA2Plexin A2OCT; PLXN2

Sema3A, 6A, 6B; NRP1, 2

17* 95KS 95

Sema3ASemaphorin 3A

SEMA1; SEMAD; SEMAIII; COLL1; HH16; Hsema-1; Hsema-III

PLXNA1, A2, A3, A4, B1, D1; NRP1

18* 135K1▲ 93

Sema5ASemaphorin 5A

SEMAF; SemF

PLXNA1, A3, B3; SYND3

19* 125–135KG/ G 95

CNTN4Contactin-4BIG-2; AXCAM

APP; APLP-1

20* 120–135K1 91

APLP-2Amyloid b Precursor-like

Protein 2APPH; APPL2; CDEBP; WALPLP2;

YWK-II

APP; APLP-1

21* 80–90K1 98

LINGO-1LRR and Ig Domain

Containing Nogo Receptor-Interacting Protein 1

LERN1; LRRN6A

NgR; NGF R; TROY; TrkB

22 63–66K1 88

AMIGO2Amphoterin-Induced

Gene and ORF 2Alivin-1; ALI1; DEGA

AMIGO

23* 300K1 91

Notch-1Neurogenic Locus Notch

Homolog Protein 1TAN1

CNTN1, 6; Delta; Jagged 1, 2

24* 240–250K1 88

ITGA1Integrin a1CD49a; VLA-1

Laminin; Collagen; Sema7A; Integrin b1

25* 75K1SS 90

NGF RNerve Growth Factor

Receptorp75NTR; Gp80-LNGFR;

TNFRSF16; CD271

LINGO-1; NGF; BDNF; NT-3, -4; SORT1; NgR

26* 110–120K1 97

NLGN1Neuroligin 1

NL1

NRXN1a, 1b, 2a, 2b, 3a, 3b; NLGN3

27* 100–170K 89

GPC1Glypican 1

Slit1, 2; FGF basic

28* 135–140KG 95

MDGA1MAM Domain Containing

GPI Anchor 1GPIM; MAMDC3; GPI

and MAM Protein

NLGN2

29* 130–140K1/ 1 98

FGF R1cFibroblast Growth Factor

Receptor 1c N-SAM; Flt-2; bFGF-R-1; CD331;

FLG; CEK

Nectin-1; NCAM-1; N-Cadherin; multiple FGFs

30* 50–60KG 93

GFRa-1Glial Cell Line-Derived Neurotrophic Factor

Receptor a1GDNF Ra-1; TRNR1; RETL1;

GFRA1

GDNF; Ret; NRTN; ARTN

31* 95–115K1 96

SynCAM1Synaptic Cell Adhesion

Molecule 1IGSF4A; CADM1; Necl-2; TSLC1;

RA175; ST17; BL2

Nectin-3; SynCAM2, 3; FARP1; CRTAM; ErbB3; Integrin a6b4

32* 190–210KS 96

Slit2SLIT Homolog 2

SLIL3

Glypican 1; GREM1; ROBO1, 2; EVA1C; APP

33* 15–17KS 76

ARTNArtemin

Enovin; EVN; Neublastin

GFRa-1, -3; SYND3

34 220 –240K1▲ 94

PLXNA3Plexin A3

SEX; PLXN3; PLXN4; XAP-6

Sema3A, 3F, 5A, 5B; NRP1, 2

35* 95KS 97

Sema3CSemaphorin 3C

SEMAE; SemE

PLXNA1, D1; NRP1:NRP2 (heterodimer)

