CO4A2_CAEEL
ID CO4A2_CAEEL Reviewed; 1758 AA.
AC P17140; Q19098; Q19099;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Collagen alpha-2(IV) chain;
DE AltName: Full=Lethal protein 2;
DE Flags: Precursor;
GN Name=let-2 {ECO:0000312|WormBase:F01G12.5a};
GN Synonyms=clb-1 {ECO:0000312|WormBase:F01G12.5a};
GN ORFNames=F01G12.5 {ECO:0000312|WormBase:F01G12.5a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, FUNCTION, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2;
RX PubMed=7691828; DOI=10.1083/jcb.123.1.255;
RA Sibley M.H., Johnson J.J., Mello C.C., Kramer J.M.;
RT "Genetic identification, sequence, and alternative splicing of the
RT Caenorhabditis elegans alpha 2(IV) collagen gene.";
RL J. Cell Biol. 123:255-264(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP PRELIMINARY NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1495-1758.
RC STRAIN=Bristol N2;
RX PubMed=2793871; DOI=10.1016/s0021-9258(18)71530-5;
RA Guo X., Kramer J.M.;
RT "The two Caenorhabditis elegans basement membrane (type IV) collagen genes
RT are located on separate chromosomes.";
RL J. Biol. Chem. 264:17574-17582(1989).
RN [4]
RP FUNCTION, AND MUTAGENESIS.
RX PubMed=8045258; DOI=10.1002/j.1460-2075.1994.tb06629.x;
RA Sibley M.H., Graham P.L., von Mende N., Kramer J.M.;
RT "Mutations in the alpha 2(IV) basement membrane collagen gene of
RT Caenorhabditis elegans produce phenotypes of differing severities.";
RL EMBO J. 13:3278-3285(1994).
RN [5]
RP ALTERNATIVE SPLICING, AND DEVELOPMENTAL STAGE.
RX PubMed=18230701; DOI=10.1101/gad.1620608;
RA Ohno G., Hagiwara M., Kuroyanagi H.;
RT "STAR family RNA-binding protein ASD-2 regulates developmental switching of
RT mutually exclusive alternative splicing in vivo.";
RL Genes Dev. 22:360-374(2008).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP GLY-1125; GLY-1286; GLY-1465 AND SER-1610.
RX PubMed=19104038; DOI=10.1073/pnas.0804055106;
RA Kubota Y., Ohkura K., Tamai K.K., Nagata K., Nishiwaki K.;
RT "MIG-17/ADAMTS controls cell migration by recruiting nidogen to the
RT basement membrane in C. elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:20804-20809(2008).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF GLY-877.
RX PubMed=25080592; DOI=10.1523/jneurosci.5128-13.2014;
RA Qin J., Liang J., Ding M.;
RT "Perlecan antagonizes collagen IV and ADAMTS9/GON-1 in restricting the
RT growth of presynaptic boutons.";
RL J. Neurosci. 34:10311-10324(2014).
RN [8]
RP MUTAGENESIS OF GLU-479; PRO-587 AND SER-1610.
RX PubMed=29440357; DOI=10.1534/genetics.118.300731;
RA Gotenstein J.R., Koo C.C., Ho T.W., Chisholm A.D.;
RT "Genetic Suppression of Basement Membrane Defects in Caenorhabditis elegans
RT by Gain of Function in Extracellular Matrix and Cell-Matrix Attachment
RT Genes.";
RL Genetics 208:1499-1512(2018).
CC -!- FUNCTION: Collagen type IV is specific for basement membranes
CC (Probable). Together with fbl-1 and downstream of metalloprotease mig-
CC 17, recruits nidogen nid-1 to the gonad basement membrane thereby
CC probably inducing basement membrane remodeling required for the
CC directional migration of distal tip cells (PubMed:19104038). Required
CC to restrict presynaptic growth at the neuromuscular junctions in late
CC larval stage and in adult motor neurons (PubMed:25080592). Vital for
CC embryonic development (PubMed:7691828, PubMed:8045258).
CC {ECO:0000269|PubMed:19104038, ECO:0000269|PubMed:25080592,
CC ECO:0000269|PubMed:7691828, ECO:0000269|PubMed:8045258, ECO:0000305}.
