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Protein

Collagen alpha-4(IV) chain

Gene

Col4a4

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

Functioni

Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.By similarity2 Publications

GO - Molecular functioni

  • extracellular matrix structural constituent Source: UniProtKB

GO - Biological processi

  • glomerular basement membrane development Source: MGI
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-MMU-1442490. Collagen degradation.
R-MMU-1474244. Extracellular matrix organization.
R-MMU-1650814. Collagen biosynthesis and modifying enzymes.
R-MMU-186797. Signaling by PDGF.
R-MMU-2022090. Assembly of collagen fibrils and other multimeric structures.
R-MMU-216083. Integrin cell surface interactions.
R-MMU-2214320. Anchoring fibril formation.
R-MMU-3000157. Laminin interactions.
R-MMU-3000171. Non-integrin membrane-ECM interactions.
R-MMU-419037. NCAM1 interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Collagen alpha-4(IV) chain
Gene namesi
Name:Col4a4Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:104687. Col4a4.

Subcellular locationi

  • Secretedextracellular spaceextracellular matrixbasement membrane PROSITE-ProRule annotation1 Publication

  • Note: Colocalizes with COL4A3 and COL4A5 in GBM, tubular basement membrane (TBM) and synaptic basal lamina (BL).By similarity1 Publication

GO - Cellular componenti

  • basal lamina Source: UniProtKB
  • basement membrane Source: MGI
  • collagen type IV trimer Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Basement membrane, Extracellular matrix, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232Sequence analysisAdd
BLAST
Chaini33 – 16821650Collagen alpha-4(IV) chainSequence analysisPRO_0000283793Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi43 – 431N-linked (GlcNAc...)Sequence analysis
Glycosylationi134 – 1341N-linked (GlcNAc...)Sequence analysis
Glycosylationi661 – 6611N-linked (GlcNAc...)Sequence analysis
Disulfide bondi1472 ↔ 1561Or C-1472 with C-1558PROSITE-ProRule annotationBy similarity
Disulfide bondi1505 ↔ 1558Or C-1505 with C-1561PROSITE-ProRule annotationBy similarity
Disulfide bondi1517 ↔ 1523PROSITE-ProRule annotationBy similarity
Disulfide bondi1580 ↔ 1678Or C-1580 with C-1675PROSITE-ProRule annotationBy similarity
Disulfide bondi1614 ↔ 1675Or C-1614 with C-1678PROSITE-ProRule annotationBy similarity
Disulfide bondi1626 ↔ 1633PROSITE-ProRule annotationBy similarity

Post-translational modificationi

Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.PROSITE-ProRule annotationBy similarity
Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.PROSITE-ProRule annotationBy similarity
The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei1197 – 11982Cleavage; by collagenaseBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Hydroxylation

Proteomic databases

MaxQBiQ9QZR9.
PaxDbiQ9QZR9.
PRIDEiQ9QZR9.

PTM databases

iPTMnetiQ9QZR9.
PhosphoSiteiQ9QZR9.

Expressioni

Tissue specificityi

Highly expressed in kidney and lung. Detected at lower levels in heart, muscle and skin.1 Publication

Developmental stagei

The expression of collagen IV undergoes a developmental shift in the developing lens capsule. During the early stages of lens capsule development expression of collagens alpha 1(IV), alpha 2(IV), alpha 5(IV) and alpha 6(IV) is observed; this is consistent with the presence of fibrillar alpha 1(IV)-alpha 1(IV)-alpha 2(IV) protomers and of elastic alpha 5(IV)-alpha 5(IV)-alpha 6(IV) protomers. In the later stages of development components of the more cross-linked alpha 3(IV)-alpha 4(IV)-alpha 5(IV) protomer appear.1 Publication

Gene expression databases

BgeeiQ9QZR9.
CleanExiMM_COL4A4.
GenevisibleiQ9QZR9. MM.

Interactioni

Subunit structurei

There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. The alpha 3(IV) chain forms a triple helical protomer with alpha 4(IV) and alpha 5(IV); this triple helical structure dimerizes through NC1-NC1 domain interactions such that the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of one protomer connect with the alpha 5(IV), alpha 4(IV) and alpha 3(IV) chains of the opposite protomer, respectively (By similarity). Associates with LAMB2 at the neuromuscular junction and in GBM.By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000084282.

