CO4A4_MOUSE
ID CO4A4_MOUSE Reviewed; 1682 AA.
AC Q9QZR9; Q149M2; Q64457;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Collagen alpha-4(IV) chain;
DE Flags: Precursor;
GN Name=Col4a4 {ECO:0000312|MGI:MGI:104687};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAD50450.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Embryonic kidney {ECO:0000312|EMBL:AAD50450.1};
RX PubMed=10534397; DOI=10.1006/geno.1999.5943;
RA Lu W., Phillips C.L., Killen P.D., Hlaing T., Harrison W.R., Elder F.F.B.,
RA Miner J.H., Overbeek P.A., Meisler M.H.;
RT "Insertional mutation of the collagen genes Col4a3 and Col4a4 in a mouse
RT model of Alport syndrome.";
RL Genomics 61:113-124(1999).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAI17710.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3] {ECO:0000305, ECO:0000312|EMBL:CAA84530.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1371-1682 (ISOFORM 1), FUNCTION, ASSOCIATED
RP WITH LAMB2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ {ECO:0000312|EMBL:CAA84530.1};
RC TISSUE=Kidney {ECO:0000312|EMBL:CAA84530.1};
RX PubMed=7962065; DOI=10.1083/jcb.127.3.879;
RA Miner J.H., Sanes J.R.;
RT "Collagen IV alpha 3, alpha 4, and alpha 5 chains in rodent basal laminae:
RT sequence, distribution, association with laminins, and developmental
RT switches.";
RL J. Cell Biol. 127:879-891(1994).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=10639489; DOI=10.1177/002215540004800208;
RA Miosge N., Quondamatteo F., Klenczar C., Herken R.;
RT "Nidogen-1. Expression and ultrastructural localization during the onset of
RT mesoderm formation in the early mouse embryo.";
RL J. Histochem. Cytochem. 48:229-238(2000).
RN [5] {ECO:0000305}
RP DEVELOPMENTAL STAGE.
RX PubMed=12225806; DOI=10.1016/s0945-053x(02)00014-8;
RA Kelley P.B., Sado Y., Duncan M.K.;
RT "Collagen IV in the developing lens capsule.";
RL Matrix Biol. 21:415-423(2002).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=29777959; DOI=10.1016/j.actbio.2018.05.023;
RA Felemban M., Dorgau B., Hunt N.C., Hallam D., Zerti D., Bauer R., Ding Y.,
RA Collin J., Steel D., Krasnogor N., Al-Aama J., Lindsay S., Mellough C.,
RA Lako M.;
RT "Extracellular matrix component expression in human pluripotent stem cell-
RT derived retinal organoids recapitulates retinogenesis in vivo and reveals
RT an important role for IMPG1 and CD44 in the development of photoreceptors
RT and interphotoreceptor matrix.";
RL Acta Biomater. 74:207-221(2018).
CC -!- FUNCTION: Type IV collagen is the major structural component of
CC glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork
CC together with laminins, proteoglycans and entactin/nidogen.
CC {ECO:0000250|UniProtKB:P53420, ECO:0000269|PubMed:10639489,
CC ECO:0000269|PubMed:7962065}.
CC -!- SUBUNIT: There are six type IV collagen isoforms, alpha 1(IV)-alpha
CC 6(IV), each of which can form a triple helix structure with 2 other
CC chains to generate type IV collagen network. The alpha 3(IV) chain
CC forms a triple helical protomer with alpha 4(IV) and alpha 5(IV); this
CC triple helical structure dimerizes through NC1-NC1 domain interactions
CC such that the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of one
CC protomer connect with the alpha 5(IV), alpha 4(IV) and alpha 3(IV)
CC chains of the opposite protomer, respectively (By similarity).
CC Associates with LAMB2 at the neuromuscular junction and in GBM.
CC {ECO:0000250|UniProtKB:P53420, ECO:0000269|PubMed:7962065}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix, basement membrane {ECO:0000255|PROSITE-ProRule:PRU00736,
CC ECO:0000269|PubMed:7962065}. Note=Colocalizes with COL4A3 and COL4A5 in
CC GBM, tubular basement membrane (TBM) and synaptic basal lamina (BL).