36* 140–150K3▲ 90

Sema5BSemaphorin 5B

SEMAG; SemG

PLXNA1, A3

37* 125–135KG/ G 90

CNTN5Contactin-5NB-2; HNB-2s

APLP-1; L1CAM

38* 150–200K1 97

NRXN1aNeurexin 1a

NLGN1, 2, 3, 4X, 4Y; NXPH1, 2, 3; LRRTM1, 2, 4; Granuphilin

39* 80K1▲ 98



LERN3; LRRN6C

ligand unknown

40* 50–52K1 77

AMIGO3Amphoterin-Induced

Gene and ORF 3Alivin-3; ALI3

AMIGO; NgR

41* 12–13KS 85

b-NGFb-Nerve Growth Factor

NGF; NGFB; HSAN5B

NGF R; TrkA; Integrin a9b1

42 120–140K1 90

ITGA6Integrin a6

CD49f; VLA-6; Platelet gpl

Laminin; Integrin b1, b4, b6; Netrin-1; SynCAM1, 2, 4

43* 44–48K1▲ 69

TROYTNF Receptor

Superfamily, Member 19TAJ; TRADE; TNFRSF19

LINGO-1:NgR complex

44* 90–120K1▲ 98

NLGN2Neuroligin 2

NRXN1a, 1b, 2a, 2b, 3a, 3b; NLGN3; MDGA1, 2

45 190–210K1 95

ROBO1Roundabout Homolog 1

DUTT1

NRP1; ROBO2; exists in a complex for Sema3A and Sema3F; Slit1, 2, 3

46* 125–130KG 98

MDGA2MAM Domain Containing

GPI Anchor 2MAMDC1

NLGN2

47* 200K1 83

RetProto-Oncogene RTK Ret

CDHF12; CDHF16; HSCR1; MEN2A; MEN2B; MTC1;

PTC-ELE1; RET51

GFRa-1, -2, -3; PCDHA4; PCDHGB7

48* 58KG 89


Receptor a2GDNF Ra-2; GDNFRB; TRNR2;

RETL2; GFRA2; NRTNRa

GDNF; NRTN; Ret; NCAM-1

49* 52K1 97


Molecule 2IGSF4D; CADM2; Necl-3

SynCAM1, 3, 4; Integrin a6b4

50* 200KS▲ 94

Slit3SLIT Homolog 3

SLIL2; MEGF5

ROBO1, 2

51* 13–14KS 64

PSPNPersephin

PSP

GFRa-4

52* 240–250K1▲ 98

PLXNA4Plexin A4

PLEXA4

Sema3A, 6A, 6B, 6D; NRP1, 2

53* 90–95KS 93

Sema3DSemaphorin 3D

Sema-Z2; COLL2

NRP1

54* 110–125K1 95

Sema6ASemaphorin 6ASEMAQ; Sema-VIA;

SEMA1; HT018

PLXNA2, A4

55 125–135KG/ G 89

CNTN6Contactin-6

NB3

Notch-1

56* 182K1▲ 98

NRXN2aNeurexin 2a

GABA A Rg2; NLGN1, 2, 3; Dystroglycan; NXPH1, 2, 3

57 62K1▲ 88



LERN2; LRRN6B

ligand unknown

58 140K1 86

TrkANeurotrophic Tyrosine

Kinase Receptor ANTRK1; p140-TrkA; MTC

NGF; NT-3; SORT1

59* 13KS/ S/ S 97

BDNFBrain-Derived

Neurotrophic FactorIntegrin a9b1; NGF R; NCAM-1; TNC; TrkB;

TrkB:TrkC (heterodimer); NT-3, -4 (non-covalent heterodimers)

60 150–160K1 89

ITGA9Integrin a9ITGA4L; RLC-a

VCAM-1; OPN; NGF; BDNF; NT-3; Integrin b1; TNC

61* 29–31KS 99

NXPH1Neurexophilin-1

NPH1

NRXN1a, 2a, 3a

62* 110–125K1 96

NLGN3Neuroligin 3

ASPGX1; AUTSX1; HNL3; NL3; Gliotactin

NRXN1a, 1b, 2a, 2b, 3a, 3b; NLGN1, 2

63 200–210K1 94


SAX3

ROBO1; Slit1, 2, 3

64* 120–130K1 86

PCDHA4Protocadherin a4CNRN1; CRNR1; CNR1

Ret; PCDHGB7

65* 190K1 89

c-METHepatocyte Growth

Factor ReceptorHGF R; MET; AUTS9; RCCP2;

Scatter Factor Receptor

HGF; PLXNB1, B2, B3; Sema4D

66* 50–56KG 76


Receptor a3GDNF Ra-3; GDNFR3; GFRA3

ARTN; Ret

67* 50–60K1 95


Molecule 3IGSF4B; CADM3; Necl-1;

TSLL1; BIgR

SynCAM1, 2, 4; Nectin-1, -3

68* 70K1 97

LRRTM1Leucine-rich Repeat

Transmembrane Neuronal 1

LRRT1; LRRTM Neuronal Protein 1

NRXN1a, 1b

69* 205–225K 76

Nogo-AReticulon 4A

RTN4; RTN4A; NI220; ASY; RTN-X; NSP

NgR

70* 250–270K1▲ 87

PLXNB1Plexin B1SEP; PLXN5

Sema3A, 4C, 4D; PLXNA1, B2; c-MET; NRP1, 2; ErbB2; MSP R

71* 90–95KS 90

Sema3ESemaphorin 3E

SEMAH; M-SemaK; COLL5

PLXNA1, D1; NRP1; VEGF R2

72* 100–110K1 89

Sema6BSemaphorin 6B

SEMAN; Sema-VIB; SEM-SEMA-Y

PLXNA2, A4

73* 200–220K1 88

L1CAMNeural Cell Adhesion

Molecule L1CAML1; CD171; HSAS1;