Structurei

3D structure databases

ProteinModelPortaliQ9QZR9.
SMRiQ9QZR9. Positions 1457-1680.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1457 – 1682226Collagen IV NC1PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni31 – 56267S domainBy similarityAdd
BLAST
Regioni57 – 14511395Triple-helical regionBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi86 – 883Cell attachment siteSequence analysis
Motifi137 – 1393Cell attachment siteSequence analysis
Motifi181 – 1833Cell attachment siteSequence analysis
Motifi587 – 5893Cell attachment siteSequence analysis
Motifi593 – 5953Cell attachment siteSequence analysis
Motifi716 – 7183Cell attachment siteSequence analysis
Motifi980 – 9823Cell attachment siteSequence analysis
Motifi992 – 9943Cell attachment siteSequence analysis
Motifi1144 – 11463Cell attachment siteSequence analysis

Domaini

Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.PROSITE-ProRule annotationBy similarity

Sequence similaritiesi

Belongs to the type IV collagen family.PROSITE-ProRule annotation
Contains 1 collagen IV NC1 (C-terminal non-collagenous) domain.PROSITE-ProRule annotation

Keywords - Domaini

Collagen, Repeat, Signal

Phylogenomic databases

eggNOGiKOG3544. Eukaryota.
ENOG410XNMM. LUCA.
GeneTreeiENSGT00840000129673.
HOGENOMiHOG000085652.
HOVERGENiHBG004933.
InParanoidiQ9QZR9.
KOiK06237.
OMAiPPGYKGF.
OrthoDBiEOG7RZ5P3.
PhylomeDBiQ9QZR9.
TreeFamiTF344135.

