Reviewed, UniProtKB/Swiss-Prot Q9QZR9 (CO4A4_MOUSE)

Names and origin

Protein names

Recommended name:
    Collagen alpha-4(IV) chain

Gene names

Name:

Col4a4

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	1682 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	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. Ref.3 Ref.4 UniProtKB P53420
Subunit structure	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. Ref.3 UniProtKB P53420
Subcellular location	Secreted › extracellular space › extracellular matrix › basement membrane. Note: Colocalizes with COL4A3 and COL4A5 in GBM, tubular basement membrane (TBM) and synaptic basal lamina (BL). Ref.3
Tissue specificity	Highly expressed in kidney and lung. Detected at lower levels in heart, muscle and skin. Ref.3
Developmental stage	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. Ref.5
Domain	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 By similarity. UniProtKB P53420
Post-translational modification	Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains By similarity. UniProtKB P53420 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 By similarity. UniProtKB P53420
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. Ref.1
Sequence similarities	Belongs to the type IV collagen family. Contains 1 collagen IV NC1 (C-terminal non-collagenous) domain.

Ontologies

Keywords
Cellular component	Basement membrane Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing
Domain	Collagen Repeat Signal
PTM	Disulfide bond Glycoprotein Hydroxylation
Gene Ontology (GO)
Cellular component	collagen type IV Ref.3 Inferred from direct assay. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	binding Inferred from electronic annotation. Source: InterPro extracellular matrix structural constituent Ref.3 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.3 Ref.1 (identifier: Q9QZR9-1)

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.