CC -!- SUBUNIT: Trimers of two alpha 1(IV) and one alpha 2(IV) chain. Type IV
CC collagen forms a mesh-like network linked through intermolecular
CC interactions between 7S domains and between NC1 domains.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000255|PROSITE-ProRule:PRU00736,
CC ECO:0000269|PubMed:19104038}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Exons 9 and 10 are mutually exclusive splicing exons. There
CC is alternative usage of either exon 9 (isoform a) or exon 10 (isoform
CC b). {ECO:0000305};
CC Name=a {ECO:0000312|WormBase:F01G12.5a}; Synonyms=I
CC {ECO:0000303|PubMed:7691828};
CC IsoId=P17140-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:F01G12.5b}; Synonyms=II
CC {ECO:0000303|PubMed:7691828};
CC IsoId=P17140-2; Sequence=VSP_001160;
CC -!- TISSUE SPECIFICITY: Localizes to the basement membrane between distal
CC tip cells and the germline. Localizes to the intestinal basement
CC membrane. {ECO:0000269|PubMed:19104038}.
CC -!- DEVELOPMENTAL STAGE: Alternatively spliced, in part by RNA-binding
CC protein asd-2, to produce isoforms which are expressed at different
CC developmental stages (PubMed:18230701). Isoform a: Predominantly
CC expressed in embryos (PubMed:7691828, PubMed:18230701). Isoform b:
CC Predominantly expressed in larvae and adults (PubMed:7691828,
CC PubMed:18230701). {ECO:0000269|PubMed:18230701,
CC ECO:0000269|PubMed:7691828}.
CC -!- DOMAIN: Alpha chains of type IV collagen have a non-collagenous domain
CC (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats
CC in the long central triple-helical domain (which may cause flexibility
CC in the triple helix), and a short N-terminal triple-helical 7S domain.
CC {ECO:0000255|PROSITE-ProRule:PRU00736}.
CC -!- PTM: Prolines at the third position of the tripeptide repeating unit
CC (G-X-Y) are hydroxylated in some or all of the chains.
CC {ECO:0000255|PROSITE-ProRule:PRU00736}.
CC -!- PTM: Type IV collagens contain numerous cysteine residues which are
CC involved in inter- and intramolecular disulfide bonding. 12 of these,
CC located in the NC1 domain, are conserved in all known type IV
CC collagens. {ECO:0000255|PROSITE-ProRule:PRU00736}.
CC -!- PTM: The trimeric structure of the NC1 domains is stabilized by
CC covalent bonds between Lys and Met residues. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the type IV collagen family.
CC {ECO:0000255|PROSITE-ProRule:PRU00736}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA64312.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; Z22964; CAA80536.1; -; Genomic_DNA.
DR EMBL; Z22964; CAA80537.1; -; Genomic_DNA.
DR EMBL; U22327; AAA64312.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BX284606; CCD68907.1; -; Genomic_DNA.
DR EMBL; BX284606; CCD68906.1; -; Genomic_DNA.
DR EMBL; J05066; AAA27989.1; -; Genomic_DNA.
DR PIR; A34476; A34476.
DR PIR; T29350; T29350.
DR PIR; T29351; T29351.
DR RefSeq; NP_510663.1; NM_078262.4.
DR RefSeq; NP_510664.1; NM_078263.3.
DR AlphaFoldDB; P17140; -.
DR BioGRID; 46593; 1.
DR STRING; 6239.F01G12.5b.1; -.
DR EPD; P17140; -.
DR PaxDb; P17140; -.
DR PeptideAtlas; P17140; -.
DR EnsemblMetazoa; F01G12.5a.1; F01G12.5a.1; WBGene00002280.
DR EnsemblMetazoa; F01G12.5b.1; F01G12.5b.1; WBGene00002280.
DR GeneID; 181708; -.
DR KEGG; cel:CELE_F01G12.5; -.
DR UCSC; F01G12.5b.1; c. elegans. [P17140-1]
DR CTD; 181708; -.