MASA; MIC5; NgCAM; NCAM-L1; S10; SPG1

CNTN1, 2, 5; Integrin b1, b3, b5; NCAM-1

74* 178K1 98

NRXN3aNeurexin 3a

C14orf60

NXPH1, 2, 3; Dystroglycan; NLGN1, 2, 3

75 61K1▲ 94



LRRN6D

ligand unknown

76* 145K1 94

TrkBNeurotrophic Tyrosine

Kinase Receptor BNTRK2; GP145-TrkB

NMDA R; BDNF; NT-3; NT-4; LINGO-1; SORT1

77* 14KS 96

NT-3Neurotrophin 3NTF3; HDNF; NGF-2

BDNF (non-covalent heterodimer); NGF R; TrkB; TrkC; Integrin a9b1; TNC;

NT-4 (non-covalent heterodimer)

78* 120–140K1 92

ITGB1Integrin b1

GPIIA; VLA-b; CD29; FNRB; MDF2; MSK12

Integrin a1-a11, aV; Laminin; Fibronectin; VCAM-1; TSP; Vitronectin; BGD motif; NGF;

BDNF; NT-3; L1CAM; APP; TNC

79 29KS 89


NPH2

NRXN1a, 2a, 3a

80* 105–115K1 57

NLGN4XNeuroligin 4, X-linked

ASPGX2; AUTSX2; HNL4; HNLX; NL4

NRXN1a, 1b

81* 195–210K1▲ 81


RIG-1; HGPPS; HGPS; RBIG1

NELL2

82* 110–120K1 82

PCDHGB7Protocadherin gB7

Ret; PCDHA4

83* 185K1 74

MSP RMacrophage Stimulating

Protein ReceptorCD136; MST1R; Ron; PTK8

MSP; PLXNB1, B2, B3; Sema4D

84* 30–32KG 57


Receptor a4GDNF Ra-4; GFRA4

PSPN; NCAM-1

85* 55–65K1 98


Molecule 4IGSF4C; CADM4; Necl-4; TSLL2;

TSLC1-like 2

SynCAM2, 3; ErbB3; Integrin a6b4

86 75–80K1 98


Transmembrane Neuronal 2LRRT2; LRRN2

GluR1; NRXN1a, 1b (without an SS4 insert)

87* 95–110K1 91

SORT1Sortilin

Gp95; Neurotensin Receptor 3; Ntr3; LDLCQ6

Neurotensin; ProNGF; ProBDNF; LPL; TrkA, B, C; NGF R

88* 240–250K1 87

PLXNB2Plexin B2

MM1; PLEXB2

Sema4A, 4C, 4D, 4G; PLXNB1; c-MET; MSP R

89* 90KS 96

Sema3FSemaphorin 3F

Sema-IV; SEMA4; SEMAK

PLXNA1, A3; NRP1, 2; NrCAM

90* 110–120K1 88

Sema6CSemaphorin 6C

SEMAY; M-SemaY

NrCAM

91* 190–200K1▲ 93

NrCAMNeuronal Cell

Adhesion MoleculeBRAVO

Gliomedin; CNTN1, 2; PTPRZ; NFASC; Sema 3F, 6C, 6D

92* 180–190K1 93

Caspr1Contactin Associated

Protein-like 1CNTN; AP1; p190; NRXN4

CNTN1 (in-cis); NFASC

93* 80–85K1 89

AMIGOAmphoterin-Induced

Gene and ORFAlivin-2; ALI2; AMIGO1

AMIGO2, 3

94* 135–140K1 96

TrkCNeurotrophic Tyrosine

Kinase Receptor CNTRK3; NT-3 Growth Factor

Receptor; gp145(trkC)

NT-3; BDNF; SORT1

95 13–14KS 91

NT-4Neurotrophin 4

NT-5; NTF4; NTF5; GLC10

TrkB; NGF R; BDNF(non-covalent heterodimer); NT-3 (non-covalent heterodimer)