Family and domain databases

Gene3Di2.170.240.10. 1 hit.
InterProiIPR016187. C-type_lectin_fold.
IPR008160. Collagen.
IPR001442. Collagen_VI_NC.
[Graphical view]
PfamiPF01413. C4. 2 hits.
PF01391. Collagen. 15 hits.
[Graphical view]
SMARTiSM00111. C4. 2 hits.
[Graphical view]
SUPFAMiSSF56436. SSF56436. 2 hits.
PROSITEiPS51403. NC1_IV. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 12 Publications (identifier: Q9QZR9-1) [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
MRCFFRWTKS FVTAPWSLIF ILFTIQYEYG SGKKYGGPCG GRNCSVCQCF
60 70 80 90 100
PEKGSRGHPG PLGPQGPIGP LGPLGPIGIP GEKGERGDSG SPGPPGEKGD
110 120 130 140 150
KGPTGVPGFP GVDGVPGHPG PPGPRGKPGV DGYNGSRGDP GYPGERGAPG
160 170 180 190 200
PGGPPGQPGE NGEKGRSVYI TGGVKGIQGD RGDPGPPGLP GSRGAQGSPG
210 220 230 240 250
PMGHAGAPGL AGPIGHPGSP GLKGNPATGL KGQRGEPGEV GQRGPPGPTL
260 270 280 290 300
LVQPPDLSIY KGEKGVKGMP GMIGPPGPPG RKGAPGVGIK GEKGIPGFPG
310 320 330 340 350
PRGEPGSHGP PGFPGFKGIQ GAAGEPGLFG FLGPKGDLGD RGYPGPPGIL
360 370 380 390 400
LTPAPPLKGV PGDPGPPGYY GEIGDVGLPG PPGPPGRPGE TCPGMMGPPG
410 420 430 440 450
PPGVPGPPGF PGEAGVPGRL DCAPGKPGKP GLPGLPGAPG PEGPPGSDVI
460 470 480 490 500
YCRPGCPGPM GEKGKVGPPG RRGAKGAKGN KGLCTCPPGP MGPPGPPGPP
510 520 530 540 550
GRQGSKGDLG LPGWHGEKGD PGQPGAEGPP GPPGRPGAMG PPGHKGEKGD
560 570 580 590 600
MVISRVKGQK GERGLDGPPG FPGPHGQDGG DGRPGERGDP GPRGDHKDAA
610 620 630 640 650
PGERGLPGLP GPPGRTGPEG PPGLGFPGPP GQRGLPGEPG RPGTRGFDGT
660 670 680 690 700
KGQKGDSILC NVSYPGKPGL PGLDGPPGLK GFPGPPGAPG MRCPDGQKGQ
710 720 730 740 750
RGKPGMSGIP GPPGFRGDMG DPGIKGEKGT SPIGPPGPPG SPGKDGQKGI
760 770 780 790 800
PGDPAFGDPG PPGERGLPGA PGMKGQKGHP GCPGAGGPPG IPGSPGLKGP
810 820 830 840 850
KGREGSRGFP GIPGSPGHSC ERGAPGIPGQ PGLPGTPGDP GAPGWKGQPG
860 870 880 890 900
DMGPSGPAGM KGLPGLPGLP GADGLRGPPG IPGPNGEDGL PGLPGLKGLP
910 920 930 940 950
GLPGFPGFPG ERGKPGPDGE PGRKGEVGEK GWPGLKGDLG ERGAKGDRGL
960 970 980 990 1000
PGDAGEAVTS RKGEPGDAGP PGDGGFSGER GDKGSSGMRG GRGDPGRDGL
1010 1020 1030 1040 1050
PGLHRGQPGI DGPPGPPGPP GPPGSPGLRG VIGFPGFPGD QGDPGSPGPP
1060 1070 1080 1090 1100
GFPGDDGARG PKGYKGDPAS QCGPPGPKGE PGSPGYQGRT GVPGEKGFPG
1110 1120 1130 1140 1150
DEGPRGPPGR PGQPGSFGPP GCPGDPGMPG LKGHPGEVGD PGPRGDAGDF
1160 1170 1180 1190 1200
GRPGPAGVKG PLGSPGLNGL HGLKGEKGTK GASGLLEMGP PGPMGMPGQK
1210 1220 1230 1240 1250
GEKGDPGSPG ISPPGLPGEK GFPGPPGRPG PPGPAGAPGR AAKGDIPDPG
1260 1270 1280 1290 1300
PPGDRGPPGP DGPRGVPGPP GSPGNVDLLK GDPGDCGLPG PPGSRGPPGP
1310 1320 1330 1340 1350
PGCQGPPGCD GKDGQKGPMG LPGLPGPPGL PGAPGEKGLP GPPGRKGPVG
1360 1370 1380 1390 1400
PPGCRGEPGP PADVDSCPRI PGLPGVPGPR GPEGAMGEPG RRGLPGPGCK
1410 1420 1430 1440 1450
GEPGPDGRRG QDGIPGSPGP PGRKGDTGEA GCPGAPGPPG PTGDPGPKGF
1460 1470 1480 1490 1500
GPGSLSGFLL VLHSQTDQEP ACPVGMPRLW TGYSLLYMEG QEKAHNQDLG
1510 1520 1530 1540 1550
LAGSCLPVFS TLPFAYCNIH QVCHYAQRND RSYWLSSAAP LPMMPLSEEE
1560 1570 1580 1590 1600
IRSYISRCAV CEAPAQAVAV HSQDQSIPPC PRTWRSLWIG YSFLMHTGAG
1610 1620 1630 1640 1650
DQGGGQALMS PGSCLEDFRA APFVECQGRQ GTCHFFANEY SFWLTTVNPD
1660 1670 1680
LQFASGPSPD TLKEVQAQRR KISRCQVCMK HS
Length:1,682
Mass (Da):164,096
Last modified:May 1, 2000 - v1
Checksum:i6F7B679EDD76E904
GO
Isoform 21 Publication (identifier: Q9QZR9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     470-488: GRRGAKGAKGNKGLCTCPP → PLWIKQTLYMWSCSPFSFY
     489-1682: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:488
Mass (Da):47,945
Checksum:i480DF110A11293C3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1373 – 13731L → F in CAA84530 (PubMed:7962065).Curated
Sequence conflicti1654 – 16541A → P in CAA84530 (PubMed:7962065).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei470 – 48819GRRGA…CTCPP → PLWIKQTLYMWSCSPFSFY in isoform 2. 1 PublicationVSP_052356Add
BLAST
Alternative sequencei489 – 16821194Missing in isoform 2. 1 PublicationVSP_052357Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169388 mRNA. Translation: AAD50450.1.
BC117709 mRNA. Translation: AAI17710.1.
Z35167 mRNA. Translation: CAA84530.1.
CCDSiCCDS35630.1. [Q9QZR9-1]
PIRiI48303.
RefSeqiNP_031761.1. NM_007735.2. [Q9QZR9-1]
UniGeneiMm.40253.
Mm.479772.

Genome annotation databases

EnsembliENSMUST00000087050; ENSMUSP00000084282; ENSMUSG00000067158. [Q9QZR9-1]
GeneIDi12829.
KEGGimmu:12829.
UCSCiuc033fjy.1. mouse. [Q9QZR9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169388 mRNA. Translation: AAD50450.1.
BC117709 mRNA. Translation: AAI17710.1.
Z35167 mRNA. Translation: CAA84530.1.
CCDSiCCDS35630.1. [Q9QZR9-1]
PIRiI48303.
RefSeqiNP_031761.1. NM_007735.2. [Q9QZR9-1]
UniGeneiMm.40253.
Mm.479772.

