Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Protein madd-4

Gene

madd-4

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of an extracellular matrix cue that is involved in the guidance of dorsoventral midline migrations and in the specification of postsynaptic domains at neuromuscular junctions (NMJs) (PubMed:22014523, PubMed:24896188, PubMed:25122090, PubMed:26028575, PubMed:26028574). Acts as a ligand for the netrin receptor unc-40 and the neuroligin receptor nlg-1 (PubMed:22014523, PubMed:26028575, PubMed:25122090, PubMed:24896188). Secreted by the dorsal and ventral nerve cords to attract sensory axons and muscle membrane extensions called muscle arms (PubMed:22014523). In parallel with unc-6 and slt-1, involved in the netrin receptor unc-40 dependent guidance of the AVM and PVM mechanosensory axons along the dorsal-ventral axis (PubMed:22014523). The unc-40 coreceptor eva-1 is enhancing the responsiveness of unc-40 to the madd-4 guidance cue to attract the muscle arm extensions and AVM mechanosensory axons towards the dorsoventral midline (PubMed:25122090). Acts as a synaptic organizer and is required for the specification of inhibitory GABAergic and excitatory cholinergic identities of postsynaptic domains at neuromuscular junctions (NMJs) (PubMed:24896188, PubMed:26028575, PubMed:26028574). Required for the recruitment of unc-40 to both cholinergic and GABAergic NMJs (PubMed:26028575). Promotes the clustering of ACh receptors and GABA(A) receptors at postsynaptic sites during synaptogenesis (PubMed:24896188). The binding to the presynaptic adhesion protein nrx-1 and to the neuroligin nlg-1 at postsynaptic sites promotes clustering of GABAergic receptors at postsynaptic NMJs, thereby contributing to normal GABAergic synaptic transmission (PubMed:26028574).5 Publications
Isoform a and isoform c: Promote the clustering of acetylcholine receptors (AChR) at excitatory cholinergic synapses of NMJs via the netrin receptor unc-40.1 Publication
Isoform b: Acts as a guidance cue in the attraction of muscle membrane extensions (muscle arms) to the dorsal cord and in cooperation with unc-6 to the ventral cord via the netrin receptor unc-40 and via the unc-40 coreceptor eva-1 (PubMed:22014523, PubMed:25122090). Together with nrx-1, clusters netrin receptor unc-40 and neuroligin nlg-1 at postsynaptic sites of GABAergic NMJs, thereby promoting the recruitment of GABA(A) receptors at GABAergic synapses (PubMed:24896188, PubMed:26028575, PubMed:26028574). Prevents the recruitment of GABAergic receptors to cholinergic synapses (PubMed:24896188).5 Publications

GO - Molecular functioni

  • metalloendopeptidase activity Source: InterPro
  • receptor binding Source: WormBase
  • zinc ion binding Source: InterPro

GO - Biological processi

  • dorsal/ventral axon guidance Source: WormBase
  • synapse organization Source: WormBase

Enzyme and pathway databases

ReactomeiR-CEL-5173214. O-glycosylation of TSR domain-containing proteins.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein madd-4Curated
Alternative name(s):
Punctin1 Publication
Gene namesi
Name:madd-4Imported
ORF Names:F53B6.2Imported
OrganismiCaenorhabditis elegansImported
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome I

Organism-specific databases

WormBaseiF53B6.2a; CE36859; WBGene00009958; madd-4.
F53B6.2b; CE32429; WBGene00009958; madd-4.
F53B6.2c; CE32428; WBGene00009958; madd-4.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell projection, Extracellular matrix, Secreted, Synapse

Pathology & Biotechi

Disruption phenotypei

Disrupts the clustering of the cholinergic receptor subunits unc-29, unc-38 and acr-16 and the GABAergic receptor subunit unc-49 at postsynaptic domains of neuromuscular junctions (NMJs), and the receptors are redistributed to extrasynaptic areas (PubMed:24896188, PubMed:26028575). Loss of neuroligin receptor nlg-1 and netrin receptor unc-40 localization to NMJs (PubMed:26028575). Isoform a and isoform c: Defects in AChR localization to cholinergic synapses (PubMed:24896188). Decreased AChR-dependent currents triggered by motoneuron stimulation (PubMed:24896188). Isoform b: Extensive dorsal muscle arm extension defects and weaker ventral muscle arm extension defects (PubMed:24896188, PubMed:22014523). Relocalization of GABAergic receptors from GABAergic to cholinergic synapses (PubMed:24896188, PubMed:26028575). Redistribution of the neuroligin receptor nlg-1 from GABAergic to cholinergic NMJs (PubMed:26028575). In a unc-6 mutant background, extensive ventral muscle arm extension defects (PubMed:22014523). Loss of unc-40 localization at GABAergic NMJs (PubMed:26028575).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi398R → H: Disrupts the attraction of the muscle arm extensions. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_500416177524 – 1045Protein madd-4Sequence analysisAdd BLAST1022

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi35 ↔ 65PROSITE-ProRule annotation
Disulfide bondi39 ↔ 70PROSITE-ProRule annotation
Disulfide bondi50 ↔ 55PROSITE-ProRule annotation
Glycosylationi268N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1
Glycosylationi280N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1
Disulfide bondi674 ↔ 722PROSITE-ProRule annotation
Glycosylationi730N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1
Glycosylationi781N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1
Glycosylationi899N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1
Glycosylationi906N-linked (GlcNAc...) asparaginePROSITE-ProRule annotation1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP90884.