96* 205–210K1 83

ITGB4Integrin b4

CD104

Integrin a6; Laminin; Netrin-1; SynCAM1, 2, 4

97* 26KS 96


NPH3

NRXN1a, 2a, 3a

98* 105–115K1 60

NLGN4YNeuroligin 4, Y-linked

Neuroligin 5

NRXN1a

99 125–135K1 97

N-CadherinNeural Cadherin

CD325; Cadherin-2; CDH2; CDHN; NCAD

PCDH8; FGF R1

100* 180K1G/S 94

NCAM-1Neural Cell Adhesion

Molecule-1CD56; MSK39

FGF R1; L1CAM; CNTN2; BDNF; GFRa-2, -4

101 50–52K 86

EVA1CEpithelial V-like Antigen 1

Homolog CFAM176C; SUE21; C21orf63; C21orf64; PRED34; B18; B19

Heparin; Slit1, 2

102* 200–330K S 84

TNCTenascin C

GMEM; Cytotactin; Hexabrachion f; HXB; Tenascin J1; DFNA56

Integrin a9b1; NT-3; BDNF; BMP-2; VEGF; TGF-b1; Fibronectin

103 80–85KG/ G 89

NgRNogo Receptor

Nogo-66 Receptor; NgR1; RTN4R; Reticulon 4 Receptor

OMgp; MAG; LINGO-1; TROY; AMIGO3; NGF R; Nogo-A

104* 60–70K1 97


Transmembrane Neuronal 3

AMPA R complex

105* 110–125K1 93

NRP1Neuropilin-1

NP1; CD304; VEGF 165 R; BDCA4

VEGF 165; Sema3A, 3B, 3C, 3D, 3E, 3F; PLXNA1, A2, A3, A4, B1, D1; NRP2;

ROBO1; VEGF R2

106* 230–260K1 84

PLXNB3Plexin B3

PLXN6; PLEXB3; PLEXR

Sema4G, 5A; c-MET; MSP R

107 100–110K1 88

Sema4CSemaphorin 4C

Sema-I; SEMAF; M-SEMA-F; SEMACL1

PLXNB1, B2

108* 130K1 95

Sema6DSemaphorin 6D

PLXNA1, A4; NrCAM

109* 180–190K1 96

NFASCNeurofascin

NF; NRCAML

Gliomedin; NrCAM; Myocilin; CNTN1; Caspr1

110* 180K1 94

Caspr2Contactin Associated

Protein-like 2CNTNAP2; CDFE; NRXN4;

AUTS15; PTHSL1

Kv1.1, 1.2; CNTN2

111 74–78K1 94


Transmembrane Neuronal 4LRRT4; LRRN4

AMPA R complex; GPC1–6; NRXN1a, 1b

112* 120–140K1 95

NRP2Neuropilin-2

NP2; NPN2; PRO2714; VEGF 165 R2

VEGF 165; VEGF 145; Sema3C, 3F; PLXNA1, A2; A3, A4, B1; NRP1

113 210–220K1 90

PLXNC1Plexin C1

CD232; VESPR

Sema7A

114* 140–150K1 85

Sema4DSemaphorin 4D

CD100; SEMAJ; M-SEMA-G; BB18; A8; COLL4; C9orf164

PLXNB1, B2; c-MET; ErbB2; MSP R

115* 76–80KG 89

Sema7ASemaphorin 7ACD108; H-Sema-L; SEMAL; SEMAK1;

JMH Blood Group Antigen

PLXNC1; Integrin a1b1

Table 1. Families

Note: There is no association between families and color.

I Contactin IX TNFRSF XVII IgCAM XXV SLIT

II L1CAM X Neurexophilin XVIII Tyrosine Kinase/ Protein Kinase Superfamily XXVI LRRTM

III APP XI Type B Carboxypeptidase XIX EVA1 XXVII TGF-b

IV Neurexin XII Glypican XX GDNF Receptor XXVIII Reticulon Protein

V LRRIg Protein XIII ROBO XXI Tenascin XXIX VPS10P-Related Sortilin

VI Notch XIV Type I Cadherin XXII Nectin XXX Neuropilin

VII b-NGF XV Ig/MAM/FNIII-Domain Containing Proteins XXIII Nogo Receptor XXXI Plexin

VIII Integrin a- and b-chain XVI Protocadherin a and g XXIV Syndecan Proteoglycan XXXII Semaphorin