CC {ECO:0000250|UniProtKB:P53420, ECO:0000269|PubMed:7962065}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:10534397, ECO:0000269|PubMed:7962065};
CC IsoId=Q9QZR9-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334};
CC IsoId=Q9QZR9-2; Sequence=VSP_052356, VSP_052357;
CC -!- TISSUE SPECIFICITY: Expressed in Bruch's membrane, outer plexiform
CC layer, inner nuclear layer, inner plexiform layer, ganglion cell layer,
CC inner limiting membrane and around the blood vessels of the retina (at
CC protein level) (PubMed:29777959). Highly expressed in kidney and lung
CC (PubMed:7962065). Detected at lower levels in heart, muscle and skin
CC (PubMed:7962065). {ECO:0000269|PubMed:29777959,
CC ECO:0000269|PubMed:7962065}.
CC -!- DEVELOPMENTAL STAGE: The expression of collagen IV undergoes a
CC developmental shift in the developing lens capsule. During the early
CC stages of lens capsule development expression of collagens alpha 1(IV),
CC alpha 2(IV), alpha 5(IV) and alpha 6(IV) is observed; this is
CC consistent with the presence of fibrillar alpha 1(IV)-alpha 1(IV)-alpha
CC 2(IV) protomers and of elastic alpha 5(IV)-alpha 5(IV)-alpha 6(IV)
CC protomers. In the later stages of development components of the more
CC cross-linked alpha 3(IV)-alpha 4(IV)-alpha 5(IV) protomer appear.
CC {ECO:0000269|PubMed:12225806}.
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:0000250|UniProtKB:P53420, 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:0000250|UniProtKB:P53420, 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:0000250|UniProtKB:P53420, ECO:0000255|PROSITE-
CC 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 -!- MISCELLANEOUS: The kidneys of transgenic mice where the 5' portions of
CC both COL4A3 and COL4A4 and the shared intergenic promoter region were
CC deleted exhibit morphological and ultrastructural features
CC characteristic of the human hereditary disorder Alport syndrome,
CC including disorganization and multilamellar structure of the GBM and
CC delayed onset glomerulonephritis. {ECO:0000269|PubMed:10534397}.
CC -!- SIMILARITY: Belongs to the type IV collagen family.
CC {ECO:0000255|PROSITE-ProRule:PRU00736}.
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DR EMBL; AF169388; AAD50450.1; -; mRNA.
DR EMBL; BC117709; AAI17710.1; -; mRNA.
DR EMBL; Z35167; CAA84530.1; -; mRNA.
DR CCDS; CCDS35630.1; -. [Q9QZR9-1]
DR PIR; I48303; I48303.
DR RefSeq; NP_031761.1; NM_007735.2. [Q9QZR9-1]
DR AlphaFoldDB; Q9QZR9; -.
DR BioGRID; 198819; 1.
DR ComplexPortal; CPX-2961; Collagen type IV trimer variant 3.
DR STRING; 10090.ENSMUSP00000084282; -.
DR GlyGen; Q9QZR9; 3 sites.
DR iPTMnet; Q9QZR9; -.
DR PhosphoSitePlus; Q9QZR9; -.
DR MaxQB; Q9QZR9; -.
DR PaxDb; Q9QZR9; -.
DR PRIDE; Q9QZR9; -.
DR ProteomicsDB; 279130; -. [Q9QZR9-1]
DR ProteomicsDB; 279131; -. [Q9QZR9-2]
DR Antibodypedia; 54339; 138 antibodies from 23 providers.
DR DNASU; 12829; -.
DR Ensembl; ENSMUST00000087050; ENSMUSP00000084282; ENSMUSG00000067158. [Q9QZR9-1]
DR GeneID; 12829; -.
DR KEGG; mmu:12829; -.
DR UCSC; uc033fjy.1; mouse. [Q9QZR9-1]
DR CTD; 1286; -.
DR MGI; MGI:104687; Col4a4.
DR VEuPathDB; HostDB:ENSMUSG00000067158; -.
DR eggNOG; KOG3544; Eukaryota.
DR GeneTree; ENSGT00940000153991; -.
DR HOGENOM; CLU_002023_1_0_1; -.
DR InParanoid; Q9QZR9; -.