DR WormBase; F01G12.5a; CE04334; WBGene00002280; let-2.
DR WormBase; F01G12.5b; CE04335; WBGene00002280; let-2.
DR eggNOG; KOG3544; Eukaryota.
DR GeneTree; ENSGT00940000164076; -.
DR HOGENOM; CLU_002023_1_0_1; -.
DR InParanoid; P17140; -.
DR OrthoDB; 63831at2759; -.
DR PhylomeDB; P17140; -.
DR PRO; PR:P17140; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00002280; Expressed in larva and 3 other tissues.
DR GO; GO:0005604; C:basement membrane; IDA:UniProtKB.
DR GO; GO:0005587; C:collagen type IV trimer; IMP:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005201; F:extracellular matrix structural constituent; IDA:WormBase.
DR GO; GO:0030020; F:extracellular matrix structural constituent conferring tensile strength; IMP:UniProtKB.
DR GO; GO:0016043; P:cellular component organization; NAS:UniProtKB.
DR GO; GO:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0035262; P:gonad morphogenesis; IGI:UniProtKB.
DR GO; GO:0008104; P:protein localization; IMP:UniProtKB.
DR GO; GO:1903354; P:regulation of distal tip cell migration; IGI:UniProtKB.
DR Gene3D; 2.170.240.10; -; 1.
DR InterPro; IPR008160; Collagen.
DR InterPro; IPR001442; Collagen_IV_NC.
DR InterPro; IPR036954; Collagen_IV_NC_sf.
DR InterPro; IPR016187; CTDL_fold.
DR Pfam; PF01413; C4; 2.
DR Pfam; PF01391; Collagen; 17.
DR SMART; SM00111; C4; 2.
DR SUPFAM; SSF56436; SSF56436; 2.
DR PROSITE; PS51403; NC1_IV; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Basement membrane; Collagen; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Hydroxylation; Proteoglycan;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..1758
FT /note="Collagen alpha-2(IV) chain"
FT /id="PRO_0000005829"
FT DOMAIN 1531..1754
FT /note="Collagen IV NC1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT REGION 27..42
FT /note="7S domain"
FT REGION 42..1527
FT /note="Triple-helical region"
FT REGION 47..943
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 955..1304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1316..1339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1367..1525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 133..147
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..389
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 719..733
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 248
FT /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT /evidence="ECO:0000255"
FT DISULFID 1546..1635
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1579..1632
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1591..1597
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1654..1750
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1688..1747
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1700..1707
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT VAR_SEQ 229..264
FT /note="GDLGSVGPPGPPGPREFTGSGSIVGPRGNPGEKGDK -> GDIGAMGPAGPP
FT GPIASTMSKGTIIGPKGDLGEKGEK (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_001160"
FT MUTAGEN 48
FT /note="G->E: In MN114; 73% lethal."
FT /evidence="ECO:0000269|PubMed:8045258"
FT MUTAGEN 366
FT /note="A->T: In MN126; 100% lethal."
FT /evidence="ECO:0000269|PubMed:8045258"
FT MUTAGEN 479
FT /note="E->K: In ju1166; suppresses the lethal phenotypes of
FT the pxn-2 tm3464 mutant."
FT /evidence="ECO:0000269|PubMed:29440357"
FT MUTAGEN 570
FT /note="G->E: In MN109; 37% lethal."
FT /evidence="ECO:0000269|PubMed:8045258"
FT MUTAGEN 587
FT /note="P->L: In ju1180; suppresses the lethal phenotypes of
FT the pxn-2 tm3464 mutant."
FT /evidence="ECO:0000269|PubMed:29440357"
FT MUTAGEN 588
FT /note="G->R: In MN103 and MN151; 96% lethal."
FT /evidence="ECO:0000269|PubMed:8045258"
FT MUTAGEN 597
FT /note="G->R: In MN152; 50% lethal."
FT /evidence="ECO:0000269|PubMed:8045258"
FT MUTAGEN 690
FT /note="G->E: In MN129; 100% lethal."
FT /evidence="ECO:0000269|PubMed:8045258"
FT MUTAGEN 690
FT /note="G->R: In MN101; 100% lethal."