Isoform 2 Ref.2 (identifier: Q9QZR9-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 32	32	Potential
	Chain	33 – 1682	1650	Collagen alpha-4(IV) chain		PRO_0000283793
Regions
	Domain	1457 – 1682	226	Collagen IV NC1
	Region	31 – 56	26	7S domain By similarity UniProtKB P53420
	Region	57 – 1451	1395	Triple-helical region By similarity UniProtKB P53420
	Motif	86 – 88	3	Cell attachment site Potential
	Motif	137 – 139	3	Cell attachment site Potential
	Motif	181 – 183	3	Cell attachment site Potential
	Motif	587 – 589	3	Cell attachment site Potential
	Motif	593 – 595	3	Cell attachment site Potential
	Motif	716 – 718	3	Cell attachment site Potential
	Motif	980 – 982	3	Cell attachment site Potential
	Motif	992 – 994	3	Cell attachment site Potential
	Motif	1144 – 1146	3	Cell attachment site Potential
Sites
	Site	1197 – 1198	2	Cleavage; by collagenase By similarity UniProtKB P53420
Amino acid modifications
	Glycosylation	43	1	N-linked (GlcNAc...) Potential
	Glycosylation	134	1	N-linked (GlcNAc...) Potential
	Glycosylation	661	1	N-linked (GlcNAc...) Potential
	Disulfide bond	1472 ↔ 1561		Or C-1472 with C-1558 By similarity UniProtKB P53420
	Disulfide bond	1505 ↔ 1558		Or C-1505 with C-1561 By similarity UniProtKB P53420
	Disulfide bond	1517 ↔ 1523		By similarity UniProtKB P53420
	Disulfide bond	1580 ↔ 1678		Or C-1580 with C-1675 By similarity UniProtKB P53420
	Disulfide bond	1614 ↔ 1675		Or C-1614 with C-1678 By similarity UniProtKB P53420
	Disulfide bond	1626 ↔ 1633		By similarity UniProtKB P53420
Natural variations
	Alternative sequence	470 – 488	19	GRRGA…CTCPP → PLWIKQTLYMWSCSPFSFY in isoform 2. Ref.2		VSP_052356
	Alternative sequence	489 – 1682	1194	Missing in isoform 2. Ref.2		VSP_052357
Experimental info
	Sequence conflict	1373	1	L → F in CAA84530. Ref.3
	Sequence conflict	1654	1	A → P in CAA84530. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 6F7B679EDD76E904	FASTA	1,682	164,096
	10 20 30 40 50 60 MRCFFRWTKS FVTAPWSLIF ILFTIQYEYG SGKKYGGPCG GRNCSVCQCF PEKGSRGHPG 70 80 90 100 110 120 PLGPQGPIGP LGPLGPIGIP GEKGERGDSG SPGPPGEKGD KGPTGVPGFP GVDGVPGHPG 130 140 150 160 170 180 PPGPRGKPGV DGYNGSRGDP GYPGERGAPG PGGPPGQPGE NGEKGRSVYI TGGVKGIQGD 190 200 210 220 230 240 RGDPGPPGLP GSRGAQGSPG PMGHAGAPGL AGPIGHPGSP GLKGNPATGL KGQRGEPGEV 250 260 270 280 290 300 GQRGPPGPTL LVQPPDLSIY KGEKGVKGMP GMIGPPGPPG RKGAPGVGIK GEKGIPGFPG 310 320 330 340 350 360 PRGEPGSHGP PGFPGFKGIQ GAAGEPGLFG FLGPKGDLGD RGYPGPPGIL LTPAPPLKGV 370 380 390 400 410 420 PGDPGPPGYY GEIGDVGLPG PPGPPGRPGE TCPGMMGPPG PPGVPGPPGF PGEAGVPGRL 430 440 450 460 470 480 DCAPGKPGKP GLPGLPGAPG PEGPPGSDVI YCRPGCPGPM GEKGKVGPPG RRGAKGAKGN 490 500 510 520 530 540 KGLCTCPPGP MGPPGPPGPP GRQGSKGDLG LPGWHGEKGD PGQPGAEGPP GPPGRPGAMG 550 560 570 580 590 600 PPGHKGEKGD MVISRVKGQK GERGLDGPPG FPGPHGQDGG DGRPGERGDP GPRGDHKDAA 610 620 630 640 650 660 PGERGLPGLP GPPGRTGPEG PPGLGFPGPP GQRGLPGEPG RPGTRGFDGT KGQKGDSILC 670 680 690 700 710 720 NVSYPGKPGL PGLDGPPGLK GFPGPPGAPG MRCPDGQKGQ RGKPGMSGIP GPPGFRGDMG 730 740 750 760 770 780 DPGIKGEKGT SPIGPPGPPG SPGKDGQKGI PGDPAFGDPG PPGERGLPGA PGMKGQKGHP 790 800 810 820 830 840 GCPGAGGPPG IPGSPGLKGP KGREGSRGFP GIPGSPGHSC ERGAPGIPGQ PGLPGTPGDP 850 860 870 880 890 900 GAPGWKGQPG DMGPSGPAGM KGLPGLPGLP GADGLRGPPG IPGPNGEDGL PGLPGLKGLP 910 920 930 940 950 960 GLPGFPGFPG ERGKPGPDGE PGRKGEVGEK GWPGLKGDLG ERGAKGDRGL PGDAGEAVTS 970 980 990 1000 1010 1020 RKGEPGDAGP PGDGGFSGER GDKGSSGMRG GRGDPGRDGL PGLHRGQPGI DGPPGPPGPP 1030 1040 1050 1060 1070 1080 GPPGSPGLRG VIGFPGFPGD QGDPGSPGPP GFPGDDGARG PKGYKGDPAS QCGPPGPKGE 1090 1100 1110 1120 1130 1140 PGSPGYQGRT GVPGEKGFPG DEGPRGPPGR PGQPGSFGPP GCPGDPGMPG LKGHPGEVGD 1150 1160 1170 1180 1190 1200 PGPRGDAGDF GRPGPAGVKG PLGSPGLNGL HGLKGEKGTK