DR OMA; KGFPGCD; -.
DR OrthoDB; 63831at2759; -.
DR PhylomeDB; Q9QZR9; -.
DR TreeFam; TF344135; -.
DR Reactome; R-MMU-1442490; Collagen degradation.
DR Reactome; R-MMU-1474244; Extracellular matrix organization.
DR Reactome; R-MMU-1650814; Collagen biosynthesis and modifying enzymes.
DR Reactome; R-MMU-186797; Signaling by PDGF.
DR Reactome; R-MMU-2022090; Assembly of collagen fibrils and other multimeric structures.
DR Reactome; R-MMU-216083; Integrin cell surface interactions.
DR Reactome; R-MMU-2214320; Anchoring fibril formation.
DR Reactome; R-MMU-2243919; Crosslinking of collagen fibrils.
DR Reactome; R-MMU-3000157; Laminin interactions.
DR Reactome; R-MMU-3000171; Non-integrin membrane-ECM interactions.
DR Reactome; R-MMU-419037; NCAM1 interactions.
DR Reactome; R-MMU-8948216; Collagen chain trimerization.
DR BioGRID-ORCS; 12829; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Col4a4; mouse.
DR PRO; PR:Q9QZR9; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9QZR9; protein.
DR Bgee; ENSMUSG00000067158; Expressed in epithelium of lens and 90 other tissues.
DR Genevisible; Q9QZR9; MM.
DR GO; GO:0005604; C:basement membrane; IDA:MGI.
DR GO; GO:0005587; C:collagen type IV trimer; IDA:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
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; IPI:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0032836; P:glomerular basement membrane development; IMP:MGI.
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; 15.
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; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..1682
FT /note="Collagen alpha-4(IV) chain"
FT /evidence="ECO:0000255"
FT /id="PRO_0000283793"
FT DOMAIN 1457..1682
FT /note="Collagen IV NC1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00736"
FT REGION 31..56
FT /note="7S domain"
FT /evidence="ECO:0000250|UniProtKB:P53420"
FT REGION 56..255
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 57..1451
FT /note="Triple-helical region"
FT /evidence="ECO:0000250|UniProtKB:P53420"
FT REGION 379..1453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 86..88
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 137..139
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 181..183
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 587..589
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 593..595
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 716..718
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 980..982
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 992..994
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 1144..1146
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT COMPBIAS 379..412
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..443
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 487..501
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 525..539
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 548..562
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 580..602
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 606..636
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 916..931
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1010..1026
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1104..1126
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1210..1236
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1250..1270
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1290..1305