3D structure databases

ProteinModelPortaliQ9QZR9.
SMRiQ9QZR9. Positions 1457-1680.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000084282.

PTM databases

iPTMnetiQ9QZR9.
PhosphoSiteiQ9QZR9.

Proteomic databases

MaxQBiQ9QZR9.
PaxDbiQ9QZR9.
PRIDEiQ9QZR9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000087050; ENSMUSP00000084282; ENSMUSG00000067158. [Q9QZR9-1]
GeneIDi12829.
KEGGimmu:12829.
UCSCiuc033fjy.1. mouse. [Q9QZR9-1]

Organism-specific databases

CTDi1286.
MGIiMGI:104687. Col4a4.

Phylogenomic databases

eggNOGiKOG3544. Eukaryota.
ENOG410XNMM. LUCA.
GeneTreeiENSGT00840000129673.
HOGENOMiHOG000085652.
HOVERGENiHBG004933.
InParanoidiQ9QZR9.
KOiK06237.
OMAiPPGYKGF.
OrthoDBiEOG7RZ5P3.
PhylomeDBiQ9QZR9.
TreeFamiTF344135.

Enzyme and pathway databases

ReactomeiR-MMU-1442490. Collagen degradation.
R-MMU-1474244. Extracellular matrix organization.
R-MMU-1650814. Collagen biosynthesis and modifying enzymes.
R-MMU-186797. Signaling by PDGF.
R-MMU-2022090. Assembly of collagen fibrils and other multimeric structures.
R-MMU-216083. Integrin cell surface interactions.
R-MMU-2214320. Anchoring fibril formation.
R-MMU-3000157. Laminin interactions.
R-MMU-3000171. Non-integrin membrane-ECM interactions.
R-MMU-419037. NCAM1 interactions.

Miscellaneous databases

PROiQ9QZR9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9QZR9.
CleanExiMM_COL4A4.
GenevisibleiQ9QZR9. MM.

Family and domain databases

Gene3Di2.170.240.10. 1 hit.
InterProiIPR016187. C-type_lectin_fold.
IPR008160. Collagen.
IPR001442. Collagen_VI_NC.
[Graphical view]
PfamiPF01413. C4. 2 hits.
PF01391. Collagen. 15 hits.
[Graphical view]
SMARTiSM00111. C4. 2 hits.
[Graphical view]
SUPFAMiSSF56436. SSF56436. 2 hits.
PROSITEiPS51403. NC1_IV. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Insertional mutation of the collagen genes Col4a3 and Col4a4 in a mouse model of Alport syndrome."
    Lu W., Phillips C.L., Killen P.D., Hlaing T., Harrison W.R., Elder F.F.B., Miner J.H., Overbeek P.A., Meisler M.H.
    Genomics 61:113-124(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Embryonic kidneyImported.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  3. "Collagen IV alpha 3, alpha 4, and alpha 5 chains in rodent basal laminae: sequence, distribution, association with laminins, and developmental switches."
    Miner J.H., Sanes J.R.
    J. Cell Biol. 127:879-891(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1371-1682 (ISOFORM 1), FUNCTION, ASSOCIATED WITH LAMB2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Strain: BALB/cJImported.
    Tissue: KidneyImported.
  4. "Nidogen-1. Expression and ultrastructural localization during the onset of mesoderm formation in the early mouse embryo."
    Miosge N., Quondamatteo F., Klenczar C., Herken R.
    J. Histochem. Cytochem. 48:229-238(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Collagen IV in the developing lens capsule."
    Kelley P.B., Sado Y., Duncan M.K.
    Matrix Biol. 21:415-423(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiCO4A4_MOUSE
AccessioniPrimary (citable) accession number: Q9QZR9
Secondary accession number(s): Q149M2, Q64457
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 17, 2007
Last sequence update: May 1, 2000
Last modified: June 8, 2016
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

The kidneys of transgenic mice where the 5' portions of both COL4A3 and COL4A4 and the shared intergenic promoter region were deleted exhibit morphological and ultrastructural features characteristic of the human hereditary disorder Alport syndrome, including disorganization and multilamellar structure of the GBM and delayed onset glomerulonephritis.1 Publication

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

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 one 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.