I/II

III/IV

V V VI/VII VIII IX/X XI XII/XIII/XIV XV/XVI/XVII XVIII/XIX XX/XXI

XXII/XXIII XXIV/XXV/XXVI XXVII/XXVIII/XXIX/XXX XXXI XXXI/XXXII

XXXII

1* 135KG/ G 95

CNTN1Contactin-1

GP135; F3; MYPCN

Notch-1; PTPRZ; NrCAM; Neurofascin 155; L1CAM; Caspr1; TNC

Molecule Number

Native MWORF % aa Sequence ID (Human to Mouse)Abbreviated

Name

Receptors or Ligands

Full NameAlternate Name

Additional Information in Notes SectionStructure

NrCAM

Sema3A-D, 3F, 3G Sema3E Sema4C

cis

PLXNB3

Domain Key:

Ig-like

Sema

PSI

IPT

Split GAP

Convertase Cleavage

Tyrosine Kinase

PDZ-Binding

Basic

Meprin

GTPase-Binding

Complement-Binding

Coagulation Factor V/VIII

Ligand-Binding

Thrombospondin-like

GPI Anchor

Sema6A Sema7

PLXNB2 PLXNB1

PLXNA2Sema4D Sema5A

PLXNC1

Integrinα1β1

PLXNA4PLXNA3

NRP2

VEGF R2

c-MetSYND3

PLXND1

NRP1 PLXND1

Figure 1. Semaphorin Domain Structure and Receptor InteractionsDomain Key:

Ig-like

Coagulation Factor V/VIII

Laminin-like

EGF-like 1

Fibrinogen C-terminal

Fibronectin Type-III

PEST

Transcriptional Activation

Nuclear Localization Signal

Ankyrin/CDC10 Repeat

RAM

Lin-Notch Repeat

EGF Repeat

GPI Anchor

NrCAM NCAML1CAM L1CAM

NrCAMCaspr1

NFASC

Notch-1

CNTN1CNTN1 CNTN2 CNTN5 CNTN3 CNTN4 CNTN2CNTN1CNTN6

CNTN2Caspr2

APLP-1 APLP-1APP APP

Figure 2. Contactin Domain Structure and Receptor Interactions

(GDNF:GFRα-1)2: (NCAM-1)2

GDNF2: SYND3

GDNF2: SYND3

GDNF2: SYND3:c-Met

GDNF

GFRα-1 GFRα-2NCAM-1SYND3

SYND3

Ret

PCDHA4/PCDHGB7

(GDNF:GFRα-1)2 (GDNF:GFRα-2)2

(GDNF:GFRα-1:Ret)2 (GDNF:GFRα-2 :Ret)2

(GDNF:GFRα-1:Ret:PCDHA4/PCDHGB7)2 (GDNF:GFRα-2 :Ret:PCDHA4/PCDHGB7)2

Ret

PCDHA4/PCDHGB7

c-Met

Figure 3. GFRa-1 and GFRa-2 Ligand Interactions

Structure Key

MonomerHomodimerHomo-oligomer

HeterodimerG GPI-LinkedS Secreted

SS DisulfideBond-Linked1 Single Pass (Type I) Transmembrane3 Single Pass (Type III) Transmembrane

▲ Hypothesized structure, based on the structure of the other members in its protein family.

* Notes 1. CNTN1 has two isoforms that have open reading frames (ORFs) of 1007 amino acids (aa) and 627 aa. 2. Sema4F is found on oligodendrocytes and postsynaptic dendrites. 3. CNTN2 mutations are associated with epilepsy. 4. APP has multiple splice variants and cleavage-generated fragments. 5. There are at least two splice variants for Nectin-1. One variant is secreted with a MW of approximately 52K–54K, while the other isoform is a transmembrane protein

truncated to 458 aa. Nectin-1 dimers are important for maximizing synapse size. 6. SYND3 is attached to 100K–120K of heparin sulfate, which binds to immobilized GDNF. 7. It has been suggested that GDNF signaling may require concurrent TGF-b signaling in select cell types. There are four traditional splice variants of GDNF, which are 159 aa,

185 aa, 202 aa, and 228 aa in length. Additionally, an opposite-strand derived form of GDNF that translates into a 77 aa mature molecule also exists. 8. In general, NRPs bind Semas, while PLXNs transduce the signal. 9. PLXND1 plays a critical role in the development of basal ganglia glutamatergic signaling. 10. Sema4G is highly expressed in cerebellar Purkinje cells. 12. APLP-1 has one splice variant, which has an ORF that is 651 aa in length. Multiple cleavage isoforms arise during apoptosis. 13. Nectin-3, which is postsynpatic, binds to presynaptic Nectin-1 in-trans. Binding of Nectin-3 to Nectin-2 occurs on endothelial cells during leukocyte migration. 15. NRTN is a potent trophic factor for dopaminergic neurons. 17. Homodimeric, and not monomeric, Sema3A is active. The 95K Sema3A monomer can be cleaved between Arg555 and Gln556, generating a 65K–70K N-terminal and a