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1321..1338
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1344..1378
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 1197..1198
FT /note="Cleavage; by collagenase"
FT /evidence="ECO:0000250"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 661
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 1472..1561
FT /note="Or C-1472 with C-1558"
FT /evidence="ECO:0000250|UniProtKB:P53420,
FT ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1505..1558
FT /note="Or C-1505 with C-1561"
FT /evidence="ECO:0000250|UniProtKB:P53420,
FT ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1517..1523
FT /evidence="ECO:0000250|UniProtKB:P53420,
FT ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1580..1678
FT /note="Or C-1580 with C-1675"
FT /evidence="ECO:0000250|UniProtKB:P53420,
FT ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1614..1675
FT /note="Or C-1614 with C-1678"
FT /evidence="ECO:0000250|UniProtKB:P53420,
FT ECO:0000255|PROSITE-ProRule:PRU00736"
FT DISULFID 1626..1633
FT /evidence="ECO:0000250|UniProtKB:P53420,
FT ECO:0000255|PROSITE-ProRule:PRU00736"
FT VAR_SEQ 470..488
FT /note="GRRGAKGAKGNKGLCTCPP -> PLWIKQTLYMWSCSPFSFY (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052356"
FT VAR_SEQ 489..1682
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052357"
FT CONFLICT 1373
FT /note="L -> F (in Ref. 3; CAA84530)"
FT /evidence="ECO:0000305"
FT CONFLICT 1654
FT /note="A -> P (in Ref. 3; CAA84530)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1682 AA; 164096 MW; 6F7B679EDD76E904 CRC64;
MRCFFRWTKS FVTAPWSLIF ILFTIQYEYG SGKKYGGPCG GRNCSVCQCF PEKGSRGHPG
PLGPQGPIGP LGPLGPIGIP GEKGERGDSG SPGPPGEKGD KGPTGVPGFP GVDGVPGHPG
PPGPRGKPGV DGYNGSRGDP GYPGERGAPG PGGPPGQPGE NGEKGRSVYI TGGVKGIQGD
RGDPGPPGLP GSRGAQGSPG PMGHAGAPGL AGPIGHPGSP GLKGNPATGL KGQRGEPGEV
GQRGPPGPTL LVQPPDLSIY KGEKGVKGMP GMIGPPGPPG RKGAPGVGIK GEKGIPGFPG
PRGEPGSHGP PGFPGFKGIQ GAAGEPGLFG FLGPKGDLGD RGYPGPPGIL LTPAPPLKGV
PGDPGPPGYY GEIGDVGLPG PPGPPGRPGE TCPGMMGPPG PPGVPGPPGF PGEAGVPGRL
DCAPGKPGKP GLPGLPGAPG PEGPPGSDVI YCRPGCPGPM GEKGKVGPPG RRGAKGAKGN
KGLCTCPPGP MGPPGPPGPP GRQGSKGDLG LPGWHGEKGD PGQPGAEGPP GPPGRPGAMG
PPGHKGEKGD MVISRVKGQK GERGLDGPPG FPGPHGQDGG DGRPGERGDP GPRGDHKDAA
PGERGLPGLP GPPGRTGPEG PPGLGFPGPP GQRGLPGEPG RPGTRGFDGT KGQKGDSILC
NVSYPGKPGL PGLDGPPGLK GFPGPPGAPG MRCPDGQKGQ RGKPGMSGIP GPPGFRGDMG
DPGIKGEKGT SPIGPPGPPG SPGKDGQKGI PGDPAFGDPG PPGERGLPGA PGMKGQKGHP
GCPGAGGPPG IPGSPGLKGP KGREGSRGFP GIPGSPGHSC ERGAPGIPGQ PGLPGTPGDP
GAPGWKGQPG DMGPSGPAGM KGLPGLPGLP GADGLRGPPG IPGPNGEDGL PGLPGLKGLP
GLPGFPGFPG ERGKPGPDGE PGRKGEVGEK GWPGLKGDLG ERGAKGDRGL PGDAGEAVTS
RKGEPGDAGP PGDGGFSGER GDKGSSGMRG GRGDPGRDGL PGLHRGQPGI DGPPGPPGPP
GPPGSPGLRG VIGFPGFPGD QGDPGSPGPP GFPGDDGARG PKGYKGDPAS QCGPPGPKGE
PGSPGYQGRT GVPGEKGFPG DEGPRGPPGR PGQPGSFGPP GCPGDPGMPG LKGHPGEVGD
PGPRGDAGDF GRPGPAGVKG PLGSPGLNGL HGLKGEKGTK GASGLLEMGP PGPMGMPGQK
GEKGDPGSPG ISPPGLPGEK GFPGPPGRPG PPGPAGAPGR AAKGDIPDPG PPGDRGPPGP
DGPRGVPGPP GSPGNVDLLK GDPGDCGLPG PPGSRGPPGP PGCQGPPGCD GKDGQKGPMG
LPGLPGPPGL PGAPGEKGLP GPPGRKGPVG PPGCRGEPGP PADVDSCPRI PGLPGVPGPR
GPEGAMGEPG RRGLPGPGCK GEPGPDGRRG QDGIPGSPGP PGRKGDTGEA GCPGAPGPPG
PTGDPGPKGF GPGSLSGFLL VLHSQTDQEP ACPVGMPRLW TGYSLLYMEG QEKAHNQDLG
LAGSCLPVFS TLPFAYCNIH QVCHYAQRND RSYWLSSAAP LPMMPLSEEE IRSYISRCAV
CEAPAQAVAV HSQDQSIPPC PRTWRSLWIG YSFLMHTGAG DQGGGQALMS PGSCLEDFRA
APFVECQGRQ GTCHFFANEY SFWLTTVNPD LQFASGPSPD TLKEVQAQRR KISRCQVCMK
HS