FT /evidence="ECO:0000269|PubMed:8045258"
FT MUTAGEN 737
FT /note="G->E: In MN143; 100% lethal."
FT /evidence="ECO:0000269|PubMed:8045258"
FT MUTAGEN 877
FT /note="G->R: In g30; temperature-sensitive mutant. At the
FT restrictive temperature, causes 90 percent lethality. At
FT the permissive temperature of 16 degrees Celsius, causes
FT the formation of ectopic presynaptic boutons on the ventral
FT cord axons."
FT /evidence="ECO:0000269|PubMed:25080592,
FT ECO:0000269|PubMed:8045258"
FT MUTAGEN 904
FT /note="G->R: In E1470; 94% lethal."
FT /evidence="ECO:0000269|PubMed:8045258"
FT MUTAGEN 1003
FT /note="G->E: In MN139; 20% lethal."
FT /evidence="ECO:0000269|PubMed:8045258"
FT MUTAGEN 1125
FT /note="G->D: In g25; temperature-sensitive mutant. At the
FT restrictive temperature of 25 degrees Celsius, causes 96
FT percent embryonic lethality. At the permissive temperature
FT of 22.5 degrees Celsius, partially restores normal distal
FT tip cell migration in a mig-17 (k174) mutant background."
FT /evidence="ECO:0000269|PubMed:19104038,
FT ECO:0000269|PubMed:8045258"
FT MUTAGEN 1152
FT /note="G->D: In MN147; 7% lethal."
FT /evidence="ECO:0000269|PubMed:8045258"
FT MUTAGEN 1286
FT /note="G->D: In g37 and b246; 9% lethal. Moderate reduction
FT in basement membrane localization associated with a
FT moderate accumulation in muscle cell cytoplasm. At the
FT restrictive temperature of 25 degrees Celsius, causes a
FT reduction of nid-1 recruitment to the gonad basement
FT membrane. At the permissive temperature of 22.5 degrees
FT Celsius, partially restores normal distal tip cell
FT migration in a mig-17 (k174) mutant background."
FT /evidence="ECO:0000269|PubMed:19104038,
FT ECO:0000269|PubMed:8045258"
FT MUTAGEN 1465
FT /note="G->R: In k196; temperature-sensitive mutant. At the
FT restrictive temperature of 25 degrees Celsius, causes 85
FT percent larval lethality. Slight reduction in basement
FT membrane localization associated with a slight
FT intracellular accumulation in muscle and distal tip cells
FT (DTC). In a mig-17 (k174) mutant background, restores
FT normal DTC migration and nid-1 basement membrane
FT localization."
FT /evidence="ECO:0000269|PubMed:19104038,
FT ECO:0000269|PubMed:8045258"
FT MUTAGEN 1610
FT /note="S->L: In k193; temperature-sensitive mutant. At both
FT the restrictive and permissive temperatures, causes 16-20
FT percent embryonic lethality. Slight reduction in basement
FT membrane localization associated with a slight
FT intracellular accumulation in muscle and distal tip cells
FT (DTC). In a mig-17 (k174) mutant background, restores
FT normal DTC migration and nid-1 basement membrane
FT localization. Enhances the lethality of the pxn-2 mutant
FT (ju432)."