33K–50K C-terminal fragment (note: some reports state the native MW of Sema3A is approximately 125K; thus, cleavage would generate an 80K–90K N-terminal fragment). 18. Sema5a is secreted with a MW of approximately 110K. Sema5A interacts with heparin sulfate to promote cell attraction and with chrondroitin sulfate to promote cell

repulsion. 19. CNTN4 plays a key role in olfaction. There are three isoforms that have ORFs that are of 282 aa, 697 aa, and 698 aa in length. 20. APLP-2 is presynaptic while its trans-heterodimerizing partner, APLP-1 is postsynaptic. 21. LINGO-1 is a potential member of the Nogo-66 receptor complex. 23. Notch-1 undergoes cleavage at three sites: Arg1664, Gly1710 and Ala1720. 24. Unlike many Integrins, ITGA1 contains an internal “I” domain that precludes proteolysis. 25. NGF R may be cleaved to generate a 20K and 25K intracellular domain fragment that exhibit growth arrest activity. 26. NLGNs are postsynaptic proteins that bind presynaptic b-Neurexins. If NLGN1 has a site-B insert of eight aa after Glu297, it will bind only to b-Neurexins.

If this site-B insert is absent, NLGN1 will bind to both a- and b-Neurexins. Functionally, NLGNS that contain the site-B insert promote synapse formation while those that lack it promote synapse size expansion. NLGN1 is considered to be a glutamatergic NLGN.

27. GPC1 is believed to undergo cleavage to generate an 80K–100K soluble isoform. 28.MDGA1influencesinhibitorysynapsedevelopmentbybindingNLGN2in-cis and blocking its association with NRXN in-trans. 29.Therearemorethan20splicevariantsofFGFR1.FGFR1cexhibitsanunusualactivityprofile.ItisinactivewhenitbindstoNCAM-1in-cis; however, when it binds to poly-

sialylated NCAM-1 in-trans, it is active. The presence of an “acid box” (aa 126–133) is essential for FGF R1c to interact with NCAM-1 and N-Cadherin. 30. The GDNF Receptor family member GFRAL (GDNF Receptor-a-like) has been shown to be a receptor for GDF-15 and play a putative role in obesity. 31. NLGNS help form synapses, and SynCAMs lock these synapses into place. SynCAM1 binds to SynCAM3 in-trans, but it interacts with ErbB3/Her3 and Integrin a6b4 in-cis.

SynCAM1 forms glia:neuron bonds in-trans by homo-oligomerizing. Up to 50% of the MW of SynCAM1 is attributed to variable glycosylation and alternative splicing. 32. Proteolytic cleavage of Slit2 generates a 140K N-terminal and a 55K–60K C-terminal fragment. The 200K and 140K isoforms of Slit2 activate ROBOs. The 60K C-terminal

fragment binds to GPC1. Slit2 has two splice variants, which are 1521 aa and 1525 aa in length. 33. ARTN is associated with pain-sensing neurons. 35. Sema3C is cleaved at Arg745 by ADAMTS1 to generate a highly active 94K–95K polypeptide. 36. Sema5B is believed to be a type III transmembrane protein (i.e. it resembles a type I transmembrane protein but lacks a signal sequence). 37. CNTN5 has two isoforms that have ORFs that are 998 aa and 911 aa in length. 38. NRXN1a has an SS4 site that lies between aa 1241–1270. Multiple isoforms have been reported including a 73K, 442 aa b-isoform that binds “B-site” positive NLGN1.

NRXN1a promotes GABAergic synapse organization while NRXN1b promotes glutamatergic synapse organization. 39. It has been suggested that LINGO-2variationinfluencesriskandonsetageofessentialtremorandParkinson’sdisease. 40. AMIGO3 is thought to be a member of the NgR:TROY complex, which serves as the Nogo-66 receptor. 41. The b-NGF precursor consists of an N-terminal 14K proregion that is coupled to a 12K–13K mature region. When the 25K–30K proform is released, it binds to an