GASGLLEMGP PGPMGMPGQK 1210 1220 1230 1240 1250 1260 GEKGDPGSPG ISPPGLPGEK GFPGPPGRPG PPGPAGAPGR AAKGDIPDPG PPGDRGPPGP 1270 1280 1290 1300 1310 1320 DGPRGVPGPP GSPGNVDLLK GDPGDCGLPG PPGSRGPPGP PGCQGPPGCD GKDGQKGPMG 1330 1340 1350 1360 1370 1380 LPGLPGPPGL PGAPGEKGLP GPPGRKGPVG PPGCRGEPGP PADVDSCPRI PGLPGVPGPR 1390 1400 1410 1420 1430 1440 GPEGAMGEPG RRGLPGPGCK GEPGPDGRRG QDGIPGSPGP PGRKGDTGEA GCPGAPGPPG 1450 1460 1470 1480 1490 1500 PTGDPGPKGF GPGSLSGFLL VLHSQTDQEP ACPVGMPRLW TGYSLLYMEG QEKAHNQDLG 1510 1520 1530 1540 1550 1560 LAGSCLPVFS TLPFAYCNIH QVCHYAQRND RSYWLSSAAP LPMMPLSEEE IRSYISRCAV 1570 1580 1590 1600 1610 1620 CEAPAQAVAV HSQDQSIPPC PRTWRSLWIG YSFLMHTGAG DQGGGQALMS PGSCLEDFRA 1630 1640 1650 1660 1670 1680 APFVECQGRQ GTCHFFANEY SFWLTTVNPD LQFASGPSPD TLKEVQAQRR KISRCQVCMK HS
	Isoform 2. Checksum: 480DF110A11293C3	FASTA	488	47,945
	10 20 30 40 50 60 MRCFFRWTKS FVTAPWSLIF ILFTIQYEYG SGKKYGGPCG GRNCSVCQCF PEKGSRGHPG 70 80 90 100 110 120 PLGPQGPIGP LGPLGPIGIP GEKGERGDSG SPGPPGEKGD KGPTGVPGFP GVDGVPGHPG 130 140 150 160 170 180 PPGPRGKPGV DGYNGSRGDP GYPGERGAPG PGGPPGQPGE NGEKGRSVYI TGGVKGIQGD 190 200 210 220 230 240 RGDPGPPGLP GSRGAQGSPG PMGHAGAPGL AGPIGHPGSP GLKGNPATGL KGQRGEPGEV 250 260 270 280 290 300 GQRGPPGPTL LVQPPDLSIY KGEKGVKGMP GMIGPPGPPG RKGAPGVGIK GEKGIPGFPG 310 320 330 340 350 360 PRGEPGSHGP PGFPGFKGIQ GAAGEPGLFG FLGPKGDLGD RGYPGPPGIL LTPAPPLKGV 370 380 390 400 410 420 PGDPGPPGYY GEIGDVGLPG PPGPPGRPGE TCPGMMGPPG PPGVPGPPGF PGEAGVPGRL 430 440 450 460 470 480 DCAPGKPGKP GLPGLPGAPG PEGPPGSDVI YCRPGCPGPM GEKGKVGPPP LWIKQTLYMW SCSPFSFY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 10534397] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Embryonic kidney.
[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: 15489334] [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: 7962065] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1371-1682 (ISOFORM 1), FUNCTION, ASSOCIATED WITH LAMB2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: BALB/c. Tissue: Kidney.
[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: 10639489] [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: 12225806] [Abstract] Cited for: DEVELOPMENTAL STAGE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF169388 mRNA. Translation: AAD50450.1. BC117709 mRNA. Translation: AAI17710.1. Z35167 mRNA. Translation: CAA84530.1.
IPI	IPI00626353. IPI00844776.
PIR	I48303.
RefSeq	NP_031761.1.
UniGene	Mm.40253 Mm.460425
3D structure databases
HSSP	HSSP built from PDB template 1LI1 based on UniProtKB P08572.
ModBase	Search...
PTM databases
PhosphoSite	Q9QZR9.
Genome annotation databases
Ensembl	ENSMUSG00000067158. Mus musculus. [Contig view]
GeneID	12829.
KEGG	mmu:12829.
Organism-specific databases
MGI	MGI:104687. Col4a4.
Phylogenomic databases
HOVERGEN	Q9QZR9.
OMA	Q9QZR9. DMGDPGF.
Gene expression databases
ArrayExpress	Q9QZR9.
Bgee	Q9QZR9.
CleanEx	MM_COL4A4.
Family and domain databases
InterPro	IPR008160. Collagen. IPR001442. Procollagn4_C. [Graphical view]
Gene3D	G3DSA:2.170.240.10. Procollagn4_C. 1 hit.
Pfam	PF01413. C4. 2 hits. PF01391. Collagen. 23 hits. [Graphical view]
ProDom	PD000007. Clg_helix. 6 hits. PD003923. Procollagn4_C. 2 hits. [Graphical view] [Entries sharing at least one domain]
SMART	SM00111. C4. 2 hits. [Graphical view]
PROSITE	PS51403. NC1_IV. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	282326.
SOURCE	Search...

Entry information

Entry name

CO4A4_MOUSE

Accession

Primary (citable) accession number: Q9QZR9
Secondary accession number(s): Q149M2, Q64457

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 17, 2007
Last sequence update:	May 1, 2000
Last modified:	June 16, 2009
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)