FT /evidence="ECO:0000269|PubMed:19104038,
FT ECO:0000269|PubMed:29440357, ECO:0000269|PubMed:8045258"
FT CONFLICT 1604
FT /note="E -> D (in Ref. 2; CCD68907/CCD68906)"
FT /evidence="ECO:0000305"
FT CONFLICT 1682
FT /note="P -> L (in Ref. 2; CCD68907/CCD68906)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1758 AA; 167751 MW; 97EE3F3DBB2D2AC5 CRC64;
MKQRAALGPV LRLAILALLA VSYVQSQATC RDCSNRGCFC VGEKGSMGAP GPQGPPGTQG
IRGFPGPEGL AGPKGLKGAQ GPPGPVGIKG DRGAVGVPGF PGNDGGNGRP GEPGPPGAPG
WDGCNGTDGA PGIPGRPGPP GMPGFPGPPG MDGLKGEPAI GYAGAPGEKG DGGMPGMPGL
PGPSGRDGYP GEKGDRGDTG NAGPRGPPGE AGSPGNPGIG SIGPKGDPGD LGSVGPPGPP
GPREFTGSGS IVGPRGNPGE KGDKGEPGEG GQRGYPGNGG LSGQPGLPGM KGEKGLSGPA
GPRGKEGRPG NAGPPGFKGD RGLDGLGGIP GLPGQKGEAG YPGRDGPKGN SGPPGPPGGG
TFNDGAPGPP GLPGRPGNPG PPGTDGYPGA PGPAGPIGNT GGPGLPGYPG NEGLPGPKGD
KGDGGIPGAP GVSGPSGIPG LPGPKGEPGY RGTPGQSIPG LPGKDGKPGL DGAPGRKGEN
GLPGVRGPPG DSLNGLPGAP GQRGAPGPNG YDGRDGVNGL PGAPGTKGDR GGTCSACAPG
TKGEKGLPGY SGQPGPQGDR GLPGMPGPVG DAGDDGLPGP AGRPGSPGPP GQDGFPGLPG
QKGEPTQLTL RPGPPGYPGL KGENGFPGQP GVDGLPGPSG PVGPPGAPGY PGEKGDAGLP
GLSGKPGQDG LPGLPGNKGE AGYGQPGQPG FPGAKGDGGL PGLPGTPGLQ GMPGEPAPEN
QVNPAPPGQP GLPGLPGTKG EGGYPGRPGE VGQPGFPGLP GMKGDSGLPG PPGLPGHPGV
PGDKGFGGVP GLPGIPGPKG DVGNPGLPGL NGQKGEPGVG VPGQPGSPGF PGLKGDAGLP
GLPGTPGLEG QRGFPGAPGL KGGDGLPGLS GQPGYPGEKG DAGLPGVPGR EGSPGFPGQD
GLPGVPGMKG EDGLPGLPGV TGLKGDLGAP GQSGAPGLPG APGYPGMKGN AGIPGVPGFK
GDGGLPGLPG LNGPKGEPGV PGMPGTPGMK GNGGLPGLPG RDGLSGVPGM KGDRGFNGLP
GEKGEAGPAA RDGQKGDAGL PGQPGLRGPQ GPSGLPGVPG FKGETGLPGY GQPGQPGEKG
LPGIPGKAGR QGAPGSPGQD GLPGFPGMKG ESGYPGQDGL PGRDGLPGVP GQKGDLGQSG
QPGLSGAPGL DGQPGVPGIR GDKGQGGLPG IPGDRGMDGY PGQKGENGYP GQPGLPGLGG
EKGFAGTPGF PGLKGSPGYP GQDGLPGIPG LKGDSGFPGQ PGQEGLPGLS GEKGMGGLPG
MPGQPGQSIA GPVGPPGAPG LQGKDGFPGL PGQKGESGLS GLPGAPGLKG ESGMPGFPGA
KGDLGANGIP GKRGEDGLPG VPGRDGQPGI PGLKGEVGGA GLPGQPGFPG IPGLKGEGGL
PGFPGAKGEA GFPGTPGVPG YAGEKGDGGL PGLPGRDGLP GADGPVGPPG PSGPQNLVEP
GEKGLPGLPG APGLRGEKGM PGLDGPPGND GPPGLPGQRG NDGYPGAPGL SGEKGMGGLP
GFPGLDGQPG GPGAPGLPGA PGAAGPAYRD GFVLVKHSQT TEVPRCPEGQ TKLWDGYSLL
YIEGNEKSHN QDLGHAGSCL QRFSTMPFLF CDFNNVCNYA SRNEKSYWLS TSEAIPMMPV
NEREIEPYIS RCAVCEAPAN TIAVHSQTIQ IPNCPAGWSS LWIGYSFAMH TGAGAEGGGQ
SPSSPGSCLE DFRATPFIEC NGARGSCHYF ANKFSFWLTT IDNDSEFKVP ESQTLKSGNL
RTRVSRCQVC VKSTDGRH