NGF R:SORT1 complex and induces apoptosis. Mature b-NGF does not bind to this complex. ProNGF will also bind to TrkA. 43. TROY is thought to be a marker for microglia but not macrophages. 44. NLGN2 is considered to be a GABAergic NLGN. Unlike most NLGNs, which are typically localized to postsynaptic membranes, retina NLGN is presynaptic. 46. MDGA2 has two splice variants, which are 727 aa and 1025 aa in length. 47. Ret has one splice variant, called Ret-9, that is 1072 aa in length. Ret can be cleaved after Asp707 and Asp1017. The fragment that lies between Ala708 and Asp1017

appears to be apoptotic. 48. GFR-a2 has two splice variants that are 331 aa and 359 aa in length. The shorter GFR-a2 isoform negatively regulates the activity of the full-length protein and the 359 aa

isoform. The GDNF Receptor family member GFRAL (GDNF Receptor-a-like) has been shown to be a receptor for GDF-15 and play a putative role in obesity. 49. Neuronal SynCAM2 interacts with SynCAM3 located on oligodendrocytes. 50. Slit3 has three splice variants, which are 1423 aa, 1472 aa, and 1530 aa in length. 51. The PSPN:GFRa-4complexinefficientlyrecruitsRet. 52.PLXNA4mutationsmaybeinvolvedinthepathogenesisoffamilialParkinson’sdisease.PLXNA3andPLXNA4appeartoregulateautonomicsympatheticneuronmigrationand

neurite extension. 53. Sema3D is cleaved to generate a 65K–70K fragment that is necessary for full activity. 54. Sema6A mediates granule cell migration. 56. The b splice variant of NRXN2 has a MW of 76K–80K, is 666 aa in length, and binds to NLGN1 proteins that contain the site-B insert. 59. The BDNF precursor consists of an N-terminal 16K–18K proregion that is coupled to a 13K mature region. When the 30K-32K proform is released, it binds to a NGF R:SORT1

complex, which may also interact with TrkB. ProBDNF does not bind to Trk-B. There are four BDNF splice variants, which are 255 aa, 262 aa, 276 aa, and 329 aa in length. 61. NXPHs appear to be secreted only by inhibitory neurons. NXPHs bind a-Neurexins while NLGNs bind b-Neurexins. ProNXPH1 has a MW of approximately 46–50K. 62. NLGN3 participates in both GABAergic and glutamatergic synapse development. 64. PCDHA4 has only one alternative splice variant that is 798 aa in length. Cleavage of the full-length 120K protein is believed to generate a second isoform that contains

a 75K soluble fragment plus a 40K transmembrane truncated segment. 65.Thec-METprecursorcanbecleavedtogenerateadisulfide-linkedheterodimerthatconsistsofa50Kextracellulardomain(ECD)anda140Ktransmembrane/cytoplasmic

segment.Ingeneral,therearemorethat50isoformvariantsofc-MET,manyofwhicharepresumedtobesoluble.ThenameMETisderivedfromthefirstthreeletters(methyl-) of the carcinogen that was used during its discovery.

66. Soluble GFRa-3 has a MW of approximately 50K. It has one splice variant that is 369 aa in length. The GDNF Receptor family member GFRAL (GDNF Receptor-a-like) has been shown to be a receptor for GDF-15 and play a putative role in obesity.

67. Carbohydrate moiety regulates SynCAM3 adhesive properties. 68. LRRTM1 is a postsynaptic protein that participates in excitatory synapse formation. The entire molecule is encoded by one exon, and thus, there are no splice variants. 69. There are two alternative splice variants, Nogo-B and Nogo-C, which are 373 aa and 199 aa in length, respectively. 70. PLXNB1 is cleaved to generate a 180K–200K soluble fragment and a 90K–100K membrane-bound fragment. Cleavage occurs between Arg1305 and Val1306, and the two

fragments may remain non-covalently associated. 71. Sema3E binds PLXND1 in the absence of NRPs. It is also cleaved into a 60K–61K isoform, which promotes cell migration. 72. Sema6B is found on neuronal dendrites. 73. L1CAM undergoes cleavage to generate a 35K, 85K and 140K fragment. 74. The b splice variant of NRXN3 has a MW of 80K–85K, is 668 aa in length, and shows increased binding strength to NLGNs when the SS4 site is present in the molecule. 76. Multiple isoforms of TrkB exist. 77. Human NT-3 circulates in the blood at concentrations of 5–10 pg/mL. In contrast, human BDNF circulates in the blood at a concentration of approximately 2000 pg/mL. 78. ITGB1 is one part of the Integrin a9b1 complex, which binds neurotrophins and promotes cell survival. 80. NLGN4X is an X-chromosome gene. NLGN4X mutations are associated with impaired synapse formation in autism. 81. ROBO3 is thought to also exist as a 1034 aa secreted isoform with a MW of approximately 160K. 82. PCDHGB7 is thought to serve as a signaling receptor or subunit for Ret. PCDHGB7 binds to PCDHA4 in-cis. 83.TheMSPRprecursorcanbecleavedtogenerateadisulfide-linkedheterodimerthatconsistsofa35KECDanda150Ktransmembrane/cytoplasmicfragment.Although

associatedwiththeimmunesystem,MSPisneurotrophicforNGF-responsivepainfibers.Thealternatename,Ron,isderivedfromRecepteurd’OrigineNantais(Receptor“Discovered” in Nantes, France).

84. GFRa-4 has two splice varients, which are 182 aa and 269 aa in length. The GDNF Receptor family member GFRAL (GDNF Receptor-a-like) has been shown to be a receptor for GDF-15 and play a putative role in obesity.

85. SynCAM4 is believed to not undergo splicing and is principally expressed by Schwann cells. 87. SORT1 is only active after cleavage of aa 34–77. Additional cleavage generates a 100K soluble isoform. 88. PLXNB2 is cleaved in the region between Arg1161 and Asp1165, generating a 170K soluble and 80K transmembrane fragment. It is thought that processing of PLXNB2

occurs prior to its interaction with Sema4D. 89. Sema3F binds to NRP1 but exhibits no activity. 90.Sema6Cparticipatesinsensoryneurondevelopment;however,intheadult,Sema6Cisfoundonlyonskeletalmusclefibers. 91. Cleavage of NrCAM generates a 130K–140K a-chain and a 60K-80K b-chain. There are at least 5 splice variants, which have ORFs that are 1174 aa, 1180 aa, 1192 aa,

1236 aa, and 1308 aa in length. 92. Caspr1 binds to g-secretase and blocks the conversion of Ab to Ab42. 93. AMIGO serves as a subunit for the Kv2.1 K+ channel. 94. TrkC has four splice variants that have ORFs that are 612 aa, 817 aa, 831 aa, and 825 aa in length. 96. ITGB4 has four splice variants that have ORFs that are 858 aa, 1745 aa, 1752 aa, and 1805 aa in length. 97. ProNXPH3 has a MW of approximately 41K. 98. NLGN4Y is a Y-chromosome gene whose expression is necessary for synapse formation. There are three splice variants, which are 134 aa, 256 aa, and 648 aa in length. 100. There are multiple splice variants for NCAM-1 including a “full-length” 180K isoform, a 140K transmembrane short form, a 120K GPI-linked isoform, and a 200-230K poly-

sialicacid(PSA)modifiedisoform.Non-PSA-NCAM-1formstrans-homo-oligomersthatmediatebothFGFR1dimerizationandGFRa signaling.102.HumanTNCbloodconcentrationisapproximately10–20ng/mL.Therearefivesplicevariants,whichare1655aa,1564aa,1746aa,1837aa,and2110aainlength. 104. LRRTM3 promotes APP processing by activating BACE1. There is one splice variant that is 513 aa in length.105.NRP1mayhavebothchrondroitinsulfateandheparinsulfateposttranslationalmodifications.NRP1homodimersbindtoSema3A. 106. PLXNB3 does not undergo proteolytic cleavage. PLXNB3-mediated axon guidance is responsible for language development. 108. Sema6D plays a key role in establishing contralateral and ipsilateral connections of the optic nerve. Multiple Sema6D splice variants exist, and proteolysis of the protein

generates an 80K fragment.109.NFASChasmultiplesplicevariants,twoofwhichareNF155andNF186(namesreflecttheirrespectiveMWs).NF155isfoundonoligodendrocyteswhileNF186isexpressed

in neurons. 110. Caspr2 is thought to be crucial for the proper placement of K+ channels in the nodes of Ranvier. 112. NRP2 homodimers bind Sema3F. NRP1:NRP2 heterodimers bind Sema3C. 114. Sema4D is an oligodendrocyte marker. It undergoes proteolysis to generate a circulating 130K bioactive molecule. Sema4D is also reported to use multiple RTKs for cell

signaling including MSP R and ErbB2/Her2. 115. Sema7A binding to Integrins promotes neuron migration, while Sema7A bonding to PLXNC1 blocks cell migration.

NOTE:Thisposterconveysageneraloverviewandshouldbeconsideredneithercomprehensivenordefinitive.Thedetailsofthisinformationareunderstoodtobesubjecttointerpretation.©2014R&DSystems

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