Expressioni

Tissue specificityi

Isoform a: Expressed in the commissural GABAergic and cholinergic motor neurons in the first larval stage but only in the cholinergic motor neurons in later larval stages and in adult animals (PubMed:22014523). At the L1 larval stage, mainly localized at the nerve ring and at the dorsal cord (PubMed:24896188). Isoform b: Expressed in the commissural GABAergic and cholinergic motor neurons whose cell bodies reside in the ventral nerve cord and which extend axons into the ventral and dorsal nerve cord (PubMed:22014523, PubMed:24896188). Also expressed in the head neurons RIA, RIC, lateral IL1s, lateral IL2s, OLLs, RMEs and SABs, all of which extend axons into the nerve ring (PubMed:22014523, PubMed:24896188). Expressed in the embryogenic blast cells and the corresponding terminally differentiated ventral cord motor neurons and head neurons (PubMed:22014523).2 Publications

Developmental stagei

Isoform a: Expressed in larval stages L1 and L2 and in adult animals. Isoform b: Expressed in embryos, larval stages L1 and L2 and in adult animals.1 Publication

Gene expression databases

BgeeiWBGene00009958.
ExpressionAtlasiP90884. baseline and differential.

Interactioni

Subunit structurei

Interacts with eva-1 (via the SUEL-type lectin domain) (PubMed:25122090). Interacts with unc-5 (PubMed:25122090). Interacts with unc-40; the interaction is required for the localization of unc-40 to postsynaptic domains (PubMed:25122090, PubMed:26028575). Isoform a forms homodimers and heterodimers with isoform b (PubMed:24896188). Isoform b forms homodimers and heterodimers with isoform a (PubMed:24896188). Isoform b interacts with nlg-1 (via extracellular domain); the interaction is required for nlg-1 localization to postsynaptic domains (PubMed:26028574, PubMed:26028575). Isoform b interacts (via the Ig-like C2-type domain) with nrx-1 (via C-terminus) (PubMed:26028574).4 Publications

GO - Molecular functioni

  • receptor binding Source: WormBase

Protein-protein interaction databases

STRINGi6239.F53B6.2a.

Structurei

3D structure databases

ProteinModelPortaliP90884.
SMRiP90884.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 71TSP type-1 1PROSITE-ProRule annotationAdd BLAST48
Domaini236 – 292TSP type-1 2PROSITE-ProRule annotationAdd BLAST57
Domaini294 – 510TSP type-1 3PROSITE-ProRule annotationAdd BLAST217
Domaini512 – 572TSP type-1 4PROSITE-ProRule annotationAdd BLAST61
Domaini576 – 635TSP type-1 5Sequence analysisAdd BLAST60
Domaini637 – 732Ig-like C2-typePROSITE-ProRule annotationAdd BLAST96
Domaini811 – 873TSP type-1 6Sequence analysisAdd BLAST63
Domaini932 – 990TSP type-1 7PROSITE-ProRule annotationAdd BLAST59
Domaini1004 – 1041PLACPROSITE-ProRule annotationAdd BLAST38

Domaini

The Ig-like C2-type domain is required for the attraction of the muscle arm extensions.1 Publication

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410INDC. Eukaryota.
ENOG410YY5R. LUCA.
GeneTreeiENSGT00900000140774.
HOGENOMiHOG000019636.
InParanoidiP90884.
OMAiHDEVERC.
OrthoDBiEOG091G00XI.
PhylomeDBiP90884.

Family and domain databases

Gene3Di2.20.100.10. 11 hits.
2.60.40.10. 1 hit.
InterProiView protein in InterPro
IPR007110. Ig-like_dom.
IPR036179. Ig-like_dom_sf.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR010909. PLAC.
IPR000884. TSP1_rpt.
IPR036383. TSP1_rpt_sf.
PfamiView protein in Pfam
PF07679. I-set. 1 hit.
PF00090. TSP_1. 5 hits.
PRINTSiPR01857. ADAMTSFAMILY.
SMARTiView protein in SMART
SM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
SM00209. TSP1. 9 hits.
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF82895. SSF82895. 9 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 1 hit.
PS50900. PLAC. 1 hit.
PS50092. TSP1. 6 hits.

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Isoform aImported (identifier: P90884-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKCSYTVVFL LFYLLIASFH VDALSWAAWS PWSSCTKTCG GGVSRQLRRC
60 70 80 90 100
LTSKCSGESV RFKVCAQKTC ESKSRLARDT ICGGEEIVSR GQCEVVCRSR
110 120 130 140 150
LTGANFLWRV DDGTPCQAAT SRAVCSKGSC QIVGCDGLIS SSFRFDACGV
160 170 180 190 200
CGGRGDTCDN GKFIWKVSEE YTACASNCDD IVDWSGAGRS IASTSQPIVV
210 220 230 240 250
CVNAITGRVV PEKLCADKLR PKVEARPCPM LICPSRCRWM AADWTECVPH
260 270 280 290 300
CGEGTRKREV YCVQTAHNVT VHVPDTFCEN GTRPAAEENC VSTSCGRWEA
310 320 330 340 350
GKWSKCTASC GQGVRRRHVA CVGGSDCDEG GRPRQETTCY AGIPCSIATN
360 370 380 390 400
SLDWNDRAYL DGNTFGSMDN HNDWQAPRLV AGEWSTCSST CGTGVMSRTV
410 420 430 440 450
ECVAVNPISS APIKLPMSEC QDQEQPKLFE SCEVRSCPLQ EDSKLSEDEA
460 470 480 490 500
PYQWRYGDWT QCSASCLGGK QKAALKCIQV STGKSVQWSQ CDARRRPPEK
510 520 530 540 550
SRPCNQHPCP PFWLTSKYSD CSMSCGSGTA RRSVKCAQTV SKTDGADAHI
560 570 580 590 600
VLRDDRCHFK KPQETETCNV VACPATWVTA QWTECSRSCD SGERRRQVWC
610 620 630 640 650
EIRDSRGKTQ RRPDVECDAN TKPQTVEVCS FGSCSRPELL SNRVFEQNAE
660 670 680 690 700
QKKLTLGIGG VATLYQGTSI KIKCPAKKFD KKKIYWKKNG KKIKNDAHIK
710 720 730 740 750
VSANGNLRVF HARMEDAGVY ECFTDRLQGN VTLNFKYRDF PASRVDLAPK
760 770 780 790 800
PQIPSTKNRQ RVQVSKEDVL REQASVLHKM NVSLIEALLT APNDEKAREQ
810 820 830 840 850
LRKYGNELVA RWDIGHWSEC RQKTCHVAGY QARGISCKVT FHGEIRNVDN
860 870 880 890 900
SICESLASVR PPETRPCHRE DCPRWEASQW SECSSQRCVS SMLAQKRRNV
910 920 930 940 950
TCRFTNGTSV DIQHCDITNR PATTMDCPNQ NCKAEWRTSD WGSCSSECGT
960 970 980 990 1000
GGVQLRLLSC VWISSGRPAG RNCEQMRRPH SARACVADEP LPPCMPTASA
1010 1020 1030 1040
LYQRDASCQD QSRFCDIIKL FHSCDSLEVR QKCCSTCTFV ERKKF
Length:1,045
Mass (Da):116,125
Last modified:September 13, 2004 - v5
Checksum:iF78269D1D50228B1
GO
Isoform bImported (identifier: P90884-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-351: MKCSYTVVFL...GIPCSIATNS → MLPLLLILSAPLGVSAF

Note: Produced by alternative promoter usage.
Show »
Length:711
Mass (Da):79,946
Checksum:i9695028B9636AE94
GO
Isoform cImported (identifier: P90884-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     237-238: Missing.

Note: Produced by alternative splicing of isoform a.
Show »
Length:1,043
Mass (Da):115,865
Checksum:iA670346A1DBF1AF0
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0592741 – 351MKCSY…IATNS → MLPLLLILSAPLGVSAF in isoform b. CuratedAdd BLAST351
Alternative sequenceiVSP_059275237 – 238Missing in isoform c. Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BX284601 Genomic DNA. Translation: CAB03121.3.
BX284601 Genomic DNA. Translation: CAD56586.1.
BX284601 Genomic DNA. Translation: CCH63796.1.
PIRiT22545.
RefSeqiNP_001250933.1. NM_001264004.1.
NP_492405.3. NM_060004.4.
NP_871884.1. NM_182084.5.
UniGeneiCel.5959.

Genome annotation databases

EnsemblMetazoaiF53B6.2a; F53B6.2a; WBGene00009958. [P90884-1]
F53B6.2b; F53B6.2b; WBGene00009958. [P90884-2]
F53B6.2c; F53B6.2c; WBGene00009958. [P90884-3]
GeneIDi172706.
KEGGicel:CELE_F53B6.2.
UCSCiF53B6.2b. c. elegans. [P90884-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMADD4_CAEEL
AccessioniPrimary (citable) accession number: P90884
Secondary accession number(s): I2HA89, Q8I4I1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 20, 2017
Last sequence update: September 13, 2004
Last modified: January 31, 2018
This is version 129 of the entry and version 5 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase